Nutrition and Different Diseases

**29**

meats, and salt).

**Chapter 3**

**Abstract**

presented.

**1. Introduction**

Nutrition

*and María Pilar Zafrilla*

Cardiovascular Disease and

*Javier Marhuenda, Débora Villaño, Begoña Cerdá* 

**Keywords:** nutrition, cardiovascular diseases, CVR, omega-3

Many studies have been published on the relationship between the risk of cardiovascular disease and various nutrients, foods, and eating patterns. Despite the well-accepted concept that diet has a significant influence on the development and prevention of cardiovascular disease, foods considered healthy or harmful have varied over the years. Cardiovascular diseases are one of the main causes of illness and death in Western countries, and cardiovascular drugs are the most commonly used medications. There are two types of factors involved in the development of cardiovascular disease. Some factor can be modified, like lifestyle, diet, environment, or smoking. Others such as genetic factors, gender, history, or age cannot be modified. In this chapter, some food, nutrients, and bioactive compounds that are susceptible to exert beneficial of harmful properties on cardiovascular disease are

Diet and healthy lifestyle are the best tools to have good cardiovascular health.

This relationship is so direct because the majority of cardiovascular diseases have their origin atherosclerotic plaque, hypertension, and obesity. These three cardiovascular risk factors are directly related to dietary habits and lifestyle. It is widely demonstrated from the scientific point of view that dietary habits influence cardiovascular health. There are diets such as the Dietary Approaches to Stop Hypertension (DASH) as the Mediterranean diet, which are clear examples of heart-healthy diets. However, there are discrepancies with regard to what are the components of a heart-healthy diet. There are foods that are considered healthy for the heart in all editions of food guides and recommendations, among which we can find fruits, vegetables, and whole grains, which have always been considered fundamental for health, and there are other foods that can currently be considered heart-healthy, since there are numerous studies that this is supported, such as virgin olive oil, pulses, fish, and nuts (especially nuts). This chapter focuses on the most recent food evidence (e.g., fruits and vegetables) and nutrients (such as fiber and omega-3) considered to be cardio-healthy today and as a counterpoint, the scientific clairvoyance that exists on those foods considered less heart-healthy because they are considered to increase cardiovascular risk (eggs, dairy products,

#### **Chapter 3**

## Cardiovascular Disease and Nutrition

*Javier Marhuenda, Débora Villaño, Begoña Cerdá and María Pilar Zafrilla*

#### **Abstract**

Many studies have been published on the relationship between the risk of cardiovascular disease and various nutrients, foods, and eating patterns. Despite the well-accepted concept that diet has a significant influence on the development and prevention of cardiovascular disease, foods considered healthy or harmful have varied over the years. Cardiovascular diseases are one of the main causes of illness and death in Western countries, and cardiovascular drugs are the most commonly used medications. There are two types of factors involved in the development of cardiovascular disease. Some factor can be modified, like lifestyle, diet, environment, or smoking. Others such as genetic factors, gender, history, or age cannot be modified. In this chapter, some food, nutrients, and bioactive compounds that are susceptible to exert beneficial of harmful properties on cardiovascular disease are presented.

**Keywords:** nutrition, cardiovascular diseases, CVR, omega-3

#### **1. Introduction**

Diet and healthy lifestyle are the best tools to have good cardiovascular health. This relationship is so direct because the majority of cardiovascular diseases have their origin atherosclerotic plaque, hypertension, and obesity. These three cardiovascular risk factors are directly related to dietary habits and lifestyle. It is widely demonstrated from the scientific point of view that dietary habits influence cardiovascular health. There are diets such as the Dietary Approaches to Stop Hypertension (DASH) as the Mediterranean diet, which are clear examples of heart-healthy diets. However, there are discrepancies with regard to what are the components of a heart-healthy diet. There are foods that are considered healthy for the heart in all editions of food guides and recommendations, among which we can find fruits, vegetables, and whole grains, which have always been considered fundamental for health, and there are other foods that can currently be considered heart-healthy, since there are numerous studies that this is supported, such as virgin olive oil, pulses, fish, and nuts (especially nuts). This chapter focuses on the most recent food evidence (e.g., fruits and vegetables) and nutrients (such as fiber and omega-3) considered to be cardio-healthy today and as a counterpoint, the scientific clairvoyance that exists on those foods considered less heart-healthy because they are considered to increase cardiovascular risk (eggs, dairy products, meats, and salt).

#### **2. Cardiovascular disease and its association with dietary patterns and nutrients**

#### **2.1 Meta-analysis related to dietary patterns and cardiovascular disease**

Nowadays, most of the evidence supporting the beneficial and harmful effects of food and nutrients is based on observational epidemiological studies. The information of the present section aims to elucidate the current knowledge about dietary patterns and cardiovascular problems. The information is divided in food groups, in order to clarify as most as possible.

Fruits and vegetables have traditionally been considered promoting health foods. This is due to the association between the greater consumption of these products and the reduction of the risk of suffering chronic diseases, such as cardiovascular disease (CVD). Consequently, the current dietary guidelines recommend an increase in the consumption of fruits and vegetables up to five servings a day [1].

Current evidence is largely based on prospective cohort studies showing uniform associations between increased consumption of fruits and vegetables and reduced risk of both coronary artery disease (CAD) and stroke. However, these studies do not have the highest level of scientific evidence. In contrast, the number of controlled intervention trials (which provide a higher level of scientific evidence) in which the relationship between fruit and vegetable consumption and clinical endpoints has been investigated is unusual. However, the results of these studies show associations between increased consumption of fruits and vegetables and improvement of blood pressure and microvascular function. Meanwhile, associations with plasma lipid concentrations, risk of diabetes mellitus (DM), and body weight have not yet been definitely recognized [2].

The dietary habits of English population between 2001 and 2013 have been studied and reported in a recent study. It was observed that the consumption (seven daily servings of fruits and vegetables) reduces the specific risks of death from cancer and heart disease in 25 and 31%, respectively [3]. This report also showed that vegetables have a significantly greater beneficial health effect than fruits. It is important to emphasize that, whatever the starting point, the data indicate that the highest consumption of fruits and vegetables always provides a benefit. In addition, many confounding factors, such as poor access to fresh fruits and vegetables for people with preexisting health conditions or complicated lifestyles or those living in disadvantaged areas, affect the experimental approach used by these researchers. In conclusion, as reported by Berciano and Ordovás [2], the evidence indicating consumption of fruits and vegetables as dismissal of the risk of CVD is largely limited to observational epidemiology. Therefore, new intervention studies will be necessary to establish the existing real relationship.

Fruits and vegetables are very rich in both soluble and insoluble fibers, which structural and functional characteristics may vary greatly. Insoluble fibers, such as cellulose and lignin, are non-hydrolyzable and hardly undergo fermentation, while soluble fibers, such as pectin or inulin, are not hydrolyzed in the stomach but can be fermented by the gut microbiota. The main physiological effect associated with the consumption of insoluble fibers is the reduction of intestinal transit time which allows water retention, promotes an increase in fecal mass, and facilitates the movement of food through the intestine, due to mechanical stimulation of the intestinal walls. The distension caused also increases the feeling of fullness and can contribute to reducing caloric intake [4].

On the other hand, the main physicochemical properties of the soluble fibers that characterize their effects are viscosity, the ability to form gels, and fermentability. The increase in viscosity slows gastric emptying (which contributes to satiety)

**31**

*Cardiovascular Disease and Nutrition*

*DOI: http://dx.doi.org/10.5772/intechopen.84370*

and increases transit time. This helps to produce the stabilization of the glucose and

Regarding CVD, the most important property of dietary fiber is fermentability that reduces the concentration of low-density lipoproteins (LDL) in the blood. The mechanism is mediated by short-chain fatty acids produced by colon bacteria. Apart from this effect, there are other important considerations related to the lymphocyte activation, the inhibition of cell proliferation and the anti-inflammatory effects and the bile acid binding activity exerted by the dietary fiber, which act as a kidnapper [5]. Despite knowing the different properties and effects on health that may have the various types and origins of fiber, most studies have provided insufficient data, which prevents an independent assessment of the associated risks of disease. However, total fiber intake is uniformly associated with a small reduction in

All existing reviews conclude that diets rich in fiber are significantly associated with lower risk of stroke, CVD, and CD. This inverse association reinforces what is indicated in the current guidelines, which recommend an increase in fiber consumption, although studies that have described results related to fractions of fiber are too scarce to establish specific recommendations on soluble/insoluble fiber and the types of origins of those fibers. Dose-response analyses have identified cutoff values that have not been validated and appear to show wide differences between different types of fiber. The broader study on this topic indicates that the existence of a threshold effect has not been verified and that the message to be retained must be rather than the greater the consumption of fiber, the greater the protection [2, 5, 6]. In the last years, coffee has been relegated to the background with the boom

in tea consumption. Green tea is considered a healthy drink and consumed worldwide and has been attributed various beneficial effects to its regular intake, such as reducing the risk of suffering from diseases ranging from certain cancers to dementia and obesity. With regard to CVD, regular consumption of green tea has been associated with small reductions in CVD risk factors, such as LDL and blood pressure, which may have clinical relevance [7]. However, the number of studies reviewed is too low to be able to draw definitive conclusions, and there is a significant lack of long-term follow-up data and cardiovascular events to assess the

Similar to green tea, wine and coffee are two beverages containing a wide variety

of phytochemical substances that have been associated with a protective effect against heart disease. Although these compounds, mostly polyphenols, have been intensively studied over the past two decades, the main effects of wine (or alcoholic beverages in general) and coffee consumption continue to be attributed to ethanol and caffeine, respectively [8]. Recent reviews indicate that beer and especially red wine [7, 8] are associated with a greater reduction in the risk of CVD due to its high polyphenol content [9, 10]. The protective effects of coffee against CVD are not well established. In fact, a moderate consumption of coffee (two to four cups a day) has not shown any adverse effects in the long term [2]. However, it is well known that an excessive consumption of caffeine leads to hypertension, and in particular unfiltered coffee contributes to elevate the serum concentration of LDL, total cholesterol, and triglycerides [11]. It is important to note that the mentioned effects are subject to interpersonal differences, since there are many genetic polymorphisms that are known to affect different enzymes that are involved in their metabolism [2]. Regarding animal food, blue fish (like other many high-fat foods), such as olive oil, was on the list of "unhealthy" foods because of its high-fat content. However, from the earliest 1970s, omega-3 fats from blue fish were reported as beneficial to health and especially to health related to CVD [12]. However, there are still wide discrepancies regarding their effects on optimal doses, as well as their relationship

insulin response and reduces the absorption of dietary cholesterol [4].

the risk of CVD, coronary disease (CD), and stroke [6].

long-term effects of green tea consumption.

#### *Cardiovascular Disease and Nutrition DOI: http://dx.doi.org/10.5772/intechopen.84370*

*Nutrition in Health and Disease - Our Challenges Now and Forthcoming Time*

**nutrients**

order to clarify as most as possible.

body weight have not yet been definitely recognized [2].

necessary to establish the existing real relationship.

to reducing caloric intake [4].

**2. Cardiovascular disease and its association with dietary patterns and** 

Nowadays, most of the evidence supporting the beneficial and harmful effects of food and nutrients is based on observational epidemiological studies. The information of the present section aims to elucidate the current knowledge about dietary patterns and cardiovascular problems. The information is divided in food groups, in

Fruits and vegetables have traditionally been considered promoting health foods. This is due to the association between the greater consumption of these products and the reduction of the risk of suffering chronic diseases, such as cardiovascular disease (CVD). Consequently, the current dietary guidelines recommend an increase in the consumption of fruits and vegetables up to five servings a day [1]. Current evidence is largely based on prospective cohort studies showing uniform associations between increased consumption of fruits and vegetables and reduced risk of both coronary artery disease (CAD) and stroke. However, these studies do not have the highest level of scientific evidence. In contrast, the number of controlled intervention trials (which provide a higher level of scientific evidence) in which the relationship between fruit and vegetable consumption and clinical endpoints has been investigated is unusual. However, the results of these studies show associations between increased consumption of fruits and vegetables and improvement of blood pressure and microvascular function. Meanwhile, associations with plasma lipid concentrations, risk of diabetes mellitus (DM), and

The dietary habits of English population between 2001 and 2013 have been studied and reported in a recent study. It was observed that the consumption (seven daily servings of fruits and vegetables) reduces the specific risks of death from cancer and heart disease in 25 and 31%, respectively [3]. This report also showed that vegetables have a significantly greater beneficial health effect than fruits. It is important to emphasize that, whatever the starting point, the data indicate that the highest consumption of fruits and vegetables always provides a benefit. In addition, many confounding factors, such as poor access to fresh fruits and vegetables for people with preexisting health conditions or complicated lifestyles or those living in disadvantaged areas, affect the experimental approach used by these researchers. In conclusion, as reported by Berciano and Ordovás [2], the evidence indicating consumption of fruits and vegetables as dismissal of the risk of CVD is largely limited to observational epidemiology. Therefore, new intervention studies will be

Fruits and vegetables are very rich in both soluble and insoluble fibers, which structural and functional characteristics may vary greatly. Insoluble fibers, such as cellulose and lignin, are non-hydrolyzable and hardly undergo fermentation, while soluble fibers, such as pectin or inulin, are not hydrolyzed in the stomach but can be fermented by the gut microbiota. The main physiological effect associated with the consumption of insoluble fibers is the reduction of intestinal transit time which allows water retention, promotes an increase in fecal mass, and facilitates the movement of food through the intestine, due to mechanical stimulation of the intestinal walls. The distension caused also increases the feeling of fullness and can contribute

On the other hand, the main physicochemical properties of the soluble fibers that characterize their effects are viscosity, the ability to form gels, and fermentability. The increase in viscosity slows gastric emptying (which contributes to satiety)

**2.1 Meta-analysis related to dietary patterns and cardiovascular disease**

**30**

and increases transit time. This helps to produce the stabilization of the glucose and insulin response and reduces the absorption of dietary cholesterol [4].

Regarding CVD, the most important property of dietary fiber is fermentability that reduces the concentration of low-density lipoproteins (LDL) in the blood. The mechanism is mediated by short-chain fatty acids produced by colon bacteria. Apart from this effect, there are other important considerations related to the lymphocyte activation, the inhibition of cell proliferation and the anti-inflammatory effects and the bile acid binding activity exerted by the dietary fiber, which act as a kidnapper [5]. Despite knowing the different properties and effects on health that may have the various types and origins of fiber, most studies have provided insufficient data, which prevents an independent assessment of the associated risks of disease. However, total fiber intake is uniformly associated with a small reduction in the risk of CVD, coronary disease (CD), and stroke [6].

All existing reviews conclude that diets rich in fiber are significantly associated with lower risk of stroke, CVD, and CD. This inverse association reinforces what is indicated in the current guidelines, which recommend an increase in fiber consumption, although studies that have described results related to fractions of fiber are too scarce to establish specific recommendations on soluble/insoluble fiber and the types of origins of those fibers. Dose-response analyses have identified cutoff values that have not been validated and appear to show wide differences between different types of fiber. The broader study on this topic indicates that the existence of a threshold effect has not been verified and that the message to be retained must be rather than the greater the consumption of fiber, the greater the protection [2, 5, 6].

In the last years, coffee has been relegated to the background with the boom in tea consumption. Green tea is considered a healthy drink and consumed worldwide and has been attributed various beneficial effects to its regular intake, such as reducing the risk of suffering from diseases ranging from certain cancers to dementia and obesity. With regard to CVD, regular consumption of green tea has been associated with small reductions in CVD risk factors, such as LDL and blood pressure, which may have clinical relevance [7]. However, the number of studies reviewed is too low to be able to draw definitive conclusions, and there is a significant lack of long-term follow-up data and cardiovascular events to assess the long-term effects of green tea consumption.

Similar to green tea, wine and coffee are two beverages containing a wide variety of phytochemical substances that have been associated with a protective effect against heart disease. Although these compounds, mostly polyphenols, have been intensively studied over the past two decades, the main effects of wine (or alcoholic beverages in general) and coffee consumption continue to be attributed to ethanol and caffeine, respectively [8]. Recent reviews indicate that beer and especially red wine [7, 8] are associated with a greater reduction in the risk of CVD due to its high polyphenol content [9, 10]. The protective effects of coffee against CVD are not well established. In fact, a moderate consumption of coffee (two to four cups a day) has not shown any adverse effects in the long term [2]. However, it is well known that an excessive consumption of caffeine leads to hypertension, and in particular unfiltered coffee contributes to elevate the serum concentration of LDL, total cholesterol, and triglycerides [11]. It is important to note that the mentioned effects are subject to interpersonal differences, since there are many genetic polymorphisms that are known to affect different enzymes that are involved in their metabolism [2].

Regarding animal food, blue fish (like other many high-fat foods), such as olive oil, was on the list of "unhealthy" foods because of its high-fat content. However, from the earliest 1970s, omega-3 fats from blue fish were reported as beneficial to health and especially to health related to CVD [12]. However, there are still wide discrepancies regarding their effects on optimal doses, as well as their relationship

with omega-6 fatty acids or other components of the diet. In fact, the results of the published randomized clinical trials (a total of 48 studies that included 36,913 individuals) have not shown a reduction in the risk of total mortality or the set of cardiovascular events in people who take supplementary omega-3 fats [2]. Consequently, despite the known effect of omega-3 fat on plasma triglyceride concentrations, there is no unequivocal evidence that omega-3 fats in the diet or supplements modify total mortality or the set of cardiovascular events. In fact, a recent study [13] raises certain doubts about the validity of the premises used to support the initial hypothesis on omega-3 and CVD [14].

Continuing with foods of animal origin, one of the most ancient are eggs, which were introduced in the diet prior to the appearance in the evolution of *Homo sapiens*. It is not surprising that eggs are an important source of nutrients such as proteins, unsaturated fats, fat-soluble vitamins, folate, choline, and minerals. The possible counterpoint derives from the fact that, on average, an egg contains 200 mg of cholesterol, one-third of the recommended daily amount. The rationale for this recommendation continues to be linked to the diet-heart hypothesis. In contrast, epidemiological evidence has consistently shown that it is unlikely that the consumption of one egg a day has any significant impact on the risk of CVD in healthy people.

Similarly, the relationship between egg consumption and the clinically relevant elevation of plasma cholesterol concentrations is too old. Newer studies revealed the actual hypothesis about egg consumption. One of the most recent studies is the HELENA study, showing that egg consumption was not associated with the lipid profile, adiposity, insulin resistance, blood pressure, good cardiorespiratory function, or the integrated CVD risk score [15]. In general, current evidence supports that egg consumption is not associated with risk of CVD, CD, or cardiac death in the general population and may even have a protective value against hemorrhagic stroke [16].

In contrast, egg consumption may be associated with an increase in the incidence of type 2 diabetes mellitus in the general population and the comorbidity of CVD in diabetic patients [17]. Consequently, it seems that the most recent results exonerate the eggs from their intended role of significant dietary factor of the CVD epidemic. In this regard, it is important to bear in mind that the absorption of cholesterol has great interindividual differences, and only a fifth of the population can respond with increases in plasma cholesterol to the presence of cholesterol in the diet [17]. Therefore, it is important to identify the genetic determinants of this variability.

Regarding meat, scientific literature has been focused on the relationship between diet meat, CVD, and total mortality, which have led to a situation less clear than in the case of egg consumption. What seems to be clear is the association between red meat consumption and total mortality related to CVD, as well as the risk of CVD, ischemic stroke, and type 2 diabetes mellitus.

However, this association can often be caused by the consumption of processed meats and not always by fresh red meat. In fact, it has been pointed out that the harmful effects observed by processed meat may be related to other components, such as sodium, nitrites, heme iron, and l-carnitine. For example, the effects of elevating blood pressure associated with the high sodium content of processed foods could explain the increased risk of people sensitive to salt. There is recent evidence reporting that trimethylamine, phosphatidylcholine, choline, and lcarnitine in processed and red meat can promote CVD [18]. The scientific literature indicates that the consumption of unprocessed red meat and processed red meat is not beneficial for cardiometabolic health. In fact, it can be observed that clinical and public health guidelines prioritize above all the reduction of consumption of processed meat.

**33**

*Cardiovascular Disease and Nutrition*

traditional varieties.

*DOI: http://dx.doi.org/10.5772/intechopen.84370*

Finally, other foods demonized in recent years are dairy products, in part due to their relatively high content of saturated fats and cholesterol. Consequently, after having occupied for decades a prominent place among recommended foods, dairy products also suffered the consequences of the "non-healthy anti-saturated fat fever." However, this group of foods had a relatively easy way out, and the dairy industry started to produce a whole range of low-fat products. As observed by Berciano and Ordovás [2], these products already have enough time on the market to evaluate them regarding the intrinsic benefits in terms of CVD compared to more

The comparison between fatty and non-fatty dairy products is important because the relationship between CVD and saturated fats may not be as simple as

First, not all fats would be the same and were, in origin, classified as good (unsaturated) and bad (saturated). However, actual knowledge seems to discuss that theory. In fact, it was appreciated that "healthy" fats as polyunsaturated fats omega-6 could not be as good as thought. Contrariwise, some of the "bad fats"

Second, the replacement of saturated fats in the diet with simple carbohydrates has led to an increase in obesity and health complications. Therefore, it is probable that some of the adverse effects associated with saturated fats in the past must be factors other than saturated fats. Thus, in recent times the relationship between dairy foods and the risk of CVD has been revisited on multiple occasions [19]. In an interesting study, Huth and Park [20] reviewed the published evidence on milk products with milk fat content and cardiovascular health. The results of this review indicate that most of the observational studies found no association between the consumption of dairy products and increased risk of CVD, CD, and stroke, regard-

In general, it can be concluded that the consumption of dairy products provides protection against CVD or, at least, has no adverse effects. Consequently, the existing data support the concept that milk and low-fat milk products contribute to the prevention of hypertension and reduce the risk of stroke and, potentially, other CVD events. Another review revised the scientific literature related to observational studies on the relationship between the fat of dairy products and high-fat dairy foods, obesity, and cardiometabolic disease [21]. Of a total of 16 studies, in 68% there was an inverse association between the consumption of high-fat dairy products and the parameters of assessment of adiposity. In fact, studies conducted to examine the relationship between the consumption of high-fat dairy products and metabolic health has described an inverse association or no association [21]. Consequently, these results indicate that milk fat or high-fat dairy foods do not contribute to obesity or cardiometabolic risk and imply that the consumption of high-fat dairy products within the usual dietary patterns has an inverse association with the obesity risk.

It is commonly accepted by scientific community that oxidative stress is within the base of the etiology of cardiovascular diseases. However, the understanding of the role of reactive oxygen and nitrogen species (RONS) has evolved somewhat. They are not further seen in a whole negative perspective, but current knowledge supports that they are generated as part of normal metabolism, as well as a defense mechanism of cells from immune system to combat against infections; besides, they are implicated in intracellular signaling pathways [22]. Hence, low concentrations seem protective by triggering defense mechanisms that prevent cellular damage [23].

initially thought. That fact can be due to multiple reasons.

less of the concentration of fat in the milk.

**3. Oxidative stress and antioxidants**

could be healthy (the case of fats saturated from dairy foods) [19].

#### *Cardiovascular Disease and Nutrition DOI: http://dx.doi.org/10.5772/intechopen.84370*

*Nutrition in Health and Disease - Our Challenges Now and Forthcoming Time*

support the initial hypothesis on omega-3 and CVD [14].

with omega-6 fatty acids or other components of the diet. In fact, the results of the published randomized clinical trials (a total of 48 studies that included 36,913 individuals) have not shown a reduction in the risk of total mortality or the set of cardiovascular events in people who take supplementary omega-3 fats [2]. Consequently, despite the known effect of omega-3 fat on plasma triglyceride concentrations, there is no unequivocal evidence that omega-3 fats in the diet or supplements modify total mortality or the set of cardiovascular events. In fact, a recent study [13] raises certain doubts about the validity of the premises used to

Continuing with foods of animal origin, one of the most ancient are eggs, which were introduced in the diet prior to the appearance in the evolution of *Homo sapiens*. It is not surprising that eggs are an important source of nutrients such as proteins, unsaturated fats, fat-soluble vitamins, folate, choline, and minerals. The possible counterpoint derives from the fact that, on average, an egg contains 200 mg of cholesterol, one-third of the recommended daily amount. The rationale for this recommendation continues to be linked to the diet-heart hypothesis. In contrast, epidemiological evidence has consistently shown that it is unlikely that the consumption of one egg a day has any significant impact on the risk of CVD in healthy people. Similarly, the relationship between egg consumption and the clinically relevant elevation of plasma cholesterol concentrations is too old. Newer studies revealed the actual hypothesis about egg consumption. One of the most recent studies is the HELENA study, showing that egg consumption was not associated with the lipid profile, adiposity, insulin resistance, blood pressure, good cardiorespiratory function, or the integrated CVD risk score [15]. In general, current evidence supports that egg consumption is not associated with risk of CVD, CD, or cardiac death in the general population and may even have a protective value against hemorrhagic

In contrast, egg consumption may be associated with an increase in the incidence of type 2 diabetes mellitus in the general population and the comorbidity of CVD in diabetic patients [17]. Consequently, it seems that the most recent results exonerate the eggs from their intended role of significant dietary factor of the CVD epidemic. In this regard, it is important to bear in mind that the absorption of cholesterol has great interindividual differences, and only a fifth of the population can respond with increases in plasma cholesterol to the presence of cholesterol in the diet [17]. Therefore, it is important to identify the genetic determinants of this

Regarding meat, scientific literature has been focused on the relationship between diet meat, CVD, and total mortality, which have led to a situation less clear than in the case of egg consumption. What seems to be clear is the association between red meat consumption and total mortality related to CVD, as well as the

However, this association can often be caused by the consumption of processed meats and not always by fresh red meat. In fact, it has been pointed out that the harmful effects observed by processed meat may be related to other components, such as sodium, nitrites, heme iron, and l-carnitine. For example, the effects of elevating blood pressure associated with the high sodium content of processed foods could explain the increased risk of people sensitive to salt. There is recent evidence reporting that trimethylamine, phosphatidylcholine, choline, and lcarnitine in processed and red meat can promote CVD [18]. The scientific literature indicates that the consumption of unprocessed red meat and processed red meat is not beneficial for cardiometabolic health. In fact, it can be observed that clinical and public health guidelines prioritize above all the reduction of consumption of

risk of CVD, ischemic stroke, and type 2 diabetes mellitus.

**32**

processed meat.

stroke [16].

variability.

Finally, other foods demonized in recent years are dairy products, in part due to their relatively high content of saturated fats and cholesterol. Consequently, after having occupied for decades a prominent place among recommended foods, dairy products also suffered the consequences of the "non-healthy anti-saturated fat fever." However, this group of foods had a relatively easy way out, and the dairy industry started to produce a whole range of low-fat products. As observed by Berciano and Ordovás [2], these products already have enough time on the market to evaluate them regarding the intrinsic benefits in terms of CVD compared to more traditional varieties.

The comparison between fatty and non-fatty dairy products is important because the relationship between CVD and saturated fats may not be as simple as initially thought. That fact can be due to multiple reasons.

First, not all fats would be the same and were, in origin, classified as good (unsaturated) and bad (saturated). However, actual knowledge seems to discuss that theory. In fact, it was appreciated that "healthy" fats as polyunsaturated fats omega-6 could not be as good as thought. Contrariwise, some of the "bad fats" could be healthy (the case of fats saturated from dairy foods) [19].

Second, the replacement of saturated fats in the diet with simple carbohydrates has led to an increase in obesity and health complications. Therefore, it is probable that some of the adverse effects associated with saturated fats in the past must be factors other than saturated fats. Thus, in recent times the relationship between dairy foods and the risk of CVD has been revisited on multiple occasions [19]. In an interesting study, Huth and Park [20] reviewed the published evidence on milk products with milk fat content and cardiovascular health. The results of this review indicate that most of the observational studies found no association between the consumption of dairy products and increased risk of CVD, CD, and stroke, regardless of the concentration of fat in the milk.

In general, it can be concluded that the consumption of dairy products provides protection against CVD or, at least, has no adverse effects. Consequently, the existing data support the concept that milk and low-fat milk products contribute to the prevention of hypertension and reduce the risk of stroke and, potentially, other CVD events. Another review revised the scientific literature related to observational studies on the relationship between the fat of dairy products and high-fat dairy foods, obesity, and cardiometabolic disease [21]. Of a total of 16 studies, in 68% there was an inverse association between the consumption of high-fat dairy products and the parameters of assessment of adiposity. In fact, studies conducted to examine the relationship between the consumption of high-fat dairy products and metabolic health has described an inverse association or no association [21]. Consequently, these results indicate that milk fat or high-fat dairy foods do not contribute to obesity or cardiometabolic risk and imply that the consumption of high-fat dairy products within the usual dietary patterns has an inverse association with the obesity risk.

#### **3. Oxidative stress and antioxidants**

It is commonly accepted by scientific community that oxidative stress is within the base of the etiology of cardiovascular diseases. However, the understanding of the role of reactive oxygen and nitrogen species (RONS) has evolved somewhat. They are not further seen in a whole negative perspective, but current knowledge supports that they are generated as part of normal metabolism, as well as a defense mechanism of cells from immune system to combat against infections; besides, they are implicated in intracellular signaling pathways [22]. Hence, low concentrations seem protective by triggering defense mechanisms that prevent cellular damage [23].

The levels of RONS are counteracted by cellular defenses in the form of antioxidants, to maintain an adequate balanced oxidative status. However, when an imbalance in the production/elimination of these reactive species occurs, a specific cellular function can be altered [24].

The excess of free radicals attacks macromolecules, mainly polyunsaturated fatty acids (PUFA) of cell membranes [25] that leads to cell death and conducts to different pathological conditions, as vascular diseases. Oxidation of PUFA generates fatty acid radicals, which adds oxygen to form fatty acid peroxyl radicals. These radicals can further oxidize PUFA molecules and initiate new chain reactions, producing lipid hydroperoxides that can produce more radical species [25].

Oxidative stress contributes markedly to endothelial dysfunction, with a reduced activity of nitric oxide (NO). NO induces vasodilation, inhibits platelet aggregation, prevents LDL oxidation, and decreases production of proinflammatory cytokines. Free radicals oxidize and inactivate NO impeding its protective action. Besides, vascular cells generate reactive species principally by NADPH oxidase pathway [26]. The increased NADPH oxidase activity and the decrease in antioxidant enzyme defenses and cysteine/cystine redox potential increase the risk of cardiovascular disease [22].

Free radicals induce the expression of adhesion molecules in vascular wall, as intercellular adhesion molecule 1 (ICAM-1), what activates the migration of monocytes and T cells to the vessel [27] and helps to their attachment to the endothelial surface. The oxidation of low-density lipoproteins (LDL) by free radicals is followed by their uptake by macrophages. Macrophage cells are converted into foam cells, accumulating in the wall and further activating cells from the immune system, perpetuating the damage. This is the hallmark of initiation of the process of atherosclerosis.

These oxidative changes can be prevented/ameliorated or mitigated by antioxidants. From a chemical point of view, antioxidants are molecules able to react with oxidative species, as free radicals, thus preventing oxidation of a third molecule. Based on their nature, antioxidants have been classified as enzymatic and nonenzymatic forms. Enzymes that break down and remove free radicals include superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). SOD converts the superoxide radical O2 •<sup>−</sup> into O2 and H2O2 in the presence of metal ion cofactors as copper, zinc, or manganese. CAT converts H2O2 in H2O and O2, and GPx converts H2O2 to H2O and fatty acid hydroperoxides to their corresponding alcohol forms. All of them show synergistic effect and play the major role in prevention of oxidative damage [25].

Low molecular weight antioxidants react due to one-electron reactions with free radicals and possess a chemical structure able to delocalize the one electron that resulted. They form relative stable radicals by delocalization of the unpaired electron within their structure. The term includes both endogenous (glutathione, uric acid, bilirubin) and exogenous antioxidants from dietary origin (ascorbic acid, α-tocopherol, carotenoids, and polyphenols, among others).

α-Tocopherol is the main antioxidant in lipid environment, as it scavenges lipid peroxides in cell membranes and lipid particles, including low-density lipoprotein (LDL), forming an α-tocopheroxyl radical. It intercepts lipid peroxyl radicals and terminates lipid peroxidation reactions [25].

Vitamin C has been considered the most important water-soluble antioxidant in extracellular environment. It scavenges various RONS and regenerates the α-tocopheroxyl radical back to tocopherol [28]. It forms ascorbyl radical, and two molecules react rapidly to produce one molecule of ascorbate and one molecule of dehydroascorbate.

Dietary polyphenols behave as scavenging antioxidants due to their chemical structure of benzo-ɣ-pyrene cycle. They are able to delocalize the unpaired electron formed after the reaction with free radicals, as they possess an ortho-dihydroxy

**35**

apple [41].

*Cardiovascular Disease and Nutrition*

generation of free radicals [29].

physiological situation [35].

antioxidants to maintain a balanced redox status.

is reduced back by ascorbic acid [25].

phase II detoxification enzymes.

*DOI: http://dx.doi.org/10.5772/intechopen.84370*

structure in the B-ring and a [2, 3] double bond in conjugation, as well as the 4-hydroxyl function in C ring. Besides, they can chelate metal ions implicated in the

failed to prevent or delay the development of atherosclerosis [33, 34].

It must be pointed out that most in vitro and animal models used pharmacological doses of antioxidants in imposed oxidative stress conditions, far from the real

The contradictory results obtained in the human intervention studies prompted the investigators to undertake a better understanding toward the mechanisms of

The classic perception of antioxidants as free radical scavengers has evolved to their action on cell signaling to stimulate enzymatic antioxidant protection. In fact, most free radicals and electrophile species are removed through enzymatic reactions using reducing power in the form of NADPH, GSH, and reduced thioredoxin [36]. Moreover, free radicals are extremely reactive within the cell, and the most effective protection mechanism is to prevent their formation, by enzyme-catalyzed reactions, rather than trying to scavenge them once formed. Catalase dismutates H2O2 to H2O and O2, and peroxidase reduces hydroperoxides using GSH. The only possible biologically relevant antioxidant able to react with hydroxyperoxyl radicals is α-tocopherol [37]. Its subsequent radical formed, and the α-tocopheroxyl radical

Cells are able to adapt its redox potential increasing antioxidant enzymes, leading to transcription factors that act as redox sensors. Some antioxidants possess hormetic actions by upregulating the expression and activity of antioxidant defense enzymes, as well as by activating endothelial nitric oxide synthase (eNOS) that increases NO production and hence ameliorates vascular tone. The reaction of phytochemical antioxidants with free radicals gives oxidized products that are involved in signal transduction pathways. The last consequence is the activation of enzyme antioxidant activity and repair systems. Enzyme-catalyzed reactions occur at higher reaction rates than free radical scavenging by exogenous antioxidants. One of the main pathways involved is nuclear factor erythroid 2-related factor 2 (Nrf2). Nrf2 is linked to the protein Keap 1 and remains inactive in the cytosol until Keap1 is oxidized. Nrf2 then translocates to nucleus where it activates ARE genes. The activation of the Nrf2 transcription factor and the antioxidant response element (ARE) to which Nrf2 binds conducts to the transcription of genes encoding

Reports about the activation of this signaling pathway by compounds within the diet are increasing recently. Dietary soy has shown to inhibit atherosclerotic lesion progression by a mechanism that involves this Nrf2 gene transcription. Other phytochemicals include curcumin from turmeric [38], diallyl sulfide from garlic [39], isothiocyanates as sulforaphane from broccoli [40], and polyphenols from

Epidemiological studies have shown that a regular intake of fruits and vegetables, rich in antioxidants, reduces the risk of degenerative diseases and cancer [30]. Animal models and in vitro studies performed with particular antioxidants have supported this point of view. There is a generalized and accepted idea that the excessive production of free radicals causes damage and that the scavenging of these radicals is health protective. Hence, a number of human clinical trials on different populations with antioxidant supplementation were performed some decades ago. However, they showed non-antioxidant effects or even negative outcomes [31]. A meta-analysis of more than 300,000 individuals showed no prevention of cardiovascular disease after supplementation with vitamins E, C, and A and an increased risk of cancer in smokers with β-carotene supplementation [32]. Antioxidants have

#### *Cardiovascular Disease and Nutrition DOI: http://dx.doi.org/10.5772/intechopen.84370*

*Nutrition in Health and Disease - Our Challenges Now and Forthcoming Time*

cellular function can be altered [24].

of cardiovascular disease [22].

superoxide radical O2

The levels of RONS are counteracted by cellular defenses in the form of antioxidants, to maintain an adequate balanced oxidative status. However, when an imbalance in the production/elimination of these reactive species occurs, a specific

The excess of free radicals attacks macromolecules, mainly polyunsaturated fatty acids (PUFA) of cell membranes [25] that leads to cell death and conducts to different pathological conditions, as vascular diseases. Oxidation of PUFA generates fatty acid radicals, which adds oxygen to form fatty acid peroxyl radicals. These radicals can further oxidize PUFA molecules and initiate new chain reactions, producing lipid hydroperoxides that can produce more radical species [25]. Oxidative stress contributes markedly to endothelial dysfunction, with a reduced activity of nitric oxide (NO). NO induces vasodilation, inhibits platelet aggregation, prevents LDL oxidation, and decreases production of proinflammatory cytokines. Free radicals oxidize and inactivate NO impeding its protective action. Besides, vascular cells generate reactive species principally by NADPH oxidase pathway [26]. The increased NADPH oxidase activity and the decrease in antioxidant enzyme defenses and cysteine/cystine redox potential increase the risk

Free radicals induce the expression of adhesion molecules in vascular wall, as intercellular adhesion molecule 1 (ICAM-1), what activates the migration of monocytes and T cells to the vessel [27] and helps to their attachment to the endothelial surface. The oxidation of low-density lipoproteins (LDL) by free radicals is followed by their uptake by macrophages. Macrophage cells are converted into foam cells, accumulating in the wall and further activating cells from the immune system, perpetuating the damage. This is the hallmark of initiation of the process of atherosclerosis. These oxidative changes can be prevented/ameliorated or mitigated by antioxidants. From a chemical point of view, antioxidants are molecules able to react with oxidative species, as free radicals, thus preventing oxidation of a third molecule. Based on their nature, antioxidants have been classified as enzymatic and nonenzymatic forms. Enzymes that break down and remove free radicals include superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). SOD converts the

per, zinc, or manganese. CAT converts H2O2 in H2O and O2, and GPx converts H2O2 to H2O and fatty acid hydroperoxides to their corresponding alcohol forms. All of them show synergistic effect and play the major role in prevention of oxidative damage [25]. Low molecular weight antioxidants react due to one-electron reactions with free radicals and possess a chemical structure able to delocalize the one electron that resulted. They form relative stable radicals by delocalization of the unpaired electron within their structure. The term includes both endogenous (glutathione, uric acid, bilirubin) and exogenous antioxidants from dietary origin (ascorbic acid,

α-Tocopherol is the main antioxidant in lipid environment, as it scavenges lipid peroxides in cell membranes and lipid particles, including low-density lipoprotein (LDL), forming an α-tocopheroxyl radical. It intercepts lipid peroxyl radicals and

Vitamin C has been considered the most important water-soluble antioxidant

Dietary polyphenols behave as scavenging antioxidants due to their chemical structure of benzo-ɣ-pyrene cycle. They are able to delocalize the unpaired electron formed after the reaction with free radicals, as they possess an ortho-dihydroxy

in extracellular environment. It scavenges various RONS and regenerates the α-tocopheroxyl radical back to tocopherol [28]. It forms ascorbyl radical, and two molecules react rapidly to produce one molecule of ascorbate and one molecule of

α-tocopherol, carotenoids, and polyphenols, among others).

terminates lipid peroxidation reactions [25].

•<sup>−</sup> into O2 and H2O2 in the presence of metal ion cofactors as cop-

**34**

dehydroascorbate.

structure in the B-ring and a [2, 3] double bond in conjugation, as well as the 4-hydroxyl function in C ring. Besides, they can chelate metal ions implicated in the generation of free radicals [29].

Epidemiological studies have shown that a regular intake of fruits and vegetables, rich in antioxidants, reduces the risk of degenerative diseases and cancer [30]. Animal models and in vitro studies performed with particular antioxidants have supported this point of view. There is a generalized and accepted idea that the excessive production of free radicals causes damage and that the scavenging of these radicals is health protective. Hence, a number of human clinical trials on different populations with antioxidant supplementation were performed some decades ago. However, they showed non-antioxidant effects or even negative outcomes [31]. A meta-analysis of more than 300,000 individuals showed no prevention of cardiovascular disease after supplementation with vitamins E, C, and A and an increased risk of cancer in smokers with β-carotene supplementation [32]. Antioxidants have failed to prevent or delay the development of atherosclerosis [33, 34].

It must be pointed out that most in vitro and animal models used pharmacological doses of antioxidants in imposed oxidative stress conditions, far from the real physiological situation [35].

The contradictory results obtained in the human intervention studies prompted the investigators to undertake a better understanding toward the mechanisms of antioxidants to maintain a balanced redox status.

The classic perception of antioxidants as free radical scavengers has evolved to their action on cell signaling to stimulate enzymatic antioxidant protection. In fact, most free radicals and electrophile species are removed through enzymatic reactions using reducing power in the form of NADPH, GSH, and reduced thioredoxin [36]. Moreover, free radicals are extremely reactive within the cell, and the most effective protection mechanism is to prevent their formation, by enzyme-catalyzed reactions, rather than trying to scavenge them once formed. Catalase dismutates H2O2 to H2O and O2, and peroxidase reduces hydroperoxides using GSH. The only possible biologically relevant antioxidant able to react with hydroxyperoxyl radicals is α-tocopherol [37]. Its subsequent radical formed, and the α-tocopheroxyl radical is reduced back by ascorbic acid [25].

Cells are able to adapt its redox potential increasing antioxidant enzymes, leading to transcription factors that act as redox sensors. Some antioxidants possess hormetic actions by upregulating the expression and activity of antioxidant defense enzymes, as well as by activating endothelial nitric oxide synthase (eNOS) that increases NO production and hence ameliorates vascular tone. The reaction of phytochemical antioxidants with free radicals gives oxidized products that are involved in signal transduction pathways. The last consequence is the activation of enzyme antioxidant activity and repair systems. Enzyme-catalyzed reactions occur at higher reaction rates than free radical scavenging by exogenous antioxidants.

One of the main pathways involved is nuclear factor erythroid 2-related factor 2 (Nrf2). Nrf2 is linked to the protein Keap 1 and remains inactive in the cytosol until Keap1 is oxidized. Nrf2 then translocates to nucleus where it activates ARE genes. The activation of the Nrf2 transcription factor and the antioxidant response element (ARE) to which Nrf2 binds conducts to the transcription of genes encoding phase II detoxification enzymes.

Reports about the activation of this signaling pathway by compounds within the diet are increasing recently. Dietary soy has shown to inhibit atherosclerotic lesion progression by a mechanism that involves this Nrf2 gene transcription. Other phytochemicals include curcumin from turmeric [38], diallyl sulfide from garlic [39], isothiocyanates as sulforaphane from broccoli [40], and polyphenols from apple [41].

These mechanistic studies have been performed with pure compounds, and it is conceivable that supplementation with antioxidants in concentrations that saturate this system can exert none or even harmful effects [24]. Hence, it is advisable to provide an adequate level of antioxidants by nutritional intake to regulate the antioxidant system in a physiological basis.

#### **4. Bioactive compounds**

"Bioactive compounds" are extranutritional constituents that typically occur in small quantities in foods. Epidemiological studies have demonstrated that nutritional habits, like those based on high consumption of foods rich in bioactive substances (natural products derived from plants, marine organisms, and animals), have been associated with a longer life expectancy and a significant decrease in the incidence and prevalence of several chronic diseases with inflammatory basis, such as CVD [42].

These bioactive compounds possess a wide range of biological activities including antitumor, anti-inflammatory, anticarcinogenic, antiviral, antimicrobial, antidiarrheal, antioxidant, and other activities [43].

Dietary supplementation with bioactive natural compounds demonstrated that lipid-lowering effects (cholesterol synthesis inhibitors, intestinal cholesterol absorption inhibitors, and LDL-C excretion stimulants) are currently supported by the international guidelines for CVD prevention and some international expert panels [44].

#### **4.1 Omega-3**

The functions of the fatty acids are diverse. In addition to their energetic value, they are also part of the phospholipids found in the membranes of the body's cells and determine in a greater or lesser extent the structure and functionality of the cell. Such functionality refers to aspects like fluidity and permeability, lipid peroxidation, etc. [45]. Experimental, epidemiological, and interventional studies have demonstrated the beneficial cardiovascular effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which have anti-atherosclerotic, antithrombotic, antiarrhythmic, and anti-inflammatory effects.

Food contains omega-3 fatty acids in three main active forms: eicosapentaenoic acid (20: 5 omega 3, EPA), docosahexaenoic acid (22: 6 omega-3, DHA) and alphalinolenic acid (18: 3 omega-3, a-ALA). EPA and DHA forms can be found in fish oils, fish that mainly live in cold waters such as salmon, tuna, and sardines, among other varieties. EPA, DHA, and ALA are essential fatty acids, and they need to be ingested in the diet, since the body cannot synthesize them [46].

In a study, it was showed that the intake of EPA and DHA is inversely related to cardiovascular risk in a dose-dependent manner up to about 250 mg/day in healthy populations, and the intake of 1 g/day is associated with a marked protection from a sudden cardiac death [47]. The daily recommended intake of omega-3 fatty acids varies from 250 mg to 1 g of EPA and DHA.

#### **4.2 Polyphenols**

Polyphenols are bioactive compounds that can be found mostly in foods like fruits, cereals, vegetables, dry legumes, and chocolate and beverages such as coffee, tea, and wine. They are extensively used in the prevention and treatment of cardiovascular disease (CVD) providing protection against many chronic illnesses [48].

**37**

*Cardiovascular Disease and Nutrition*

(CPT1) and decreasing NF-κB [50].

**4.3 Phytosterols**

*DOI: http://dx.doi.org/10.5772/intechopen.84370*

biomarker levels in high-CVD-risk participants [49].

depend on the amount consumed and on their bioavailability.

conditions for atherosclerotic plaque formation and development. The cardioprotective effects of polyphenols have been linked mainly to its antioxidant properties; however, recent findings attribute its anti-atherosclerotic potential to modulate simultaneous signaling and mechanistic pathways [42]. Recently, the PREDIMED study reported that dietary polyphenols intake such as extra-virgin olive oil and nuts were associated with improved CVD risk factors and decreased inflammatory

Moreover, polyphenols alter hepatic cholesterol absorption, triglyceride biosynthesis and lipoprotein secretion, the processing of lipoproteins in plasma, and inflammation [48]. A recent study showed that polyphenols intake decreased blood pressure (BP), increased plasma high-density lipoprotein (HDL) and decreased the inflammatory biomarkers of CVD, including vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), IL-6, TNF-α as well as MCP-1. Treatment with quercetin ameliorated the high-fat diet-induced MetS such as abdominal obesity, cardiovascular remodeling, and liver complications in rats by increasing the expression of Nrf2, HO-1, and carnitine palmitoyltransferase 1

Finally, it has been reported that the effects of polyphenols on human health

Phytosterols are bioactive compounds found in foods of plant origin, which can be divided into plant sterols and plant stanols. Food sources of phytosterols include vegetable oils, mainly corn (909 mg/100 mL), sunflower (411 mg/100 mL), soybean (320 mg/100 mL), and olive (300 mg/100 mL); oleaginous fruits such as almonds (183 mg/100 g); cereals like wheat germ (344 mg/100 g) and wheat bran (200 mg/100 g); and in addition fruits and vegetables, such as passion fruit (44 mg/100 g), orange (24 mg/100 g), and cauliflower (40 mg/100 g) [51].

Clinical studies consistently indicate that the intake of phytosterols (2 g/day) is associated with a significant reduction (8–10%) in levels of low-density lipoprotein cholesterol (LDL-cholesterol). A typical Western diet contains approximately 300 mg of sterols and 30 mg of plant stanols, while vegetarian diets can achieve a higher content (300–500 mg/day). Phytosterols intake based on regular diets is considered too low to achieve their recommended daily intake -which are able to

and the consumption of foods enriched with phytosterols or, alternatively, the use

In the last decades, purified plant sterols or stanols have been added to various food items to obtain functional foods with remarkable hypocholesterolemic activity. A daily intake of plant sterols or stanols of 1.6–2 g/day, incorporated in these foods, is able to reduce cholesterol absorption from the gut by about 30% and plasma

Most guidelines and consensus on the treatment of dyslipidemia and/or prevention of CVD recommend the intake of phytosterols in the amount of approximately 2 g/day with the goal of reducing LDL-cholesterol by approximately 10%, in

Hydroxytyrosol, 2-(3,4-dihydroxyphenyl)-ethanol (OHTYR), is a phenolic compound present in the fruit and leaf of the olive (*Olea europaea* L.), which belongs to the family Oleaceae, comprising species distributed throughout the temperate

present therapeutic effects on LDL-cholesterol reduction-, (~2 g/day),

of supplements of phytosterol are generally required [52].

LDL-cholesterol levels by 8–10% [53].

association with lifestyle changes [54].

**4.4 Hydroxytyrosol**

Polyphenols can regulate cellular lipid metabolism, vascular and endothelial function, hemostasis, as well as platelet function, which represent primary

#### *Cardiovascular Disease and Nutrition DOI: http://dx.doi.org/10.5772/intechopen.84370*

*Nutrition in Health and Disease - Our Challenges Now and Forthcoming Time*

antioxidant system in a physiological basis.

antidiarrheal, antioxidant, and other activities [43].

antiarrhythmic, and anti-inflammatory effects.

varies from 250 mg to 1 g of EPA and DHA.

ingested in the diet, since the body cannot synthesize them [46].

**4. Bioactive compounds**

**4.1 Omega-3**

These mechanistic studies have been performed with pure compounds, and it is conceivable that supplementation with antioxidants in concentrations that saturate this system can exert none or even harmful effects [24]. Hence, it is advisable to provide an adequate level of antioxidants by nutritional intake to regulate the

"Bioactive compounds" are extranutritional constituents that typically occur in small quantities in foods. Epidemiological studies have demonstrated that nutritional habits, like those based on high consumption of foods rich in bioactive substances (natural products derived from plants, marine organisms, and animals), have been associated with a longer life expectancy and a significant decrease in the incidence and prevalence of several chronic diseases with inflammatory basis, such as CVD [42]. These bioactive compounds possess a wide range of biological activities includ-

ing antitumor, anti-inflammatory, anticarcinogenic, antiviral, antimicrobial,

Dietary supplementation with bioactive natural compounds demonstrated that lipid-lowering effects (cholesterol synthesis inhibitors, intestinal cholesterol absorption inhibitors, and LDL-C excretion stimulants) are currently supported by the international guidelines for CVD prevention and some international expert panels [44].

The functions of the fatty acids are diverse. In addition to their energetic value, they are also part of the phospholipids found in the membranes of the body's cells and determine in a greater or lesser extent the structure and functionality of the cell. Such functionality refers to aspects like fluidity and permeability, lipid peroxidation, etc. [45]. Experimental, epidemiological, and interventional studies have demonstrated the beneficial cardiovascular effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which have anti-atherosclerotic, antithrombotic,

Food contains omega-3 fatty acids in three main active forms: eicosapentaenoic acid (20: 5 omega 3, EPA), docosahexaenoic acid (22: 6 omega-3, DHA) and alphalinolenic acid (18: 3 omega-3, a-ALA). EPA and DHA forms can be found in fish oils, fish that mainly live in cold waters such as salmon, tuna, and sardines, among other varieties. EPA, DHA, and ALA are essential fatty acids, and they need to be

In a study, it was showed that the intake of EPA and DHA is inversely related to cardiovascular risk in a dose-dependent manner up to about 250 mg/day in healthy populations, and the intake of 1 g/day is associated with a marked protection from a sudden cardiac death [47]. The daily recommended intake of omega-3 fatty acids

Polyphenols are bioactive compounds that can be found mostly in foods like fruits, cereals, vegetables, dry legumes, and chocolate and beverages such as coffee, tea, and wine. They are extensively used in the prevention and treatment of cardiovascular disease (CVD) providing protection against many chronic illnesses [48]. Polyphenols can regulate cellular lipid metabolism, vascular and endothelial function, hemostasis, as well as platelet function, which represent primary

**36**

**4.2 Polyphenols**

conditions for atherosclerotic plaque formation and development. The cardioprotective effects of polyphenols have been linked mainly to its antioxidant properties; however, recent findings attribute its anti-atherosclerotic potential to modulate simultaneous signaling and mechanistic pathways [42]. Recently, the PREDIMED study reported that dietary polyphenols intake such as extra-virgin olive oil and nuts were associated with improved CVD risk factors and decreased inflammatory biomarker levels in high-CVD-risk participants [49].

Moreover, polyphenols alter hepatic cholesterol absorption, triglyceride biosynthesis and lipoprotein secretion, the processing of lipoproteins in plasma, and inflammation [48]. A recent study showed that polyphenols intake decreased blood pressure (BP), increased plasma high-density lipoprotein (HDL) and decreased the inflammatory biomarkers of CVD, including vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), IL-6, TNF-α as well as MCP-1. Treatment with quercetin ameliorated the high-fat diet-induced MetS such as abdominal obesity, cardiovascular remodeling, and liver complications in rats by increasing the expression of Nrf2, HO-1, and carnitine palmitoyltransferase 1 (CPT1) and decreasing NF-κB [50].

Finally, it has been reported that the effects of polyphenols on human health depend on the amount consumed and on their bioavailability.

#### **4.3 Phytosterols**

Phytosterols are bioactive compounds found in foods of plant origin, which can be divided into plant sterols and plant stanols. Food sources of phytosterols include vegetable oils, mainly corn (909 mg/100 mL), sunflower (411 mg/100 mL), soybean (320 mg/100 mL), and olive (300 mg/100 mL); oleaginous fruits such as almonds (183 mg/100 g); cereals like wheat germ (344 mg/100 g) and wheat bran (200 mg/100 g); and in addition fruits and vegetables, such as passion fruit (44 mg/100 g), orange (24 mg/100 g), and cauliflower (40 mg/100 g) [51].

Clinical studies consistently indicate that the intake of phytosterols (2 g/day) is associated with a significant reduction (8–10%) in levels of low-density lipoprotein cholesterol (LDL-cholesterol). A typical Western diet contains approximately 300 mg of sterols and 30 mg of plant stanols, while vegetarian diets can achieve a higher content (300–500 mg/day). Phytosterols intake based on regular diets is considered too low to achieve their recommended daily intake -which are able to present therapeutic effects on LDL-cholesterol reduction-, (~2 g/day), and the consumption of foods enriched with phytosterols or, alternatively, the use of supplements of phytosterol are generally required [52].

In the last decades, purified plant sterols or stanols have been added to various food items to obtain functional foods with remarkable hypocholesterolemic activity. A daily intake of plant sterols or stanols of 1.6–2 g/day, incorporated in these foods, is able to reduce cholesterol absorption from the gut by about 30% and plasma LDL-cholesterol levels by 8–10% [53].

Most guidelines and consensus on the treatment of dyslipidemia and/or prevention of CVD recommend the intake of phytosterols in the amount of approximately 2 g/day with the goal of reducing LDL-cholesterol by approximately 10%, in association with lifestyle changes [54].

#### **4.4 Hydroxytyrosol**

Hydroxytyrosol, 2-(3,4-dihydroxyphenyl)-ethanol (OHTYR), is a phenolic compound present in the fruit and leaf of the olive (*Olea europaea* L.), which belongs to the family Oleaceae, comprising species distributed throughout the temperate

regions of the world, and essentially localized in the Mediterranean basin. Another natural source of OHTYR is red wine [55]. In fact, daily intake of hydroxytyrosol in the Mediterranean area would be 2mg (considering the maximum 50mg/day). This amount would be insufficient to reach the recommended amount of 5mg to develop the benefit of protection of LDL particles from oxidative damage [56].

Numerous human and animal studies have shown that olive polyphenols, particularly hydroxytyrosol, can improve blood cholesterol profiles and reduce the risk of potentially lethal thrombosis [57]. Hydroxytyrosol can be considered antithrombotic, since it significantly reduces platelet aggregation [58].

Various authors support the potential beneficial effects of hydroxytyrosol in atherogenesis through the reduction of LDL oxidation. In addition to hydroxytyrosol, oleuropein has also been shown to effectively inhibit LDL oxidation induced by copper sulfate [59].

#### **4.5 Melatonin**

Melatonin (N-acetyl-5-methoxytryptamine) is a neuroendocrine hormone, which is synthesized primarily by the pineal gland. The synthesis and secretion of melatonin are regulated by light intensity [60]. Melatonin-rich foods include various food components from both animal and plant origins such as chicken, lamb, pork, cow milk, strawberries, tomatoes, olives, grapes, wines, cereals, and cherries. Interestingly, melatonin concentrations are significantly higher in plants than in animals [61].

Importantly, recent research suggests that melatonin plays an important role in various cardiovascular diseases, including myocardial ischemia-reperfusion injury, atherosclerosis, hypertension, heart failure, drug-induced myocardial injury, pulmonary hypertension, vascular diseases, valvular heart diseases, and lipid metabolism.

Early experiments showed that treatment with melatonin can improve dyslipidemia. In patients with nonalcoholic fatty liver disease, treatment with melatonin (2 × 5 mg/day) for 14 months significantly reduced levels of triglycerides and LDLcholesterol (LDL-C) compared with controls [62].

Yang et al. [63] demonstrated that melatonin reduces flow shear stress-induced bone marrow mesenchymal stem cell injury by acting on melatonin receptors and the adenosine monophosphate-activated protein kinase/acetyl-CoA carboxylase signaling pathway. These findings suggest that targeting melatonin relating signaling in tissue-engineered heart valves may be an effective strategy in treating valvular heart disease.

Melatonin may improve vascular dysfunction by affecting epigenetic regulation. In mice generated with assisted reproductive technologies, treatment with melatonin resulted in decreased arterial hypertension, which was thought to be due to its effects on normalizing nitric oxide levels by preventing impaired methylation of endothelial nitric oxide synthase [64].

Borghi and Cicero [65] confirmed the blood pressure (BP)-lowering effects of melatonin. It was shown that patients treated with melatonin (2–5mg/day for 7–90 days) had a decrease in nocturnal SBP as well as DBP. Additionally, it was demonstrated that the effect of melatonin on decreasing BP was most pronounced from 3:00 am to 8:00 am [66].

Pulmonary hypertension is a disease characterized by elevated pulmonary arterial pressure, which leads to right ventricular hypertrophy and failure. Various authors reported that treatment with melatonin alleviated right ventricular hypertrophy and dysfunction and also reduced interstitial fibrosis and plasma oxidative stress in a rat model of pulmonary hypertension [67].

As an inexpensive and well-tolerated drug, melatonin may be a new therapeutic option for cardiovascular disease [54].

**39**

**Author details**

Murcia, Spain

provided the original work is properly cited.

\*Address all correspondence to: mpzafrilla@ucam.edu

*Cardiovascular Disease and Nutrition*

**5. Conclusions**

effects on CVD.

emia, respectively.

**Acknowledgements**

**Conflict of interest**

*DOI: http://dx.doi.org/10.5772/intechopen.84370*

There is a clear relationship between diet and cardiovascular health. A hearthealthy diet should contain fruits and vegetables, which are rich in fiber and bioactive compounds. Foods rich in omega-3 fatty acids such as nuts or blue fish should not be missing from this diet. There is no scientific evidence relating egg or daily products consumption with increased cardiovascular risk (CVR). In fact, dairy products protects against CVR. Finally, consumption of processed meats is related to increased CVR, due to its high salt content. In fact, dietary guidelines

On the other hand, given that oxidative stress is the basis of CVD, a diet rich in antioxidants may be useful in prevention. Among the antioxidants we must highlight the α-tocopherols, vitamin C, and the polyphenols present in fruits and vegetables. However, supplementation has not been shown to have preventive

Both omega-3, polyphenols, and phytosterols have been shown to decrease CVR

Finally, we must highlight the hydroxytyrosol and melatonin, which are involved in the reduction of LDL oxidation and in the improvement of dyslipid-

The authors want to thanks the UCAM for supporting the present chapter.

recommend the reduction consumption of these processed meats.

factors and inflammatory markers in patients with elevated CVR.

The authors declare that they have no conflict of interest.

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

Javier Marhuenda, Débora Villaño, Begoña Cerdá and María Pilar Zafrilla\* Bachelor in Pharmacy, Health Sciences Faculty, Catholic University of Murcia,

### **5. Conclusions**

*Nutrition in Health and Disease - Our Challenges Now and Forthcoming Time*

the benefit of protection of LDL particles from oxidative damage [56].

botic, since it significantly reduces platelet aggregation [58].

cholesterol (LDL-C) compared with controls [62].

copper sulfate [59].

valvular heart disease.

endothelial nitric oxide synthase [64].

option for cardiovascular disease [54].

stress in a rat model of pulmonary hypertension [67].

from 3:00 am to 8:00 am [66].

**4.5 Melatonin**

regions of the world, and essentially localized in the Mediterranean basin. Another natural source of OHTYR is red wine [55]. In fact, daily intake of hydroxytyrosol in the Mediterranean area would be 2mg (considering the maximum 50mg/day). This amount would be insufficient to reach the recommended amount of 5mg to develop

Numerous human and animal studies have shown that olive polyphenols, particularly hydroxytyrosol, can improve blood cholesterol profiles and reduce the risk of potentially lethal thrombosis [57]. Hydroxytyrosol can be considered antithrom-

Various authors support the potential beneficial effects of hydroxytyrosol in atherogenesis through the reduction of LDL oxidation. In addition to hydroxytyrosol, oleuropein has also been shown to effectively inhibit LDL oxidation induced by

Melatonin (N-acetyl-5-methoxytryptamine) is a neuroendocrine hormone, which is synthesized primarily by the pineal gland. The synthesis and secretion of melatonin are regulated by light intensity [60]. Melatonin-rich foods include various food components from both animal and plant origins such as chicken, lamb, pork, cow milk, strawberries, tomatoes, olives, grapes, wines, cereals, and cherries. Interestingly, melatonin concentrations are significantly higher in plants than in animals [61]. Importantly, recent research suggests that melatonin plays an important role in various cardiovascular diseases, including myocardial ischemia-reperfusion injury, atherosclerosis, hypertension, heart failure, drug-induced myocardial injury, pulmonary hypertension, vascular diseases, valvular heart diseases, and lipid metabolism. Early experiments showed that treatment with melatonin can improve dyslipidemia. In patients with nonalcoholic fatty liver disease, treatment with melatonin (2 × 5 mg/day) for 14 months significantly reduced levels of triglycerides and LDL-

Yang et al. [63] demonstrated that melatonin reduces flow shear stress-induced bone marrow mesenchymal stem cell injury by acting on melatonin receptors and the adenosine monophosphate-activated protein kinase/acetyl-CoA carboxylase signaling pathway. These findings suggest that targeting melatonin relating signaling in tissue-engineered heart valves may be an effective strategy in treating

Melatonin may improve vascular dysfunction by affecting epigenetic regulation. In mice generated with assisted reproductive technologies, treatment with melatonin resulted in decreased arterial hypertension, which was thought to be due to its effects on normalizing nitric oxide levels by preventing impaired methylation of

Borghi and Cicero [65] confirmed the blood pressure (BP)-lowering effects of melatonin. It was shown that patients treated with melatonin (2–5mg/day for 7–90 days) had a decrease in nocturnal SBP as well as DBP. Additionally, it was demonstrated that the effect of melatonin on decreasing BP was most pronounced

Pulmonary hypertension is a disease characterized by elevated pulmonary arterial pressure, which leads to right ventricular hypertrophy and failure. Various authors reported that treatment with melatonin alleviated right ventricular hypertrophy and dysfunction and also reduced interstitial fibrosis and plasma oxidative

As an inexpensive and well-tolerated drug, melatonin may be a new therapeutic

**38**

There is a clear relationship between diet and cardiovascular health. A hearthealthy diet should contain fruits and vegetables, which are rich in fiber and bioactive compounds. Foods rich in omega-3 fatty acids such as nuts or blue fish should not be missing from this diet. There is no scientific evidence relating egg or daily products consumption with increased cardiovascular risk (CVR). In fact, dairy products protects against CVR. Finally, consumption of processed meats is related to increased CVR, due to its high salt content. In fact, dietary guidelines recommend the reduction consumption of these processed meats.

On the other hand, given that oxidative stress is the basis of CVD, a diet rich in antioxidants may be useful in prevention. Among the antioxidants we must highlight the α-tocopherols, vitamin C, and the polyphenols present in fruits and vegetables. However, supplementation has not been shown to have preventive effects on CVD.

Both omega-3, polyphenols, and phytosterols have been shown to decrease CVR factors and inflammatory markers in patients with elevated CVR.

Finally, we must highlight the hydroxytyrosol and melatonin, which are involved in the reduction of LDL oxidation and in the improvement of dyslipidemia, respectively.

### **Acknowledgements**

The authors want to thanks the UCAM for supporting the present chapter.

### **Conflict of interest**

The authors declare that they have no conflict of interest.

### **Author details**

Javier Marhuenda, Débora Villaño, Begoña Cerdá and María Pilar Zafrilla\* Bachelor in Pharmacy, Health Sciences Faculty, Catholic University of Murcia, Murcia, Spain

\*Address all correspondence to: mpzafrilla@ucam.edu

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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#### *Cardiovascular Disease and Nutrition DOI: http://dx.doi.org/10.5772/intechopen.84370*

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**40**

*Nutrition in Health and Disease - Our Challenges Now and Forthcoming Time*

consumption and subsequent risk of acute myeloid leukemia and myelodysplastic syndromes in Japan. International Journal of Cancer.

[9] Roth I, Casas R, Medina-Remón A, Lamuela-Raventós RM, Estruch R. Consumption of aged white wine modulates cardiovascular risk factors via circulating endothelial progenitor cells and inflammatory biomarkers.

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[11] Rebello SA, van Dam RM. Coffee consumption and cardiovascular health: Getting to the heart of the matter. Current Cardiology Reports.

[12] Vergroesen AJ. Dietary fat and cardiovascular disease: Possible modes of action of linoleic acid. The Proceedings of the Nutrition Society.

[13] Fodor JG, Helis E, Yazdekhasti N, Vohnout B. "Fishing" for the origins of the "Eskimos and heart disease" story: Facts or wishful thinking? The Canadian Journal of Cardiology.

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2018;**142**(6):1130-1138

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1972;**31**(3):323-329

2014;**30**(8):864-868

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Health. 2014;**68**:856-862

USA. 2018

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Arcidiacono S, Soares J, Racicot K, et al. Effects of dietary fiber by-product short-chain fatty acids on intestinal cell physiology and health. In: Abstracts of Papers of the American Chemical Society. AMER Chemical SOC 1155 16TH St, NW, Washington, DC 20036

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*Nutrition in Health and Disease - Our Challenges Now and Forthcoming Time*

[40] Houghton CA, Fassett RG, Coombes JS. Sulforaphane and other nutrigenomic Nrf2 activators: Can the clinician's expectation be matched by the reality? Oxidative Medicine and Cellular Longevity. 2016;**2016**

2016;**35**(12):1264-1275

[42] Santhakumar AB, Battino M, Alvarez-Suarez JM. Dietary

and protective effects against atherosclerosis. Food and Chemical

[43] Wang TH, Wang SY, Wang XD, Jiang HQ , Yang YQ , Wang Y, et al. Fisetin exerts antioxidant and neuroprotective effects in multiple mutant hSOD1 models of amyotrophic

lateral sclerosis by activating

2018;**17**(12):1185-1196

ERK. Neuroscience. 2018;**379**:152-166

[44] Wastesson JW, Morin L, Tan EC, Johnell K. An update on the clinical consequences of polypharmacy in older adults: A narrative review. Expert Opinion on Drug Safety.

[45] Piñeiro-Corrales G, Lago Rivero N, Culebras-Fernández JM. Papel de los ácidos grasos omega-3 en la prevención de enfermedades cardiovasculares. Nutrición Hospitalaria. 2013;**28**(1):1-5

[46] Castellanos L, Rodriguez M. El efecto de omega 3 en la salud humana y consideraciones en la ingesta. Revista Chilena de Nutricion. 2015;**42**(1):90-95

[47] Kirkhus B, Lamglait A, Eilertsen K-E, Falch E, Haider T, Vik H, et al. Effects of similar intakes of marine n-3 fatty acids from enriched food products and fish oil on cardiovascular

Toxicology. 2018;**113**:49-65

polyphenols: Structures, bioavailability

[41] Sharma S, Rana S, Patial V, Gupta M, Bhushan S, Padwad YS. Antioxidant and hepatoprotective effect of polyphenols from apple pomace extract via apoptosis inhibition and Nrf2 activation in mice. Human & Experimental Toxicology.

mineral supplements in the primary prevention of cardiovascular disease and cancer: An updated systematic evidence review for the US Preventive Services Task Force. Annals of Internal Medicine. 2013;**159**(12):824-834

[33] Yoshihara D, Fujiwara N, Suzuki K. Antioxidants: Benefits and risks for long-term health. Maturitas.

[34] Ye Y, Li J, Yuan Z. Effect of antioxidant vitamin supplementation on cardiovascular outcomes: A metaanalysis of randomized controlled trials.

PLoS One. 2013;**8**(2):e56803

[35] Ristow M. Unraveling the truth about antioxidants: Mitohormesis explains ROS-induced health benefits. Nature Medicine. 2014;**20**(7):709

[36] Forman HJ, Davies KJ, Ursini F. How do nutritional antioxidants really work: Nucleophilic tone and para-hormesis versus free radical scavenging in vivo. Free Radical Biology & Medicine.

[37] Karbownik M, Lewinski A, Reiter RJ. Anticarcinogenic actions of melatonin which involve antioxidative processes: Comparison with other antioxidants. The International Journal of Biochemistry & Cell Biology.

[38] Fattori V, Pinho-Ribeiro FA, Borghi SM, Alves-Filho JC, Cunha TM, Cunha FQ , et al. Curcumin inhibits superoxide anion-induced pain-like behavior and leukocyte recruitment by increasing Nrf2 expression and reducing NF-κB activation. Inflammation Research.

2010;**67**(2):103-107

2014;**66**:24-35

2001;**33**(8):735-753

2015;**64**(12):993-1003

[39] Kim S, Lee H-G, Park S-A, Kundu JK, Keum Y-S, Cha Y-N, et al. Keap1 cysteine 288 as a potential target for diallyl trisulfide-induced

Nrf2 activation. PLoS One.

2014;**9**(1):e85984

**42**

risk markers in healthy human subjects. The British Journal of Nutrition. 2012;**107**(9):1339-1349

[48] Giglio RV, Patti AM, Cicero AF, Lippi G, Rizzo M, Toth PP, et al. Polyphenols: Potential use in the prevention and treatment of cardiovascular diseases. Current Pharmaceutical Design. 2018;**24**(2):239-258

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[50] Panchal SK, Poudyal H, Brown L. Quercetin ameliorates cardiovascular, hepatic, and metabolic changes in diet-induced metabolic syndrome in rats. The Journal of Nutrition. 2012;**142**(6):1026-1032

[51] Gupta A, Jacobson GA, Burgess JR, Jelinek HF, Nichols DS, Narkowicz CK, et al. Citrus bioflavonoids possess dipeptidyl peptidase-4 inhibition activity similar to gliptin antidiabetic medication. Biochemical and Biophysical Research Communications. 2018

[52] Cabral CE, Klein MRST. Phytosterols in the treatment of hypercholesterolemia and prevention of cardiovascular diseases. Arquivos Brasileiros de Cardiologia. 2017;**109**(5):475-482

[53] Marangoni F, Poli A. Phytosterols and cardiovascular health. Pharmacological Research. 2010;**61**(3):193-199

[54] Pirro M, Vetrani C, Bianchi C, Mannarino MR, Bernini F, Rivellese AA. Joint position statement on "Nutraceuticals for the treatment of hypercholesterolemia" of the Italian Society of Diabetology (SID) and of the Italian Society for the Study of Arteriosclerosis (SISA). Nutrition, Metabolism, and Cardiovascular Diseases. 2017;**27**(1):2-17

[55] Marhuenda J, Medina S, Martínez-Hernández P, Arina S, Zafrilla P, Mulero J, et al. Effect of the dietary intake of melatonin-and hydroxytyrosol-rich wines by healthy female volunteers on the systemic lipidomic-related oxylipins. Food & Function. 2017;**8**(10):3745-3757

[56] De La Torre R, Covas MI, Pujadas MA, Fitó M, Farré M. Is dopamine behind the health benefits of red wine? European Journal of Nutrition. 2006;**45**(5):307-310

[57] Vilaplana-Pérez C, Auñón D, García-Flores LA, Gil-Izquierdo A. Hydroxytyrosol and potential uses in cardiovascular diseases, cancer, and AIDS. Frontiers in Nutrition. 2014;**1**:18

[58] Dell'Agli M, Buscialà A, Bosisio E. Vascular effects of wine polyphenols. Cardiovascular Research. 2004;**63**(4):593-602

[59] Killeen MJ, Pontoniere P, Crea RH. An examination of its potential role in cardiovascular disease, inflammation, and longevity. Agro Food Industry Hi Tech. 2011;**22**:16-19

[60] Arendt J, Bojkowski C, Franey C, Wright J, Marks V. Immunoassay of 6-hydroxymelatonin sulfate in human plasma and urine: Abolition of the urinary 24-hour rhythm with atenolol. The Journal of Clinical Endocrinology and Metabolism. 1985;**60**(6):1166-1173

[61] Tan DX, Hardeland R, Manchester LC, Rosales-Corral S, Coto-Montes A, Boga JA, et al. Emergence of naturally occurring melatonin isomers and their proposed nomenclature. Journal of Pineal Research. 2012;**53**(2):113-121

Chapter 4

Abstract

by human beings.

1. Introduction

benefits in humans [1–5].

ment in immune system.

45

2. Overview of fatty acids

in Humans

Role of Poultry Research in

Hanan Al-Khalaifah and Afaf Al-Nasser

Increasing Consumption of PUFA

In recent years, polyunsaturated fatty acids (PUFA) have received considerable attention in both human and animal nutrition. As a mean of increasing the low consumption of long chain n-3 PUFA by humans consuming diets, there has been some interest in the enrichment of poultry meat with these fatty acids for people seeking healthy lifestyles. Dietary supplementation with n-3 PUFA, such as these found in fish oil and linseed oil, were found to have nutritional benefits in humans. Modulation of fatty acid profiles as a result of n-3 PUFA incorporation is well documented in humans, rodents, and poultry. The current chapter focuses on enriching poultry meat with these beneficial fatty acids to increase its consumption

Recently, PUFA have received considerable attention in both human and animal nutrition, particularly those of the n-3 family; which are distinct due to the placement of the first double bond onto the third carbon atom from the methyl end of the fatty acid molecule. Long-chain fatty acids primarily those with more than 18 carbon atoms, derived mainly from fish oils are consumed quite less along with the other PUFAs. In order to increase their consumption through human diets, has led to studies for enriching the poultry meat infused with these fatty acids and thus enabling people to live healthier lifestyles. Dietary supplementation with n-3 PUFA, such as these found in fish oil and linseed oil, were found to have nutritional

This chapter will shed light on the overview, sources, and metabolism of PUFA, their incorporation into cell membrane structure, their involvement in health and clinical problems, enrichment of poultry products with PUFA, and their involve-

All fatty acids are carboxylic acids characterized by a chain-like structure with a carboxyl group (COOH) at one end, and a methyl group (CH3) at the other end.

Keywords: health, n-3 fatty acids, polyunsaturated fatty acids, poultry

[62] Celinski K, Konturek PC, Slomka M, Cichoz-Lach H, Brzozowski T, Konturek SJ, et al. Effects of treatment with melatonin and tryptophan on liver enzymes, parameters of fat metabolism and plasma levels of cytokines in patients with non-alcoholic fatty liver disease—14 months follow up. Journal of Physiology and Pharmacology. 2014;**65**(1):75-82

[63] Yang Y, Fan C, Deng C, Zhao L, Hu W, Di S, et al. Melatonin reverses flow shear stress-induced injury in bone marrow mesenchymal stem cells via activation of AMP-activated protein kinase signaling. Journal of Pineal Research. 2016;**60**(2):228-241

[64] Rexhaj E, Pireva A, Paoloni-Giacobino A, Allemann Y, Cerny D, Dessen P, et al. Prevention of vascular dysfunction and arterial hypertension in mice generated by assisted reproductive technologies by addition of melatonin to culture media. American Journal of Physiology-Heart and Circulatory Physiology. 2015;**309**(7):H1151-H1156

[65] Borghi C, Cicero AF. Nutraceuticals with a clinically detectable blood pressure-lowering effect: A review of available randomized clinical trials and their meta-analyses. British Journal of Clinical Pharmacology. 2017;**83**(1):163-171

[66] Gubin DG, Gubin GD, Gapon LI, Weinert D. Daily melatonin administration attenuates agedependent disturbances of cardiovascular rhythms. Current Aging Science. 2016;**9**(1):5-13

[67] Torres F, González-Candia A, Montt C, Ebensperger G, Chubretovic M, Serón-Ferré M, et al. Melatonin reduces oxidative stress and improves vascular function in pulmonary hypertensive newborn sheep. Journal of Pineal Research. 2015;**58**(3):362-373

#### Chapter 4

*Nutrition in Health and Disease - Our Challenges Now and Forthcoming Time*

[62] Celinski K, Konturek PC, Slomka M, Cichoz-Lach H, Brzozowski T, Konturek SJ, et al. Effects of treatment with melatonin and tryptophan on liver enzymes, parameters of fat metabolism and plasma levels of cytokines in patients with non-alcoholic fatty liver disease—14 months follow up. Journal of Physiology and Pharmacology.

[63] Yang Y, Fan C, Deng C, Zhao L, Hu W, Di S, et al. Melatonin reverses flow shear stress-induced injury in bone marrow mesenchymal stem cells via activation of AMP-activated protein kinase signaling. Journal of Pineal Research. 2016;**60**(2):228-241

[64] Rexhaj E, Pireva A, Paoloni-Giacobino A, Allemann Y, Cerny D, Dessen P, et al. Prevention of vascular dysfunction and arterial hypertension in mice generated by assisted reproductive technologies by addition of melatonin to culture media. American Journal of Physiology-Heart and Circulatory Physiology. 2015;**309**(7):H1151-H1156

[65] Borghi C, Cicero AF. Nutraceuticals with a clinically detectable blood pressure-lowering effect: A review of available randomized clinical trials and their meta-analyses. British Journal of Clinical Pharmacology.

[66] Gubin DG, Gubin GD, Gapon LI, Weinert D. Daily melatonin administration attenuates agedependent disturbances of

cardiovascular rhythms. Current Aging

[67] Torres F, González-Candia A, Montt C, Ebensperger G, Chubretovic M, Serón-Ferré M, et al. Melatonin reduces oxidative stress and improves vascular function in pulmonary hypertensive newborn sheep. Journal of Pineal Research. 2015;**58**(3):362-373

2017;**83**(1):163-171

Science. 2016;**9**(1):5-13

2014;**65**(1):75-82

**44**

## Role of Poultry Research in Increasing Consumption of PUFA in Humans

Hanan Al-Khalaifah and Afaf Al-Nasser

#### Abstract

In recent years, polyunsaturated fatty acids (PUFA) have received considerable attention in both human and animal nutrition. As a mean of increasing the low consumption of long chain n-3 PUFA by humans consuming diets, there has been some interest in the enrichment of poultry meat with these fatty acids for people seeking healthy lifestyles. Dietary supplementation with n-3 PUFA, such as these found in fish oil and linseed oil, were found to have nutritional benefits in humans. Modulation of fatty acid profiles as a result of n-3 PUFA incorporation is well documented in humans, rodents, and poultry. The current chapter focuses on enriching poultry meat with these beneficial fatty acids to increase its consumption by human beings.

Keywords: health, n-3 fatty acids, polyunsaturated fatty acids, poultry

#### 1. Introduction

Recently, PUFA have received considerable attention in both human and animal nutrition, particularly those of the n-3 family; which are distinct due to the placement of the first double bond onto the third carbon atom from the methyl end of the fatty acid molecule. Long-chain fatty acids primarily those with more than 18 carbon atoms, derived mainly from fish oils are consumed quite less along with the other PUFAs. In order to increase their consumption through human diets, has led to studies for enriching the poultry meat infused with these fatty acids and thus enabling people to live healthier lifestyles. Dietary supplementation with n-3 PUFA, such as these found in fish oil and linseed oil, were found to have nutritional benefits in humans [1–5].

This chapter will shed light on the overview, sources, and metabolism of PUFA, their incorporation into cell membrane structure, their involvement in health and clinical problems, enrichment of poultry products with PUFA, and their involvement in immune system.

#### 2. Overview of fatty acids

All fatty acids are carboxylic acids characterized by a chain-like structure with a carboxyl group (COOH) at one end, and a methyl group (CH3) at the other end.

The rest of the chain consists of carbon atoms varying in length from 2 to 20 or more with hydrocarbon bonds (CH2). Fatty acids (FA) differ in the number of hydrogen atoms and the number and location of the double bonds between adjacent carbon atoms if hydrogen atoms are removed. If a fatty acid chain is fully loaded with hydrogen atoms, the FA is termed saturated. Consequently, saturated fatty acids form straight chains as there are no double bonds between carbon atoms. These usually contain between 12 and 24 carbon atoms. This kind of FA is abundantly present in adipose tissues of animals, including poultry and used as a source of energy if needed. An example of a saturated FA is stearic acid (C18:0). This is one way to name a fatty acid (C:D) where C is the number of carbon atoms in the fatty acid and D is the number of double bonds in the fatty acid. Sources of saturated FA include meat, dairy products, palm oil, coconut oil and vegetable shortening [6].

the diet is consumed. In a similar manner, EPA along with DHA can be synthesized from α-LNA although synthesis between them is inadequate in most conditions. Due to the absence of specific desaturase enzymes, the n-3 and n-6 fatty acids are not inter-convertible. On the other hand, saturated FA such as palmitic acid (C16:0)

(C18:1 n-9) can be synthesized in the human body from precursors such as glucose

Common name FA name Butyric C4:0 Caproic C6:0 Caprylic C8:0 Capric C10:0 Undecanoic C11:0 Lauric C12:0 Tridecanoic C13:0 Myristic C14:0 Myristoleic C14:1 Pentadecanoic acid C15:0 c10 Pentadecanoic acid C15:1 Palmitic C16:0 Palmitoleic C16:1 cis-10-heptadecanoic C17:1 Stearic C18:0 Elaidic C18:1n9t Oleic C18:1n9c Linolelaidic C18:2n6t Linoleic C18:2n6c Arachidic C20:0 γ-Linolenic C18:3n6 α-Linolenic C18:3n3 Heneicosanoic C21:0 c11, 14 Eicosadienoic C20:2 Behenic C22:0 c8,11,14 Eicosatrienoic C20:3n6 Erucic acid C22:1 n9 c11,14,17 Eicosatrienoic C20:3n3 Arachidonic C20:4n6 Tricosanoic C23:0 c13,16 Docosadienoic C22:2 Eicosapentaenoic acid (EPA) C20:5n3 Lignoceric C24:0 Nervonic C24:1 Docosapentaenoic acid (DPA) C22:5n3 Docosahexaenoic acid (DHA) C22:6n3

and stearic acid (C18:0) and most monounsaturated FA such as oleic acid

Role of Poultry Research in Increasing Consumption of PUFA in Humans

DOI: http://dx.doi.org/10.5772/intechopen.85099

or amino acids [12, 13]. Table 1 shows a list of the common saturated and

unsaturated fatty acids.

Table 1.

47

List of common saturated and unsaturated fatty acids.

If a pair of hydrogen atoms is removed under the influence of specific enzymes, a double bond is formed between adjacent carbon atoms and the saturated FA becomes monounsaturated. An example of a monounsaturated FA is oleic acid (18:1), an n-9 FA that constitutes 74% of total FA in olives. n-x is a nomenclature of fatty acids where a double bond is located on the xth carbon▬carbon bond, counting from the terminal methyl carbon (designated as n). Other sources of monosaturated FA are avocados, rapeseed, peanuts and soybeans [7]. If two or more double bonds are formed due to removal of more than a pair of hydrogen atoms, the FA is termed polyunsaturated. The more double bonds a fatty acid has, the more unsaturated it is [8–10]. The main sources of PUFA are seeds and seed oils, oily fish and fish oils [10].

Moreover, the orientation of the fatty acid chain at the site of a double bond determines and characterizes a fatty acid. For example, a FA called cis-configured when both segments of the molecule lie at the same side. On the other hand, in the trans configuration, the two parts of the molecule face opposite with respect to the bond directions (see Figure 1). Most PUFA in plants and sea foods are of cis configuration [11].

The two major types of PUFA which play a crucial role in the biological functioning of both, humans and animals are the n-3 and n-6 PUFA. The n-3 PUFA consists of linolenic acid (LNA, C18:3), eicosapentaenoic acid (EPA, C20:5) and docosahexaenoic acid (DHA, C22:6) whereas the n-6 PUFAs comprise mainly linoleic acid (LA, C18:2) and arachidonic acid (AA, C20:4). LA and α-LNA are classified as essential fatty acids (EFA) due to their inability to be synthesized by the body. However, these EFAs should be consumed through the diet because of shortage of specific desaturation enzymes. AA can be synthesized in from LA when

Figure 1. cis and trans configuration of FA molecules.

#### Role of Poultry Research in Increasing Consumption of PUFA in Humans DOI: http://dx.doi.org/10.5772/intechopen.85099

the diet is consumed. In a similar manner, EPA along with DHA can be synthesized from α-LNA although synthesis between them is inadequate in most conditions. Due to the absence of specific desaturase enzymes, the n-3 and n-6 fatty acids are not inter-convertible. On the other hand, saturated FA such as palmitic acid (C16:0) and stearic acid (C18:0) and most monounsaturated FA such as oleic acid (C18:1 n-9) can be synthesized in the human body from precursors such as glucose or amino acids [12, 13]. Table 1 shows a list of the common saturated and unsaturated fatty acids.


#### Table 1.

List of common saturated and unsaturated fatty acids.

The rest of the chain consists of carbon atoms varying in length from 2 to 20 or more with hydrocarbon bonds (CH2). Fatty acids (FA) differ in the number of hydrogen atoms and the number and location of the double bonds between adjacent carbon atoms if hydrogen atoms are removed. If a fatty acid chain is fully loaded with hydrogen atoms, the FA is termed saturated. Consequently, saturated fatty acids form straight chains as there are no double bonds between carbon atoms. These usually contain between 12 and 24 carbon atoms. This kind of FA is abundantly present in adipose tissues of animals, including poultry and used as a source of energy if needed. An example of a saturated FA is stearic acid (C18:0). This is one way to name a fatty acid (C:D) where C is the number of carbon atoms in the fatty acid and D is the number of double bonds in the fatty acid. Sources of saturated FA include meat, dairy products, palm oil, coconut oil and vegetable shortening [6]. If a pair of hydrogen atoms is removed under the influence of specific enzymes,

Nutrition in Health and Disease - Our Challenges Now and Forthcoming Time

a double bond is formed between adjacent carbon atoms and the saturated FA becomes monounsaturated. An example of a monounsaturated FA is oleic acid (18:1), an n-9 FA that constitutes 74% of total FA in olives. n-x is a nomenclature of fatty acids where a double bond is located on the xth carbon▬carbon bond, counting from the terminal methyl carbon (designated as n). Other sources of monosaturated FA are avocados, rapeseed, peanuts and soybeans [7]. If two or more double bonds are formed due to removal of more than a pair of hydrogen atoms, the FA is termed polyunsaturated. The more double bonds a fatty acid has, the more unsaturated it is [8–10]. The main sources of PUFA are seeds and seed oils, oily fish

Moreover, the orientation of the fatty acid chain at the site of a double bond determines and characterizes a fatty acid. For example, a FA called cis-configured when both segments of the molecule lie at the same side. On the other hand, in the trans configuration, the two parts of the molecule face opposite with respect to the bond directions (see Figure 1). Most PUFA in plants and sea foods are of cis

The two major types of PUFA which play a crucial role in the biological functioning of both, humans and animals are the n-3 and n-6 PUFA. The n-3 PUFA consists of linolenic acid (LNA, C18:3), eicosapentaenoic acid (EPA, C20:5) and docosahexaenoic acid (DHA, C22:6) whereas the n-6 PUFAs comprise mainly linoleic acid (LA, C18:2) and arachidonic acid (AA, C20:4). LA and α-LNA are classified as essential fatty acids (EFA) due to their inability to be synthesized by the body. However, these EFAs should be consumed through the diet because of shortage of specific desaturation enzymes. AA can be synthesized in from LA when

and fish oils [10].

configuration [11].

Figure 1.

46

cis and trans configuration of FA molecules.

#### 3. Sources and metabolism of fatty acids

General speaking, there are small amounts of AA in fish. However Brown et al. [14] have reported that there is 4.8–14.3% AA in some Australian fish species. However, fish oil contains high amounts of EPA and DHA. These fatty acids are synthesized by phytoplankton that are consumed by fish. Some fish species may contain more than 30% n-3 PUFA about 50% of the FA in fish is PUFA, of which about 30% are n-3 FA [15, 16].

addition, there are considerable amounts of α-linolenic acid and γ-linolenic acid in the echium oil as well. Rymer et al. [29] showed that γ-linolenic acid is accumulated

N-3 PUFA, particularly EPA and DHA, are reported to compete with AA for incorporation in the phospholipid bilayer of cell membranes of all body cells, especially erythrocytes, platelets, neutrophils, monocytes and liver cells [30, 31]. Both AA and EPA are parent precursors of different kinds of eicosanoids that play a crucial role in the inflammatory responses in both humans and animals, including

Initially, the dietary essential fatty acid α-LNA is converted to EPA and DHA while LA is converted to AA by elongation and desaturation reactions [32–34]. These conversion reactions are mediated in humans by three desaturases, Δ9, Δ6, and Δ5. The desaturases work by introducing a double bond at a specific position of the carbon backbone. Nakamura and Nara [35] have reported that desaturases in mammals are regulated at the transcriptional level and their transcription is genetically controlled. However, regulation of Δ9 desaturase differs from Δ6 and Δ5 desaturases because the Δ 9-desaturase converts the nonessential stearic acid (18:0) to oleic acid (18:1 n-9). Oleic acid can go through the same steps of desaturation and elongation as LA and α-LNA, resulting in the synthesis of the fatty acids 20:3 n-9 and 22:4 n-9. Consequently, the Δ 9-desaturation provides an alternative to Δ6 and Δ5 desaturation when the cell is subject to essential fatty acid deficiency. However in the case of availability of sufficient amounts of essential fatty acids, AA and EPA act as precursors for eicosanoid synthesis, although EPA metabolism predominates [32, 33, 36, 37]. When sources rich in stearidonic acid (SDA) such as echium oil are consumed, the body deposits EPA directly in tissues such as plasma, blood leukocytes, liver, breast and legs of human, rodents and chicken because SDA does not

Under the influence of Δ6 desaturase, free α-LNA is converted to SDA (18:4 n-3) then to eicosatetraenoic acid (20:4 n-3) by an elongase. Next, Δ5 desaturase acts on eicosatetraenoic acid and converts it into EPA (20:5 n-3). Elongase converts EPA into the FA (24:5 n-3) that is converted into the FA (24:6 n-3) by the action of Δ6 desaturase. Then, oxidation of (24:6 n-3) by β-oxidase produces DHA. During this metabolic pathway, eicosanoids such as leukotriene 5-series, prostaglandins E3 and thromboxane A3 are derived from EPA [37, 41, 44–50]. Figure 2 shows the

Cell membranes consist of a variety of molecules that enable cells to survive via various biological interactions. Proteins and lipids are the main elements of cell membranes. Different cell types have different cell membrane lipids and proteins

Lipids in the cell membranes are arranged in a bilayer structure with the hydrophobic moieties in the center of the membrane and the hydrophilic heads at the two surfaces, facing the inner cytoplasm and the outside surrounding. There are three main types of lipids in the cell membranes, namely: phospholipids, glycolipids, and steroids. Both saturated and unsaturated FA are attached to the glycerol moiety in the cell membrane, with the saturated FA attached to the first carbon atom in the glycerol backbone (sn-1), while PUFA occupy the sn-2 position [17]. Membrane fluidity is highly affected by the length and the degree of unsaturation of FA chains. Lipid moieties within the cell membrane determine different biological cellular functions such as intracellular pathways and receptors formation. In humans, EPA,

as stearidonic acid increases in the chicken's diet.

DOI: http://dx.doi.org/10.5772/intechopen.85099

Role of Poultry Research in Increasing Consumption of PUFA in Humans

require Δ6 desaturase activity to form EPA [28, 38–43].

metabolic pathway of the long chain n-3 and n-6 PUFA [35].

that reflect different biological functions and specializations of cells.

4. Incorporation into cell membrane structure

poultry.

49

Conversely, the presence of α–LNA in seafood is almost nil; although plant sources like chia, linseed, rapeseed, perilla and blackcurrant possess high amounts of this FA, this is because these plant sources have Δ12-desaturase that converts oleic acid into LA, this is further converted into α-LNA under the influence of Δ 15 desaturase [10]. Linseed is one of the richest know sources of α-LNA, as it contains almost 60% of this fatty acid in its oil [17].

Some algal oil and algal biomass obtained from marine regions are known to be good sources of DHA and EPA and thus can be used as a means to enrich meats and eggs using these long chain fatty acids. This has proved to be successful and is well documented in literature, even though DHA is mostly obtained from these algal biomasses [18–26].

In addition, echium oil from the plant Echium plantagineum has been recognized as an ideal source of stearidonic acid (C18:4n-3) that is naturally converted to the important long-chain n-3 fatty acid, EPA, when metabolized in the body [27, 28]. In

Figure 2.

Metabolic pathways of the long chain n-3 and n-6 PUFA.

#### Role of Poultry Research in Increasing Consumption of PUFA in Humans DOI: http://dx.doi.org/10.5772/intechopen.85099

addition, there are considerable amounts of α-linolenic acid and γ-linolenic acid in the echium oil as well. Rymer et al. [29] showed that γ-linolenic acid is accumulated as stearidonic acid increases in the chicken's diet.

N-3 PUFA, particularly EPA and DHA, are reported to compete with AA for incorporation in the phospholipid bilayer of cell membranes of all body cells, especially erythrocytes, platelets, neutrophils, monocytes and liver cells [30, 31]. Both AA and EPA are parent precursors of different kinds of eicosanoids that play a crucial role in the inflammatory responses in both humans and animals, including poultry.

Initially, the dietary essential fatty acid α-LNA is converted to EPA and DHA while LA is converted to AA by elongation and desaturation reactions [32–34]. These conversion reactions are mediated in humans by three desaturases, Δ9, Δ6, and Δ5. The desaturases work by introducing a double bond at a specific position of the carbon backbone. Nakamura and Nara [35] have reported that desaturases in mammals are regulated at the transcriptional level and their transcription is genetically controlled. However, regulation of Δ9 desaturase differs from Δ6 and Δ5 desaturases because the Δ 9-desaturase converts the nonessential stearic acid (18:0) to oleic acid (18:1 n-9). Oleic acid can go through the same steps of desaturation and elongation as LA and α-LNA, resulting in the synthesis of the fatty acids 20:3 n-9 and 22:4 n-9. Consequently, the Δ 9-desaturation provides an alternative to Δ6 and Δ5 desaturation when the cell is subject to essential fatty acid deficiency. However in the case of availability of sufficient amounts of essential fatty acids, AA and EPA act as precursors for eicosanoid synthesis, although EPA metabolism predominates [32, 33, 36, 37]. When sources rich in stearidonic acid (SDA) such as echium oil are consumed, the body deposits EPA directly in tissues such as plasma, blood leukocytes, liver, breast and legs of human, rodents and chicken because SDA does not require Δ6 desaturase activity to form EPA [28, 38–43].

Under the influence of Δ6 desaturase, free α-LNA is converted to SDA (18:4 n-3) then to eicosatetraenoic acid (20:4 n-3) by an elongase. Next, Δ5 desaturase acts on eicosatetraenoic acid and converts it into EPA (20:5 n-3). Elongase converts EPA into the FA (24:5 n-3) that is converted into the FA (24:6 n-3) by the action of Δ6 desaturase. Then, oxidation of (24:6 n-3) by β-oxidase produces DHA. During this metabolic pathway, eicosanoids such as leukotriene 5-series, prostaglandins E3 and thromboxane A3 are derived from EPA [37, 41, 44–50]. Figure 2 shows the metabolic pathway of the long chain n-3 and n-6 PUFA [35].

#### 4. Incorporation into cell membrane structure

Cell membranes consist of a variety of molecules that enable cells to survive via various biological interactions. Proteins and lipids are the main elements of cell membranes. Different cell types have different cell membrane lipids and proteins that reflect different biological functions and specializations of cells.

Lipids in the cell membranes are arranged in a bilayer structure with the hydrophobic moieties in the center of the membrane and the hydrophilic heads at the two surfaces, facing the inner cytoplasm and the outside surrounding. There are three main types of lipids in the cell membranes, namely: phospholipids, glycolipids, and steroids. Both saturated and unsaturated FA are attached to the glycerol moiety in the cell membrane, with the saturated FA attached to the first carbon atom in the glycerol backbone (sn-1), while PUFA occupy the sn-2 position [17]. Membrane fluidity is highly affected by the length and the degree of unsaturation of FA chains. Lipid moieties within the cell membrane determine different biological cellular functions such as intracellular pathways and receptors formation. In humans, EPA,

3. Sources and metabolism of fatty acids

of which about 30% are n-3 FA [15, 16].

almost 60% of this fatty acid in its oil [17].

biomasses [18–26].

Figure 2.

48

Metabolic pathways of the long chain n-3 and n-6 PUFA.

General speaking, there are small amounts of AA in fish. However

Nutrition in Health and Disease - Our Challenges Now and Forthcoming Time

Brown et al. [14] have reported that there is 4.8–14.3% AA in some Australian fish species. However, fish oil contains high amounts of EPA and DHA. These fatty acids are synthesized by phytoplankton that are consumed by fish. Some fish species may contain more than 30% n-3 PUFA about 50% of the FA in fish is PUFA,

Conversely, the presence of α–LNA in seafood is almost nil; although plant sources like chia, linseed, rapeseed, perilla and blackcurrant possess high amounts of this FA, this is because these plant sources have Δ12-desaturase that converts oleic acid into LA, this is further converted into α-LNA under the influence of Δ 15 desaturase [10]. Linseed is one of the richest know sources of α-LNA, as it contains

Some algal oil and algal biomass obtained from marine regions are known to be good sources of DHA and EPA and thus can be used as a means to enrich meats and eggs using these long chain fatty acids. This has proved to be successful and is well documented in literature, even though DHA is mostly obtained from these algal

In addition, echium oil from the plant Echium plantagineum has been recognized as an ideal source of stearidonic acid (C18:4n-3) that is naturally converted to the important long-chain n-3 fatty acid, EPA, when metabolized in the body [27, 28]. In DHA, AA and oleic acid are the main PUFA incorporated into the cell membranes. Interestingly, changes in these lipid moieties leads to changes in biological functions of different cell types due to the production of different cellular intermediates such as leukotrienes, prostacyclins and prostaglandins. These intermediates are involved in the immunomodulatory effect of PUFA [42, 49, 51–60].

white than in dark meat. In order to confirm the effect of dietary fatty acid modulation in broiler chickens, another study was conducted by Lopez-Ferrer et al. [83]. Here, a diet enriched with 8.2% FO was fed to broilers for duration of 5 weeks, after this it was replaced by diets containing 8.2% linseed or rapeseed in three different periods: the last week before slaughtering, the last 2 weeks and throughout the experiment. The end results for the fatty acid analysis of thigh and breast showed that the total amounts of n-3 PUFA were significantly decreased after removal of FO diet. Upon replacement of FO with the linseed diet caused a substantial increase in α-linolenic acid, furthermore there was an increase in the total amounts of n-6 PUFA and a decrease in the DHA proportions due to its limited conversion to longer n-3 PUFA. When FO was replaced by rapeseed there was an increase in the total

Recently, Zelenka et al. [84] studied the effect of increasing levels of linseed oil in the diets of chickens and its influence on the fatty acid content in breast and thigh meat of chickens. Linseed oil at levels of 1, 3, 5 or 7% were fed to broiler chickens from 25 to 40 days of age. Oils were derived from the linseed cultivar Atalante with a high content of α-linolenic acid or the cultivar Lola with a high content of linoleic acid. Results showed that feeding a diet with a high content of α-linolenic acid significantly increased all n-3 PUFA, decreased n-6 PUFA and decreased the ratio of n-6/n-3 PUFA. On the contrary, when the birds were fed a diet with a high content of linoleic acid, this caused a significant increase in the levels of all n-6 PUFA in thigh and breast of chickens. Similarly, a study by Kartikasari et al. [85] showed that feeding broilers on diets with a high content of α-linolenic acid, while keeping a constant linoleic acid level, significantly increased the incorporation of all n-3 PUFA into breast and thigh meat by 5 and 4-fold compared to chickens fed low α-linolenic acid content. In another experiment [86], the authors fed broiler chickens on diets with constant level

of α-linolenic acid (2.1%) and different levels of linoleic acid, which included 2.9–4.4%, and consisted of pure or blended vegetable oils such as macadamia, flaxseed and sunflower oils. The overall lipid content was kept at a constant of 5%. Post analysis it was observed that chickens when fed diets the lowest linoleic acid content (2.9%) contributed towards higher incorporation of total n-3 PUFA in the breast by 16% compared with feeding the highest linoleic acid content (4.4%). When the chickens were fed with a diet with a high content of linoleic acid, this resulted in a significant reduction in EPA levels in both thigh and breast tissues. The levels for DPA and DHA were not affected by dietary linoleic acid. Authors suggested that this could be due to fact that linoleic acid competes with α-linolenic acid for Δ<sup>6</sup> desaturase. In other words, high dietary level of linoleic acid might reduce the conversion of αlinolenic to n-3 PUFAs. In a further study [87], the authors fed broiler chickens on diets containing 0, 2, or 4% linseed oil plus tallow to make 8% added fat throughout 38 growth period. The total amounts of saturated and monounsaturated fatty acids were significantly decreased after feeding increased levels of linseed. Conversely, the total amounts of PUFA were significantly increased. A recent study [88] showed that upon supplementing n-3 PUFA, in the form of linseed oil (3/100 g mixed feed), in the diet of laying hens resulted in a significant increase in α-linolenic of the plasma. The same study also revealed that, FO administration (same dose as linseed) caused a

significant increase in the proportion of plasma EPA and DHA.

The immunomodulatory effect of PUFA in broiler chickens occurs by affecting intercellular communications and signals that change the reactivity of leukocytes upon antigenic stimulation. This effect is highly associated with down-regulation or

7. Involvement in avian immune function

51

amounts of monounsaturated fatty acids, especially oleic acid.

Role of Poultry Research in Increasing Consumption of PUFA in Humans

DOI: http://dx.doi.org/10.5772/intechopen.85099

#### 5. Involvement in health and clinical problems

Vitality of living cells depends profoundly on dietary lipids that are incorporated into phospholipid layers of cellular membranes as a result there is a constant competition between the omega-3 fatty acids; eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), with arachidonic acid (AA) for this incorporation. As AA controls the upregulation of eicosanoids such as leukotrienes, this competitive inhibition downregulates inflammation responses related to man, which are associated to numerous diseases and disorders such as cardiovascular disease, increased triglycerides, blood pressure, thrombosis, atherosclerosis, stress, mental problems, asthma and rheumatoid arthritis [21, 50, 61–79]. These benefits of an optimal ratio of n-3/n-6 PUFAs on health are just a few examples of a wide range of clinical problems that are improved by consumption of the very long chain n-3 fatty acids.

#### 6. n-3 enrichment of poultry diet

Traditionally, fish and fish oil are the main sources of essential, long chain n-3 PUFA that induce modifications in the lipid composition of poultry products because marine sources in general contain high levels of EPA and DHA PUFA. Of less nutritional importance are plant sources such as linseed that is rich in αlinolenic acid (α-LNA). α-LNA is an 18 carbon n-3 fatty acid that is the precursor to the long chain n-3 PUFA, but because the efficiency of conversion is so low in humans, the accumulation of α-LNA is of little real nutritional benefit.

In chickens, there are number of studies that investigated effects of PUFA on fatty acid profile of different tissues, if sources rich in these fatty acids are added to the poultry feed. Bou et al. [80] reported that supplementing the diet of broilers with 2.5% fish oil produced double the amount of EPA and DHA in their carcass than diets supplied with 1.25% fish oil. In another study, Ratnayake et al. [81] fed broiler chickens increasing levels of redfish meal (40–120 g/kg) for a period of 42 days. The effect of this dietary manipulation on fatty acid composition of breast and thigh muscles was investigated. Authors of this study observed a linear relationship between the level of the dietary fish meal and the proportions of DHA, DPA and EPA in the meat muscles. Givens and Rymer [82] also conducted an experiment to investigate the effect of poultry species and genotype on the efficiency of incorporation of n-3 PUFA in poultry meat. The two genotypes of turkeys (Wrolstad and BUT T8) and broilers (Ross 308 and Cobb 500) were fed one or four diets that contained 50 g/kg added oil; either vegetable oil (control), partially replaced with linseed (20 or 40 g/kg), FO (20 or 40 g/kg), or mixture of linseed and FO (20 g linseed and 20 g FO/kg diet). It was observed that on replacement of the control diet with either low or high levels of FO caused a significant increase in the concentration of EPA and DHA in all the meats whereas feeding linseed-enriched diet significantly increased the concentration of α-linolenic acid. No significant difference was noted with the incorporation of n-3 PUFA between the two broiler genotypes. Turkey genotypes were only different in the case of α-linolenic acid incorporation. It was also seen that there was a greater incorporation of DHA in

#### Role of Poultry Research in Increasing Consumption of PUFA in Humans DOI: http://dx.doi.org/10.5772/intechopen.85099

white than in dark meat. In order to confirm the effect of dietary fatty acid modulation in broiler chickens, another study was conducted by Lopez-Ferrer et al. [83]. Here, a diet enriched with 8.2% FO was fed to broilers for duration of 5 weeks, after this it was replaced by diets containing 8.2% linseed or rapeseed in three different periods: the last week before slaughtering, the last 2 weeks and throughout the experiment. The end results for the fatty acid analysis of thigh and breast showed that the total amounts of n-3 PUFA were significantly decreased after removal of FO diet. Upon replacement of FO with the linseed diet caused a substantial increase in α-linolenic acid, furthermore there was an increase in the total amounts of n-6 PUFA and a decrease in the DHA proportions due to its limited conversion to longer n-3 PUFA. When FO was replaced by rapeseed there was an increase in the total amounts of monounsaturated fatty acids, especially oleic acid.

Recently, Zelenka et al. [84] studied the effect of increasing levels of linseed oil in the diets of chickens and its influence on the fatty acid content in breast and thigh meat of chickens. Linseed oil at levels of 1, 3, 5 or 7% were fed to broiler chickens from 25 to 40 days of age. Oils were derived from the linseed cultivar Atalante with a high content of α-linolenic acid or the cultivar Lola with a high content of linoleic acid. Results showed that feeding a diet with a high content of α-linolenic acid significantly increased all n-3 PUFA, decreased n-6 PUFA and decreased the ratio of n-6/n-3 PUFA. On the contrary, when the birds were fed a diet with a high content of linoleic acid, this caused a significant increase in the levels of all n-6 PUFA in thigh and breast of chickens. Similarly, a study by Kartikasari et al. [85] showed that feeding broilers on diets with a high content of α-linolenic acid, while keeping a constant linoleic acid level, significantly increased the incorporation of all n-3 PUFA into breast and thigh meat by 5 and 4-fold compared to chickens fed low α-linolenic acid content. In another experiment [86], the authors fed broiler chickens on diets with constant level of α-linolenic acid (2.1%) and different levels of linoleic acid, which included 2.9–4.4%, and consisted of pure or blended vegetable oils such as macadamia, flaxseed and sunflower oils. The overall lipid content was kept at a constant of 5%. Post analysis it was observed that chickens when fed diets the lowest linoleic acid content (2.9%) contributed towards higher incorporation of total n-3 PUFA in the breast by 16% compared with feeding the highest linoleic acid content (4.4%). When the chickens were fed with a diet with a high content of linoleic acid, this resulted in a significant reduction in EPA levels in both thigh and breast tissues. The levels for DPA and DHA were not affected by dietary linoleic acid. Authors suggested that this could be due to fact that linoleic acid competes with α-linolenic acid for Δ<sup>6</sup> desaturase. In other words, high dietary level of linoleic acid might reduce the conversion of αlinolenic to n-3 PUFAs. In a further study [87], the authors fed broiler chickens on diets containing 0, 2, or 4% linseed oil plus tallow to make 8% added fat throughout 38 growth period. The total amounts of saturated and monounsaturated fatty acids were significantly decreased after feeding increased levels of linseed. Conversely, the total amounts of PUFA were significantly increased. A recent study [88] showed that upon supplementing n-3 PUFA, in the form of linseed oil (3/100 g mixed feed), in the diet of laying hens resulted in a significant increase in α-linolenic of the plasma. The same study also revealed that, FO administration (same dose as linseed) caused a significant increase in the proportion of plasma EPA and DHA.

#### 7. Involvement in avian immune function

The immunomodulatory effect of PUFA in broiler chickens occurs by affecting intercellular communications and signals that change the reactivity of leukocytes upon antigenic stimulation. This effect is highly associated with down-regulation or

DHA, AA and oleic acid are the main PUFA incorporated into the cell membranes. Interestingly, changes in these lipid moieties leads to changes in biological functions of different cell types due to the production of different cellular intermediates such as leukotrienes, prostacyclins and prostaglandins. These intermediates are involved

Vitality of living cells depends profoundly on dietary lipids that are incorporated into phospholipid layers of cellular membranes as a result there is a constant competition between the omega-3 fatty acids; eicosapentaenoic acid (EPA) and

docosahexaenoic acid (DHA), with arachidonic acid (AA) for this incorporation. As AA controls the upregulation of eicosanoids such as leukotrienes, this competitive inhibition downregulates inflammation responses related to man, which are associated to numerous diseases and disorders such as cardiovascular disease, increased triglycerides, blood pressure, thrombosis, atherosclerosis, stress, mental problems, asthma and rheumatoid arthritis [21, 50, 61–79]. These benefits of an optimal ratio of n-3/n-6 PUFAs on health are just a few examples of a wide range of clinical problems that are improved by consumption of the very long chain n-3 fatty acids.

Traditionally, fish and fish oil are the main sources of essential, long chain n-3

In chickens, there are number of studies that investigated effects of PUFA on fatty acid profile of different tissues, if sources rich in these fatty acids are added to the poultry feed. Bou et al. [80] reported that supplementing the diet of broilers with 2.5% fish oil produced double the amount of EPA and DHA in their carcass than diets supplied with 1.25% fish oil. In another study, Ratnayake et al. [81] fed broiler chickens increasing levels of redfish meal (40–120 g/kg) for a period of 42 days. The effect of this dietary manipulation on fatty acid composition of breast and thigh muscles was investigated. Authors of this study observed a linear relationship between the level of the dietary fish meal and the proportions of DHA, DPA and EPA in the meat muscles. Givens and Rymer [82] also conducted an experiment to investigate the effect of poultry species and genotype on the efficiency of incorporation of n-3 PUFA in poultry meat. The two genotypes of turkeys (Wrolstad and BUT T8) and broilers (Ross 308 and Cobb 500) were fed one or four diets that contained 50 g/kg added oil; either vegetable oil (control), partially replaced with linseed (20 or 40 g/kg), FO (20 or 40 g/kg), or mixture of linseed and FO (20 g linseed and 20 g FO/kg diet). It was observed that on replacement of the control diet with either low or high levels of FO caused a significant increase in the concentration of EPA and DHA in all the meats whereas feeding linseed-enriched diet significantly increased the concentration of α-linolenic acid. No significant difference was noted with the incorporation of n-3 PUFA between the two broiler genotypes. Turkey genotypes were only different in the case of α-linolenic acid incorporation. It was also seen that there was a greater incorporation of DHA in

PUFA that induce modifications in the lipid composition of poultry products because marine sources in general contain high levels of EPA and DHA PUFA. Of less nutritional importance are plant sources such as linseed that is rich in αlinolenic acid (α-LNA). α-LNA is an 18 carbon n-3 fatty acid that is the precursor to the long chain n-3 PUFA, but because the efficiency of conversion is so low in

humans, the accumulation of α-LNA is of little real nutritional benefit.

in the immunomodulatory effect of PUFA [42, 49, 51–60].

Nutrition in Health and Disease - Our Challenges Now and Forthcoming Time

5. Involvement in health and clinical problems

6. n-3 enrichment of poultry diet

50

up-regulation of different cytokines that are believed to affect the avian immune function such as IL-1β, IFNγ, MGF, IL-1, IL-4, IL-2 [89–92].

References

319-326

1-4

[1] Al-Khalifa H. Production of addedvalue poultry meat: Enrichment with n-3 polyunsaturated fatty acids. World's Poultry Science Journal. 2015;71(2):

DOI: http://dx.doi.org/10.5772/intechopen.85099

Role of Poultry Research in Increasing Consumption of PUFA in Humans

[8] Castro-Gonzalez MI. Omega 3 fatty acids: Benefits and sources. Interciencia.

[9] Budowski P. Oils rich in omega-3 fatty acids—health implications. Harefuah. 1995;128(2):121-125

[10] Nettleton JA. omega 3 fatty acids: Comparison of plant and seafood sources in human nutrition. Journal of the American Dietetic Association. 1991;

[11] Ackman RG, Marine lipids and omega-3 fatty acids. In: Akoh CC, editor. (Functional Foods and

Nutraceuticals Series), in Handbook of functional lipids. Boca Raton: Taylor &

[12] Landmark K. Alpha-linolenic acid, cardiovascular disease and sudden death. Tidsskrift for den Norske Lægeforening. 2006;126(21):2792-2794

[13] Herbaut C. Omega-3 and health. Revue Médicale de Bruxelles. 2006;

[14] Brown AJ, Robrts DCK, Truswell AS. Fatty acid composition of australian

[15] Kris-Etherton MKP, Harris WS, Appel LJ. Fish consumption, fish oil, omega-3 fattyacids, and cardiovascular disease. Journal of the American Heart Association. 2002;106:2747-2773

[16] Kartal M, Kurucu S, Aslan S, Ozbay O, Ceyhan T, Sayar E, et al. Comparison

of n-3 fatty acids by GC-MS in frequently consumed fish and fish oil preparations on the turkish market. FABAD Journal of Pharmaceutical

Sciences. 2003;28:201-205

marine finfish: A review. Food Australia. 1989;1:655-666

2002;27(3):128-136

91(3):331-337

Francis; p. 311-324

27(4):355-360

[2] Al-Khalifa H, Al-Nasser A, Al-Bahouh M, Ragheb G, Al-Qalaf S, Al-

polyunsaturated fatty acids on avian immune cell subpopulations in peripheral blood, spleen, and thymus. World's Poultry Science Journal. 2016;1:

[3] Abbaci K, Joachirn S, Garric J, Boisseaux P, Exbrayat JM, Porcher JM, et al. Anatomical and histological characterization of the gametogenesis of Radix balthica (linnaeus, 1758) in comparison with Lymnaea stagnalis (linnaeus, 1758). Journal of Histology &

[4] Apperson KD, Cherian G. Effect of whole flax seed and carbohydrase enzymes on gastrointestinal

morphology, muscle fatty acids, and production performance in broiler chickens. Poultry Science. 2017;96(5):

[5] Colussi G, Catena C, Novello M, Bertin N, Sechi LA. Impact of omega-3 polyunsaturated fatty acids on vascular function and blood pressure: Relevance for cardiovascular outcomes. Nutrition, Metabolism, and Cardiovascular Diseases. 2017;27(3):191-200

[6] Rees AM, Austin MP, Parker G. Role of omega-3 fatty acids as a treatment for depression in the perinatal peiod. Australian and New Zealand Journal of Psychiatry. 2005;39(4):274-280

[7] Reeves JB, Weihrauch JL.

DC: USDA; 1979

53

Composition of Foods. Fats and Oils. Agriculture Handbook. Washington,

Histopathology. 2017;4:5

1228-1234

Omani N, et al. The effect of

There is some concern that diets enriched with n-3 PUFA have detrimental effects on chicken immunity and impair resistance to infection. However, it is not clear whether this concern is justified, since some studies show no effect [93], some show a detrimental effect [94] while some show an improvement [89, 90, 93, 95–97] in chicken immune response following feeding of n-3 PUFA.

#### 8. Conclusion

Consumption of omega-3 fatty acids should be increased in human diets to get the beneficial effects of these fatty acids. One way to achieve this goal is by enriching poultry meat and eggs with omega-3 fatty acids, which is proved to be very successful. This role of poultry production in enhancing health aspects of human needs more research and interest from nutritionists and poultry producers.

#### Acknowledgements

The authors would like to extend their gratitude and appreciation to the management of Kuwait Institute for Scientific Research for their continuous technical and financial support of scientific research.

#### Conflict of interest

There is no conflict of interest related to the current work.

#### Author details

Hanan Al-Khalaifah\* and Afaf Al-Nasser Environment and Life Sciences Research Centre, Kuwait Institute for Scientific Research, Safat, Kuwait

\*Address all correspondence to: hkhalifa@kisr.edu.kw

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Role of Poultry Research in Increasing Consumption of PUFA in Humans DOI: http://dx.doi.org/10.5772/intechopen.85099

#### References

up-regulation of different cytokines that are believed to affect the avian immune

There is some concern that diets enriched with n-3 PUFA have detrimental effects on chicken immunity and impair resistance to infection. However, it is not clear whether this concern is justified, since some studies show no effect [93], some show a detrimental effect [94] while some show an improvement [89, 90,

Consumption of omega-3 fatty acids should be increased in human diets to get

The authors would like to extend their gratitude and appreciation to the management of Kuwait Institute for Scientific Research for their continuous technical

Environment and Life Sciences Research Centre, Kuwait Institute for Scientific

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

93, 95–97] in chicken immune response following feeding of n-3 PUFA.

the beneficial effects of these fatty acids. One way to achieve this goal is by enriching poultry meat and eggs with omega-3 fatty acids, which is proved to be very successful. This role of poultry production in enhancing health aspects of human needs more research and interest from nutritionists and poultry producers.

There is no conflict of interest related to the current work.

function such as IL-1β, IFNγ, MGF, IL-1, IL-4, IL-2 [89–92].

Nutrition in Health and Disease - Our Challenges Now and Forthcoming Time

8. Conclusion

Acknowledgements

Conflict of interest

Author details

52

Research, Safat, Kuwait

and financial support of scientific research.

Hanan Al-Khalaifah\* and Afaf Al-Nasser

provided the original work is properly cited.

\*Address all correspondence to: hkhalifa@kisr.edu.kw

[1] Al-Khalifa H. Production of addedvalue poultry meat: Enrichment with n-3 polyunsaturated fatty acids. World's Poultry Science Journal. 2015;71(2): 319-326

[2] Al-Khalifa H, Al-Nasser A, Al-Bahouh M, Ragheb G, Al-Qalaf S, Al-Omani N, et al. The effect of polyunsaturated fatty acids on avian immune cell subpopulations in peripheral blood, spleen, and thymus. World's Poultry Science Journal. 2016;1: 1-4

[3] Abbaci K, Joachirn S, Garric J, Boisseaux P, Exbrayat JM, Porcher JM, et al. Anatomical and histological characterization of the gametogenesis of Radix balthica (linnaeus, 1758) in comparison with Lymnaea stagnalis (linnaeus, 1758). Journal of Histology & Histopathology. 2017;4:5

[4] Apperson KD, Cherian G. Effect of whole flax seed and carbohydrase enzymes on gastrointestinal morphology, muscle fatty acids, and production performance in broiler chickens. Poultry Science. 2017;96(5): 1228-1234

[5] Colussi G, Catena C, Novello M, Bertin N, Sechi LA. Impact of omega-3 polyunsaturated fatty acids on vascular function and blood pressure: Relevance for cardiovascular outcomes. Nutrition, Metabolism, and Cardiovascular Diseases. 2017;27(3):191-200

[6] Rees AM, Austin MP, Parker G. Role of omega-3 fatty acids as a treatment for depression in the perinatal peiod. Australian and New Zealand Journal of Psychiatry. 2005;39(4):274-280

[7] Reeves JB, Weihrauch JL. Composition of Foods. Fats and Oils. Agriculture Handbook. Washington, DC: USDA; 1979

[8] Castro-Gonzalez MI. Omega 3 fatty acids: Benefits and sources. Interciencia. 2002;27(3):128-136

[9] Budowski P. Oils rich in omega-3 fatty acids—health implications. Harefuah. 1995;128(2):121-125

[10] Nettleton JA. omega 3 fatty acids: Comparison of plant and seafood sources in human nutrition. Journal of the American Dietetic Association. 1991; 91(3):331-337

[11] Ackman RG, Marine lipids and omega-3 fatty acids. In: Akoh CC, editor. (Functional Foods and Nutraceuticals Series), in Handbook of functional lipids. Boca Raton: Taylor & Francis; p. 311-324

[12] Landmark K. Alpha-linolenic acid, cardiovascular disease and sudden death. Tidsskrift for den Norske Lægeforening. 2006;126(21):2792-2794

[13] Herbaut C. Omega-3 and health. Revue Médicale de Bruxelles. 2006; 27(4):355-360

[14] Brown AJ, Robrts DCK, Truswell AS. Fatty acid composition of australian marine finfish: A review. Food Australia. 1989;1:655-666

[15] Kris-Etherton MKP, Harris WS, Appel LJ. Fish consumption, fish oil, omega-3 fattyacids, and cardiovascular disease. Journal of the American Heart Association. 2002;106:2747-2773

[16] Kartal M, Kurucu S, Aslan S, Ozbay O, Ceyhan T, Sayar E, et al. Comparison of n-3 fatty acids by GC-MS in frequently consumed fish and fish oil preparations on the turkish market. FABAD Journal of Pharmaceutical Sciences. 2003;28:201-205

[17] Alexander JW. Immunonutrition: The role of omega 3 fatty acids. Nutrition. 1998;14(7/8):627-633

[18] Holub BJ. Clinical nutrition: 4. Omega-3 fatty acids in cardiovascular care. Canadian Medical Association Journal. 2002;166(5):608-615

[19] Simopoulos AP. Health effects of [Omega]3 polyunsaturated fatty acids in seafoods. In: World Review of Nutrition and Dietetics. Vol. 66. Basel; London: Karger; 1991

[20] Simopoulos AP. Human requirement for n-3 polyunsaturated fatty acids. Poultry Science. 2000;79(7): 961-970

[21] Simopoulos AP. Importance of the ratio of omega-6/omega-3 essential fatty acids: Evolutionary aspects. (World Review of Nutrition and Dietetics). In: Simopoulos AP, Cleland LG, editors. Omega-6/Omega-3 Essential Fatty Acid Ratio: The Scientific Evidence. Vol. 92. Basel, Switzerland: Karger AG; 2003. pp. 1-22

[22] Singer P, Wirth M. Omega-3 fatty acids of marine and vegetable origin: State of the art. Ernahrungs-Umschau. 2003;50(8):296-304

[23] Rymer C, Givens DI. N-3 fatty acid enrichment of edible tissue of poultry: A review. Lipids. 2005;40(2):121-129

[24] Cheng CH, Shen TF, Chen WL, Ding ST. Effects of dietary algal docosahexaenoic acid oil supplementation on fatty acid deposition and gene expression in laying leghorn hens. The Journal of Agricultural Science. 2004;142:683-690

[25] Cachaldora P, Grcia-Rebollar P, Alvarez C, Mendez J, de Blas JC, Mendez J. Effect of type and level of basal fat and level of fish oil supplementation on yolk fat composition and n-3 fatty acids deposition efficiency in laying hens.

Animal Feed Science and Technology. 2008;141:104-114

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[26] WooCheol J, Jeong Yeoul L, Sangho K, Sangjin L, ByeongDae C, SeokJoong K. Production of DHA-rich meats and eggs from chickens fed fermented soybean meal by marine microalgae (Schizochytrium mangrivei MM103). Korean Journal of Poultry Science. 2008; 35:255-265

[27] Miller MR, Nichols PD, Carter CG. Replacement of dietary fish oil for atlantic salmon parr (Salmo salar L.) with a stearidonic acid containing oil has no effect on omega-3 long-chain polyunsaturated fatty acid concentrations. Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology. 2007;109:1226-1236

[28] Kitessa SM, Young P. Echium oil is better than rapeseed oil in enriching poultry meat with n-3 polyunsaturated fatty acids, including eicosapentaenoic acid and docosapentaenoic acid. British Journal of Nutrition. 2009;101:709-715

[29] Rymer C, Gibbs RA, Givens DI. Comparison of algal and fish sources on the oxidative stability of poultry meat and its enrichment with omega-3 polyunsaturated fatty acids. Poultry Science. 2010;89(1):150-159

[30] Simonpoulos AP. Is insulin resistance influenced by dietary linoleic acid and trans fatty acids? Free Radical Biology and Medicine. 1994;17(4): 367-372

[31] Surai PF, Sparks NHC. Tissuespecific fatty acid and alpha -tocopherol profiles in male chickens depending on dietary tuna oil and vitamin E provision. Poultry Science. 2000;79(8): 1132-1142

[32] Voss A, Reinhart M, Sankarappa S, Sprecher H. The metabolism of 7,10,13,16,19-docosapentaenoic acid to 4,7,10,13,16,19-docosahexaenoic acid in Role of Poultry Research in Increasing Consumption of PUFA in Humans DOI: http://dx.doi.org/10.5772/intechopen.85099

rat liver is independent of a 4 desaturase. The Journal of Biological Chemistry. 1991;266:19995-20000

[17] Alexander JW. Immunonutrition: The role of omega 3 fatty acids. Nutrition. 1998;14(7/8):627-633

Nutrition in Health and Disease - Our Challenges Now and Forthcoming Time

Animal Feed Science and Technology.

[26] WooCheol J, Jeong Yeoul L, Sangho K, Sangjin L, ByeongDae C, SeokJoong K. Production of DHA-rich meats and eggs from chickens fed fermented soybean meal by marine microalgae (Schizochytrium mangrivei MM103). Korean Journal of Poultry Science. 2008;

[27] Miller MR, Nichols PD, Carter CG. Replacement of dietary fish oil for atlantic salmon parr (Salmo salar L.) with a stearidonic acid containing oil has

no effect on omega-3 long-chain polyunsaturated fatty acid concentrations. Comparative

2007;109:1226-1236

Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology.

[28] Kitessa SM, Young P. Echium oil is better than rapeseed oil in enriching poultry meat with n-3 polyunsaturated fatty acids, including eicosapentaenoic acid and docosapentaenoic acid. British Journal of Nutrition. 2009;101:709-715

[29] Rymer C, Gibbs RA, Givens DI. Comparison of algal and fish sources on the oxidative stability of poultry meat and its enrichment with omega-3 polyunsaturated fatty acids. Poultry

Science. 2010;89(1):150-159

367-372

1132-1142

[30] Simonpoulos AP. Is insulin

[31] Surai PF, Sparks NHC. Tissuespecific fatty acid and alpha -tocopherol profiles in male chickens depending on dietary tuna oil and vitamin E provision. Poultry Science. 2000;79(8):

[32] Voss A, Reinhart M, Sankarappa S,

7,10,13,16,19-docosapentaenoic acid to 4,7,10,13,16,19-docosahexaenoic acid in

Sprecher H. The metabolism of

resistance influenced by dietary linoleic acid and trans fatty acids? Free Radical Biology and Medicine. 1994;17(4):

2008;141:104-114

35:255-265

[18] Holub BJ. Clinical nutrition: 4. Omega-3 fatty acids in cardiovascular care. Canadian Medical Association Journal. 2002;166(5):608-615

[19] Simopoulos AP. Health effects of [Omega]3 polyunsaturated fatty acids in seafoods. In: World Review of Nutrition and Dietetics. Vol. 66. Basel; London:

requirement for n-3 polyunsaturated fatty acids. Poultry Science. 2000;79(7):

[21] Simopoulos AP. Importance of the ratio of omega-6/omega-3 essential fatty acids: Evolutionary aspects. (World Review of Nutrition and Dietetics). In: Simopoulos AP, Cleland LG, editors. Omega-6/Omega-3 Essential Fatty Acid Ratio: The Scientific Evidence. Vol. 92. Basel, Switzerland: Karger AG; 2003.

[22] Singer P, Wirth M. Omega-3 fatty acids of marine and vegetable origin: State of the art. Ernahrungs-Umschau.

[23] Rymer C, Givens DI. N-3 fatty acid enrichment of edible tissue of poultry: A review. Lipids. 2005;40(2):121-129

[24] Cheng CH, Shen TF, Chen WL, Ding ST. Effects of dietary algal docosahexaenoic acid oil supplementation on fatty acid

leghorn hens. The Journal of

basal fat and level of fish oil supplementation on yolk fat composition and n-3 fatty acids deposition efficiency in laying hens.

54

deposition and gene expression in laying

Agricultural Science. 2004;142:683-690

[25] Cachaldora P, Grcia-Rebollar P, Alvarez C, Mendez J, de Blas JC, Mendez J. Effect of type and level of

[20] Simopoulos AP. Human

Karger; 1991

961-970

pp. 1-22

2003;50(8):296-304

[33] Mohammed B, Sankarappa S, Geiger M, Sprecher H. Reevaluation of the pathway for the metabolism of 7,10,13, 16-docosatetraenoic acid to 4,7,10,13,16 docosapentaenoic acid in rat liver. Archives of Biochemistry and Biophysics. 1995;317:179-184

[34] Yaqoob P, Calder PC. N-3 polyunsaturated fatty acids and the immune system. Recent Research Developments in Lipids - Research. 1997;1:31-61

[35] Nakamura MT, Nara TY. Structure, function, and dietary regulation of Delta 6, Delta 5, and Delta 9 desaturases. Annual Review of Nutrition. 2004;24: 345-376

[36] Calder PC. N-3 polyunsaturated fatty acids and mononuclear phagocyte function. In: Kremer J, editor. Medical Fatty Acids in Inflammation. Switzerland: Birkhauser Verlag Basel; 1998

[37] Calder PC, Bond JA, Harvey DJ, Gordon S, Newsholme EA. Uptake and incorporation of saturated and unsaturated fatty acids into macrophage lipids and their effect upon macrophage adhesion and phagocytosis. The Biochemical Journal. 1990;269(3): 807-814

[38] Surette ME, Edens M, Chilton FH, Tramposch KM. Dietary echium oil increases plasma and neutrophil longchain (n-3) fatty acids and lowers serum triacylglycerols in hypertriglyceridemic humans. The Journal of Nutrition. 2004; 134(6):1406-1411

[39] Yang Q, O'Shea TM. Dietary echium oil increases tissue (n-3) long-chain polyunsaturated fatty acids without elevating hepatic lipid concentrations in premature neonatal rats. The Journal of Nutrition. 2009;139(7):1353-1359

[40] Whelan J. Dietary stearidonic acid is a long chain (n-3) polyunsaturated fatty acid with potential health benefits. The Journal of Nutrition. 2009;139:5-10

[41] Whelan J, Rust C. Innovative dietary sources of n-3 fatty acids. Annual Review of Nutrition. 2006;26: 75-103

[42] Miles EA, Banerjee T, Dooper MM, M'Rabet L, Graus YM, Calder PC. The influence of different combinations of gamma-linoleinic acid, stearidonic acid and EPA on immune function in healthy young male subjects. The British Journal of Nutrition. 2004;91:893-903

[43] James MJ, Ursin VM, Cleland LG. Metabolism of stearidonic acid in human subjects: Comparison with the metabolism of other n-3 fatty acids. The American Journal of Clinical Nutrition. 2003;77:1140-1145

[44] Lopez-Ferrer S, Baucells MD, Barroeta AC, Grashorn MA. Metabolism and nutrition. n-3 Enrichment of chicken meat using fish oil: Alternative substitution with rapeseed and linseed oils. Poultry Science. 1999;78(3):356-365

[45] Bibus DM, Stitt PA. Metabolism of alpha -linolenic acid from flaxseed in dogs. In: The Return of Omega 3 Fatty Acids into the Food Supply. 1. Land-Based Animal Food Products and Their Health Effects. Basel, Switzerland: S Karger AG; 1998. pp. 186-198

[46] Drevon CA, Baksaas I, Krokan H. Omega-3 fatty acids: Metabolism and Biological Effects. Basel, Boston: Birkhéauser Verlag; 1993;1:389

[47] Fischer S, Von Schacky C, Siess W, Strasser T, Weber PC. Uptake, release and metabolism of docosahexaenoic acid in human platelets and neutrophils. Biochemical and Biophysical Research Communications. 1984;120:907-918

[48] Calder PC. Polyunsaturated fatty acids and inflammation. Prostaglandins, Leukotrienes and Essential Fatty Acids. 2006;75:197-202

[49] Calder PC. The relationship between the fatty acid compostion of immune cells and their function. Prostaglandins, Leukotrienes and Essential Fatty Acids. 2008;79:101-108

[50] Calder PC, Yaqoob P, Thies F, Wallace FA, Miles EA. Fatty acids and lymphocyte functions. British Journal of Nutrition. 2002;87(Supplement 1: S31-S48

[51] Calder PC. n-3 Polyunsaturated fatty acids, inflammation, and inflammatory diseases. The American Journal of Clinical Nutrition. 2006; 83(1):1505-1519

[52] Kew S, Banerjee T, Minihane AM, Finnegan YE, Williams CM, Calder PC. Relation between the fatty acid composition of peripheral blood mononuclear cells and measures of immune cell function in healthy, freeliving subjects aged 25-72 y. The American Journal of Clinical Nutrition. 2003;77(5):1278-1286

[53] Yaqoob P, Pala HS, Cortina-Borja M, Newsholme EA, Calder PC. Encapsulated fish oil enriched in alphatocopherol alters plasma phospholipid and mononuclear cell fatty acid compositions but not mononuclear cell functions. European Journal of Clinical Investigation. 2000;30(3): 260-274

[54] Calder PC. Dietary fish oil appears to prevent the activation of phospholipase c -gamma in lymphocytes. Biochimica et Biophysica Acta. 1998;1392:300-308

[55] Calder PC. N-3 polyunsaturated fatty acids, inflammation and immunity: Pouring oil on troubled waters or another fishy tale? (Special issue: Celebrating exciting nutrition research in the next century). Nutrition Research. 2001;21(1/2):309-341

[56] Calder PC. Fatty acids and lymphocytes functions. British Journal of Nutrition. 2002;87(1):31-48

[65] Arm P, Horton C, Mencia-Huerta J. Effect of dietary supplementation with fish oil lipids on mild asthma. Thorax.

DOI: http://dx.doi.org/10.5772/intechopen.85099

Role of Poultry Research in Increasing Consumption of PUFA in Humans

[74] Woods A, Brull D, Humphries S,

[75] Connor WE, Neuringer M, Lin DS. Dietary effects on brain fatty acid composition: The reversibility of n-3 fatty acid deficiency and turnover of docosahexaenoic acid in the brain, erythrocytes and plasma of rhesus monkeys. Journal of Lipid Research.

[76] Nkondjock A, Shatenstein B, Maisonneuve P, Ghadirian P. Specific fatty acids and human colorectal cancer: An overview. Cancer Detection and Prevention. 2003;27(1):55-66

[77] Prasad KN, Kumar B, Yan XD, Hanson AJ, Cole WC. Alpha -

Tocopheryl succinate, the most effective form of vitamin E for adjuvant cancer treatment: A review. Journal of the American College of Nutrition. 2003;

[78] Cotter PF, Sefton AE, Lilburn MS. Manipulating the immune system of layers and breeders: Novel applications of mannan oligosaccharides. In: Lyons TP, Jacques KA editors. Nutritional Biotechnology in the Feed and Food Industries. UK, Stamford: Alltech; 2002.

[79] Koller M, Senkal M, Kemen M, Konig W, Zumtobel V, Muhr G. Impact of omega-3 fatty acid enriched TPN on leukotriene synthesis by leukocytes after major surgery. Clinical Nutrition.

[80] Bou R, Guardiola F, Tres A, Barroeta AC, Codony R. Effect of dietary fish oil, alpha-tocopherl acetate, and zinc supplementation on the

composition and consumer acceptability of chicken meat. Poultry Science. 2004;

Montgomery H. Genetics of inflammation and risk of coronary artery disease: The central role of interleukin-6. European Heart Journal.

2000;21:1574-1583

1990;31:237-247

22(2):108-117

p. 21-27

2003;22(1):59-64

83:282-292

[66] Arm I, Horton C, Spur B, Mencia-Huerta J, Lee T, Am T. The effects of dietary supplementation with fish oil lipids on the airways response to inhaledallergen in bronchial asthma. American Review of Respiratory Diseases. 1989;139:1395-1400

[67] Simopoulos AP. Omega-3 fatty acids in inflammation and autoimmune diseases. Journal of the American College of Nutrition. 2002;21(6):

[68] Sellmayer A, Schrepf R, Theisen K, Weber PC. Role of omega-3 fatty acids in cardiovascular disease prevention. Deutsche Medizinische Wochenschrift.

[69] Schwalfenberg G. Omega-3 fatty

cardiovascular health. Canadian Family Physician. 2006;52(JUN):734-740

[70] Nettleton JA. Omega-3 Fatty Acids and Health. New York; London: Chapman & Hall; 1995. p. 359

[71] Leaf A, Kang JX. Omega-3 fatty acids and cardiovascular disease (World Review of Nutriton and Dietetics, Vol. 89). In: Simopoulos AP, Pavlou KN, editors. Nutrition and Fitness 1: Diet, Genes, Physical Activity and Health. Basel Switzerland: S Karger AG; 2001.

[72] Connor WE. Omega 3 Fatty acids and heart disease. In: Kritchevsky D, Carroll KK, editors. Nutrition and Disease Update: Heart Disease. Champaign: American Oil Chemists' Society (AOCS); 1994. pp. 1-137

[73] Budowski P. Omega 3-Fatty acids in health and disease. World Review of Nutrition and Dietetics. 1988;57:214-274

2004;129(38):1993-1996

acids: Their beneficial role in

1988;43:84-92

495-505

pp. 161-172

57

[57] Calder PC. Long-chain polyunsaturated fatty acids and inflammation. Scandinavian Journal of Food and Nutrition. 2006;50(1 sup. 2): 54-61

[58] Yaqoob P, Calder P. Effects of dietary lipid manipulation upon inflammatory mediator production by murine macrophages. Cellular Immunology. 1995;163(1):120-128

[59] Yaqoob P, Newsholme EA, Calder PC. The effect of fatty acids on leucocyte subsets and proliferation in rat whole blood. Nutrition Research. 1995;15(2):279-287

[60] Yaqoob P, Newsholmee EA, Calder PC. The effect of dietary lipid manipulation on rat lymphocyte subsets and proliferation. Immunology. 1994; 82:603-610

[61] Bavelaar FJ, Hovenier R, Lemmens AG, Beynen AC. High intake of linoleic or alpha -linolenic acid in relation to plasma lipids, atherosclerosis and tissue fatty acid composition in the Japanese quail. International Journal of Poultry Science. 2004;3(11):704-714

[62] Cyrus T. Disruption of the 12/15 lipoxygenase gene diminishes atherosclerosis in apo E-deficient mice. The Journal of Clinical Investigation. 1999;103:1597-1604

[63] Calder PC. Dietary modification of inflammation with lipids. Proceedings of the Nutrition Society. 2002;61(3): 345-358

[64] Volker DH. Fat manipulation in the treatment of rheumatoid arthritis: A review. Journal of Nutraceuticals, Functional & Medical Foods. 2000;3(1): 5-31

Role of Poultry Research in Increasing Consumption of PUFA in Humans DOI: http://dx.doi.org/10.5772/intechopen.85099

[65] Arm P, Horton C, Mencia-Huerta J. Effect of dietary supplementation with fish oil lipids on mild asthma. Thorax. 1988;43:84-92

Leukotrienes and Essential Fatty Acids.

Nutrition in Health and Disease - Our Challenges Now and Forthcoming Time

[56] Calder PC. Fatty acids and

of Nutrition. 2002;87(1):31-48

[58] Yaqoob P, Calder P. Effects of dietary lipid manipulation upon inflammatory mediator production by

[59] Yaqoob P, Newsholme EA, Calder PC. The effect of fatty acids on leucocyte subsets and proliferation in rat whole blood. Nutrition Research.

[60] Yaqoob P, Newsholmee EA, Calder

manipulation on rat lymphocyte subsets and proliferation. Immunology. 1994;

[61] Bavelaar FJ, Hovenier R, Lemmens AG, Beynen AC. High intake of linoleic or alpha -linolenic acid in relation to plasma lipids, atherosclerosis and tissue fatty acid composition in the Japanese quail. International Journal of Poultry

[62] Cyrus T. Disruption of the 12/15-

atherosclerosis in apo E-deficient mice. The Journal of Clinical Investigation.

[63] Calder PC. Dietary modification of inflammation with lipids. Proceedings of the Nutrition Society. 2002;61(3):

[64] Volker DH. Fat manipulation in the treatment of rheumatoid arthritis: A review. Journal of Nutraceuticals, Functional & Medical Foods. 2000;3(1):

PC. The effect of dietary lipid

Science. 2004;3(11):704-714

lipoxygenase gene diminishes

1999;103:1597-1604

345-358

5-31

murine macrophages. Cellular Immunology. 1995;163(1):120-128

1995;15(2):279-287

82:603-610

[57] Calder PC. Long-chain polyunsaturated fatty acids and inflammation. Scandinavian Journal of Food and Nutrition. 2006;50(1 sup. 2):

54-61

lymphocytes functions. British Journal

[49] Calder PC. The relationship between the fatty acid compostion of immune cells and their function. Prostaglandins, Leukotrienes and Essential Fatty Acids. 2008;79:101-108

[50] Calder PC, Yaqoob P, Thies F, Wallace FA, Miles EA. Fatty acids and lymphocyte functions. British Journal of Nutrition. 2002;87(Supplement 1:

[51] Calder PC. n-3 Polyunsaturated fatty acids, inflammation, and

inflammatory diseases. The American Journal of Clinical Nutrition. 2006;

[52] Kew S, Banerjee T, Minihane AM, Finnegan YE, Williams CM, Calder PC.

[53] Yaqoob P, Pala HS, Cortina-Borja M,

Encapsulated fish oil enriched in alphatocopherol alters plasma phospholipid and mononuclear cell fatty acid compositions but not mononuclear cell functions. European Journal of Clinical Investigation. 2000;30(3):

[54] Calder PC. Dietary fish oil appears to prevent the activation of phospholipase c -gamma in lymphocytes. Biochimica et Biophysica Acta. 1998;1392:300-308

[55] Calder PC. N-3 polyunsaturated fatty acids, inflammation and immunity: Pouring oil on troubled waters or another fishy tale? (Special issue: Celebrating exciting nutrition research

in the next century). Nutrition Research. 2001;21(1/2):309-341

Relation between the fatty acid composition of peripheral blood mononuclear cells and measures of immune cell function in healthy, freeliving subjects aged 25-72 y. The American Journal of Clinical Nutrition.

2003;77(5):1278-1286

260-274

56

Newsholme EA, Calder PC.

2006;75:197-202

S31-S48

83(1):1505-1519

[66] Arm I, Horton C, Spur B, Mencia-Huerta J, Lee T, Am T. The effects of dietary supplementation with fish oil lipids on the airways response to inhaledallergen in bronchial asthma. American Review of Respiratory Diseases. 1989;139:1395-1400

[67] Simopoulos AP. Omega-3 fatty acids in inflammation and autoimmune diseases. Journal of the American College of Nutrition. 2002;21(6): 495-505

[68] Sellmayer A, Schrepf R, Theisen K, Weber PC. Role of omega-3 fatty acids in cardiovascular disease prevention. Deutsche Medizinische Wochenschrift. 2004;129(38):1993-1996

[69] Schwalfenberg G. Omega-3 fatty acids: Their beneficial role in cardiovascular health. Canadian Family Physician. 2006;52(JUN):734-740

[70] Nettleton JA. Omega-3 Fatty Acids and Health. New York; London: Chapman & Hall; 1995. p. 359

[71] Leaf A, Kang JX. Omega-3 fatty acids and cardiovascular disease (World Review of Nutriton and Dietetics, Vol. 89). In: Simopoulos AP, Pavlou KN, editors. Nutrition and Fitness 1: Diet, Genes, Physical Activity and Health. Basel Switzerland: S Karger AG; 2001. pp. 161-172

[72] Connor WE. Omega 3 Fatty acids and heart disease. In: Kritchevsky D, Carroll KK, editors. Nutrition and Disease Update: Heart Disease. Champaign: American Oil Chemists' Society (AOCS); 1994. pp. 1-137

[73] Budowski P. Omega 3-Fatty acids in health and disease. World Review of Nutrition and Dietetics. 1988;57:214-274 [74] Woods A, Brull D, Humphries S, Montgomery H. Genetics of inflammation and risk of coronary artery disease: The central role of interleukin-6. European Heart Journal. 2000;21:1574-1583

[75] Connor WE, Neuringer M, Lin DS. Dietary effects on brain fatty acid composition: The reversibility of n-3 fatty acid deficiency and turnover of docosahexaenoic acid in the brain, erythrocytes and plasma of rhesus monkeys. Journal of Lipid Research. 1990;31:237-247

[76] Nkondjock A, Shatenstein B, Maisonneuve P, Ghadirian P. Specific fatty acids and human colorectal cancer: An overview. Cancer Detection and Prevention. 2003;27(1):55-66

[77] Prasad KN, Kumar B, Yan XD, Hanson AJ, Cole WC. Alpha - Tocopheryl succinate, the most effective form of vitamin E for adjuvant cancer treatment: A review. Journal of the American College of Nutrition. 2003; 22(2):108-117

[78] Cotter PF, Sefton AE, Lilburn MS. Manipulating the immune system of layers and breeders: Novel applications of mannan oligosaccharides. In: Lyons TP, Jacques KA editors. Nutritional Biotechnology in the Feed and Food Industries. UK, Stamford: Alltech; 2002. p. 21-27

[79] Koller M, Senkal M, Kemen M, Konig W, Zumtobel V, Muhr G. Impact of omega-3 fatty acid enriched TPN on leukotriene synthesis by leukocytes after major surgery. Clinical Nutrition. 2003;22(1):59-64

[80] Bou R, Guardiola F, Tres A, Barroeta AC, Codony R. Effect of dietary fish oil, alpha-tocopherl acetate, and zinc supplementation on the composition and consumer acceptability of chicken meat. Poultry Science. 2004; 83:282-292

[81] Ratnayake WMN, Ackman RG, Hulan HW. Effect of redfish meal enriched diets on the taste and n-3 pufa of 42-day-old broiler chickens. Journal of the Science of Food and Agriculture. 1986;49(1):59-74

[82] Givens DI, Rymer C. Effect of species and genotype on the efficiency of enrichment of poultry meat with n-3 polyunsaturated fatty acid. Lipids. 2006;41(5):445-451

[83] Lopez-Ferrer S, Baucells MD, Barroeta AC, Grashorn MA. N-3 enrichment of chicken meat using fish oil: Alternative substituation with rapeseed and linseed oils. Poultry Science. 1999;78:356-365

[84] Zelenka J, Schneiderova D, Mrkvicova E, Dolezal P. The effect of dietary linseed oils with different fatty acid pattern on the content of fatty acids in chicken meat. Veterinary Medicine. 2008;53(2):77-85

[85] Kartikasari LR, Hughes RJ, Geier MS, Makrides M, Gibson RA. World Congress on Oils and Fats 28th ISF Congress; 2009. pp. 62-63

[86] Kartikasari LR, Hughes RJ, Geier MS, Makrides M, Gibson RA. Diets high in linoleic acid reduce omega-3 long chain polyunsaturated fatty acids in chicken tissues. In: Aust. Poult. Sci. Symp. Australia; 2010. pp. 64-67

[87] Lopez-Ferrer S, Baucells MD, Barroeta AC, Galobart J, Grashorn MA. n-3 Enrichment of chicken meat. 2. Use of precursors of long-chain polyunsaturated fatty acids: Linseed oil. Poultry Science. 2001;80(6):753-761

[88] Svedova M, Vasko L, Trebunova A, Kastel R, Tuckova M, Certik M. Influence of linseed and fish oil on metabolic and immunological indicators of laying hens. Acta Veterinaria. 2008; 77:39-44

[89] Yang X, Yuming G. Modulation of intestinal mucosal immunity by dietary polyunsaturated fatty acids in chickens. Food and Agricultural Immunology. 2006;17(2):129-137

[90] Korver DR, Klasing KC. Dietary fish oil alters specific and inflammatory immune responses in chicks. Journal of Nutrition. 1997;127(10):2039-2046

[91] Leshchinsky TV, Klasing KC. Vitamin E and leukocytic cytokine expression in broilers. Poultry Science. 2000;79(1):37

[92] Koutsos EA, Klasing KC. Effect of intra-abdominal injection of lipopolysaccharide or muramyl dipeptide on the acute phase response in Japanese quail (Coturnix coturnix japonica). Poultry Science. 2000; 79(1):37

[93] Puthpongsiriporn U, Scheideler SE. Effects of dietary ratio of linoleic to linolenic acid on performance, antibody production, and in vitro lymphocyte proliferation in two strains of Leghorn pullet chicks. Poultry Science. 2005; 84(6):846-857

[94] Adam O. Dietary fatty acids and immune reactions in synovial tissue. European Journal of Medical Research, 2003;8(8):381-387

[95] Phipps RP, Stein SH, Roper RL. A new view of prostaglandin regulation of the immune response. Immunology Today. 1991;12:349-352

[96] Parmentier HK, Nieuwland MGB, Barwegen MW, Kwakkel RP, Schrama JW. Dietary unsaturated fatty acids affect antibody responses and growth of chickens divergently selected for humoral responses to sheep red blood cells. Poultry Science. 1997;76(8): 1164-1171

[97] Sijben JWC, Groot Hd, Nieuwland MGB, Schrama JW, Parmentier HK. Dietary linoleic acid divergently affects immune responsiveness of growing layer hens. Poultry Science. 2000;79(8): 1106-1115

**59**

**Chapter 5**

**Abstract**

**1. Introduction**

Antidiabetic Potential of Plants

Used in Bulgarian Folk Medicine

The idea of this chapter is that currently available antidiabetic drugs specifically target several points of the T2D pathophysiology but they do not cover all aspects of the disease. In addition, many adverse effects of synthetic antidiabetic agents have been reported. The suggested manuscript is an overview of the available scientific literature focused on antiobesity and antidiabetic potential of selected 42 medicinal and edible plants of the Bulgarian flora. Most of the reports reveal the effect of extracts or their active components on specific biochemical mechanisms. Mechanistic data about hypoglycemic and hypolipidemic action are presented for some of the plants. An essential part of this review is dedicated to the target mechanisms behind the effects of the selected plant species. The authors hope that this review will serve as a starting point for future investigations with a contribution to the prevention and therapy of diabetes.

Diabetes is an endocrine disease related to impaired glucose metabolism due to either impaired insulin secretion or decreased sensitivity to its function, classified, respectively, as type 1 diabetes (T1D) and type 2 diabetes (T2D). Over time, chronic hyperglycemia can cause secondary micro- and macrovascular complications affecting the functions of the eyes, kidneys, peripheral nerves, and arteries. According to recent alarming data, the number of adults living with diabetes has almost quadrupled since 1980 to 2014. This dramatic rise is largely due to the number of T2D sufferers [1]. Although some of the characteristics of the modern lifestyle (obesity, stress, low physical activity) are considered to be risk factors with regard to the occurrence of diabetes, it should be noted that cases of the disease are described in written sources dating back to 3500 years [2–4]. Also, records exist from ancient Egypt, India, and Persia, indicating a long history of medicinal use of plants for treatment of conditions associated with diabetes [5]. Historical and archeological sources indicate that Thracians, the most ancient tribes on the territory of Bulgaria, were familiar with the healing power of the plants [6]. Over the years, empirical data about healing properties of plants used in Bulgarian folk medicine and traditional nutrition have been collected in several reference books [7–10]. Although plants have been used to treat diabetes for centuries, the number of species with completely clarified antidiabetic mechanisms of action is still limited.

**Keywords:** medicinal plants, diabetes, folk medicine, traditional diet

and Traditional Diet

*and Diana G. Ivanova*

*Milka Nashar, Yoana D. Kiselova-Kaneva* 

#### **Chapter 5**

[81] Ratnayake WMN, Ackman RG, Hulan HW. Effect of redfish meal enriched diets on the taste and n-3 pufa of 42-day-old broiler chickens. Journal of the Science of Food and Agriculture.

Nutrition in Health and Disease - Our Challenges Now and Forthcoming Time

polyunsaturated fatty acids in chickens. Food and Agricultural Immunology.

[90] Korver DR, Klasing KC. Dietary fish oil alters specific and inflammatory immune responses in chicks. Journal of Nutrition. 1997;127(10):2039-2046

[91] Leshchinsky TV, Klasing KC. Vitamin E and leukocytic cytokine expression in broilers. Poultry Science.

[92] Koutsos EA, Klasing KC. Effect of

dipeptide on the acute phase response in Japanese quail (Coturnix coturnix japonica). Poultry Science. 2000;

[93] Puthpongsiriporn U, Scheideler SE. Effects of dietary ratio of linoleic to linolenic acid on performance, antibody production, and in vitro lymphocyte proliferation in two strains of Leghorn pullet chicks. Poultry Science. 2005;

[94] Adam O. Dietary fatty acids and immune reactions in synovial tissue. European Journal of Medical Research,

[95] Phipps RP, Stein SH, Roper RL. A new view of prostaglandin regulation of the immune response. Immunology

[96] Parmentier HK, Nieuwland MGB, Barwegen MW, Kwakkel RP, Schrama JW. Dietary unsaturated fatty acids affect antibody responses and growth of chickens divergently selected for humoral responses to sheep red blood cells. Poultry Science. 1997;76(8):

[97] Sijben JWC, Groot Hd, Nieuwland MGB, Schrama JW, Parmentier HK. Dietary linoleic acid divergently affects immune responsiveness of growing layer hens. Poultry Science. 2000;79(8):

intra-abdominal injection of lipopolysaccharide or muramyl

2006;17(2):129-137

2000;79(1):37

79(1):37

84(6):846-857

2003;8(8):381-387

Today. 1991;12:349-352

1164-1171

1106-1115

[82] Givens DI, Rymer C. Effect of species and genotype on the efficiency of enrichment of poultry meat with n-3 polyunsaturated fatty acid. Lipids.

[83] Lopez-Ferrer S, Baucells MD, Barroeta AC, Grashorn MA. N-3 enrichment of chicken meat using fish oil: Alternative substituation with rapeseed and linseed oils. Poultry

1986;49(1):59-74

2006;41(5):445-451

Science. 1999;78:356-365

2008;53(2):77-85

[84] Zelenka J, Schneiderova D, Mrkvicova E, Dolezal P. The effect of dietary linseed oils with different fatty acid pattern on the content of fatty acids in chicken meat. Veterinary Medicine.

[85] Kartikasari LR, Hughes RJ, Geier MS, Makrides M, Gibson RA. World Congress on Oils and Fats 28th ISF

[86] Kartikasari LR, Hughes RJ, Geier MS, Makrides M, Gibson RA. Diets high in linoleic acid reduce omega-3 long chain polyunsaturated fatty acids in chicken tissues. In: Aust. Poult. Sci. Symp. Australia; 2010. pp. 64-67

[87] Lopez-Ferrer S, Baucells MD, Barroeta AC, Galobart J, Grashorn MA. n-3 Enrichment of chicken meat. 2. Use

polyunsaturated fatty acids: Linseed oil. Poultry Science. 2001;80(6):753-761

[88] Svedova M, Vasko L, Trebunova A,

[89] Yang X, Yuming G. Modulation of intestinal mucosal immunity by dietary

Kastel R, Tuckova M, Certik M. Influence of linseed and fish oil on metabolic and immunological indicators of laying hens. Acta Veterinaria. 2008;

77:39-44

58

of precursors of long-chain

Congress; 2009. pp. 62-63

## Antidiabetic Potential of Plants Used in Bulgarian Folk Medicine and Traditional Diet

*Milka Nashar, Yoana D. Kiselova-Kaneva and Diana G. Ivanova*

#### **Abstract**

The idea of this chapter is that currently available antidiabetic drugs specifically target several points of the T2D pathophysiology but they do not cover all aspects of the disease. In addition, many adverse effects of synthetic antidiabetic agents have been reported. The suggested manuscript is an overview of the available scientific literature focused on antiobesity and antidiabetic potential of selected 42 medicinal and edible plants of the Bulgarian flora. Most of the reports reveal the effect of extracts or their active components on specific biochemical mechanisms. Mechanistic data about hypoglycemic and hypolipidemic action are presented for some of the plants. An essential part of this review is dedicated to the target mechanisms behind the effects of the selected plant species. The authors hope that this review will serve as a starting point for future investigations with a contribution to the prevention and therapy of diabetes.

**Keywords:** medicinal plants, diabetes, folk medicine, traditional diet

#### **1. Introduction**

Diabetes is an endocrine disease related to impaired glucose metabolism due to either impaired insulin secretion or decreased sensitivity to its function, classified, respectively, as type 1 diabetes (T1D) and type 2 diabetes (T2D). Over time, chronic hyperglycemia can cause secondary micro- and macrovascular complications affecting the functions of the eyes, kidneys, peripheral nerves, and arteries. According to recent alarming data, the number of adults living with diabetes has almost quadrupled since 1980 to 2014. This dramatic rise is largely due to the number of T2D sufferers [1].

Although some of the characteristics of the modern lifestyle (obesity, stress, low physical activity) are considered to be risk factors with regard to the occurrence of diabetes, it should be noted that cases of the disease are described in written sources dating back to 3500 years [2–4]. Also, records exist from ancient Egypt, India, and Persia, indicating a long history of medicinal use of plants for treatment of conditions associated with diabetes [5]. Historical and archeological sources indicate that Thracians, the most ancient tribes on the territory of Bulgaria, were familiar with the healing power of the plants [6]. Over the years, empirical data about healing properties of plants used in Bulgarian folk medicine and traditional nutrition have been collected in several reference books [7–10]. Although plants have been used to treat diabetes for centuries, the number of species with completely clarified antidiabetic mechanisms of action is still limited.


**61**

therapy of diabetes.

*Antidiabetic Potential of Plants Used in Bulgarian Folk Medicine and Traditional Diet*

**No. Plant Common name Used parts References** 30 *Rosa canina* L. (Rosaceae) Rose hip Fruits [55, 94–96]

32 *Rubus sp.* diversae Бlackberry Leaves [21, 25, 100,

33 *Salvia officinalis* L. (Liliaceae) Garden sage Leaves [19, 47,

European black elderberry

39 *Urtica dioica* L. (Urticaceae) Nettle Stalk [34, 67,

42 *Zea mays* L. (Poaceae) Corn Silk [21, 123]

Oil rose Flower [97–98]

Dwarf elderberry Fruits [33, 107–110]

Dandelion Root stalk [19, 21, 34,

Thyme Stalk [19, 77]

Lime tree Flower [37, 115]

Blueberry Leaves and fruits [13, 14, 21,

101]

Flower [34, 111–113]

102–106]

81, 114]

116–120]

81]

Stalk [121, 122]

Currently available antidiabetic drugs could specifically target several points of the T2D pathophysiology, but they do not cover all aspects of the disease [11, 12]. In addition, many adverse effects of synthetic antidiabetic agents have been reported [11]. Therefore, it is not surprising that in recent years, the scientific interest is focused on identifying naturally derived compounds and preparations with hope to

Veronica, speedwell, Paul's betony

This chapter is an overview of the available scientific literature focused on antiobesity and antidiabetic potential of selected 42 medicinal and edible plants of the Bulgarian flora. Most of the reports reveal the effect of extracts or their active components on specific biochemical mechanisms. Mechanistic data for hypoglycemic and hypolipidemic action are presented for some of the plants (references summarized in **Table 1**). An essential part of this review is dedicated to the target

Without claiming exhaustiveness, the authors hope that this review will serve as a starting point for future investigations with a contribution to the prevention and

**2. Effects of plants and plant-derived compounds on glucose homeostasis**

Carbohydrates are an essential part of the human diet and are the main energy source of the body. Starch, sucrose, lactose, and glycogen are the main utilizable

**2.1 Inhibition of digestive enzymes and glucose absorption in the intestine**

address more aspects of the disease without undesirable side effects.

*References in support of potentially antidiabetic properties of 42 selected plants.*

mechanisms behind the effects of the selected plant species.

*DOI: http://dx.doi.org/10.5772/intechopen.85445*

31 *Rosa damascen*а *auct.* non-Mill. (Rosaceae)

34 *Sambucus ebulus* L. (Caprifoliaceae)

35 *Sambucus nigra* L. (Caprifoliaceae)

37 *Thymus* sp. diversae (Liliaceae)

38 *Tilia platyphyllos* Scop*.* (Tiliaceae)

40 *Vaccinium myrtillus* L. (Ericaceae)

41 *Veronica officinalis* L. (Scrophulariaceae)

**Table 1.**

36 *Taraxacum officinale* Wigg. (Asteraceae)


*Antidiabetic Potential of Plants Used in Bulgarian Folk Medicine and Traditional Diet DOI: http://dx.doi.org/10.5772/intechopen.85445*

#### **Table 1.**

*Nutrition in Health and Disease - Our Challenges Now and Forthcoming Time*

1 *Achillea millefolium* L. (Asteraceae)

2 *Agrimonia eupatoria* L. (Rosaceae)

3 *Alchemilla vulgaris* L. (Rosaceae)

5 *Arctostaphylos uva-ursi* L*.* (Ericaceae)

6 *Asparagus officinalis* L. (Liliaceae)

7 *Berberis vulgaris* L. (Berberidaceae)

9 *Cichorium intybus* L. (Asteraceae)

10 *Cotinus coggygria* Scop*.* (Anacardiaceae)

11 *Cydonia vulgaris* Pers*.* (Rosaceae)

12 *Foeniculum vulgare* Mill. (Apiaceae)

13 *Fragaria vesca complex* (Rosaceae)

14 *Galega officinalis* L. (Fabaceae)

15 *Hypericum perforatum* L. (Hypericaceae)

17 *Juniperus communis* L. (Cupressaceae)

19 *Melissa officinalis* L. (Liliaceae)

22 *Ocimum basilicum* L. (Liliaceae)

24 *Origanum vulgare* L. (Liliaceae)

26 *Phaseolus vulgaris* L. (Fabaceae)

27 *Plantago major* L. (Plantaginaceae)

28 *Polygonum aviculare* L. (Polygonaceae)

29 *Rheum officinale* Baill. (Polygonaceae)

18 *Lavandula angustifolia* Mill. (Liliaceae)

**No. Plant Common name Used parts References**

4 *Arctium lappa* L. (Asteraceae) Burdock Root [21, 34–36]

8 *Betula* sp. (Betulaceae) Birch Leaves [45, 46]

16 *Juglans regia* L. (Juglandaceae) Walnut Leaves [62–69]

20 *Mentha piperita* L. (Liliaceae) Mint Leaves [33, 71]

23 *Ononis spinosa* L. (Lamiaceae) Spiny restharrow Root [62]

25 *Pelargonium sp.* (Geraniaceae) Pelargonium Leaves [86, 87]

Prostrate knotweed, birdweed, pigweed

21 *Morus nigra* L. (Moraceae) Мulberry Leaves, fruits, root

Blue daisy, blue dandelion

White yarrow Aerial parts [13–20]

Agrimony Aerial parts [21–31]

Bearberry Leaves [37, 38]

Sparrow grass Stalk [39–41]

Barberry Fruits [42–44]

Smoke tree, sumach Leaves [25, 48]

Quince Leaves [49–51]

Dill Fruits [52–54]

Wild strawberry Leaves [33, 55, 56]

Goat's rue Stalk [21, 57–59]

St. John's wort Stalk [25, 60, 61]

Juniper Fruits [13, 14, 21,

Lavender Flower [21, 25, 70,

Melissa, lemon balm Stalk [25, 58, 71,

Basil Leaves [73–75]

Marjoram Stalk [25, 83–85]

Bean Pods [13, 14, 21,

Stalk [26]

Broadleaf plantain Leaves [62]

Rhubarb Root [92, 93]

bark, heartwood

Stalk, root [13, 14, 21,

47]

31]

71]

72]

[13, 14], 76–82

88–91]

Lady's Mantle Stalk [21, 32, 33]

**60**

*References in support of potentially antidiabetic properties of 42 selected plants.*

Currently available antidiabetic drugs could specifically target several points of the T2D pathophysiology, but they do not cover all aspects of the disease [11, 12]. In addition, many adverse effects of synthetic antidiabetic agents have been reported [11].

Therefore, it is not surprising that in recent years, the scientific interest is focused on identifying naturally derived compounds and preparations with hope to address more aspects of the disease without undesirable side effects.

This chapter is an overview of the available scientific literature focused on antiobesity and antidiabetic potential of selected 42 medicinal and edible plants of the Bulgarian flora. Most of the reports reveal the effect of extracts or their active components on specific biochemical mechanisms. Mechanistic data for hypoglycemic and hypolipidemic action are presented for some of the plants (references summarized in **Table 1**). An essential part of this review is dedicated to the target mechanisms behind the effects of the selected plant species.

Without claiming exhaustiveness, the authors hope that this review will serve as a starting point for future investigations with a contribution to the prevention and therapy of diabetes.

#### **2. Effects of plants and plant-derived compounds on glucose homeostasis**

#### **2.1 Inhibition of digestive enzymes and glucose absorption in the intestine**

Carbohydrates are an essential part of the human diet and are the main energy source of the body. Starch, sucrose, lactose, and glycogen are the main utilizable

carbohydrates in human diet. After the action of salivary and pancreatic α-amylase, the digestion products of starch and glycogen along with disaccharides are further digested in the small intestine epithelium, where the membrane-bound enzyme α-glucosidase, as well as various disaccharidases (saccharase, maltase, lactase), catalyze the release of glucose, fructose, and galactose. Monosaccharides are absorbed through the walls of the small intestine and reach the liver by the portal vein.

Inhibition of digestive enzymes is one possible approach to control early-stage hyperglycemia. Inhibition of α-amylase and α-glucosidase can significantly delay the increase in glucose concentration in the postprandial phase [124–127].

For a significant part of the plants presented in **Table 1**, data on the inhibitory effect of their extracts or active components on digestive enzymes in different experimental approaches were reported (**Table 2**). In vitro studies have found that aqueous extracts of basil and walnut leaves exert an inhibitory effect on α-amylase and α-glucosidase as well as on some disaccharidases without affecting insulin secretion and glucose transport proteins [63, 79]. Both studies suggest that polyphenols play a major role in the observed effects, as an extremely rich content of these active compounds in the two extracts is found. Another study [128] demonstrated a strong inhibitory activity of walnuts on the activity of α-amylase and disaccharidases.

Except aqueous extract of thyme, the extracted essential oil of the plant also exhibits an inhibitory effect on the amylase and glucosidase; Paddy et al. [19] and Pongpiriyadacha et al. [46] found that birch extract significantly reduced blood glucose levels after oral administration of sucrose to rats, a result demonstrating the inhibitory action of the extract on α-glucosidase. The same extract in an in vitro study had a concentration-dependent inhibitory effect on α-glucosidase, saccharase, and maltase.

#### **2.2 Effects on glucose homeostasis in the liver**

The liver has an essential role in maintenance of glucose homeostasis by controlling the utilization of excess glucose after meal for glycogen synthesis or secretion of free glucose into the circulation through glycogenolysis and gluconeogenesis (GNG) in fasting periods. Insulin and glucagon have a major regulatory role in the activity of these processes. In the periods when the nutrients do not enter the body, all the glucose coming into the circulation is delivered by the liver [129]. Upon food intake, increased glucose levels stimulate secretion of insulin, which has an inhibitory effect on hepatic mechanisms delivering free glucose.

In diabetic patients, this regulation is impaired, and even an increased activity of the key enzymes of gluconeogenesis and glycogenolysis is detected [130, 131].

*Galega officinalis* has been used from ancient times to alleviate polyuria in diabetic patients. Its active ingredients guanidine and gelagine have been shown to inhibit the enzyme fructose-1,6-bisphosphatase and glucose-6-phosphatase (**Table 2**).

Fructose-1,6-bisphosphatase is a rate-limiting enzyme in GNG, and its activity has been reported to be pathologically elevated in experimental models of insulin resistance (IR) and obesity [132]. Therefore, inhibition of the enzyme could be a promising target to overcome the chronic hyperglycemia and to maintain normoglycemic status during fasting periods. The search for new GNG inhibitors of natural origin may be of great importance in the control of diabetes, especially for patients intolerant to synthetic therapeutics [11].

Glucose-6-phosphatase is a key enzyme in GNG and glycogenolysis, catalyzing the last step—release of free glucose from the liver.

Several plants from our list are described to exert their hypoglycemic action by inhibiting enzymes from GNG (**Table 2**). According to folk medicine, *Melissa* sp. has

**63**

**Table 2.**

*Antidiabetic Potential of Plants Used in Bulgarian Folk Medicine and Traditional Diet*

↓ α-amylase 1, 3, 6,

↓ α-glucosidase 1, 6, 8,

**Plant No.**

8, 22, 26, 30, 31, 33, 36, 37, 39

22, 26, 30, 31, 33, 36, 37

1, 17, 33, 36, 37

21

42

1, 16, 18, 19, 20,, 26, 33, 36, 37, 41

1, 2, 4, 6, 9, 16, 28

16, 26, 30, 34

4, 9, 20, 22, 31, 39

33, 34

36

Glycogen synthesis Glucokinase 16, 19 Gene expression in hepatocytes of

↓ Disaccharidases 16, 22 Intestinal sucrase and maltase in rats

Glycogen synthase 2, 6, 35 STZ-induced diabetes in rats; mice

↓ VLDL 1 Rats with alloxan- or STZ-induced

↓ LDL 1, 2, 34 Rats with alloxan- or STZ-induced

↑ HDL/LDL ratio 2, 34 Human intervention studies

**Type of studies**

Spectrophotometrical assessment of enzyme inhibition; STZ-induced diabetes; kinetics of enzyme inhibition

Spectrophotometrical assessment of enzyme inhibition; glucose oxidasebased method

with alloxan-induced diabetes

Intestinal cell cultures; diabetic rodents

Gene expression in hepatocytes of diabetic rodents

metformin

diabetic rodents; experimental and clinical studies with metformin

diabetic rodents

muscle cell cultures

Diabetic rodents; in vitro enzyme activity in rats lences

Glucose uptake in C2C12 myotubes; gene expression in 3T3-L1 cell culture

[Ca2+] and [insulin] in pancreatic beta cells

Rats with alloxan- or STZ-induced diabetes; human intervention studies 3T3-L1 cell cultures

diabetes

Macrophage and 3T3-L1 cell cultures

Rats with alloxan- or STZ-induced diabetes; human intervention studies

diabetes; human intervention studies

Rats with alloxan- or STZ-induced diabetes; human intervention studies; cholesterol fed rabbits

14 Experimental and clinical studies with

14, 19 Gene expression in hepatocytes of

**Effects on molecular targets**

> ↓ Glucose absorption

Fructose-1,6 bisphosphatase

Glucose-6 phosphatase

translocation

channels

↓ HMG-CoA reductase

↓ Total cholesterol 1, 2, 16,

↑ HDL 16, 34,

*Mechanisms of action of selected plants in respect of their antidiabetic potential; ↑-activation, ↓-inhibition.*

GNG PEPCK 16, 19,

Polyol pathway Aldose reductase 5, 24,

Lipid metabolism ↓ TAG 1, 2, 13,

Glucose uptake in IDTs GLUT-4

Insulin secretion SUR1 and Ca2+

*Plant numbers are in the order as they are listed in Table 1.*

*DOI: http://dx.doi.org/10.5772/intechopen.85445*

**Metabolic pathway/ mechanism**

Carbohydrate digestion and absorption


*Antidiabetic Potential of Plants Used in Bulgarian Folk Medicine and Traditional Diet DOI: http://dx.doi.org/10.5772/intechopen.85445*

#### **Table 2.**

*Mechanisms of action of selected plants in respect of their antidiabetic potential; ↑-activation, ↓-inhibition.*

*Nutrition in Health and Disease - Our Challenges Now and Forthcoming Time*

carbohydrates in human diet. After the action of salivary and pancreatic α-amylase, the digestion products of starch and glycogen along with disaccharides are further digested in the small intestine epithelium, where the membrane-bound enzyme α-glucosidase, as well as various disaccharidases (saccharase, maltase, lactase), catalyze the release of glucose, fructose, and galactose. Monosaccharides are absorbed through the walls of the small intestine and reach the liver by the portal vein.

Inhibition of digestive enzymes is one possible approach to control early-stage hyperglycemia. Inhibition of α-amylase and α-glucosidase can significantly delay

For a significant part of the plants presented in **Table 1**, data on the inhibitory effect of their extracts or active components on digestive enzymes in different experimental approaches were reported (**Table 2**). In vitro studies have found that aqueous extracts of basil and walnut leaves exert an inhibitory effect on α-amylase and α-glucosidase as well as on some disaccharidases without affecting insulin secretion and glucose transport proteins [63, 79]. Both studies suggest that polyphenols play a major role in the observed effects, as an extremely rich content of these active compounds in the two extracts is found. Another study [128] demonstrated a strong inhibitory activity of walnuts on the activity of α-amylase and

Except aqueous extract of thyme, the extracted essential oil of the plant also exhibits an inhibitory effect on the amylase and glucosidase; Paddy et al. [19] and Pongpiriyadacha et al. [46] found that birch extract significantly reduced blood glucose levels after oral administration of sucrose to rats, a result demonstrating the inhibitory action of the extract on α-glucosidase. The same extract in an in vitro study had a concentration-dependent inhibitory effect on α-glucosidase, saccha-

The liver has an essential role in maintenance of glucose homeostasis by controlling the utilization of excess glucose after meal for glycogen synthesis or secretion of free glucose into the circulation through glycogenolysis and gluconeogenesis (GNG) in fasting periods. Insulin and glucagon have a major regulatory role in the activity of these processes. In the periods when the nutrients do not enter the body, all the glucose coming into the circulation is delivered by the liver [129]. Upon food intake, increased glucose levels stimulate secretion of insulin, which has an inhibi-

In diabetic patients, this regulation is impaired, and even an increased activity of

*Galega officinalis* has been used from ancient times to alleviate polyuria in diabetic patients. Its active ingredients guanidine and gelagine have been shown to inhibit the

Fructose-1,6-bisphosphatase is a rate-limiting enzyme in GNG, and its activity has been reported to be pathologically elevated in experimental models of insulin resistance (IR) and obesity [132]. Therefore, inhibition of the enzyme could be a promising target to overcome the chronic hyperglycemia and to maintain normoglycemic status during fasting periods. The search for new GNG inhibitors of natural origin may be of great importance in the control of diabetes, especially for

Glucose-6-phosphatase is a key enzyme in GNG and glycogenolysis, catalyzing

Several plants from our list are described to exert their hypoglycemic action by inhibiting enzymes from GNG (**Table 2**). According to folk medicine, *Melissa* sp. has

the key enzymes of gluconeogenesis and glycogenolysis is detected [130, 131].

enzyme fructose-1,6-bisphosphatase and glucose-6-phosphatase (**Table 2**).

the increase in glucose concentration in the postprandial phase [124–127].

**62**

disaccharidases.

rase, and maltase.

**2.2 Effects on glucose homeostasis in the liver**

tory effect on hepatic mechanisms delivering free glucose.

patients intolerant to synthetic therapeutics [11].

the last step—release of free glucose from the liver.

pronounced spasmolytic and antibacterial action and a slight anxiolytic effect [7]. Scientific data from recent years reveal the antidiabetic potential of the plant ([72]. It was demonstrated that chronic administration of neral and geranial essential oils to db/ db mice had significant hypoglycemic effect, due to their stimulatory and, respectively, inhibitory effects on the gene expression of glucokinase and glucose-6-phosphatase.

The enzyme glucokinase, also called the "glucose sensor," has a key role in the pancreas and liver to maintain glucose homeostasis. Due to the fact that the enzyme has a high Km value for glucose, its role is to provide an excess of glucose (by phosphorylation to glucose-6-phosphate) to activate insulin secretion and glycogen synthesis. The search for active compounds that can stimulate the enzyme is a relatively new concept in the pharmacological approaches to diabetes treatment [11], and probably the role of medicinal plants as sources of such activators is yet to be explored.

The key enzyme for glycogen synthesis is glycogen synthase. *Agrimonia eupatoria* L., *Asparagus officinalis* L., and *Sambucus nigra* L. have shown a stimulating effect on the enzyme activity, but the mechanisms behind this effect remain unclear. Treatment with agrimony and sparrow grass extracts has resulted in increased amount of glycogen in the muscles and liver of rats with streptozotocininduced diabetes [23, 39]. Elderberry aqueous extract applied to isolated mouse muscle cells stimulated both glucose transport and oxidation as well as glycogen synthesis [111]. Similarly, in cells and animal studies, it was found that preparations and active compounds from *Morus* sp. have inhibitory effects on gene expression of all regulatory GNG enzymes, including phosphoenolpyruvate carboxykinase (PEPCK) [133, 134].

#### **2.3 Inhibition of polyol pathway of glucose metabolism**

The most serious problems resulting from diabetes mellitus are the complications due to increased blood glucose levels.

The body has several options to metabolize the excess glucose. Among them, the polyol pathway is of utmost importance for the development of diabetic complications. Catalyzed by the aldose reductase enzyme, glucose is converted to sorbitol, an osmotically active metabolite which accumulates and damages the cells [135]. It has been shown that inhibition of aldose reductase is preventive against the development of micro- and macrovascular diabetic complications [136, 137].

For three of the selected medicinal plants, data exist about their inhibitory effect on aldose reductase (**Table 2**). Treatment of diabetic mice with ursolic acid isolated from the bearberry resulted in a reduction in fructose and sorbitol levels in the kidneys [38]. Active components of oregano (caffeic and rosmarinic acid) and of maize hair (hirsutrin) have proven in their in vitro inhibitory action on aldose reductase activity in rat lenses [83, 123].

Research on potential enzyme inhibitors has so far not led to the development of therapeutics of general usage [138]. Although scarce, data on such activity of medicinal plants is promising in future quests for such a therapeutic approach.

#### **2.4 Effects of glucose transport in insulin-dependent tissues**

Insulin modulates several metabolic pathways by activating the phosphatidylinositol-3-kinase (PI3K) cascade, including intracellular translocation of the GLUT-4 transport protein for glucose in skeletal and adipose tissues. In diabetes, the transfer of GLUT-4 towards plasma membrane cannot be accomplished.

The hypoglycemic properties of some medicinal plants are due to the ability of their active components to promote the translocation of GLUT-4 to the plasma membrane, resulting in a decrease in blood glucose concentration [20, 90, 106, 139].

**65**

*Antidiabetic Potential of Plants Used in Bulgarian Folk Medicine and Traditional Diet*

Hypoglycemic potential based on this mechanism has been reported primarily for essential oils of lavender, lemon balm, and mint [71, 72]. Luteolin, the flavan derived from *Veronica officinalis*, was shown to activate both the expression and

Much of the data with regards to the antidiabetic activity of the plants were obtained using models of pharmacologically induced diabetes in experimental animals. The most commonly used diabetes-inducing agents are streptozotocin (STZ) and alloxan [141]. Both compounds have destructive effects on pancreatic β cells by different mechanisms. STZ enters the β cells through the transport protein GLUT-2 and damages DNA, resulting in overexpression of DNA repair systems and thus leading to depletion of cell stores of ATP and oxidized nicotinamide dinucleotide (NAD+) [142, 143]; alloxan, transported by GLUT-2, depletes the thiol groups in the cells, establishing a permanent redox cycle with the dialuric acid (its reduced form). This process leads to the accumulation of ROS and hence to the destruction of β cells, which in general have very limited store of endogenous antioxidants [144]. The models of in vivo induced diabetes are informative in terms of the hypoglycemic and insulin-like effects of plant extracts. For example, such was the effect of the aqueous oregano extract applied over a period of several weeks to rats with STZ-induced diabetes. In this study, the established potential of the extract to lower blood sugar and glycated hemoglobin was comparable to that of the antidiabetic drug glibenclamide [84]. In another similar in vivo study, the plant extract exhibited an insulin-like effect normalizing blood glucose levels without affecting plasma basal insulin levels [145]. Similar data was also obtained about black mulberry leaf extract [74]. However, in addition to the hypoglycemic effect, an increase in the insulin levels was reported, which may be attributed to the protective and possibly stimulatory action of the plant on β cells' function. Data on the antidiabetic properties of *Phaseolus vulgaris* exist in folk medicine of different ethnic groups [146]. At present, many scientific studies confirm the hypoglycemic and hypolipidemic potential of the plant (predominantly of the pod extract), both in experimentally induced diabetes and in human intervention studies [147–149]. *Vaccinium myrtillus* fruits had beneficial effect on obese subjects in a 6-week intervention study as measured by improved insulin sensitivity, inflammatory biomarker levels, and lipid profile [150]. *Zea mays* hair extracts, as recommended by folk medicine as an antidiabetic remedy, was shown to reduce blood sugar and glycated hemoglobin levels, to stimulate β cells' function and increase serum insulin levels in an experimental model of diabetes [151, 152]. Hypoglycemic and insulin-like effects have also been reported for *Taraxacum officinale* roots, for fruits and flowers of *Sambucus nigra*, stalks of *Alchemilla vulgaris* and *Achillea millefolium*, roots from *Arctium lappa* and

*Urtica dioica*, *Cydonia vulgaris* leaves, and other plants presented in **Table 1**.

There are two mechanisms by which medicinal plants or their active components


• Plant active compounds bind to sulfonylurea binding site 1 (SUR1) of К<sup>+</sup>

channels resulting in channel closure and membrane depolarization.

**3. Effects of plants on insulin secretion**

possibly stimulate insulin secretion [153]:

• Direct activation of Са2+ channels.

*DOI: http://dx.doi.org/10.5772/intechopen.85445*

translocation of the glucose transport protein [140].

**2.5 Hypoglycemic activity of plants: putative mechanisms**

*Antidiabetic Potential of Plants Used in Bulgarian Folk Medicine and Traditional Diet DOI: http://dx.doi.org/10.5772/intechopen.85445*

Hypoglycemic potential based on this mechanism has been reported primarily for essential oils of lavender, lemon balm, and mint [71, 72]. Luteolin, the flavan derived from *Veronica officinalis*, was shown to activate both the expression and translocation of the glucose transport protein [140].

#### **2.5 Hypoglycemic activity of plants: putative mechanisms**

Much of the data with regards to the antidiabetic activity of the plants were obtained using models of pharmacologically induced diabetes in experimental animals. The most commonly used diabetes-inducing agents are streptozotocin (STZ) and alloxan [141]. Both compounds have destructive effects on pancreatic β cells by different mechanisms. STZ enters the β cells through the transport protein GLUT-2 and damages DNA, resulting in overexpression of DNA repair systems and thus leading to depletion of cell stores of ATP and oxidized nicotinamide dinucleotide (NAD+) [142, 143]; alloxan, transported by GLUT-2, depletes the thiol groups in the cells, establishing a permanent redox cycle with the dialuric acid (its reduced form). This process leads to the accumulation of ROS and hence to the destruction of β cells, which in general have very limited store of endogenous antioxidants [144].

The models of in vivo induced diabetes are informative in terms of the hypoglycemic and insulin-like effects of plant extracts. For example, such was the effect of the aqueous oregano extract applied over a period of several weeks to rats with STZ-induced diabetes. In this study, the established potential of the extract to lower blood sugar and glycated hemoglobin was comparable to that of the antidiabetic drug glibenclamide [84]. In another similar in vivo study, the plant extract exhibited an insulin-like effect normalizing blood glucose levels without affecting plasma basal insulin levels [145]. Similar data was also obtained about black mulberry leaf extract [74]. However, in addition to the hypoglycemic effect, an increase in the insulin levels was reported, which may be attributed to the protective and possibly stimulatory action of the plant on β cells' function. Data on the antidiabetic properties of *Phaseolus vulgaris* exist in folk medicine of different ethnic groups [146]. At present, many scientific studies confirm the hypoglycemic and hypolipidemic potential of the plant (predominantly of the pod extract), both in experimentally induced diabetes and in human intervention studies [147–149]. *Vaccinium myrtillus* fruits had beneficial effect on obese subjects in a 6-week intervention study as measured by improved insulin sensitivity, inflammatory biomarker levels, and lipid profile [150]. *Zea mays* hair extracts, as recommended by folk medicine as an antidiabetic remedy, was shown to reduce blood sugar and glycated hemoglobin levels, to stimulate β cells' function and increase serum insulin levels in an experimental model of diabetes [151, 152]. Hypoglycemic and insulin-like effects have also been reported for *Taraxacum officinale* roots, for fruits and flowers of *Sambucus nigra*, stalks of *Alchemilla vulgaris* and *Achillea millefolium*, roots from *Arctium lappa* and *Urtica dioica*, *Cydonia vulgaris* leaves, and other plants presented in **Table 1**.

#### **3. Effects of plants on insulin secretion**

There are two mechanisms by which medicinal plants or their active components possibly stimulate insulin secretion [153]:


*Nutrition in Health and Disease - Our Challenges Now and Forthcoming Time*

pronounced spasmolytic and antibacterial action and a slight anxiolytic effect [7]. Scientific data from recent years reveal the antidiabetic potential of the plant ([72]. It was demonstrated that chronic administration of neral and geranial essential oils to db/ db mice had significant hypoglycemic effect, due to their stimulatory and, respectively, inhibitory effects on the gene expression of glucokinase and glucose-6-phosphatase. The enzyme glucokinase, also called the "glucose sensor," has a key role in the pancreas and liver to maintain glucose homeostasis. Due to the fact that the enzyme has a high Km value for glucose, its role is to provide an excess of glucose (by phosphorylation to glucose-6-phosphate) to activate insulin secretion and glycogen synthesis. The search for active compounds that can stimulate the enzyme is a relatively new concept in the pharmacological approaches to diabetes treatment [11], and probably

the role of medicinal plants as sources of such activators is yet to be explored. The key enzyme for glycogen synthesis is glycogen synthase. *Agrimonia eupatoria* L., *Asparagus officinalis* L., and *Sambucus nigra* L. have shown a stimulating effect on the enzyme activity, but the mechanisms behind this effect remain unclear. Treatment with agrimony and sparrow grass extracts has resulted in increased amount of glycogen in the muscles and liver of rats with streptozotocininduced diabetes [23, 39]. Elderberry aqueous extract applied to isolated mouse muscle cells stimulated both glucose transport and oxidation as well as glycogen synthesis [111]. Similarly, in cells and animal studies, it was found that preparations and active compounds from *Morus* sp. have inhibitory effects on gene expression of all regulatory GNG enzymes, including phosphoenolpyruvate

The most serious problems resulting from diabetes mellitus are the complica-

The body has several options to metabolize the excess glucose. Among them, the polyol pathway is of utmost importance for the development of diabetic complications. Catalyzed by the aldose reductase enzyme, glucose is converted to sorbitol, an osmotically active metabolite which accumulates and damages the cells [135]. It has been shown that inhibition of aldose reductase is preventive against the develop-

For three of the selected medicinal plants, data exist about their inhibitory effect on aldose reductase (**Table 2**). Treatment of diabetic mice with ursolic acid isolated from the bearberry resulted in a reduction in fructose and sorbitol levels in the kidneys [38]. Active components of oregano (caffeic and rosmarinic acid) and of maize hair (hirsutrin) have proven in their in vitro inhibitory action on aldose reductase

Research on potential enzyme inhibitors has so far not led to the development of therapeutics of general usage [138]. Although scarce, data on such activity of medicinal plants is promising in future quests for such a therapeutic approach.

Insulin modulates several metabolic pathways by activating the phosphatidylinositol-3-kinase (PI3K) cascade, including intracellular translocation of the GLUT-4 transport protein for glucose in skeletal and adipose tissues. In diabetes, the transfer of GLUT-4 towards plasma membrane cannot be accomplished. The hypoglycemic properties of some medicinal plants are due to the ability of their active components to promote the translocation of GLUT-4 to the plasma membrane, resulting in a decrease in blood glucose concentration [20, 90, 106, 139].

carboxykinase (PEPCK) [133, 134].

activity in rat lenses [83, 123].

tions due to increased blood glucose levels.

**2.3 Inhibition of polyol pathway of glucose metabolism**

ment of micro- and macrovascular diabetic complications [136, 137].

**2.4 Effects of glucose transport in insulin-dependent tissues**

**64**

Sulfonylurea derivatives, such as glibenclamide, are applied for treatment of T2D to stimulate translocation of insulin-containing secretory granules to plasma membrane and exocytosis of insulin in the extracellular matrix [11].

Medicinal plants with an effect on insulin secretion are presented in **Table 2**.

It should be noted that according to most of the studies, the stimulatory activity of medicinal plants on insulin secretion is attributed to their antioxidative potential and ability to prevent SZT- and alloxan-induced beta cell injury in experimental models of diabetes.

#### **4. Plants that affect lipid metabolism**

Defined as abnormal accumulation of adipose tissue, obesity is a major health problem worldwide [154]. As a condition that accompanies obesity, dyslipidemia is believed to be a basic factor for the development of obesity-related diseases such as T2D, cardiovascular diseases (CVD), and atherosclerosis [155]. Dyslipidemia is characterized by increased triacylglycerol (TAG) and total cholesterol levels and unfavorable changes in HDL-/LDL-cholesterol ratio [156, 157].

Many plants that are considered to have antidiabetic potential have beneficial effects on the lipid profile in addition to their hypoglycemic activities [158, 159]. These properties are attributed to their naturally occurring secondary metabolites, such as bioflavonoides.

Anthocyanin extracts and anthocyanin-rich diet can improve the parameters of lipid profile and therefore are considered to have anti-obesity and anti-atherogenic effects in humans and in rodents [160–164].

*Sambucus ebulus* (dwarf elderberry) is a plant widely used in Bulgarian folk medicine in various pathological conditions. Its fruits are rich in anthocyanins. Studies report that anthocyanin extracts can reduce body mass and adipose tissue volume in rats fed with high-fat and high-fructose diet [160, 165–167]. There are reports describing the also hypoglycemic activity of the *S. ebulus* fruits in rats on high-fat and high-fructose diet [168, 169].

A 30-day human intervention study with *S. ebulus* fruit tea decreased significantly TAG, total cholesterol, and LDL-cholesterol levels. Slight increase of HDL and significant increase in HDL/LDL ratio were found ([110].

Low HDL levels are recognized as an independent risk factor for the development of cardiovascular diseases [170]. Inhibition of cholesteryl ester transfer protein (CETP) is a probable cause for the increased HDL-cholesterol levels, and LDLcholesterol levels decrease upon anthocyanin treatment [171]. Anthocyanins can decrease quantity and the activity of CETP in plasma of dyslipidemic patients [161].

The scientific data cited above are in support to the folk medicine reports about the healing properties of *S. ebulus* fruit preparations.

Likewise, lipid profile improving properties have been reported for *Agrimonia eupatoria* (agrimony). Its effect on lipid profile was estimated in our study in a model of metabolic disturbances in rats on high-fructose diet. Intake of 40% aqueous-ethanol extract prevented fat accumulation in the liver and adipose tissue and normalized levels of serum lipids [167].

In addition, we performed a human intervention study with 30-day agrimony tea consumption. As a result, increased levels of HDL cholesterol were established, and LDL-cholesterol levels remained unchanged at the same time [29]. These results reveal good potential of agrimony to improve lipid profile, which is important in prophylaxis of CVD and diabetes.

It can be assumed that polyphenols play a role in the mechanisms by which the plant manifests its effects. It is known that diet rich in polyphenols may improve

**67**

**5. Conclusions**

*Antidiabetic Potential of Plants Used in Bulgarian Folk Medicine and Traditional Diet*

lipid profile in individuals with normal or compromised health status [172, 173]. Polyphenol preparations and polyphenol-rich extracts have also the potential to improve lipid profile [174–177]. As it was already mentioned, *S. ebulus* fruits are a rich source of polyphenols and especially of anthocyanins [33, 108]. Also, it was found that the aqueous and aqueous alcoholic extracts of agrimony have a high polyphenol content [25, 178], although their exact polyphenol composition has not yet been identified. Polyphenols have limited bioavailability; however, many of the products of their intestinal metabolism overcome the intestinal barrier and reach

Some of the selected plants (**Table 1**) can exert their effects by inhibiting the activity of the rate-limiting enzyme in cholesterol synthesis—HMG-CoA reductase [99]. Cholesterol is the most abundant sterol in the human body and is essential for the normal functioning of the cells. Cholesterol homeostasis is of great importance for the health status. Apart from being a risk factor for atherosclerosis, increased plasma cholesterol levels are often an accompanying parameter of the metabolic disturbances, such as diabetes. Despite being applied for decades, HMG-CoA reductase inhibitors have adverse and unwanted effects, such as myopathy, liver

Even more, in a case of strictly controlled LDL-cholesterol levels by statins, not always TAG and HDL-cholesterol levels are sensitive to the therapy, and there is still a chance that CVD risk would remain high [180]. Interventions with *S. ebulus* and *A. eupatoria* tea resulted in significantly increased HDL/LDL ratio; beneficial effects of these plants on plasma TAG and total cholesterol levels were established, so it is likely that the plants improve all parameters of the lipid profile. This makes them promising sources of active compounds with a potential to prevent and

In addition to the above, scientific data about the beneficial effects of rosehip, strawberries, and raspberries on lipid metabolism and inflammation exist (**Table 1**). These plants are rich in the glycoside flavonoid tiliroside, which was shown to inhibit postprandial inflammation, to play a role in the prevention of obesity, hyperinsulinemia, and hyperlipidemia. Its action is associated with elevated levels of adiponectin and also facilitated fatty acids oxidation in the liver and skeletal muscles [181]. Strawberry anthocyanin pelargonidin sulfate and pelargonidin-3-O-glycoside reduced postprandial inflammation and increased insulin sensitivity in overweight individuals [56]. Polyphenols extracted from strawberry decreased postprandial LDL oxidation and enhanced lipid metabolism in a high-fat intervention with overweight individuals with hyperlipidemia [182]. Six of the plants listed in **Table 1** (*Arctium lappa*, *Cichorium intybus, Mentha piperita, Ocimum basilicum, Rosa damascen*а*, Urtica dioica*) had also inhibitory effect of HMG-CoA reductase. Among them, the extract of *R. damascena*

The discovery of new effective and safe in long-term application therapeutics is essential for the control and prevention of obesity-related diseases. In this respect,

The summarized scientific data give а concept about the mechanisms behind the healing effects of plants traditionally used in Bulgarian folk medicine and traditional diet. The selected plants and their active compounds could exert their hypoglycemic and antiobese effects by affecting simultaneously several molecular markers in various processes from carbohydrate and lipid metabolism. Moreover, along with their insulin-like properties, many of the plants can stimulate the insulin

the potential of medicinal and edible plants is still to be explored.

*DOI: http://dx.doi.org/10.5772/intechopen.85445*

insufficiency, etc. [99].

supplement the therapy of T2D and CVD.

was found to be the most potent one [99].

the tissues where they exert their biological effects [179].

#### *Antidiabetic Potential of Plants Used in Bulgarian Folk Medicine and Traditional Diet DOI: http://dx.doi.org/10.5772/intechopen.85445*

lipid profile in individuals with normal or compromised health status [172, 173]. Polyphenol preparations and polyphenol-rich extracts have also the potential to improve lipid profile [174–177]. As it was already mentioned, *S. ebulus* fruits are a rich source of polyphenols and especially of anthocyanins [33, 108]. Also, it was found that the aqueous and aqueous alcoholic extracts of agrimony have a high polyphenol content [25, 178], although their exact polyphenol composition has not yet been identified. Polyphenols have limited bioavailability; however, many of the products of their intestinal metabolism overcome the intestinal barrier and reach the tissues where they exert their biological effects [179].

Some of the selected plants (**Table 1**) can exert their effects by inhibiting the activity of the rate-limiting enzyme in cholesterol synthesis—HMG-CoA reductase [99]. Cholesterol is the most abundant sterol in the human body and is essential for the normal functioning of the cells. Cholesterol homeostasis is of great importance for the health status. Apart from being a risk factor for atherosclerosis, increased plasma cholesterol levels are often an accompanying parameter of the metabolic disturbances, such as diabetes. Despite being applied for decades, HMG-CoA reductase inhibitors have adverse and unwanted effects, such as myopathy, liver insufficiency, etc. [99].

Even more, in a case of strictly controlled LDL-cholesterol levels by statins, not always TAG and HDL-cholesterol levels are sensitive to the therapy, and there is still a chance that CVD risk would remain high [180]. Interventions with *S. ebulus* and *A. eupatoria* tea resulted in significantly increased HDL/LDL ratio; beneficial effects of these plants on plasma TAG and total cholesterol levels were established, so it is likely that the plants improve all parameters of the lipid profile. This makes them promising sources of active compounds with a potential to prevent and supplement the therapy of T2D and CVD.

In addition to the above, scientific data about the beneficial effects of rosehip, strawberries, and raspberries on lipid metabolism and inflammation exist (**Table 1**). These plants are rich in the glycoside flavonoid tiliroside, which was shown to inhibit postprandial inflammation, to play a role in the prevention of obesity, hyperinsulinemia, and hyperlipidemia. Its action is associated with elevated levels of adiponectin and also facilitated fatty acids oxidation in the liver and skeletal muscles [181]. Strawberry anthocyanin pelargonidin sulfate and pelargonidin-3-O-glycoside reduced postprandial inflammation and increased insulin sensitivity in overweight individuals [56]. Polyphenols extracted from strawberry decreased postprandial LDL oxidation and enhanced lipid metabolism in a high-fat intervention with overweight individuals with hyperlipidemia [182]. Six of the plants listed in **Table 1** (*Arctium lappa*, *Cichorium intybus, Mentha piperita, Ocimum basilicum, Rosa damascen*а*, Urtica dioica*) had also inhibitory effect of HMG-CoA reductase. Among them, the extract of *R. damascena* was found to be the most potent one [99].

The discovery of new effective and safe in long-term application therapeutics is essential for the control and prevention of obesity-related diseases. In this respect, the potential of medicinal and edible plants is still to be explored.

#### **5. Conclusions**

The summarized scientific data give а concept about the mechanisms behind the healing effects of plants traditionally used in Bulgarian folk medicine and traditional diet. The selected plants and their active compounds could exert their hypoglycemic and antiobese effects by affecting simultaneously several molecular markers in various processes from carbohydrate and lipid metabolism. Moreover, along with their insulin-like properties, many of the plants can stimulate the insulin

*Nutrition in Health and Disease - Our Challenges Now and Forthcoming Time*

membrane and exocytosis of insulin in the extracellular matrix [11].

unfavorable changes in HDL-/LDL-cholesterol ratio [156, 157].

and significant increase in HDL/LDL ratio were found ([110].

the healing properties of *S. ebulus* fruit preparations.

and normalized levels of serum lipids [167].

tant in prophylaxis of CVD and diabetes.

models of diabetes.

such as bioflavonoides.

**4. Plants that affect lipid metabolism**

effects in humans and in rodents [160–164].

high-fat and high-fructose diet [168, 169].

Sulfonylurea derivatives, such as glibenclamide, are applied for treatment of T2D to stimulate translocation of insulin-containing secretory granules to plasma

Medicinal plants with an effect on insulin secretion are presented in **Table 2**. It should be noted that according to most of the studies, the stimulatory activity of medicinal plants on insulin secretion is attributed to their antioxidative potential and ability to prevent SZT- and alloxan-induced beta cell injury in experimental

Defined as abnormal accumulation of adipose tissue, obesity is a major health problem worldwide [154]. As a condition that accompanies obesity, dyslipidemia is believed to be a basic factor for the development of obesity-related diseases such as T2D, cardiovascular diseases (CVD), and atherosclerosis [155]. Dyslipidemia is characterized by increased triacylglycerol (TAG) and total cholesterol levels and

Many plants that are considered to have antidiabetic potential have beneficial effects on the lipid profile in addition to their hypoglycemic activities [158, 159]. These properties are attributed to their naturally occurring secondary metabolites,

Anthocyanin extracts and anthocyanin-rich diet can improve the parameters of lipid profile and therefore are considered to have anti-obesity and anti-atherogenic

*Sambucus ebulus* (dwarf elderberry) is a plant widely used in Bulgarian folk medicine in various pathological conditions. Its fruits are rich in anthocyanins. Studies report that anthocyanin extracts can reduce body mass and adipose tissue volume in rats fed with high-fat and high-fructose diet [160, 165–167]. There are reports describing the also hypoglycemic activity of the *S. ebulus* fruits in rats on

A 30-day human intervention study with *S. ebulus* fruit tea decreased significantly TAG, total cholesterol, and LDL-cholesterol levels. Slight increase of HDL

Low HDL levels are recognized as an independent risk factor for the development of cardiovascular diseases [170]. Inhibition of cholesteryl ester transfer protein (CETP) is a probable cause for the increased HDL-cholesterol levels, and LDLcholesterol levels decrease upon anthocyanin treatment [171]. Anthocyanins can decrease quantity and the activity of CETP in plasma of dyslipidemic patients [161]. The scientific data cited above are in support to the folk medicine reports about

Likewise, lipid profile improving properties have been reported for *Agrimonia eupatoria* (agrimony). Its effect on lipid profile was estimated in our study in a model of metabolic disturbances in rats on high-fructose diet. Intake of 40% aqueous-ethanol extract prevented fat accumulation in the liver and adipose tissue

In addition, we performed a human intervention study with 30-day agrimony tea consumption. As a result, increased levels of HDL cholesterol were established, and LDL-cholesterol levels remained unchanged at the same time [29]. These results reveal good potential of agrimony to improve lipid profile, which is impor-

It can be assumed that polyphenols play a role in the mechanisms by which the plant manifests its effects. It is known that diet rich in polyphenols may improve

**66**

secretion. This makes them invaluable in prevention and therapy of socially significant diseases such as diabetes and cardiovascular diseases. Despite the capacity of biotechnology methods to develop new therapeutics, it may be worth to turn a look at the natural resources which potential is still unrevealed.

### **Author details**

Milka Nashar\*, Yoana D. Kiselova-Kaneva and Diana G. Ivanova Medical University of Varna, Varna, Bulgaria

\*Address all correspondence to: nacharbg@yahoo.com

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

**69**

*Antidiabetic Potential of Plants Used in Bulgarian Folk Medicine and Traditional Diet*

[10] Nedelcheva A. Medicinal plants from an old Bulgarian medical book. Journal of Medicinal Plants Research.

[11] Verspohl EJ. Novel pharmacological approaches to the treatment of type 2 diabetes. Pharmacological Reviews.

[12] Tahrani A. Novel therapies in type 2 diabetes: Insulin resistance. Practical

[13] Petlevski R, Hadzija M, Slijepcevic M, Juretic D. Effect of 'antidiabetis' herbal preparation on serum glucose and fructosamine in NOD mice. Journal of Ethnopharmacology.

[14] Petlevski R, Hadžija M, Slijepčević M, Juretić D, Petrik J. Glutathione S-transferases and malondialdehyde in the liver of NOD mice on short-term treatment with plant mixture extract P-9801091. Phytotherapy Research.

[15] Yazdanparast R, Ardestani A, Jamshidi S. Experimental diabetes treated with *Achillea santolina*: Effect on pancreatic oxidative parameters. Journal of Ethnopharmacology.

[16] Saeidnia S, Gohari AR, Mokhber-Dezfuli N, Kiuchi F. A review on phytochemistry and medicinal

properties of the genus *Achillea*. Daru.

[17] Mustafa KG, Ganai BA, Akbar S, Dar MY, Masood A. β-Cell protective

hypolipidemic effects of extracts of *Achillea millifolium* in diabetic rats. Chinese Journal of Natural Medicines.

[18] Zolghadri Y, Fazeli M, Kooshki M, Shomali T, Karimaghayee N, Dehghani

efficacy, hypoglycemic and

2012;**10**(3):0185-0189

Diabetes. 2017;**34**(5):161-166

2001;**75**(2-3):181-184

2003;**17**(4):311-314

2007;**112**(1):13-18

2011;**19**(3):173-186

2012;**6**(12):2324-2339

2012;**64**:188-237

*DOI: http://dx.doi.org/10.5772/intechopen.85445*

[1] WHO Report. Definition and diagnosis of diabetes mellitus and intermediate hyperglycemia. 2006.

[2] Ahmed AM. History of diabetes mellitus. Saudi Medical Journal.

[3] Eknoyan G, Nagy J. A history of diabetes mellitus or how a disease of the kidneys evolved into a kidney disease. Advances in Chronic Kidney Disease.

[4] Lasker SP, McLachlan CS, Wang L, Ali SMK, Jelinek HF. Discovery,

treatment and management of diabetes.

Journal of Diabetology. 2010;**1**:1

[5] Eddouks M, Zeggwagh NA. Hypoglycemic Plants: Folklore to modern evidence review. In: Eddouks

M, Chattopadhyay D, editors. Phytotherapy in the management of diabetes and hypertension. Bentham Science Publishers,

978-1-60805-567-8

of Sciences; 1977

Bulgaria; 1978

Bulgaria; 1979

Sharjah, U.A.E.; 2012:164-192. ISBN:

[7] Dimkov P. Bulgarian Folk Medicine. Vol. 1. Sofia, Bulgaria; BASPRESS: Publishing House of Bulgarian Academy

[8] Dimkov P. Bulgarian Folk Medicine. Vol. 2. BASPRESS: Publishing House of Bulgarian Academy of Sciences, Sofia,

[9] Dimkov P. Bulgarian Folk Medicine. Vol. 3. BASPRESS: Publishing House of Bulgarian Academy of Sciences, Sofia,

[6] Teodorov E. Ancient-Thracian Heritage in Bulgarian Folklore. Academic Publishing House of Bulgarian Academy of Sciences "Professor Marin Drinov", Sofia, Bulgaria; 1999. ISBN: 9544304983

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*Antidiabetic Potential of Plants Used in Bulgarian Folk Medicine and Traditional Diet DOI: http://dx.doi.org/10.5772/intechopen.85445*

#### **References**

*Nutrition in Health and Disease - Our Challenges Now and Forthcoming Time*

at the natural resources which potential is still unrevealed.

secretion. This makes them invaluable in prevention and therapy of socially significant diseases such as diabetes and cardiovascular diseases. Despite the capacity of biotechnology methods to develop new therapeutics, it may be worth to turn a look

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

Milka Nashar\*, Yoana D. Kiselova-Kaneva and Diana G. Ivanova

**68**

**Author details**

provided the original work is properly cited.

Medical University of Varna, Varna, Bulgaria

\*Address all correspondence to: nacharbg@yahoo.com

[1] WHO Report. Definition and diagnosis of diabetes mellitus and intermediate hyperglycemia. 2006. ISBN: 9241594934

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[4] Lasker SP, McLachlan CS, Wang L, Ali SMK, Jelinek HF. Discovery, treatment and management of diabetes. Journal of Diabetology. 2010;**1**:1

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[12] Tahrani A. Novel therapies in type 2 diabetes: Insulin resistance. Practical Diabetes. 2017;**34**(5):161-166

[13] Petlevski R, Hadzija M, Slijepcevic M, Juretic D. Effect of 'antidiabetis' herbal preparation on serum glucose and fructosamine in NOD mice. Journal of Ethnopharmacology. 2001;**75**(2-3):181-184

[14] Petlevski R, Hadžija M, Slijepčević M, Juretić D, Petrik J. Glutathione S-transferases and malondialdehyde in the liver of NOD mice on short-term treatment with plant mixture extract P-9801091. Phytotherapy Research. 2003;**17**(4):311-314

[15] Yazdanparast R, Ardestani A, Jamshidi S. Experimental diabetes treated with *Achillea santolina*: Effect on pancreatic oxidative parameters. Journal of Ethnopharmacology. 2007;**112**(1):13-18

[16] Saeidnia S, Gohari AR, Mokhber-Dezfuli N, Kiuchi F. A review on phytochemistry and medicinal properties of the genus *Achillea*. Daru. 2011;**19**(3):173-186

[17] Mustafa KG, Ganai BA, Akbar S, Dar MY, Masood A. β-Cell protective efficacy, hypoglycemic and hypolipidemic effects of extracts of *Achillea millifolium* in diabetic rats. Chinese Journal of Natural Medicines. 2012;**10**(3):0185-0189

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1989;**10**(2):69-73

*Antidiabetic Potential of Plants Used in Bulgarian Folk Medicine and Traditional Diet DOI: http://dx.doi.org/10.5772/intechopen.85445*

content of aqueous extracts from Bulgarian herbs. Phytotherapy Research. 2006;**20**:961-965

*Nutrition in Health and Disease - Our Challenges Now and Forthcoming Time*

[26] Bnouham M, Abderrahim Z, Mekhfi H, Tahri A, Legssyer A. Medicinal plants with potential antidiabetic activity—A review of ten years of herbal medicine research (1990-2000). International Journal of Diabetes and

[27] Ivanova D, Tasinov O, Vankova D, Kiselova-Kaneva Y. Antioxidative potential of *Agrimonia eupatoria* L. Science and Technology. 2011;**1**(1):20-24

[28] Patel DK, Prasad SK, Kumar R, Hemalatha S. An overview on antidiabetic medicinal plants having insulin mimetic property. Asian Pacific Journal of Tropical Biomedicine.

[29] Ivanova D, Vankova D, Nashar M. *Agrimonia eupatoria* tea consumption in relation to markers of inflammation, oxidative status and lipid metabolism in healthy subjects. Archives of Physiology and Biochemistry. 2013;**119**(1):32-37

[30] Kuczmannová A, Balažová A, Racanská E, Kameníková M, Fialová S, Majerník J, et al. *Agrimonia eupatoria* L. and *Cynara cardunculus* L. water infusions: Comparison of anti-diabetic activities. Molecules. 2016;**21**:564

[31] Alam F, Shafique Z, Amjad ST, Asad M. Enzymes inhibitors from natural sources with antidiabetic activity: A review: New targets for antidiabetic treatment. Phytotherapy Research.

[32] Neagua E, Pauna G, Albua C, Radu GL. Assessment of acetylcholinesterase

extracts. Journal of the Taiwan Institute of Chemical Engineers. 2015;**52**:1-6

[33] Kiselova Y, Ivanova D, Chervenkov T, Gerova D, Galunska B, Yankova T. Correlation between the in vitro antioxidant activity and polyphenol

and tyrosinase inhibitory and antioxidant activity of *Alchemilla vulgaris* and *Filipendula ulmaria*

Metabolism. 2006;**14**:1-25

2012;**2**(4):320-330

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H, Khalid A, Khalid H. A study of antioxidant activity, enzymatic inhibition and in vitro toxicity of selected traditional sudanese plants with anti-diabetic potential. BMC Complementary and Alternative

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> ̜ ii

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de Medici ş̧i Naturaliş̧ti din Iaş̧i.

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*Nutrition in Health and Disease - Our Challenges Now and Forthcoming Time*

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Dianat M. Antidiabetic effect of hydroalcholic *Urtica dioica* leaf extract in male rats with fructose-induced insulin resistance. Iranian Journal of Medical Sciences. 2012;**37**(3):181-186

M. Antihyperglycemic and

2012;**6**:437-440

(*Taraxacum officinale* and *T. mongolicum*). Journal of Integrative

Medicine. 2009;**8**(2):35-38

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[167] Bratoeva K, Bekyarova G, Kiselova Y, Ivanova D. Effect of Bulgarian herb extracts of polyphenols on metabolic disorders—Induced by high-fructose diet. Trakia Journal of Sciences. 2010;**8**(2):56-60

[168] Grace MH, Ribnicky DM, Kuhn P, Poulev A, Logendra S, Yousef GG, et al. Hypoglycemic activity of a novel anthocyanin-rich formulation from lowbush blueberry, *Vaccinium angustifolium* aiton. Phytomedicine. 2009;**16**(5):406-415

[169] Takikawa M, Inoue S, Horio F, Tsuda T. Dietary anthocyaninrich bilberry extract ameliorates hyperglycemia and insulin sensitivity via activation of AMP-activated protein kinase in diabetic mice. The Journal of Nutrition. 2010;**140**(3):527-533

[170] Watson RT, Kanzaki M, Pessin JE. Regulated membrane trafficking of the insulin-responsive glucose transporter 4 in adipocytes. Endocrine Reviews. 2004;**25**(2):177-204

[171] Inazu A, Brown ML, Hesler CB, Agellon LB, Koizumi J, Takata K, et al. Increased high-density lipoprotein levels caused by a common cholesterylester transfer protein gene mutation. The New England Journal of Medicine. 1990;**323**(18):1234-1238

[172] Baba S, Osakabe N, Kato Y, Natsume M, Yasuda A, Kido T, et al. Continuous intake of polyphenolic compounds containing cocoa powder reduces LDL oxidative susceptibility and has beneficial effects on plasma HDL-cholesterol concentrations in humans. The American Journal of Clinical Nutrition. 2007;**85**(3):709-717

[173] Marnewick JL, Rautenbach F, Venter I, Neethling H, Blackhurst DM, Wolmarans P, et al. Effects of rooibos (*Aspalathus linearis*) on oxidative stress and biochemical parameters in adults at risk for cardiovascular disease. Journal of Ethnopharmacology. 2011;**133**(1):46- 52. DOI: 10.1016/j.jep.2010.08.061

[174] Yugarani T, Tan BK, Das NP. The effects of tannic acid on serum and liver lipids of RAIF and RICO rats fed on high fat diet. Comparative Biochemistry and Physiology. Comparative Physiology. 1993;**104**(2):339-343

[175] Al-Assafa S, Phillips GO, Williams PA. Studies on acacia exudate gums. Part I: The molecular weight of *Acacia senegal* gum exudate. Food Hydrocolloids. 2005;**19**(4):647-660

[176] Bornhoeft J, Castaneda D, Nemoseck T, Wang P, Henning SM, Hong MY. The protective effects of green tea polyphenols: Lipid profile, inflammation, and antioxidant capacity in rats fed an atherogenic diet and dextran sodium sulfate. Journal of Medicinal Food. 2012;**15**(8):726-732. DOI: 10.1089/jmf.2011.0258

[177] Basu A, Fu DX, Wilkinson M, Simmons B, Wu M, Betts NM, et al. Strawberries decrease atherosclerotic markers in subjects with metabolic syndrome. Nutrition Research 2010;**30**(7):462-469

[178] Kiselova-Kaneva Y. Total antioxidant capacity and polyphenol content correlation in aqueous-alcoholic plant extracts used in phytotherapy. Scripta Scientifica Medica. 2004;**3**:11-13

[179] Pandey KB, Rizvi SI. Plant polyphenols as dietary antioxidants in human health and disease. Oxidative Medicine and Cellular Longevity. 2009;**2**(5):270-278

[180] Freitas WM, Quaglia LA, Santos SN, de Paula RC, Santos RD, Blaha M, et al. Low HDL cholesterol but not high LDL cholesterol is independently associated with subclinical coronary atherosclerosis in healthy octogenarians.

**81**

*Antidiabetic Potential of Plants Used in Bulgarian Folk Medicine and Traditional Diet*

*DOI: http://dx.doi.org/10.5772/intechopen.85445*

Aging Clinical and Experimental Research. 2015;**27**(1):61-67. DOI: 10.1007/s40520-014-0249-4

[181] Goto T, Teraminami A, Lee JY, Ohyama K, Funakoshi K, Kim YI, et al. Tiliroside, a glycosidic flavonoid, ameliorates obesity-induced metabolic disorders via activation of adiponectin signaling followed by enhancement of fatty acid oxidation in liver and skeletal muscle in obese-diabetic mice. The Journal of Nutritional Biochemistry.

[182] Burton-Freeman B, Linares A, Hyson D, Kappagoda T. Strawberry modulates LDL oxidation and postprandial lipemia in response to high-fat meal in overweight hyperlipidemic men and women. Journal of the American College of Nutrition. 2010;**29**(1):46-54

2012;**23**(7):768e776

*Antidiabetic Potential of Plants Used in Bulgarian Folk Medicine and Traditional Diet DOI: http://dx.doi.org/10.5772/intechopen.85445*

Aging Clinical and Experimental Research. 2015;**27**(1):61-67. DOI: 10.1007/s40520-014-0249-4

*Nutrition in Health and Disease - Our Challenges Now and Forthcoming Time*

risk for cardiovascular disease. Journal of Ethnopharmacology. 2011;**133**(1):46- 52. DOI: 10.1016/j.jep.2010.08.061

[174] Yugarani T, Tan BK, Das NP. The effects of tannic acid on serum and liver lipids of RAIF and RICO rats fed on high fat diet. Comparative Biochemistry and Physiology. Comparative Physiology.

[175] Al-Assafa S, Phillips GO, Williams PA. Studies on acacia exudate gums. Part I: The molecular weight of *Acacia senegal* gum exudate. Food Hydrocolloids. 2005;**19**(4):647-660

[176] Bornhoeft J, Castaneda D, Nemoseck T, Wang P, Henning SM, Hong MY. The protective effects of green tea polyphenols: Lipid profile, inflammation, and antioxidant capacity in rats fed an atherogenic diet and dextran sodium sulfate. Journal of Medicinal Food. 2012;**15**(8):726-732.

DOI: 10.1089/jmf.2011.0258

2010;**30**(7):462-469

2009;**2**(5):270-278

[178] Kiselova-Kaneva Y. Total antioxidant capacity and polyphenol content correlation in aqueous-alcoholic plant extracts used in phytotherapy. Scripta Scientifica Medica. 2004;**3**:11-13

[179] Pandey KB, Rizvi SI. Plant polyphenols as dietary antioxidants in human health and disease. Oxidative Medicine and Cellular Longevity.

[180] Freitas WM, Quaglia LA, Santos SN, de Paula RC, Santos RD, Blaha M, et al. Low HDL cholesterol but not high LDL cholesterol is independently associated with subclinical coronary atherosclerosis in healthy octogenarians.

[177] Basu A, Fu DX, Wilkinson M, Simmons B, Wu M, Betts NM, et al. Strawberries decrease atherosclerotic markers in subjects with metabolic syndrome. Nutrition Research

1993;**104**(2):339-343

[167] Bratoeva K, Bekyarova G, Kiselova Y, Ivanova D. Effect of Bulgarian herb extracts of polyphenols on metabolic disorders—Induced by high-fructose diet. Trakia Journal of Sciences.

[168] Grace MH, Ribnicky DM, Kuhn P, Poulev A, Logendra S, Yousef GG, et al. Hypoglycemic activity of a novel anthocyanin-rich formulation from lowbush blueberry, *Vaccinium angustifolium* aiton. Phytomedicine.

[169] Takikawa M, Inoue S, Horio F, Tsuda T. Dietary anthocyaninrich bilberry extract ameliorates hyperglycemia and insulin sensitivity via activation of AMP-activated protein kinase in diabetic mice. The Journal of

Nutrition. 2010;**140**(3):527-533

[170] Watson RT, Kanzaki M, Pessin JE. Regulated membrane trafficking of the insulin-responsive glucose transporter 4 in adipocytes. Endocrine Reviews.

[171] Inazu A, Brown ML, Hesler CB, Agellon LB, Koizumi J, Takata K, et al. Increased high-density lipoprotein levels caused by a common cholesterylester transfer protein gene mutation. The New England Journal of Medicine.

2010;**8**(2):56-60

2009;**16**(5):406-415

2004;**25**(2):177-204

1990;**323**(18):1234-1238

[172] Baba S, Osakabe N, Kato Y, Natsume M, Yasuda A, Kido T, et al. Continuous intake of polyphenolic compounds containing cocoa powder reduces LDL oxidative susceptibility and has beneficial effects on plasma HDL-cholesterol concentrations in humans. The American Journal of Clinical Nutrition. 2007;**85**(3):709-717

[173] Marnewick JL, Rautenbach F, Venter I, Neethling H, Blackhurst DM, Wolmarans P, et al. Effects of rooibos (*Aspalathus linearis*) on oxidative stress and biochemical parameters in adults at

**80**

[181] Goto T, Teraminami A, Lee JY, Ohyama K, Funakoshi K, Kim YI, et al. Tiliroside, a glycosidic flavonoid, ameliorates obesity-induced metabolic disorders via activation of adiponectin signaling followed by enhancement of fatty acid oxidation in liver and skeletal muscle in obese-diabetic mice. The Journal of Nutritional Biochemistry. 2012;**23**(7):768e776

[182] Burton-Freeman B, Linares A, Hyson D, Kappagoda T. Strawberry modulates LDL oxidation and postprandial lipemia in response to high-fat meal in overweight hyperlipidemic men and women. Journal of the American College of Nutrition. 2010;**29**(1):46-54

**83**

benefits.

type of vegetable [1–3].

**Chapter 6**

**Abstract**

phytochemicals

**1. Introduction**

*João Silva Dias*

Nutritional Quality and Effect on

Disease Prevention of Vegetables

Vegetables have remarkable nutritional and health benefits. There are good reasons to include vegetables in human diet since they are enriched in bioactive compounds and by this reason they may help reduce the risk of some diseases. In this chapter, the nutrition quality and the effect on disease prevention of vegetables were analyzed. Each vegetable family and each vegetable contain a unique combination of bioactive compounds. The health benefit of vegetables should not be linked to one type of vegetable. Some experimental research evidences that vegetables exert antioxidative, anticarcinogenic, antidiabetic, and cardiovascular disease lowering effects are presented. The mechanism by which vegetable bioactive compounds decrease the risk of some of these diseases is complex and sometimes unknown.

**Keywords:** vegetables, health benefits, healthier life, nutrition, ANDI, bioactive compounds, antioxidants, dietary fiber, vitamins, minerals,

Vegetables are important for nutritional balanced diets since they supply bioactive compounds such as dietary fiber, vitamins, minerals, and phytochemicals [1–3]. They are also associated with disease prevention by improvement of gastrointestinal health, good vision, and reduced risk of chronic and degenerative diseases such as cardiovascular diseases, certain cancers, diabetes, rheumatoid arthritis, and obesity [3–8]. In recent years consumers began to be more aware of the relation of eating patterns with nutrition and human disease prevention, and there is a general agreement among scientists, nutritionists, and dieticians that the promotion of a greater consumption of vegetables will improve nutrition quality and will bring health

The mechanisms by which vegetable consumption prevents diseases have not yet been fully understood [2, 3]. However, scientists, nutritionists, and dieticians believe that the bioactive compounds such as dietary fiber, vitamins, minerals, and phytochemical contents are responsible for mitigating some human diseases. All these different compounds may contribute to the overall health benefit. So, the health benefit of vegetables should not be linked to only one bioactive compound or one type of vegetable, but rather with a balanced diet that includes more than one

Some vegetable phytochemicals (glucosinolates, thiosulfates, polyphenols, bioactive peptides, etc.) have positive effects on health. They are strong antioxidants,

#### **Chapter 6**

## Nutritional Quality and Effect on Disease Prevention of Vegetables

*João Silva Dias*

#### **Abstract**

Vegetables have remarkable nutritional and health benefits. There are good reasons to include vegetables in human diet since they are enriched in bioactive compounds and by this reason they may help reduce the risk of some diseases. In this chapter, the nutrition quality and the effect on disease prevention of vegetables were analyzed. Each vegetable family and each vegetable contain a unique combination of bioactive compounds. The health benefit of vegetables should not be linked to one type of vegetable. Some experimental research evidences that vegetables exert antioxidative, anticarcinogenic, antidiabetic, and cardiovascular disease lowering effects are presented. The mechanism by which vegetable bioactive compounds decrease the risk of some of these diseases is complex and sometimes unknown.

**Keywords:** vegetables, health benefits, healthier life, nutrition, ANDI, bioactive compounds, antioxidants, dietary fiber, vitamins, minerals, phytochemicals

#### **1. Introduction**

Vegetables are important for nutritional balanced diets since they supply bioactive compounds such as dietary fiber, vitamins, minerals, and phytochemicals [1–3]. They are also associated with disease prevention by improvement of gastrointestinal health, good vision, and reduced risk of chronic and degenerative diseases such as cardiovascular diseases, certain cancers, diabetes, rheumatoid arthritis, and obesity [3–8].

In recent years consumers began to be more aware of the relation of eating patterns with nutrition and human disease prevention, and there is a general agreement among scientists, nutritionists, and dieticians that the promotion of a greater consumption of vegetables will improve nutrition quality and will bring health benefits.

The mechanisms by which vegetable consumption prevents diseases have not yet been fully understood [2, 3]. However, scientists, nutritionists, and dieticians believe that the bioactive compounds such as dietary fiber, vitamins, minerals, and phytochemical contents are responsible for mitigating some human diseases. All these different compounds may contribute to the overall health benefit. So, the health benefit of vegetables should not be linked to only one bioactive compound or one type of vegetable, but rather with a balanced diet that includes more than one type of vegetable [1–3].

Some vegetable phytochemicals (glucosinolates, thiosulfates, polyphenols, bioactive peptides, etc.) have positive effects on health. They are strong antioxidants, and they reduce the risk of chronic diseases by protecting against free radical damage, by modifying metabolic activation and detoxification of carcinogens, or even by influencing mechanisms that alter the course of tumor cells [1–3]. Phytochemicals are the key to better health as well as disease prevention.

All vegetables are sources of important vitamins (C, A, B1, B6, B9, E) and minerals and consequently have nutritional and health benefits [2, 3].

Dietary fiber is a major constituent of vegetables. Dietary fiber and other bioactive molecule contents have been usually addressed separately in nutritional studies. However, vegetable dietary fiber transports, through the human gut, a significant amount of phytochemicals, vitamins, and minerals linked to the fiber matrix [9, 10]. Therefore, associated phytochemicals, vitamins, and minerals of the whole aliment may contribute to the overall health benefit usually attributed to the dietary fiber of vegetables [2, 3].

The objective of this paper is to explore the nutritional quality and effect on disease prevention of vegetables.

#### **2. Nutritional quality of vegetables**

#### **2.1 Vegetables**

From more than 1000 plants that are used as vegetables, Kays and Dias [11, 12], based on a world survey, report that at least 402 vegetables are cultivated and commercialized worldwide. They represent 69 families and 230 genera. From these great diversity, leafy and stalk vegetable group comprised 53% of the total, followed by fruit and flower vegetable group (15%) and belowground (root, bulb, and tuber) vegetable group (17%). Many of these vegetable crops have more than one part used.

Leafy and stalk vegetable group include lettuce, chicory, coles (head cabbages, kales, tronchudas, collards, Brussels sprouts, etc.), Chinese cabbage, pak-choi, turnip greens, mustards, rocket, watercress, Swiss chard, spinach, purslane, New Zealand spinach, celery, asparagus, rhubarb, fennel, chives, parsley, coriander, etc.

Fruit and flower vegetable group include tomato, pepper, eggplant, watermelon, melon, cucumber, squash, pumpkin, zucchini, bitter gourd, peas, beans, lentils, okra, sweet maize, cauliflower, broccoli, kailan, broccoletti, artichoke, etc.

Root, bulb, and tuber vegetable group include carrot, garden beet, turnip, radish, rutabaga, parsnip, sweet potato, cassava, celeriac, onion, garlic, shallot, leek, Welsh onion, potato, etc.

#### **2.2 Vegetables and human nutrition**

Until few years ago, it was believed that the key for human nutrition and health was only 14 vitamins and 16 essential minerals. Recently, with the great developments in chemistry, it was found that, in addition to these vitamins and minerals, vegetables contain thousands of beneficial phytochemicals. As mentioned some vegetable's phytochemicals are robust antioxidants and are believed to reduce the risk of some chronic and degenerative diseases [2–4].

With the exclusion of the organosulfur compounds (OSCs) glucosinolates and thiosulfates (which are distinct phytochemicals of Brassicaceae and Alliaceae families, respectively), the phytochemical, vitamin, and mineral contents of many vegetables lie principally in dietary fiber, polyphenols (carotenoids, flavonoids), vitamin C, folate, calcium, and selenium [2, 3]. The principal dissimilarity is that each vegetable family incorporates a distinct amalgam and amount of these bioactive compounds, which differentiate them from other vegetables [2, 13].

**85**

*Nutritional Quality and Effect on Disease Prevention of Vegetables*

three flavonoids: kaempferol, quercetin, and luteolin [15–17].

Vegetables of the Apiaceae family (carrot, parsnip, celery, celeriac, fennel, parsley, coriander, etc.) are rich in flavonoids, carotenoids, vitamin C, and vitamin E. For example, celery and parsley are among the best vegetable sources for the flavonoid apigenin and vitamin E [2, 14], and carrots have a unique combination of

Vegetables of the Asteraceae or Compositae family (lettuce, endive and escarole chicories, stem lettuce, globe artichoke, etc.) are rich in flavonoids, tocopherols, and conjugated quercetin. Crozier et al. [18] observed sizeable variations in flavonol content within lettuce cultivars. The outer leaves of "Lollo Rosso," a red cultivar, contained 911 μg/g fresh weight of quercetin, in contrast with the common head lettuce that contained only 11 μg/g. And, the levels in iceberg lettuce were even lower than in the head lettuce. The red color of "Lollo Rosso" lettuce is due to high levels of anthocyanins, which like quercetin are products of the phenylpropanoid pathway. As one end product of the pathway has been elevated, it may well be that other related compounds, including the flavonols, are also found in higher concentrations. Roman lettuce is richer in lutein than head lettuces; and leafy and roman

The Chenopodiaceae family vegetables (Swiss chard, spinach, garden beet, quinoa, etc.) are among those that are rich in oxalates [19, 20] but also excellent sources of dietary fiber, vitamins, calcium, manganese, flavonoids, and carotenoids. When oxalates become too concentrated in body fluids, they can crystallize and cause

The Cucurbitaceae family vegetables (e.g., squash, pumpkin, cucumber, melon,

The vegetables of the Leguminosae or Fabaceae family (all the legumes, e.g., pea, bean, soybean, lentils, chickpea, etc.), mature and immature seeds, are great sources of dietary fiber, resistant starch, protein, isoflavonoids [24], calcium, and iron. Mallillin et al. [25] studied the total, soluble, and insoluble fiber and fermentability characteristics of 10 legume mature seeds (mung bean, soybean, peanut, pole sitao, cowpea, chickpea, green pea, lima bean, kidney bean, and pigeon pea). They concluded that the dietary fiber content in these ten legumes ranged from 20.9 to 46.9 g/100 g and that the best sources after in vitro fermentation using human fecal inoculum-stimulating conditions in the human colon (as mmol/g/ fiber isolate of acetate, propionate, and butyrate produced after fiber fermentation) were pole sitao and mung bean (acetate), kidney bean and pigeon pea (propionate), and peanut and cowpea (butyrate). High-flavonol legumes include sugar snap peas and mange tout, which were found to contain 98 and 145 μg quercetin/g, respectively [2]. As mentioned some legumes are also rich in iron. Trinidad et al. [26] studied the mineral availability in vitro of iron, zinc, and calcium in 10 local legumes (cowpeas, mung beans, pole sitao, chickpeas, green peas, groundnuts, pigeon peas, kidney beans, lima beans, and soybeans). They found that the highest iron availability among these legumes was for lima beans and mung bean, while for zinc and calcium, the highest availability was for kidney beans and pigeon peas. Groundnuts have the lowest iron, zinc, and calcium availability. They concluded that mineral availability of iron, zinc, and calcium from legumes differs and may be attributed to their mineral content, mineral-mineral interaction, and their phytic and tannic acid content. Mung bean either eaten as whole pod grains or grown to produce bean sprouts is an important source of iron for women and

bitter gourd, etc.) are rich in carotenoids, and tocopherols, and vitamin C [21]. Burger et al. [22] in a survey of 350 melon accessions observed a 50-fold variation in ascorbic acid content, ranging from 0.7 to 35.3 mg/100 g fresh weight. Ascorbic acid and β-carotene content ranged from 7.0 to 32.0 mg/100 g and 4.7 to 62.2 μg/100 g,

*DOI: http://dx.doi.org/10.5772/intechopen.85038*

lettuces are richer in quercetin [3, 13].

respectively, in sweet melons [23].

children throughout South Asia [1, 27].

health problems such as kidney calcium oxalate stones.

#### *Nutritional Quality and Effect on Disease Prevention of Vegetables DOI: http://dx.doi.org/10.5772/intechopen.85038*

*Nutrition in Health and Disease - Our Challenges Now and Forthcoming Time*

and they reduce the risk of chronic diseases by protecting against free radical damage, by modifying metabolic activation and detoxification of carcinogens, or even by influencing mechanisms that alter the course of tumor cells [1–3]. Phytochemicals are the key to better health as well as disease prevention.

All vegetables are sources of important vitamins (C, A, B1, B6, B9, E) and

Dietary fiber is a major constituent of vegetables. Dietary fiber and other bioactive molecule contents have been usually addressed separately in nutritional studies. However, vegetable dietary fiber transports, through the human gut, a significant amount of phytochemicals, vitamins, and minerals linked to the fiber matrix [9, 10]. Therefore, associated phytochemicals, vitamins, and minerals of the whole aliment may contribute to the overall health benefit usually attributed to the dietary

The objective of this paper is to explore the nutritional quality and effect on

From more than 1000 plants that are used as vegetables, Kays and Dias [11, 12], based on a world survey, report that at least 402 vegetables are cultivated and commercialized worldwide. They represent 69 families and 230 genera. From these great diversity, leafy and stalk vegetable group comprised 53% of the total, followed by fruit and flower vegetable group (15%) and belowground (root, bulb, and tuber) vegetable group (17%). Many of these vegetable crops have more than one part used. Leafy and stalk vegetable group include lettuce, chicory, coles (head cabbages, kales, tronchudas, collards, Brussels sprouts, etc.), Chinese cabbage, pak-choi, turnip greens, mustards, rocket, watercress, Swiss chard, spinach, purslane, New Zealand spinach, celery, asparagus, rhubarb, fennel, chives, parsley, coriander, etc. Fruit and flower vegetable group include tomato, pepper, eggplant, watermelon, melon, cucumber, squash, pumpkin, zucchini, bitter gourd, peas, beans, lentils, okra, sweet maize, cauliflower, broccoli, kailan, broccoletti, artichoke, etc.

Root, bulb, and tuber vegetable group include carrot, garden beet, turnip, radish, rutabaga, parsnip, sweet potato, cassava, celeriac, onion, garlic, shallot, leek,

Until few years ago, it was believed that the key for human nutrition and health was only 14 vitamins and 16 essential minerals. Recently, with the great developments in chemistry, it was found that, in addition to these vitamins and minerals, vegetables contain thousands of beneficial phytochemicals. As mentioned some vegetable's phytochemicals are robust antioxidants and are believed to reduce the

With the exclusion of the organosulfur compounds (OSCs) glucosinolates and thiosulfates (which are distinct phytochemicals of Brassicaceae and Alliaceae families, respectively), the phytochemical, vitamin, and mineral contents of many vegetables lie principally in dietary fiber, polyphenols (carotenoids, flavonoids), vitamin C, folate, calcium, and selenium [2, 3]. The principal dissimilarity is that each vegetable family incorporates a distinct amalgam and amount of these bioac-

tive compounds, which differentiate them from other vegetables [2, 13].

minerals and consequently have nutritional and health benefits [2, 3].

fiber of vegetables [2, 3].

Welsh onion, potato, etc.

**2.2 Vegetables and human nutrition**

risk of some chronic and degenerative diseases [2–4].

**2.1 Vegetables**

disease prevention of vegetables.

**2. Nutritional quality of vegetables**

**84**

Vegetables of the Apiaceae family (carrot, parsnip, celery, celeriac, fennel, parsley, coriander, etc.) are rich in flavonoids, carotenoids, vitamin C, and vitamin E. For example, celery and parsley are among the best vegetable sources for the flavonoid apigenin and vitamin E [2, 14], and carrots have a unique combination of three flavonoids: kaempferol, quercetin, and luteolin [15–17].

Vegetables of the Asteraceae or Compositae family (lettuce, endive and escarole chicories, stem lettuce, globe artichoke, etc.) are rich in flavonoids, tocopherols, and conjugated quercetin. Crozier et al. [18] observed sizeable variations in flavonol content within lettuce cultivars. The outer leaves of "Lollo Rosso," a red cultivar, contained 911 μg/g fresh weight of quercetin, in contrast with the common head lettuce that contained only 11 μg/g. And, the levels in iceberg lettuce were even lower than in the head lettuce. The red color of "Lollo Rosso" lettuce is due to high levels of anthocyanins, which like quercetin are products of the phenylpropanoid pathway. As one end product of the pathway has been elevated, it may well be that other related compounds, including the flavonols, are also found in higher concentrations. Roman lettuce is richer in lutein than head lettuces; and leafy and roman lettuces are richer in quercetin [3, 13].

The Chenopodiaceae family vegetables (Swiss chard, spinach, garden beet, quinoa, etc.) are among those that are rich in oxalates [19, 20] but also excellent sources of dietary fiber, vitamins, calcium, manganese, flavonoids, and carotenoids. When oxalates become too concentrated in body fluids, they can crystallize and cause health problems such as kidney calcium oxalate stones.

The Cucurbitaceae family vegetables (e.g., squash, pumpkin, cucumber, melon, bitter gourd, etc.) are rich in carotenoids, and tocopherols, and vitamin C [21]. Burger et al. [22] in a survey of 350 melon accessions observed a 50-fold variation in ascorbic acid content, ranging from 0.7 to 35.3 mg/100 g fresh weight. Ascorbic acid and β-carotene content ranged from 7.0 to 32.0 mg/100 g and 4.7 to 62.2 μg/100 g, respectively, in sweet melons [23].

The vegetables of the Leguminosae or Fabaceae family (all the legumes, e.g., pea, bean, soybean, lentils, chickpea, etc.), mature and immature seeds, are great sources of dietary fiber, resistant starch, protein, isoflavonoids [24], calcium, and iron. Mallillin et al. [25] studied the total, soluble, and insoluble fiber and fermentability characteristics of 10 legume mature seeds (mung bean, soybean, peanut, pole sitao, cowpea, chickpea, green pea, lima bean, kidney bean, and pigeon pea). They concluded that the dietary fiber content in these ten legumes ranged from 20.9 to 46.9 g/100 g and that the best sources after in vitro fermentation using human fecal inoculum-stimulating conditions in the human colon (as mmol/g/ fiber isolate of acetate, propionate, and butyrate produced after fiber fermentation) were pole sitao and mung bean (acetate), kidney bean and pigeon pea (propionate), and peanut and cowpea (butyrate). High-flavonol legumes include sugar snap peas and mange tout, which were found to contain 98 and 145 μg quercetin/g, respectively [2]. As mentioned some legumes are also rich in iron. Trinidad et al. [26] studied the mineral availability in vitro of iron, zinc, and calcium in 10 local legumes (cowpeas, mung beans, pole sitao, chickpeas, green peas, groundnuts, pigeon peas, kidney beans, lima beans, and soybeans). They found that the highest iron availability among these legumes was for lima beans and mung bean, while for zinc and calcium, the highest availability was for kidney beans and pigeon peas. Groundnuts have the lowest iron, zinc, and calcium availability. They concluded that mineral availability of iron, zinc, and calcium from legumes differs and may be attributed to their mineral content, mineral-mineral interaction, and their phytic and tannic acid content. Mung bean either eaten as whole pod grains or grown to produce bean sprouts is an important source of iron for women and children throughout South Asia [1, 27].

Vegetables of the Brassicaceae or Cruciferae family, which include kales, collards, cabbages, Brussels sprouts, cauliflower, broccoli, kailan, pak-choi, Chinese cabbage, turnip, broccoletti, swede, watercress, radish, horseradish, rocket, mustards, etc., are high sources of glucosinolates, as well as vitamin C, carotenoids, folates, and calcium, and can accumulate selenium. Comparative studies of glucosinolate profiles within each Cruciferae, and among accessions and plant parts, indicate significant quantitative and qualitative differences [28–39]. Kushad et al. [34] observed in 65 broccoli cultivars that glucoraphanin was the predominant glucosinolate and that there was more than 27-fold difference between the highest concentration in "Brigadier" and the lowest in "EV6–1." Hansen et al. [40] also observed in 21 red cabbage and 6 white cabbage cultivars, a considerable variation in the concentration of glucosinolates. Red cabbages were found to contain significantly higher concentrations of glucoraphanin compared to white ones. There were also significant differences within the red cabbages examined: "Rodima" had the highest level of glucoraphanin (7.4 mg/g), whereas "Primero" has the lowest (0.6 mg/g). The white cabbages presented significantly higher levels of glucoiberin than the red ones: white cabbage "Bartolo" had the highest concentration of glucoiberin (7.4 mg/g), whereas "Candela" has the lowest (1.7 mg/g), and red cabbages ranged from 3 to 0.3 mg/g. The red cabbages were also found to contain significantly higher levels of gluconasturtiin than white: "Amager Garo" had the highest level of gluconasturtiin (1 mg/g), whereas "Primero" had the lowest (0.1 mg/g). In turnip and rutabagas, similar differences between accessions were also observed [30]. Fahey et al. [41] evaluated glucosinolate content of broccoli sprouts and found that they contain nearly 20- to 50-fold higher glucosinolate concentrations than tissue from mature plants. In broccoli heads, the predominant glucosinolates are glucoraphanin, glucobrassicin, progoitrin, and gluconasturtiin [32, 34, 36, 38, 42, 43]. In cabbage, Brussels sprouts, cauliflower, kale, tronchuda, and collard, the most significant glucosinolates are sinigrin, progoitrin, and glucobrassicin [29, 32, 34, 39, 40, 44]. In turnip and rutabagas, the major glucosinolates are glucoerucin, glucoraphanin, and glucobrassicin [30, 33]. In radish, the most significant glucosinolates are glucoerucin, glucoraphanin, and glucobrassicin [31, 35]. Each of these Cruciferae also contains smaller amounts of other glucosinolates.

Cao et al. [45] observed that in Brassicaceae vegetables vitamin C is the most abundant vitamin in coles (cabbage, broccoli, cauliflower, Brussels sprouts, tronchuda, and kale) and that kale rated as the second highest vitamin content and the second highest among 22 vegetables. They are also excellent sources of folate. Brussels sprouts and broccoli rank among the highest vegetable sources for folate [46, 47]. Most of the Cruciferae are also good sources of calcium. Kales, tronchudas, and collards contain the highest content in fiber and calcium when compared to other Brassicaceae. Vegetables of the Cruciferae family are able to accumulate selenium when grown on selenium-enriched soils. Banuelos and Meek [48] stated that broccoli-grown soils with high-selenium levels accumulated sevenfold more selenium than cabbage, collards, and Swiss chard.

Vegetables of the Alliaceae family (e.g., onions, garlic, shallots, leek, Welsh onion, chives, etc.) are rich in thiosulfates, flavonoids, calcium, potassium, manganese, and chromium and can accumulate selenium. The types and composition of thiosulfates differ from *Allium* [49]. Kalra et al. [50] reported that garlic fresh bulbs contain 33 thiosulfates. The major thiosulfates in the cytoplasm of *Allium* species are S-allyl-cysteine sulfoxide (alliin), S-methyl-cysteine sulfoxide (methiin), and γ-glutamyl-L-cysteine [51]. Other minor thiosulfates include S-propenyl-cysteine sulfoxide (isoalliin) and S-ethyl-cysteine (ethiin) [52]. None of the thiosulfates found in *Allium* have been detected in other vegetables, except S-methyl-cysteine sulfoxide (methiin) which was detected in some Cruciferae [53]. The most

**87**

compounds.

*Nutritional Quality and Effect on Disease Prevention of Vegetables*

(8%) and trace amounts of ethiin, propiin, and isoalliin [51, 53–55].

garlic chive, and leek, the predominant flavonoid is kaempferol [58].

of inulin, a polyfructosan, that has prebiotic properties [2, 3].

important thiosulfates detected in onion bulbs are isoalliin (49%), methiin (34%), propiin (6%), ethiin (5%), and alliin (5%) and in garlic alliin (92%) and methiin

The second most important group of bioactive compounds in *Allium* is flavonoids. Miean and Mohamed [56] mentioned that onion leaves had the highest total flavonoid content among 62 different vegetables. About 55% of this total of flavonoids is quercetin, 31% kaempferol, and 14% luteolin. Two flavonoids are found in onion bulbs: anthocyanins in red onions and flavonols like quercetin (more than 95%) and kaempferol in most yellow onion varieties [57]. White onion cultivars have significantly less quercetin than the red ones [2, 3, 58]. In garlic cloves, 72% of the total flavonoids is myricetin, 23% apigenin, and 5% quercetin [56]. In chive,

Onion and garlic are excellent sources of calcium, potassium, and manganese providing up to 10% of the human daily requirements. Most of the onions and garlics contain very low concentrations of selenium but can accumulate selenium when grown on selenium-enriched soils. Ip and Lisk [59] reported that garlic fertilized with a high selenium and low sulfur fertilizer accumulated between 110 and 150 ppm selenium, while onion accumulated up to 28 ppm. Onions also contain chromium [2]. Two hundred grams of onions contain up to 20% of the daily requirements in chromium. Onions are a rich source of dietary fibers and especially

Vegetables of the Solanaceae family that includes tomato, potato, sweet and hot peppers, eggplant, etc. are very diverse, in their contribution to bioactive

Tomato is the second most produced and consumed vegetable in the world after potato. Tomato has a unique nutritional and phytochemical profile. Carotenoids are the major bioactive compounds in tomato with 60–64% lycopene, 10–12% phytoene, 7–9% neurosporene, and 10–15% carotenes [60]. Red varieties of tomato contain more lycopene (on average 90 mg/kg) than yellow ones (5 mg/kg) [61]. The average daily intake of lycopene in human diet is about 25 mg/day. Processed tomatoes (juice, sauce, paste, and ketchup) contain higher lycopene (2- to 40-fold) than fresh tomatoes [60, 62, 63]. Lycopene is a very potent antioxidant [64, 65]. Tomato contains also significant amounts of α-, β-, γ-, and δ-carotene (0.6–2.0 mg/kg) which make it for consumers a top contributor of provitamin A and vitamin A [66, 67]. Tomatoes are also an excellent source of vitamin C [68]. Tomato contains small amounts of lutein, α-, β-, and γ-tocopherols and conjugated flavonoids (quercetin and kaempferol) [66, 69–71]. About 98% of these flavonoids are present in the peel [72]. Cherry tomato cultivars have higher flavonoid contents than beef ones, and field-grown tomatoes have higher flavonoid contents than greenhouse-grown ones [18, 72]. Tomatoes are also an excellent source of potassium. Potato is usually only associated as a source of carbohydrates. But it is also an excellent source of essential amino acids (such as lysine) and other bioactive compounds [2]. In addition to superior quality proteins, potato tubers also have significant amounts of vitamins and minerals, as well as phytochemicals (phenolics, phytoalexins, etc.), and protease inhibitors [73, 74]. There are yellow-, red-, and purple-fleshed potato cultivars with high content of phytochemicals; nevertheless, some cultivars are known to have lower [2]. Other bioactive antioxidants presented in potato tubers include α-tocopherol, lutein, β-carotene, folates, and selenium [73, 74]. Peppers are excellent sources of vitamins C, K, carotenoids, and flavonoids [75]. They provide also a respectable amount of dietary fiber. Peppers contain in average 1–2 g/kg of vitamin C, which is equivalent to 200–300% of the recommended daily allowance [76]. Their content of provitamin A carotenoids (α- and β-carotene) depends in the cultivar. Some cultivars of hot pepper have 12 mg/kg total carotenoids,

*DOI: http://dx.doi.org/10.5772/intechopen.85038*

#### *Nutritional Quality and Effect on Disease Prevention of Vegetables DOI: http://dx.doi.org/10.5772/intechopen.85038*

*Nutrition in Health and Disease - Our Challenges Now and Forthcoming Time*

Vegetables of the Brassicaceae or Cruciferae family, which include kales, collards, cabbages, Brussels sprouts, cauliflower, broccoli, kailan, pak-choi, Chinese cabbage, turnip, broccoletti, swede, watercress, radish, horseradish, rocket, mustards, etc., are high sources of glucosinolates, as well as vitamin C, carotenoids, folates, and calcium, and can accumulate selenium. Comparative studies of glucosinolate profiles within each Cruciferae, and among accessions and plant parts, indicate significant quantitative and qualitative differences [28–39]. Kushad et al. [34] observed in 65 broccoli cultivars that glucoraphanin was the predominant glucosinolate and that there was more than 27-fold difference between the highest concentration in "Brigadier" and the lowest in "EV6–1." Hansen et al. [40] also observed in 21 red cabbage and 6 white cabbage cultivars, a considerable variation in the concentration of glucosinolates. Red cabbages were found to contain significantly higher concentrations of glucoraphanin compared to white ones. There were also significant differences within the red cabbages examined: "Rodima" had the highest level of glucoraphanin (7.4 mg/g), whereas "Primero" has the lowest (0.6 mg/g). The white cabbages presented significantly higher levels of glucoiberin than the red ones: white cabbage "Bartolo" had the highest concentration of glucoiberin (7.4 mg/g), whereas "Candela" has the lowest (1.7 mg/g), and red cabbages ranged from 3 to 0.3 mg/g. The red cabbages were also found to contain significantly higher levels of gluconasturtiin than white: "Amager Garo" had the highest level of gluconasturtiin (1 mg/g), whereas "Primero" had the lowest (0.1 mg/g). In turnip and rutabagas, similar differences between accessions were also observed [30]. Fahey et al. [41] evaluated glucosinolate content of broccoli sprouts and found that they contain nearly 20- to 50-fold higher glucosinolate concentrations than tissue from mature plants. In broccoli heads, the predominant glucosinolates are glucoraphanin, glucobrassicin, progoitrin, and gluconasturtiin [32, 34, 36, 38, 42, 43].

In cabbage, Brussels sprouts, cauliflower, kale, tronchuda, and collard, the most significant glucosinolates are sinigrin, progoitrin, and glucobrassicin [29, 32, 34, 39, 40, 44]. In turnip and rutabagas, the major glucosinolates are glucoerucin, glucoraphanin, and glucobrassicin [30, 33]. In radish, the most significant glucosinolates are glucoerucin, glucoraphanin, and glucobrassicin [31, 35]. Each of

these Cruciferae also contains smaller amounts of other glucosinolates.

selenium than cabbage, collards, and Swiss chard.

Cao et al. [45] observed that in Brassicaceae vegetables vitamin C is the most abundant vitamin in coles (cabbage, broccoli, cauliflower, Brussels sprouts, tronchuda, and kale) and that kale rated as the second highest vitamin content and the second highest among 22 vegetables. They are also excellent sources of folate. Brussels sprouts and broccoli rank among the highest vegetable sources for folate [46, 47]. Most of the Cruciferae are also good sources of calcium. Kales, tronchudas, and collards contain the highest content in fiber and calcium when compared to other Brassicaceae. Vegetables of the Cruciferae family are able to accumulate selenium when grown on selenium-enriched soils. Banuelos and Meek [48] stated that broccoli-grown soils with high-selenium levels accumulated sevenfold more

Vegetables of the Alliaceae family (e.g., onions, garlic, shallots, leek, Welsh onion, chives, etc.) are rich in thiosulfates, flavonoids, calcium, potassium, manganese, and chromium and can accumulate selenium. The types and composition of thiosulfates differ from *Allium* [49]. Kalra et al. [50] reported that garlic fresh bulbs contain 33 thiosulfates. The major thiosulfates in the cytoplasm of *Allium* species are S-allyl-cysteine sulfoxide (alliin), S-methyl-cysteine sulfoxide (methiin), and γ-glutamyl-L-cysteine [51]. Other minor thiosulfates include S-propenyl-cysteine sulfoxide (isoalliin) and S-ethyl-cysteine (ethiin) [52]. None of the thiosulfates found in *Allium* have been detected in other vegetables, except S-methyl-cysteine sulfoxide (methiin) which was detected in some Cruciferae [53]. The most

**86**

important thiosulfates detected in onion bulbs are isoalliin (49%), methiin (34%), propiin (6%), ethiin (5%), and alliin (5%) and in garlic alliin (92%) and methiin (8%) and trace amounts of ethiin, propiin, and isoalliin [51, 53–55].

The second most important group of bioactive compounds in *Allium* is flavonoids. Miean and Mohamed [56] mentioned that onion leaves had the highest total flavonoid content among 62 different vegetables. About 55% of this total of flavonoids is quercetin, 31% kaempferol, and 14% luteolin. Two flavonoids are found in onion bulbs: anthocyanins in red onions and flavonols like quercetin (more than 95%) and kaempferol in most yellow onion varieties [57]. White onion cultivars have significantly less quercetin than the red ones [2, 3, 58]. In garlic cloves, 72% of the total flavonoids is myricetin, 23% apigenin, and 5% quercetin [56]. In chive, garlic chive, and leek, the predominant flavonoid is kaempferol [58].

Onion and garlic are excellent sources of calcium, potassium, and manganese providing up to 10% of the human daily requirements. Most of the onions and garlics contain very low concentrations of selenium but can accumulate selenium when grown on selenium-enriched soils. Ip and Lisk [59] reported that garlic fertilized with a high selenium and low sulfur fertilizer accumulated between 110 and 150 ppm selenium, while onion accumulated up to 28 ppm. Onions also contain chromium [2]. Two hundred grams of onions contain up to 20% of the daily requirements in chromium. Onions are a rich source of dietary fibers and especially of inulin, a polyfructosan, that has prebiotic properties [2, 3].

Vegetables of the Solanaceae family that includes tomato, potato, sweet and hot peppers, eggplant, etc. are very diverse, in their contribution to bioactive compounds.

Tomato is the second most produced and consumed vegetable in the world after potato. Tomato has a unique nutritional and phytochemical profile. Carotenoids are the major bioactive compounds in tomato with 60–64% lycopene, 10–12% phytoene, 7–9% neurosporene, and 10–15% carotenes [60]. Red varieties of tomato contain more lycopene (on average 90 mg/kg) than yellow ones (5 mg/kg) [61]. The average daily intake of lycopene in human diet is about 25 mg/day. Processed tomatoes (juice, sauce, paste, and ketchup) contain higher lycopene (2- to 40-fold) than fresh tomatoes [60, 62, 63]. Lycopene is a very potent antioxidant [64, 65].

Tomato contains also significant amounts of α-, β-, γ-, and δ-carotene (0.6–2.0 mg/kg) which make it for consumers a top contributor of provitamin A and vitamin A [66, 67]. Tomatoes are also an excellent source of vitamin C [68]. Tomato contains small amounts of lutein, α-, β-, and γ-tocopherols and conjugated flavonoids (quercetin and kaempferol) [66, 69–71]. About 98% of these flavonoids are present in the peel [72]. Cherry tomato cultivars have higher flavonoid contents than beef ones, and field-grown tomatoes have higher flavonoid contents than greenhouse-grown ones [18, 72]. Tomatoes are also an excellent source of potassium.

Potato is usually only associated as a source of carbohydrates. But it is also an excellent source of essential amino acids (such as lysine) and other bioactive compounds [2]. In addition to superior quality proteins, potato tubers also have significant amounts of vitamins and minerals, as well as phytochemicals (phenolics, phytoalexins, etc.), and protease inhibitors [73, 74]. There are yellow-, red-, and purple-fleshed potato cultivars with high content of phytochemicals; nevertheless, some cultivars are known to have lower [2]. Other bioactive antioxidants presented in potato tubers include α-tocopherol, lutein, β-carotene, folates, and selenium [73, 74].

Peppers are excellent sources of vitamins C, K, carotenoids, and flavonoids [75]. They provide also a respectable amount of dietary fiber. Peppers contain in average 1–2 g/kg of vitamin C, which is equivalent to 200–300% of the recommended daily allowance [76]. Their content of provitamin A carotenoids (α- and β-carotene) depends in the cultivar. Some cultivars of hot pepper have 12 mg/kg total carotenoids, while others have trace amounts [76, 77]. In pepper, the major conjugated flavonoids are quercetin and luteolin. Their content varies among cultivars ranging from not detectable to 800 mg/kg [78]. Red bell peppers have significantly higher levels of bioactive compounds than green ones. Red bell peppers also contain lycopene [74].

In hot peppers or chilies, the major phytochemicals are capsaicinoids [2, 74]. More than 20 capsaicinoids, belonging to capsaicin and dihydrocapsaicin groups, have been identified. Capsaicin contributes about 70% for the pungent/hot fire flavor in chili peppers, while dihydrocapsaicin represents 30% [79]. Significant variations in capsaicinoids are found between and within peppers, ranging from about 220 ppm in *Capsicum annum* (sweet pepper) to 20,000 ppm in Capsicum chinense (hot pepper) [80]. Fresh chili peppers have high levels of vitamins and minerals. Just 100 g of hot peppers, red or green, provides 240% of vitamin C, 39% of vitamin B6-complex group, 32% of vitamin A, 13% of iron, 14% of copper, and 7% of potassium of the recommended daily allowance [81]. Chili peppers contain a good amount of manganese and magnesium [2].

Eggplant besides vitamins (C, K, B6-complex group, folate, and niacin) and minerals (magnesium, copper, manganese, molybdenum, potassium) also contains important phytochemicals like flavonoids, such as nasunin, and phenolic compounds, such caffeic and chlorogenic acid [2, 74]. Nasunin is the major phytochemical in purple eggplant cultivars. Nasunin is part of the anthocyanin purple pigment found in the skin of eggplant [82–84]. Matsuzoe et al. [85] examined the profile of anthocyanins in several eggplants and found that nasunin represents between 70 and 90% of the total anthocyanins in the skin. Nasunin is an antioxidant that effectively scavenges reactive oxygen species, such as hydrogen peroxide, hydroxyl, and superoxide, as well as inhibits the formation of hydroxyl radicals, probably by chelating ferrous ions in the Fenton reaction [82, 84]. The predominant phenolic compound found in all cultivars of eggplant tested by Matsuzoe et al. [85] is chlorogenic acid, which is one of the most potent free radical scavengers found in plant tissues. Benefits attributed to chlorogenic acid include antimutagenic (anticancer), antimicrobial, and anti-low-density lipoproteins and antiviral activities. In addition to chlorogenic acid, Whitaker and Stommel [86] found 13 other phenolic acids present in seven eggplant cultivars. "Black Magic" was found by these authors to have nearly three times the amount of antioxidant phenolics as the other eggplant cultivars studied. Eggplant fruits also contain several other antioxidants including flavonoids myricetin and kaempferol as well as carotenoids lycopene, lutein, and α-carotene [56, 87]. Eggplant is richer in nicotine than any other edible vegetable and contains measurable amounts of oxalates [2, 74]. Due to oxalates individuals with already existing and untreated kidney or gallbladder problems may avoid eating eggplant [74, 88].

Looking generally for the nutrition quality of vegetables groups we can say. In the leafy and stalk vegetables, they are fiber sources, rich in important minerals such as calcium, magnesium, and iron and vitamins C and A and riboflavin. In this group, young fresh leaves contain more vitamin C than mature plants. The thinner and greener leaves are more nutritious respecting vitamins and minerals but less nutritious respecting dietary fiber. The green outer leaves of the head or pseudo-head leafy vegetables such as cabbage, lettuce, and endive chicory are usually richer in calcium, magnesium, iron, and vitamins than the inner leaves. Stalk vegetables like tronchuda cabbage, pak-choi, celery, and asparagus are rich in dietary fiber.

In the fruit and belowground organ vegetables, the skin and inside color reflect different bioactive compounds/pigment present. Anthocyanins (flavonoid) give vegetable leaves, belowground organs, and fruits their purple and purple-red color appearance, such as in red anthocyanin lettuce and endive chicory, red cabbage,

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**Table 1.**

*Nutritional Quality and Effect on Disease Prevention of Vegetables*

Swiss chard, rhubarb, etc. (leafy and stalk vegetables); garden beet, purple carrot, red onion, purple- and purple-red-skinned potato, purple sweet potato, etc. (below ground vegetables); and purple eggplant, purple tomato, purple pepper, purple and black broccoli, purple corn, etc. (fruit and flowering vegetables). The most abundant carotenoids in vegetables are α-carotene, β-carotene, and lycopene (carotenes) and lutein, zeaxanthin, and β-cryptoxanthin (xanthophylls) [2, 74, 89]. The most common carotenes are β-carotene and lycopene. β-Carotene (as well as α-carotene) can be found in orange and yellow skin fruits, belowground organs, and leafy vegetables [2, 74]. As a rule of thumb, the greater the intensity of the orange color, the more β-carotene the vegetable contains [2, 74]. Lycopene can be found in red fruits (e.g., tomato), red belowground organs (e.g., red carrot), and red leafy vegetables. Lutein is the most abundant xanthophyll [2, 74]. Xanthophylls are responsible for

Aggregate Nutrient Density Index (ANDI) is a scoring system based on nutrient content, rated on a 1–1000 scale that was established by Fuhrman [90]. This index are scores attributed to a variety of vegetables (and other foods) based on how many nutrients they deliver to our body in each calorie consumed. It was calculated by evaluating the content of dietary fiber, vitamins, minerals, phytochemicals, antioxidant capacities, etc. It is an index that estimates the nutritional quality of

Three main vegetable families are shown in this table: Brassicaceae (kale, collard

**Table 2** also shows other Brassicaceae like radish, turnip, kohlrabi, cauliflower, and rutabaga. Different vegetables from various families are also shown as well as differences among the peppers, where orange pepper is better than the red and red

Leafy vegetables thus have the highest ANDI scores compared to other vegetables. They are rich in dietary fiber, carotenoids, vitamin C, vitamin E, flavonoids, calcium, magnesium, etc. All the leafy vegetables are good sources of magnesium

The leafy vegetables with high ANDI scores are Brassicaceae. They have dietary fiber, are a rich source of glucosinolates and other bioactive nutrients, and have a

**Vegetable ANDI Vegetable ANDI** 1.Kale 1000 9.Chinese cabbage 714 2.Collard greens 1000 10.Brussels sprouts 672 3.Mustard greens 1000 11.Rocket 604 4.Swiss chard 1000 12.Lettuce (green leaf) 585 5.Turnip greens 1000 13.Chicory 516 6.Watercress 1000 14.Romaine lettuce 510 7.Pak-choi 865 15.Cabbage 481 8.Spinach 739 16.Broccoletti 455

vegetables. **Table 1** presents the highest ANDI scores in leafy vegetables.

greens, mustard greens, turnip greens, watercress, pak-choi, Chinese cabbage, Brussels sprouts, rocket, cabbage and broccoletti), Chenopodiaceae (Swiss chard and spinach), and Asteraceae (green leaf lettuce, chicory, and romaine lettuce). The highest ANDI scores of non-leafy vegetables are presented in **Table 2**.

*DOI: http://dx.doi.org/10.5772/intechopen.85038*

the yellow color of vegetables.

better than the green pepper.

because they have chlorophyll.

*List of identified leafy vegetables with the highest ANDI scores.*

**2.3 ANDI and nutritional quality of vegetables**

*Nutritional Quality and Effect on Disease Prevention of Vegetables DOI: http://dx.doi.org/10.5772/intechopen.85038*

*Nutrition in Health and Disease - Our Challenges Now and Forthcoming Time*

good amount of manganese and magnesium [2].

while others have trace amounts [76, 77]. In pepper, the major conjugated flavonoids are quercetin and luteolin. Their content varies among cultivars ranging from not detectable to 800 mg/kg [78]. Red bell peppers have significantly higher levels of bioactive compounds than green ones. Red bell peppers also contain lycopene [74]. In hot peppers or chilies, the major phytochemicals are capsaicinoids [2, 74]. More than 20 capsaicinoids, belonging to capsaicin and dihydrocapsaicin groups, have been identified. Capsaicin contributes about 70% for the pungent/hot fire flavor in chili peppers, while dihydrocapsaicin represents 30% [79]. Significant variations in capsaicinoids are found between and within peppers, ranging from about 220 ppm in *Capsicum annum* (sweet pepper) to 20,000 ppm in Capsicum chinense (hot pepper) [80]. Fresh chili peppers have high levels of vitamins and minerals. Just 100 g of hot peppers, red or green, provides 240% of vitamin C, 39% of vitamin B6-complex group, 32% of vitamin A, 13% of iron, 14% of copper, and 7% of potassium of the recommended daily allowance [81]. Chili peppers contain a

Eggplant besides vitamins (C, K, B6-complex group, folate, and niacin) and minerals (magnesium, copper, manganese, molybdenum, potassium) also contains important phytochemicals like flavonoids, such as nasunin, and phenolic compounds, such caffeic and chlorogenic acid [2, 74]. Nasunin is the major phytochemical in purple eggplant cultivars. Nasunin is part of the anthocyanin purple pigment found in the skin of eggplant [82–84]. Matsuzoe et al. [85] examined the profile of anthocyanins in several eggplants and found that nasunin represents between 70 and 90% of the total anthocyanins in the skin. Nasunin is an antioxidant that effectively scavenges reactive oxygen species, such as hydrogen peroxide, hydroxyl, and superoxide, as well as inhibits the formation of hydroxyl radicals, probably by chelating ferrous ions in the Fenton reaction [82, 84]. The predominant phenolic compound found in all cultivars of eggplant tested by Matsuzoe et al. [85] is chlorogenic acid, which is one of the most potent free radical scavengers found in plant tissues. Benefits attributed to chlorogenic acid include antimutagenic (anticancer), antimicrobial, and anti-low-density lipoproteins and antiviral activities. In addition to chlorogenic acid, Whitaker and Stommel [86] found 13 other phenolic acids present in seven eggplant cultivars. "Black Magic" was found by these authors to have nearly three times the amount of antioxidant phenolics as the other eggplant cultivars studied. Eggplant fruits also contain several other antioxidants including flavonoids myricetin and kaempferol as well as carotenoids lycopene, lutein, and α-carotene [56, 87]. Eggplant is richer in nicotine than any other edible vegetable and contains measurable amounts of oxalates [2, 74]. Due to oxalates individuals with already existing and untreated kidney or gallbladder problems may avoid eating eggplant [74, 88].

Looking generally for the nutrition quality of vegetables groups we can say. In the leafy and stalk vegetables, they are fiber sources, rich in important minerals such as calcium, magnesium, and iron and vitamins C and A and riboflavin. In this group, young fresh leaves contain more vitamin C than mature plants. The thinner and greener leaves are more nutritious respecting vitamins and minerals but less nutritious respecting dietary fiber. The green outer leaves of the head or pseudo-head leafy vegetables such as cabbage, lettuce, and endive chicory are usually richer in calcium, magnesium, iron, and vitamins than the inner leaves. Stalk vegetables like tronchuda cabbage, pak-choi, celery, and asparagus are rich

In the fruit and belowground organ vegetables, the skin and inside color reflect different bioactive compounds/pigment present. Anthocyanins (flavonoid) give vegetable leaves, belowground organs, and fruits their purple and purple-red color appearance, such as in red anthocyanin lettuce and endive chicory, red cabbage,

**88**

in dietary fiber.

Swiss chard, rhubarb, etc. (leafy and stalk vegetables); garden beet, purple carrot, red onion, purple- and purple-red-skinned potato, purple sweet potato, etc. (below ground vegetables); and purple eggplant, purple tomato, purple pepper, purple and black broccoli, purple corn, etc. (fruit and flowering vegetables). The most abundant carotenoids in vegetables are α-carotene, β-carotene, and lycopene (carotenes) and lutein, zeaxanthin, and β-cryptoxanthin (xanthophylls) [2, 74, 89]. The most common carotenes are β-carotene and lycopene. β-Carotene (as well as α-carotene) can be found in orange and yellow skin fruits, belowground organs, and leafy vegetables [2, 74]. As a rule of thumb, the greater the intensity of the orange color, the more β-carotene the vegetable contains [2, 74]. Lycopene can be found in red fruits (e.g., tomato), red belowground organs (e.g., red carrot), and red leafy vegetables. Lutein is the most abundant xanthophyll [2, 74]. Xanthophylls are responsible for the yellow color of vegetables.

#### **2.3 ANDI and nutritional quality of vegetables**

Aggregate Nutrient Density Index (ANDI) is a scoring system based on nutrient content, rated on a 1–1000 scale that was established by Fuhrman [90]. This index are scores attributed to a variety of vegetables (and other foods) based on how many nutrients they deliver to our body in each calorie consumed. It was calculated by evaluating the content of dietary fiber, vitamins, minerals, phytochemicals, antioxidant capacities, etc. It is an index that estimates the nutritional quality of vegetables. **Table 1** presents the highest ANDI scores in leafy vegetables.

Three main vegetable families are shown in this table: Brassicaceae (kale, collard greens, mustard greens, turnip greens, watercress, pak-choi, Chinese cabbage, Brussels sprouts, rocket, cabbage and broccoletti), Chenopodiaceae (Swiss chard and spinach), and Asteraceae (green leaf lettuce, chicory, and romaine lettuce). The highest ANDI scores of non-leafy vegetables are presented in **Table 2**.

**Table 2** also shows other Brassicaceae like radish, turnip, kohlrabi, cauliflower, and rutabaga. Different vegetables from various families are also shown as well as differences among the peppers, where orange pepper is better than the red and red better than the green pepper.

Leafy vegetables thus have the highest ANDI scores compared to other vegetables. They are rich in dietary fiber, carotenoids, vitamin C, vitamin E, flavonoids, calcium, magnesium, etc. All the leafy vegetables are good sources of magnesium because they have chlorophyll.

The leafy vegetables with high ANDI scores are Brassicaceae. They have dietary fiber, are a rich source of glucosinolates and other bioactive nutrients, and have a


#### **Table 1.**

*List of identified leafy vegetables with the highest ANDI scores.*


#### **Table 2.**

*List of identified non-leafy vegetables with the highest ANDI scores.*

very high content in calcium and β-carotene. They are excellent sources of lutein and can also accumulate selenium.

Another important family is Chenopodiaceae. A recent research has shown that Swiss chard leaves contain at least distinct polyphenol antioxidants [91] comprising the flavonoids kaempferol and syringic acid [91–93]. Swiss chard and garden beet leaves have a unique source of the bioactive antioxidants named betalains [2, 74]. Nine betacyanin pigments were identified in the reddish-purple stems and veins of the leaves of Swiss chard and beet [94]. In the Swiss chard's yellowish stems and veins, 19 betaxanthin pigments were identified, including histamine-betaxanthin, alaninebetaxanthin, tyramine-betaxanthin, and 3-methoxytyramine-betaxanthin [94].

In Asteraceae, lettuces and chicories are the main vegetables used in raw salads. Leaf and romaine lettuces have higher ANDI scores (585 and 510, respectively) than iceberg lettuce. Besides, the nutritive value of leaf and romaine lettuce is higher than head lettuces (butter and batavia types). They have more dietary fiber, minerals, vitamins, and phytochemicals. Raw vegetables are the healthiest food we can eat since some phytochemicals are only available if we eat the vegetables raw [95].

In the non-leafy vegetables, we have after radish and turnip (both Brassicaceae) the carrots. They are high in fiber and nutrient rich. Carrots have different colors. Orange carrots have α- and β-carotene (vitamin A-rich carotenoids), and purple carrots are rich in anthocyanins (flavonoids) and low in carotenoids [96, 97]. Winter squash "Acorn" has a high β-carotene content. Kohlrabi, cauliflower, and rutabaga are also Brassicaceae, and so they are good sources of vitamins, minerals, and healthy glucosinolates. Kohlrabi (stem) and rutabaga (roots) besides having high vitamin C and antioxidant content due to glucosinolates are good alternative to potatoes since they are not starchy as potato and can be eaten raw and when sliced they do not produce discoloration. The nutritional value of the outer leaves of cauliflower is much higher than the flower buds. Artichoke is rich in fiber and a good source of minerals, namely, calcium, potassium, and phosphorus. It contains also many bioactive compounds such as glycosides and phenolics, mainly caffeicinic acid [98]. Asparagus besides rich in fiber is a very rich source of folic acid.

#### **3. Effect on disease prevention of vegetables**

#### **3.1 Effect on cancers**

The International Agency for Research on Cancer (IARC) estimates that the percentage of cancers due to unbalanced diets with low vegetable intake and low consumption of complex carbohydrates and dietary fiber ranges from 5 to 12% for all cancers and 20–30% for upper gastrointestinal tract cancers [2, 3]. The World Health Organization (WHO) states that about 14% of worldwide deaths are

**91**

*Nutritional Quality and Effect on Disease Prevention of Vegetables*

attributable to gastrointestinal cancers due to inadequate vegetable and fruit consumption [99]. The American Cancer Society observed that more than two-thirds of cancer deaths in the United States are avoidable and reported that one-third of cancer deaths can be prevented by a proper diet rich in vegetables [100, 101]. Numerous epidemiological studies conducted in the United States and in developed countries, which include results from tests on adenomatous polyps (the precursors to colorectal cancer), concluded that high vegetable intake decreases the risk of colorectal cancer [26, 102–106]. Witte et al. [107] observed significantly lower incidence of colorectal polyps in men and women ages between 50 and 74 years old who consumed higher rates of vegetables, namely, crucifers, garlic, and tofu. It is also interesting also that this research concluded that vegetables have more beneficial effects against colorectal polyps than fruits or fiber from grains. In another research with 41,837 women aged between 55 and 69 years old, Steinmetz et al. [106] found a 20–40% reduction in risk of colon cancer in populations with higher vegetable consumption. Other studies have also estimated lower risk of colon cancer, ranging from three- to eightfold due to high vegetable and fruit intake [26, 108–110]. Increasing the consumption of vegetables reduces the risk of cancer since the antioxidants in

vegetables prevent the oxidative damage of the cells in the body [111, 112]

Leafy vegetables have protective effects against cancers, especially gastrointestinal carcinomas, mainly due to dietary fiber, but also to phytochemicals, vitamins (C, E, K, and A), and minerals they contain [113]. Tewani et al. [114] state that spinach shows protective effects against gastrointestinal cancer by reducing oxidative stress thanks to vitamins (C and E), carotenes (mainly β-carotene), lutein, and

Cruciferous vegetables rich in glucosinolates have been shown to protect against lung cancer, prostate cancer, breast cancer, and chemically induced cancers [115–119]. The evidence concerning the anticarcinogenic effect of glucosinolates of cruciferous vegetables were from in vivo studies, mainly with broccoli, using

breakdown products have been shown to stimulate mixed-function oxidases involved in detoxification of carcinogens, reducing the risk of certain cancers [28, 125, 126]. Not all glucosinolate breakdown products have anticancer activity [127]. The glucosinolates glucoraphanin, glucoiberin, glucobrassicin, and gluconasturtiin are involved in the anticarcinogenic activity, and glucoraphanin is known to bolster the defenses of cells against carcinogens through an upregulation of

Intact glucosinolates have no biological activity against cancer. However, their

Epidemiological data show that a diet rich in cruciferous vegetables can reduce the risk from several cancers by an intake of at least 10 g per day [115, 116, 118]. Epidemiological studies have suggested that diets rich in broccoli may reduce the risk of prostate cancer, and consumption of one or more portions of broccoli per week can reduce the incidence and the progression from localized to aggressive forms of prostate cancer [118, 119]. There is also strong evidence that isothiocyanates (an important group of breakdown products of glucosinolates) from cruciferous vegetables prevent bladder cancer, namely, transitional cell carcinoma of the

Consumption of *Allium* vegetables has been also found to retard growth of several types of cancers. A number of epidemiological studies show inverse correlations between the consumption of *Allium* vegetables, mainly onions and garlics,

There is a strong link between the consumption of onions and the reduced incidence of stomach and intestine cancers [129, 130]. Control studies reveal that consumption of one to seven portions of onions per week reduces the risks of

*DOI: http://dx.doi.org/10.5772/intechopen.85038*

flavonoids (mainly flavones) it contains.

enzymes of carcinogen defense.

urinary bladder [128].

and the reduced incidence of cancers.

animal models and human volunteers [116, 118–124].

#### *Nutritional Quality and Effect on Disease Prevention of Vegetables DOI: http://dx.doi.org/10.5772/intechopen.85038*

*Nutrition in Health and Disease - Our Challenges Now and Forthcoming Time*

very high content in calcium and β-carotene. They are excellent sources of lutein

Another important family is Chenopodiaceae. A recent research has shown that Swiss chard leaves contain at least distinct polyphenol antioxidants [91] comprising the flavonoids kaempferol and syringic acid [91–93]. Swiss chard and garden beet leaves have a unique source of the bioactive antioxidants named betalains [2, 74]. Nine betacyanin pigments were identified in the reddish-purple stems and veins of the leaves of Swiss chard and beet [94]. In the Swiss chard's yellowish stems and veins, 19 betaxanthin pigments were identified, including histamine-betaxanthin, alaninebetaxanthin, tyramine-betaxanthin, and 3-methoxytyramine-betaxanthin [94].

**Vegetable ANDI Vegetable ANDI** 1.Radish 502 7.Cauliflower 315 2.Turnip 473 8.Rutabaga 296 3.Carrots 458 9.Bell pepper (red) 265 4.Winter squash "Acorn" 444 10.Bell pepper (green) 258 5.Bell pepper (yellow/orange) 371 11.Artichoke 244 6.Kohlrabi 352 12.Asparagus 234

In Asteraceae, lettuces and chicories are the main vegetables used in raw salads. Leaf and romaine lettuces have higher ANDI scores (585 and 510, respectively) than iceberg lettuce. Besides, the nutritive value of leaf and romaine lettuce is higher than head lettuces (butter and batavia types). They have more dietary fiber, minerals, vitamins, and phytochemicals. Raw vegetables are the healthiest food we can eat since some phytochemicals are only available if we eat the vegetables raw [95].

In the non-leafy vegetables, we have after radish and turnip (both Brassicaceae) the carrots. They are high in fiber and nutrient rich. Carrots have different colors. Orange carrots have α- and β-carotene (vitamin A-rich carotenoids), and purple carrots are rich in anthocyanins (flavonoids) and low in carotenoids [96, 97]. Winter squash "Acorn" has a high β-carotene content. Kohlrabi, cauliflower, and rutabaga are also Brassicaceae, and so they are good sources of vitamins, minerals, and healthy glucosinolates. Kohlrabi (stem) and rutabaga (roots) besides having high vitamin C and antioxidant content due to glucosinolates are good alternative to potatoes since they are not starchy as potato and can be eaten raw and when sliced they do not produce discoloration. The nutritional value of the outer leaves of cauliflower is much higher than the flower buds. Artichoke is rich in fiber and a good source of minerals, namely, calcium, potassium, and phosphorus. It contains also many bioactive compounds such as glycosides and phenolics, mainly caffeicinic

acid [98]. Asparagus besides rich in fiber is a very rich source of folic acid.

The International Agency for Research on Cancer (IARC) estimates that the percentage of cancers due to unbalanced diets with low vegetable intake and low consumption of complex carbohydrates and dietary fiber ranges from 5 to 12% for all cancers and 20–30% for upper gastrointestinal tract cancers [2, 3]. The World Health Organization (WHO) states that about 14% of worldwide deaths are

**3. Effect on disease prevention of vegetables**

and can also accumulate selenium.

*List of identified non-leafy vegetables with the highest ANDI scores.*

**Table 2.**

**90**

**3.1 Effect on cancers**

attributable to gastrointestinal cancers due to inadequate vegetable and fruit consumption [99]. The American Cancer Society observed that more than two-thirds of cancer deaths in the United States are avoidable and reported that one-third of cancer deaths can be prevented by a proper diet rich in vegetables [100, 101].

Numerous epidemiological studies conducted in the United States and in developed countries, which include results from tests on adenomatous polyps (the precursors to colorectal cancer), concluded that high vegetable intake decreases the risk of colorectal cancer [26, 102–106]. Witte et al. [107] observed significantly lower incidence of colorectal polyps in men and women ages between 50 and 74 years old who consumed higher rates of vegetables, namely, crucifers, garlic, and tofu. It is also interesting also that this research concluded that vegetables have more beneficial effects against colorectal polyps than fruits or fiber from grains. In another research with 41,837 women aged between 55 and 69 years old, Steinmetz et al. [106] found a 20–40% reduction in risk of colon cancer in populations with higher vegetable consumption. Other studies have also estimated lower risk of colon cancer, ranging from three- to eightfold due to high vegetable and fruit intake [26, 108–110]. Increasing the consumption of vegetables reduces the risk of cancer since the antioxidants in vegetables prevent the oxidative damage of the cells in the body [111, 112]

Leafy vegetables have protective effects against cancers, especially gastrointestinal carcinomas, mainly due to dietary fiber, but also to phytochemicals, vitamins (C, E, K, and A), and minerals they contain [113]. Tewani et al. [114] state that spinach shows protective effects against gastrointestinal cancer by reducing oxidative stress thanks to vitamins (C and E), carotenes (mainly β-carotene), lutein, and flavonoids (mainly flavones) it contains.

Cruciferous vegetables rich in glucosinolates have been shown to protect against lung cancer, prostate cancer, breast cancer, and chemically induced cancers [115–119]. The evidence concerning the anticarcinogenic effect of glucosinolates of cruciferous vegetables were from in vivo studies, mainly with broccoli, using animal models and human volunteers [116, 118–124].

Intact glucosinolates have no biological activity against cancer. However, their breakdown products have been shown to stimulate mixed-function oxidases involved in detoxification of carcinogens, reducing the risk of certain cancers [28, 125, 126]. Not all glucosinolate breakdown products have anticancer activity [127]. The glucosinolates glucoraphanin, glucoiberin, glucobrassicin, and gluconasturtiin are involved in the anticarcinogenic activity, and glucoraphanin is known to bolster the defenses of cells against carcinogens through an upregulation of enzymes of carcinogen defense.

Epidemiological data show that a diet rich in cruciferous vegetables can reduce the risk from several cancers by an intake of at least 10 g per day [115, 116, 118]. Epidemiological studies have suggested that diets rich in broccoli may reduce the risk of prostate cancer, and consumption of one or more portions of broccoli per week can reduce the incidence and the progression from localized to aggressive forms of prostate cancer [118, 119]. There is also strong evidence that isothiocyanates (an important group of breakdown products of glucosinolates) from cruciferous vegetables prevent bladder cancer, namely, transitional cell carcinoma of the urinary bladder [128].

Consumption of *Allium* vegetables has been also found to retard growth of several types of cancers. A number of epidemiological studies show inverse correlations between the consumption of *Allium* vegetables, mainly onions and garlics, and the reduced incidence of cancers.

There is a strong link between the consumption of onions and the reduced incidence of stomach and intestine cancers [129, 130]. Control studies reveal that consumption of one to seven portions of onions per week reduces the risks of

colon, ovary, larynx, and mouth cancers [131]. Mortality due to prostate cancer also appears to be reduced by a diet making a large consumption of onions [132]. Onion extracts prevent tumors by inhibiting the mutation process [133] and reducing the proliferation of cancer cells [134].

Epidemiological researches show the correlation between moderate garlic intake and a low esophageal and stomach tract cancer incidence [131, 135, 136]. Garlic extracts prevent tumor initiation by inhibiting the activation of pro-carcinogens and by stimulating their elimination [137, 138]. A regular consumption of garlic has been associated also with the reduction in the incidence of preneoplastic lesions occurring in the gastric mucosa of individuals infected by *Helicobacter pylori* [139]. Other studies analyzing the preventive effect of garlic have evidenced their suppressive potential on the development and progression of colorectal adenomas [110, 140]. A reduced cancer risk by regular consumption of garlic has been widely documented also for colorectal and prostate cancers [131, 136, 141, 142]. The impact of a diet rich in *Allium* vegetables in antiprostate cancer is higher in men presenting localized rather than advanced forms [142].

The impact of a regular intake of *Allium* vegetables on the incidence of cancers affecting the breast, endometrium, and lungs has been studied in a limited number of investigations [143–145]. The risk of breast cancer was shown to decrease as consumption of *Allium* increased [143]. Onion extracts have apoptosis-inducing effects in epithelial MDA-MB-231 cells that cause breast cancer [146].

In tomato several investigations have shown an inverse relationship between plasma/serum lycopene concentrations and the risk of some cancers [147–153]. Reports on 13 cancer types were identified in literature, of which breast, colorectal, gastric-gastrointestinal, and prostate cancers. For breast, colorectal, and gastric cancers, the existing data support a potential protective association between tomato and lycopene intake and cancer risk. People consuming diets rich in tomato/lycopene and tomato-based products were found to be less likely to develop stomach and rectal cancers than those who consume lesser amounts [154]. Among the cancers investigated, prostate cancer is the most widely researched. Tomato and lycopene intake is preventive against prostate cancer [13, 155]. Hadley et al. [156] in an epidemiological study found that consuming tomato and tomato products was associated with a lower incidence of prostate cancer [156]. A prostate cancer risk reduction of nearly 35% was observed when the test subjects consumed 10 or more servings of tomato per week [157]; and the effect was much stronger for patients with more aggressive and advanced stages of cancer [157].

Other Solanaceae associated with cancer prevention are chili peppers and eggplant. Chili peppers are tough to prevent cancer cells from growing, developing, and spreading due to it capsaicin content [158]. A study of Nagase et al. [159] showed that eggplant extract inhibited human fibrosarcoma HT-180 cell invasiveness.

Consumption of legumes like soybean, chickpea, and lentil rich in isoflavonoids daidzein, genistein and glycitein have been suggested to have multiple beneficial effects in a number of diseases, including certain types of cancer [160, 161]. Ziegler et al. [162] observed that Asian-American women who consumed a diet rich in soy had low risk of breast cancer incidence. Later studies of soy-rich diets confirmed that the main anti-breast cancer ingredient is genistein [163–165]. Dong et al. [166] in a meta-analysis of prospective studies pointed out that soybean isoflavonoid intake is associated with a significantly reduced risk of breast cancer incidence in Asian populations, but not in Western populations. Epidemiological indications jointly with clinical data from animal and in vitro studies highly supported a positive correlation between soybean isoflavonoid consumption and protection toward prostate cancers [164, 167]. Besides breast and prostate cancer, soy isoflavonoids also exhibit inhibitory effects on ovarian cancer, leukemia, and lung cancer [168].

**93**

*Nutritional Quality and Effect on Disease Prevention of Vegetables*

Anticarcinogenic effect of carrot juice extracts on myeloid and lymphoid leukemia cell lines was investigated by Zaini et al. [169]. Carrot juice extracts owned the ability to "kill" leukemia cells and inhibit their progression. Those researchers believed that β-carotene and falcarinol present in the carrot juice extract may have been responsible for this positive effect. As a complement of this study, Larsen et al. [170] examined the impact of carrot and falcarinol feeding toward the development of azoxymethane-induced colon preneoplastic lesions in the rat colon. The results of this study demonstrated that diets with carrot and falcarinol have the potential to delay the development of large aberrant crypt foci and colon tumors on rats. Purup et al. [171] observed also that carrot extracts which contain falcarinol and related aliphatic C17-polyacetylenes (falcarindiol and falcarindiol 3-acetate) had significant inhibitory effect on intestinal cancer cell proliferation. Pisani et al. [172] in a case–control study show that smokers who eat carrots more than once a week have a

Vegetables offer protection against cardiovascular diseases since they are free of saturated fat, trans fat, and cholesterol and rich in bioactive compounds such as dietary fibers, OSCs, flavonoids, carotenoids, phytoestrogens, monoterpenes, and sterols. Unbalanced diets with low vegetable intake have been estimated to cause about 31% of ischemic heart disease and 11% of stroke worldwide [3]. A healthy diet with high vegetable consumption has been associated with lower risk of cardiovascular disease in humans [173, 174]. Liu et al. [175] test the influence of vegetable intake on the incidence of cardiovascular disease among 15,220 male physicians without a history of heart disease or stroke. The results of this investigation show that the participators who consumed more than two servings of vegetables per day had 25% less cardiovascular disease than those who consumed less than one serving. Based on this and other researches, the American Heart Association (AHA) has concluded that a diet high in vegetables and fruits may reduce the risk of cardiovascular disease in humans [176]. Prevention of cardiovascular diseases has been attributed to regular garlic consumption. Epidemiological studies demonstrate that there is an inverse correlation between garlic consumption and incidence of cardiovascular diseases [3, 74]. Yeh and Liu [177] show that garlic extracts and their OSCs have cholesterol and lipid-lowering effects by inhibiting monooxygenase and HMG-CoA reductase, two key enzymes involved in cholesterol and fatty acid synthesis. Moriguchi et al. [178] reported that garlic extracts have fibrinolytic effect by inhibiting lipid peroxidation and hemolysis of erythrocytes. Chang et al. [179] in their studies reported also the antiplatelet effect of sodium 2-propenyl thiosulfate from garlic, by inhibiting

Similar to garlic, onions also contain a number of OSCs and flavonoids, such as quercetin, that can reduce the risks for cardiovascular diseases by increasing antioxidant capacity [3, 74, 180]. Hubbard et al. [181] in a pilot study in humans showed that the consumption of the equivalent of three onions in a soup was sufficient to significantly reduce the blood platelet aggregation. Platelet aggregation is an important risk for the development of coronary thrombosis and atherosclerosis. Briggs et al. [182] observed that by cutting raw onions S-alkenyl-L-cysteine sulfoxides are converted by enzyme alliinase into thiosulfinates and copaenes and these compounds inhibit platelet aggregation. Ried et al. [183] report also that onion and garlic had a blood pressure lowering effect by inhibiting angiotensin-converting enzyme activity and inducing intracellular nitric oxide and hydrogen sulfide production. The consumption of leafy vegetables, due to bioactive compounds, increases antioxidant capacity and protects against oxidative stress which play an important

*DOI: http://dx.doi.org/10.5772/intechopen.85038*

smaller risk of lung cancer.

**3.2 Effect on cardiovascular diseases**

cyclooxygenase enzyme activity.

*Nutritional Quality and Effect on Disease Prevention of Vegetables DOI: http://dx.doi.org/10.5772/intechopen.85038*

*Nutrition in Health and Disease - Our Challenges Now and Forthcoming Time*

proliferation of cancer cells [134].

localized rather than advanced forms [142].

colon, ovary, larynx, and mouth cancers [131]. Mortality due to prostate cancer also appears to be reduced by a diet making a large consumption of onions [132]. Onion extracts prevent tumors by inhibiting the mutation process [133] and reducing the

Epidemiological researches show the correlation between moderate garlic intake

The impact of a regular intake of *Allium* vegetables on the incidence of cancers affecting the breast, endometrium, and lungs has been studied in a limited number of investigations [143–145]. The risk of breast cancer was shown to decrease as consumption of *Allium* increased [143]. Onion extracts have apoptosis-inducing

In tomato several investigations have shown an inverse relationship between plasma/serum lycopene concentrations and the risk of some cancers [147–153]. Reports on 13 cancer types were identified in literature, of which breast, colorectal, gastric-gastrointestinal, and prostate cancers. For breast, colorectal, and gastric cancers, the existing data support a potential protective association between tomato and lycopene intake and cancer risk. People consuming diets rich in tomato/lycopene and tomato-based products were found to be less likely to develop stomach and rectal cancers than those who consume lesser amounts [154]. Among the cancers investigated, prostate cancer is the most widely researched. Tomato and lycopene intake is preventive against prostate cancer [13, 155]. Hadley et al. [156] in an epidemiological study found that consuming tomato and tomato products was associated with a lower incidence of prostate cancer [156]. A prostate cancer risk reduction of nearly 35% was observed when the test subjects consumed 10 or more servings of tomato per week [157]; and the effect was much stronger

effects in epithelial MDA-MB-231 cells that cause breast cancer [146].

for patients with more aggressive and advanced stages of cancer [157].

Other Solanaceae associated with cancer prevention are chili peppers and eggplant. Chili peppers are tough to prevent cancer cells from growing, developing, and spreading due to it capsaicin content [158]. A study of Nagase et al. [159] showed that eggplant extract inhibited human fibrosarcoma HT-180 cell invasiveness.

Consumption of legumes like soybean, chickpea, and lentil rich in isoflavonoids daidzein, genistein and glycitein have been suggested to have multiple beneficial effects in a number of diseases, including certain types of cancer [160, 161]. Ziegler et al. [162] observed that Asian-American women who consumed a diet rich in soy had low risk of breast cancer incidence. Later studies of soy-rich diets confirmed that the main anti-breast cancer ingredient is genistein [163–165]. Dong et al. [166] in a meta-analysis of prospective studies pointed out that soybean isoflavonoid intake is associated with a significantly reduced risk of breast cancer incidence in Asian populations, but not in Western populations. Epidemiological indications jointly with clinical data from animal and in vitro studies highly supported a positive correlation between soybean isoflavonoid consumption and protection toward prostate cancers [164, 167]. Besides breast and prostate cancer, soy isoflavonoids also exhibit inhibitory effects on ovarian cancer, leukemia, and lung cancer [168].

and a low esophageal and stomach tract cancer incidence [131, 135, 136]. Garlic extracts prevent tumor initiation by inhibiting the activation of pro-carcinogens and by stimulating their elimination [137, 138]. A regular consumption of garlic has been associated also with the reduction in the incidence of preneoplastic lesions occurring in the gastric mucosa of individuals infected by *Helicobacter pylori* [139]. Other studies analyzing the preventive effect of garlic have evidenced their suppressive potential on the development and progression of colorectal adenomas [110, 140]. A reduced cancer risk by regular consumption of garlic has been widely documented also for colorectal and prostate cancers [131, 136, 141, 142]. The impact of a diet rich in *Allium* vegetables in antiprostate cancer is higher in men presenting

**92**

Anticarcinogenic effect of carrot juice extracts on myeloid and lymphoid leukemia cell lines was investigated by Zaini et al. [169]. Carrot juice extracts owned the ability to "kill" leukemia cells and inhibit their progression. Those researchers believed that β-carotene and falcarinol present in the carrot juice extract may have been responsible for this positive effect. As a complement of this study, Larsen et al. [170] examined the impact of carrot and falcarinol feeding toward the development of azoxymethane-induced colon preneoplastic lesions in the rat colon. The results of this study demonstrated that diets with carrot and falcarinol have the potential to delay the development of large aberrant crypt foci and colon tumors on rats. Purup et al. [171] observed also that carrot extracts which contain falcarinol and related aliphatic C17-polyacetylenes (falcarindiol and falcarindiol 3-acetate) had significant inhibitory effect on intestinal cancer cell proliferation. Pisani et al. [172] in a case–control study show that smokers who eat carrots more than once a week have a smaller risk of lung cancer.

#### **3.2 Effect on cardiovascular diseases**

Vegetables offer protection against cardiovascular diseases since they are free of saturated fat, trans fat, and cholesterol and rich in bioactive compounds such as dietary fibers, OSCs, flavonoids, carotenoids, phytoestrogens, monoterpenes, and sterols. Unbalanced diets with low vegetable intake have been estimated to cause about 31% of ischemic heart disease and 11% of stroke worldwide [3]. A healthy diet with high vegetable consumption has been associated with lower risk of cardiovascular disease in humans [173, 174]. Liu et al. [175] test the influence of vegetable intake on the incidence of cardiovascular disease among 15,220 male physicians without a history of heart disease or stroke. The results of this investigation show that the participators who consumed more than two servings of vegetables per day had 25% less cardiovascular disease than those who consumed less than one serving. Based on this and other researches, the American Heart Association (AHA) has concluded that a diet high in vegetables and fruits may reduce the risk of cardiovascular disease in humans [176].

Prevention of cardiovascular diseases has been attributed to regular garlic consumption. Epidemiological studies demonstrate that there is an inverse correlation between garlic consumption and incidence of cardiovascular diseases [3, 74]. Yeh and Liu [177] show that garlic extracts and their OSCs have cholesterol and lipid-lowering effects by inhibiting monooxygenase and HMG-CoA reductase, two key enzymes involved in cholesterol and fatty acid synthesis. Moriguchi et al. [178] reported that garlic extracts have fibrinolytic effect by inhibiting lipid peroxidation and hemolysis of erythrocytes. Chang et al. [179] in their studies reported also the antiplatelet effect of sodium 2-propenyl thiosulfate from garlic, by inhibiting cyclooxygenase enzyme activity.

Similar to garlic, onions also contain a number of OSCs and flavonoids, such as quercetin, that can reduce the risks for cardiovascular diseases by increasing antioxidant capacity [3, 74, 180]. Hubbard et al. [181] in a pilot study in humans showed that the consumption of the equivalent of three onions in a soup was sufficient to significantly reduce the blood platelet aggregation. Platelet aggregation is an important risk for the development of coronary thrombosis and atherosclerosis. Briggs et al. [182] observed that by cutting raw onions S-alkenyl-L-cysteine sulfoxides are converted by enzyme alliinase into thiosulfinates and copaenes and these compounds inhibit platelet aggregation. Ried et al. [183] report also that onion and garlic had a blood pressure lowering effect by inhibiting angiotensin-converting enzyme activity and inducing intracellular nitric oxide and hydrogen sulfide production.

The consumption of leafy vegetables, due to bioactive compounds, increases antioxidant capacity and protects against oxidative stress which play an important role in the pathogenesis of cardiovascular diseases. Another reason is their low sodium and high calcium and magnesium content [3, 74]. Furthermore, that consumption also reduces blood pressure, inhibits platelet aggregation, and improves endothelial dysfunction due to their rich inorganic nitrate content [184]. In diets where the consumption of leafy vegetables is high, the rate of cardiovascular diseases is lower compared with diets with less consumption [3, 74, 185]. Rastogi et al. [186] observed that individuals with consumption of more than three portions of leafy vegetables a day have an incidence of about 60% less of ischemic heart disease than those consuming less than one portion. Saluk et al. [187] report that anthocyanin extracted from red cabbage has a protective effect on blood platelets.

In broccoli, indole-3-carbinol and sulforaphane, which are hydrolysis breakdown products of glucosinolate glucoraphanin, are thought to be the major bioactive compounds protective against cardiovascular diseases [188, 189]. Jeffery and Araya [189] report that indole-3-carbinol and sulforaphane besides protecting against ischemic damage of the heart also protect against inflammation by inhibiting cytokine production [189]. Murashima et al. [190] reported in a study, with multiple biomarkers for metabolism and oxidative stress, that broccoli sprouts decrease levels of total cholesterol and low-density lipoprotein cholesterol and increase levels of high-density lipoprotein cholesterol.

Jorge et al. [191] show in their studies that eggplant is effective in the treatment of high blood cholesterol. Guimarães et al. [192] showed a significant decrease in blood levels of total cholesterol and low-density lipoprotein cholesterol in human volunteers who were fed with eggplant powder. Kwon et al. [193] presented eggplant phenolics as inhibitors of key enzymes relevant for type 2 diabetes and hypertension.

Legumes are also protective against cardiovascular diseases due to their high saponin and soluble fiber content [2, 3, 74]. Soluble fiber delays gastric emptying, slows glucose absorption, and lowers serum cholesterol levels [194]. In several epidemiologic studies, a positive correlation between increased legume consumption and reduced mortality due to cardiovascular disease was observed [195, 196]. Consumption of legumes reduces the levels of total cholesterol and low-density lipoprotein cholesterol by inhibiting the absorption of bile acid from intestines and by promoting the formation of propionic acid and other short-chain fatty acids that inhibit the synthesis of cholesterol [197].

Nicolle et al. [198] suggest that carrot intake may exert a protective effect against cardiovascular disease and that this protective effect may be due to the synergistic action of dietary fiber and antioxidant polyphenols in carrot. Gramenzi et al. [199] state that the consumption of carrots is associated with smaller risk of acute myocardial infarction in women. Gilani et al. [200] examined in rats the antihypertensive effect of DC-2 and DC-3, two coumarin glycosides from carrot. Their results showed that these glycoside compounds caused a decrease in arterial blood pressure in the rats. Further in vitro studies by the same researchers demonstrate that the decreased blood pressure observed may be due to the calcium channel blocking action of coumarin glycosides DC-2 and DC-3 from carrots.

#### **3.3 Effect on diabetes**

Dias and Imai [95] highlight the nutritional and health benefits of different vegetables and their dietary fiber, vitamin C, vitamin E, carotenoids, flavonoids, thiosulfates, magnesium, selenium, zinc, and chromium contents, to prevent and reverse diabetes. Besides they also analyzed when we should eat the vegetables, and mainly the effect of eating vegetables before carbohydrates on postprandial blood glucose levels, and glycemic control. Data of these authors shows that eating

**95**

glucose [208].

the daily requirements.

*Nutritional Quality and Effect on Disease Prevention of Vegetables*

vegetables before carbohydrates is effective to reduce postprandial hyperglycemia in type 2 diabetes patients, as well as in healthy people. So, vegetables should be eaten

Carter et al. [201] in a systematic review and meta-analysis found that greater leafy vegetable consumption was colligated with 14% decrease in risk of type 2 diabetes. Another previous research reported that each daily serving of leafy green vegetables generates a 9% decrease in risk of type 2 diabetes [202]. Khan et al. [203] saw that oral feeding of regular rats for 60 days with a mustard (Brassica juncea) diet (10% w/w) led to significant hypoglycemic effect. This result was associated to the positive stimulation of glycogen synthetase and to the suppression of glycogen phosphorylase and some other gluconeogenic enzymes. As mentioned Swiss chard leaves contain syringic acid that have blood sugar-regulating properties [91–93]. Syringic acid was demonstrated to inhibit the activity of α-glucosidase enzyme. When α-glucosidase gets inhibited, fewer carbohydrates are converted to sugars, and blood sugar is able to remain more steady [204]. Garden beet leaves have the same properties, since beet and Swiss chard are both from the Chenopodiaceae family [3, 74]. Yoshikawa et al. [205] in an oral glucose tolerance test (OGTT) conducted in rats, that measures the body's ability to metabolize glucose [206], observed that several glycosides isolated from the root extract of beet increase glucose tolerance. Gu et al. [207] report that purslane had hypoglycemic effects in a study comparing the hypoglycemic and antioxidant activities of the fresh and dried purslane in insulin-resistant HepG2 cells and streptozotocin-induced diabetic mice. In another study in adult patients with type 2 diabetes, it was found that consumption of purslane extract significantly reduced HbA1c levels and postprandial blood

Alliaceae vegetables are necessary ingredients of a diabetes prevention diet. Garlic lowers blood sugar levels in diabetic patients [209], and administration of S-methyl cysteine sulfoxide isolated from onion restrained blood glucose and showed significant hypoglycemic effect in rats [2, 74]. El-Demerdash et al. [210] in a biochemical study on the hypoglycemic effects of onion and garlic in alloxaninduced diabetic rats report that these vegetables had a hypoglycemic effect. Other investigations evaluating the hypoglycemic, antioxidant, and hepatoprotective potentials of onion show that onion consumption increased the levels of enzymes superoxide dismutase, catalase, and glutathione peroxidase [211] and reduce insulin resistance [212]. Onions and other Alliaceae also contain chromium that is linked to diabetes prevention by enhancing insulin receptor kinases [213]. Clinical surveys on diabetic patients showed that chromium can decrease fasting glucose, ameliorate glucose tolerance, and bring down insulin levels. Swamy et al. [209] observed that 200 g of some cultivars of onions contain chromium up to 20% of

Nutritionists and dieticians commonly recommend diabetic eating carrots in moderation because they say that carrots contain more sugar than other vegetables. Although carrots are not a negative vegetable for the diabetic since they have fiberrich fractions that transports a significant amount of polyphenols and carotenoids linked to the fiber matrix, they are relatively low in calories and the glycemic load is only 3 [97]. Glycemic effect of carrots when eaten raw is lessened further as the body does not absorb all of the calories in raw aliments [3, 74]. Chau et al. [214] comparing the characteristics, functional properties, and in vitro hypoglycemic effects of various carrot-insoluble fiber-rich fractions confirmed the great relationship between dietary fiber intake and lower risk of type 2 diabetes since those authors concluded, from their study, that the enhanced glucose absorbance capacity and reduction of amylase activity of dietary fiber of carrot help control postprandial serum glucose level. The recent research advocates that orange carrot with

*DOI: http://dx.doi.org/10.5772/intechopen.85038*

before carbohydrates at every meal [95].

#### *Nutritional Quality and Effect on Disease Prevention of Vegetables DOI: http://dx.doi.org/10.5772/intechopen.85038*

*Nutrition in Health and Disease - Our Challenges Now and Forthcoming Time*

role in the pathogenesis of cardiovascular diseases. Another reason is their low sodium and high calcium and magnesium content [3, 74]. Furthermore, that consumption also reduces blood pressure, inhibits platelet aggregation, and improves endothelial dysfunction due to their rich inorganic nitrate content [184]. In diets where the consumption of leafy vegetables is high, the rate of cardiovascular diseases is lower compared with diets with less consumption [3, 74, 185]. Rastogi et al. [186] observed that individuals with consumption of more than three portions of leafy vegetables a day have an incidence of about 60% less of ischemic heart disease than those consuming less than one portion. Saluk et al. [187] report that anthocy-

anin extracted from red cabbage has a protective effect on blood platelets.

increase levels of high-density lipoprotein cholesterol.

inhibit the synthesis of cholesterol [197].

action of coumarin glycosides DC-2 and DC-3 from carrots.

In broccoli, indole-3-carbinol and sulforaphane, which are hydrolysis breakdown products of glucosinolate glucoraphanin, are thought to be the major bioactive compounds protective against cardiovascular diseases [188, 189]. Jeffery and Araya [189] report that indole-3-carbinol and sulforaphane besides protecting against ischemic damage of the heart also protect against inflammation by inhibiting cytokine production [189]. Murashima et al. [190] reported in a study, with multiple biomarkers for metabolism and oxidative stress, that broccoli sprouts decrease levels of total cholesterol and low-density lipoprotein cholesterol and

Jorge et al. [191] show in their studies that eggplant is effective in the treatment of high blood cholesterol. Guimarães et al. [192] showed a significant decrease in blood levels of total cholesterol and low-density lipoprotein cholesterol in human volunteers who were fed with eggplant powder. Kwon et al. [193] presented eggplant phenolics as inhibitors of key enzymes relevant for type 2 diabetes and

Legumes are also protective against cardiovascular diseases due to their high saponin and soluble fiber content [2, 3, 74]. Soluble fiber delays gastric emptying, slows glucose absorption, and lowers serum cholesterol levels [194]. In several epidemiologic studies, a positive correlation between increased legume consumption and reduced mortality due to cardiovascular disease was observed [195, 196]. Consumption of legumes reduces the levels of total cholesterol and low-density lipoprotein cholesterol by inhibiting the absorption of bile acid from intestines and by promoting the formation of propionic acid and other short-chain fatty acids that

Nicolle et al. [198] suggest that carrot intake may exert a protective effect against cardiovascular disease and that this protective effect may be due to the synergistic action of dietary fiber and antioxidant polyphenols in carrot. Gramenzi et al. [199] state that the consumption of carrots is associated with smaller risk of acute myocardial infarction in women. Gilani et al. [200] examined in rats the antihypertensive effect of DC-2 and DC-3, two coumarin glycosides from carrot. Their results showed that these glycoside compounds caused a decrease in arterial blood pressure in the rats. Further in vitro studies by the same researchers demonstrate that the decreased blood pressure observed may be due to the calcium channel blocking

Dias and Imai [95] highlight the nutritional and health benefits of different vegetables and their dietary fiber, vitamin C, vitamin E, carotenoids, flavonoids, thiosulfates, magnesium, selenium, zinc, and chromium contents, to prevent and reverse diabetes. Besides they also analyzed when we should eat the vegetables, and mainly the effect of eating vegetables before carbohydrates on postprandial blood glucose levels, and glycemic control. Data of these authors shows that eating

**94**

**3.3 Effect on diabetes**

hypertension.

vegetables before carbohydrates is effective to reduce postprandial hyperglycemia in type 2 diabetes patients, as well as in healthy people. So, vegetables should be eaten before carbohydrates at every meal [95].

Carter et al. [201] in a systematic review and meta-analysis found that greater leafy vegetable consumption was colligated with 14% decrease in risk of type 2 diabetes. Another previous research reported that each daily serving of leafy green vegetables generates a 9% decrease in risk of type 2 diabetes [202]. Khan et al. [203] saw that oral feeding of regular rats for 60 days with a mustard (Brassica juncea) diet (10% w/w) led to significant hypoglycemic effect. This result was associated to the positive stimulation of glycogen synthetase and to the suppression of glycogen phosphorylase and some other gluconeogenic enzymes. As mentioned Swiss chard leaves contain syringic acid that have blood sugar-regulating properties [91–93]. Syringic acid was demonstrated to inhibit the activity of α-glucosidase enzyme. When α-glucosidase gets inhibited, fewer carbohydrates are converted to sugars, and blood sugar is able to remain more steady [204]. Garden beet leaves have the same properties, since beet and Swiss chard are both from the Chenopodiaceae family [3, 74]. Yoshikawa et al. [205] in an oral glucose tolerance test (OGTT) conducted in rats, that measures the body's ability to metabolize glucose [206], observed that several glycosides isolated from the root extract of beet increase glucose tolerance. Gu et al. [207] report that purslane had hypoglycemic effects in a study comparing the hypoglycemic and antioxidant activities of the fresh and dried purslane in insulin-resistant HepG2 cells and streptozotocin-induced diabetic mice. In another study in adult patients with type 2 diabetes, it was found that consumption of purslane extract significantly reduced HbA1c levels and postprandial blood glucose [208].

Alliaceae vegetables are necessary ingredients of a diabetes prevention diet. Garlic lowers blood sugar levels in diabetic patients [209], and administration of S-methyl cysteine sulfoxide isolated from onion restrained blood glucose and showed significant hypoglycemic effect in rats [2, 74]. El-Demerdash et al. [210] in a biochemical study on the hypoglycemic effects of onion and garlic in alloxaninduced diabetic rats report that these vegetables had a hypoglycemic effect. Other investigations evaluating the hypoglycemic, antioxidant, and hepatoprotective potentials of onion show that onion consumption increased the levels of enzymes superoxide dismutase, catalase, and glutathione peroxidase [211] and reduce insulin resistance [212]. Onions and other Alliaceae also contain chromium that is linked to diabetes prevention by enhancing insulin receptor kinases [213]. Clinical surveys on diabetic patients showed that chromium can decrease fasting glucose, ameliorate glucose tolerance, and bring down insulin levels. Swamy et al. [209] observed that 200 g of some cultivars of onions contain chromium up to 20% of the daily requirements.

Nutritionists and dieticians commonly recommend diabetic eating carrots in moderation because they say that carrots contain more sugar than other vegetables. Although carrots are not a negative vegetable for the diabetic since they have fiberrich fractions that transports a significant amount of polyphenols and carotenoids linked to the fiber matrix, they are relatively low in calories and the glycemic load is only 3 [97]. Glycemic effect of carrots when eaten raw is lessened further as the body does not absorb all of the calories in raw aliments [3, 74]. Chau et al. [214] comparing the characteristics, functional properties, and in vitro hypoglycemic effects of various carrot-insoluble fiber-rich fractions confirmed the great relationship between dietary fiber intake and lower risk of type 2 diabetes since those authors concluded, from their study, that the enhanced glucose absorbance capacity and reduction of amylase activity of dietary fiber of carrot help control postprandial serum glucose level. The recent research advocates that orange carrot with

α- and β-carotene might help diabetics to succeed in their illness [97, 215]. Purple carrots, rich in anthocyanins and low in carotenoids, were also recently associated with reduction in impaired glucose tolerance [96].

Cucurbitaceae is a very important family for diabetics since it includes several vegetables with antidiabetic properties. Bitter gourd (Momordica charantia) has been intensively studied for its antidiabetic attributes. Different studies reported hypoglycemic and antihyperglycemic properties of bitter gourd [209, 216–218]. Clinical surveys on diabetic patients using pulp and juice extracts of bitter gourd were reported to bring down serum insulin levels, to lower fasting blood glucose levels, and to ameliorate glucose tolerance [219]. Vicine, charantin, and polypeptide-p are the principal hypoglycemic bioactive compounds from bitter gourd [220]. But there are also carotenoids (β-carotene, lutein, and zeaxanthin), triterpenoids (momordicin), alkaloids, and saponins, responsible for their side effect on glycemic control [221]. Momordicin possess insulin-like activity [222].

Besides bitter gourd other non-sweet Cucurbitaceae that have antidiabetic properties are ivy gourd (Coccinia grandis)*,* snake gourd (Trichosanthes cucumerina), and ridge gourd (Luffa acutangula). In ivy gourd, immature fruits have antihyperglycemic properties since they help regulate blood sugar levels [223]. In India, they are used to prevent or treat diabetes [223]. Bioactive compounds in the ivy gourd inhibit glucose-6-phosphatase [209], a liver enzyme involved in the regulation of sugar metabolism. Snake gourd is also considered to be useful in treating type 2 diabetes [209]. Ridge gourd contains insulin like peptides and alkaloids that help to lower fasting blood glucose levels [209, 217].

Legume consumption is also colligated with reduced risk of type 2 diabetes since they are the ideal carbohydrate source [3, 90, 224]. They are low in glycemic load due to their moderate protein and abundant dietary fiber and resistant starch (that is fermented by bacteria in the colon). This chemical composition of legumes decreases the number of calories that can be absorbed which contribute to the control of blood sugar levels.

Kwon et al. [193] presented eggplant phenolics as inhibitors of key enzymes relevant for type 2 diabetes and hypertension.

#### **4. Conclusions**

Consumption of a vegetable-rich diet has unquestionable positive effects on nutrition and health since vegetables are rich in bioactive compounds such as dietary fiber, vitamins, minerals, and phytochemicals that can protect the human body from several types of chronic and degenerative diseases. The mechanism by which vegetable bioactive compounds decrease the risk of some of these diseases is complex and sometimes unknown. In this chapter, some experimental research evidences that the bioactive compounds are responsible for mitigating some human diseases were presented. All the different bioactive compounds may contribute to the overall health benefit. Each vegetable family and each vegetable contain a unique combination of bioactive compounds. So, the health benefit of vegetables should not be linked to only one bioactive compound or one type of vegetable but rather with a balanced diet that includes more than one type of vegetable. Antioxidative, anticarcinogenic, antidiabetic, and cardiovascular disease-lowering effects of vegetables have been reported. Nutrition is both a quantity and quality issue. The availability of a large diversity of vegetables all year-round allied to increase in mean per capita incomes in recent years, and knowledge of vegetable nutritional quality and health benefits should enable consumers to include more and more a great variety of health-promoting vegetables in their diet.

**97**

**Author details**

João Silva Dias

provided the original work is properly cited.

\*Address all correspondence to: mirjsd@gmail.com

*Nutritional Quality and Effect on Disease Prevention of Vegetables*

*DOI: http://dx.doi.org/10.5772/intechopen.85038*

There is no "conflict of interest."

**Conflict of interest**

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

Instituto Superior de Agronomia, University of Lisbon, Lisbon, Portugal

*Nutritional Quality and Effect on Disease Prevention of Vegetables DOI: http://dx.doi.org/10.5772/intechopen.85038*

### **Conflict of interest**

*Nutrition in Health and Disease - Our Challenges Now and Forthcoming Time*

control [221]. Momordicin possess insulin-like activity [222].

lower fasting blood glucose levels [209, 217].

relevant for type 2 diabetes and hypertension.

control of blood sugar levels.

**4. Conclusions**

with reduction in impaired glucose tolerance [96].

α- and β-carotene might help diabetics to succeed in their illness [97, 215]. Purple carrots, rich in anthocyanins and low in carotenoids, were also recently associated

Cucurbitaceae is a very important family for diabetics since it includes several vegetables with antidiabetic properties. Bitter gourd (Momordica charantia) has been intensively studied for its antidiabetic attributes. Different studies reported hypoglycemic and antihyperglycemic properties of bitter gourd [209, 216–218]. Clinical surveys on diabetic patients using pulp and juice extracts of bitter gourd were reported to bring down serum insulin levels, to lower fasting blood glucose levels, and to ameliorate glucose tolerance [219]. Vicine, charantin, and polypeptide-p are the principal hypoglycemic bioactive compounds from bitter gourd [220]. But there are also carotenoids (β-carotene, lutein, and zeaxanthin), triterpenoids (momordicin), alkaloids, and saponins, responsible for their side effect on glycemic

Besides bitter gourd other non-sweet Cucurbitaceae that have antidiabetic properties are ivy gourd (Coccinia grandis)*,* snake gourd (Trichosanthes cucumerina), and ridge gourd (Luffa acutangula). In ivy gourd, immature fruits have antihyperglycemic properties since they help regulate blood sugar levels [223]. In India, they are used to prevent or treat diabetes [223]. Bioactive compounds in the ivy gourd inhibit glucose-6-phosphatase [209], a liver enzyme involved in the regulation of sugar metabolism. Snake gourd is also considered to be useful in treating type 2 diabetes [209]. Ridge gourd contains insulin like peptides and alkaloids that help to

Legume consumption is also colligated with reduced risk of type 2 diabetes since they are the ideal carbohydrate source [3, 90, 224]. They are low in glycemic load due to their moderate protein and abundant dietary fiber and resistant starch (that is fermented by bacteria in the colon). This chemical composition of legumes decreases the number of calories that can be absorbed which contribute to the

Kwon et al. [193] presented eggplant phenolics as inhibitors of key enzymes

Consumption of a vegetable-rich diet has unquestionable positive effects on nutrition and health since vegetables are rich in bioactive compounds such as dietary fiber, vitamins, minerals, and phytochemicals that can protect the human body from several types of chronic and degenerative diseases. The mechanism by which vegetable bioactive compounds decrease the risk of some of these diseases is complex and sometimes unknown. In this chapter, some experimental research evidences that the bioactive compounds are responsible for mitigating some human diseases were presented. All the different bioactive compounds may contribute to the overall health benefit. Each vegetable family and each vegetable contain a unique combination of bioactive compounds. So, the health benefit of vegetables should not be linked to only one bioactive compound or one type of vegetable but rather with a balanced diet that includes more than one type of vegetable. Antioxidative, anticarcinogenic, antidiabetic, and cardiovascular disease-lowering effects of vegetables have been reported. Nutrition is both a quantity and quality issue. The availability of a large diversity of vegetables all year-round allied to increase in mean per capita incomes in recent years, and knowledge of vegetable nutritional quality and health benefits should enable consumers to include more

and more a great variety of health-promoting vegetables in their diet.

**96**

There is no "conflict of interest."

### **Author details**

João Silva Dias Instituto Superior de Agronomia, University of Lisbon, Lisbon, Portugal

\*Address all correspondence to: mirjsd@gmail.com

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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H, Fidanza F, Buzina R, Nissinen A. Food intake patterns and 25-year mortality from coronary heart disease: Cross-cultural correlations in the seven countries study. European Journal of Epidemiology. 1999;**15**:507-515

[195] Menotti A, Kromhout D, Blackburn

[196] Nöthlings U, Schulze MB, Weikert C, Boeing H, Van der Schouw YT, Bamia C, et al. Intake of vegetables, legumes, and fruit, and risk for all-cause, cardiovascular, and cancer mortality in a European diabetic population. The Journal of Nutrition. 2008;**138**:775-781.

DOI: 10.1093/jn/138.4.775

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bmj.300.6727.771

[199] Gramenzi A, Gentile A, Fasoli M, Negri E, Parazzini F, La Vecchia C. Association between certain foods and risk of acute myocardial infarction in women. British Medical Journal. 1990;**300**:771-773. DOI: 10.1136/

[200] Gilani AH, Shaheeri F, Saeed SA, Bibi S, Irfamillah-Sadiq M, Faiz S. Hypotensive action of coumarin glycoside from daucus carot.

Phytomedicine. 2000;**7**:423-426. DOI: 10.1016/S0944-7113(00)80064-1

[201] Carter P, Gray LJ, Troughton J, Khunti K, Davies MJ. Fruit and vegetable intake and incidence of type 2

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[197] Lattimer JM, Haub MD. Effects of dietary fiber and its components on metabolic health. Nutrients. 2010;**2**:1266-1289. DOI: 10.3390/

[198] Nicolle C, Cardinault N, Aprikian O, Busserolles J, Grolier P, Rock E, et al. Effect of carrot intake on cholesterol metabolism and on antioxidant status in cholesterol-fed rat. European Journal of Nutrition. 2003;**42**:254-261. DOI:

1990;**29**:95-147

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[209] Swamy KRM, Nath P, Ahuja KG. Vegetables for human nutrition and health. In: Nath P, editor. The Basics of Human Civilization-Food, Agriculture and Humanity, Volume-II-Food. New Delhi, India: Prem Nath Agricultural Science Foundation (PNASF), Bangalore & New India Publishing Agency (NIPA); 2013. pp. 145-198

[210] El-Demerdash FM, Yousef MI, El-Naga NA. Biochemical study on the hypoglycemic effects of onion and garlic in alloxan-induced diabetic rats. Food and Chemical Toxicology. 2005;**43**: 57-63. DOI: 10.1016/j.fct.2004.08.012

[211] Ogunmodede OS, Saalu LC, Ogunlade B, Akunna GG, Oyewopo AO. An evaluation of the hypoglycemic, antioxidant and hepatoprotective potentials of onion (*Allium cepa* L.) on alloxan-induced diabetic rabbits. International Journal of Pharmacology. 2012;**8**:21-29. DOI: 10.3923/ ijp.2012.21.29

[212] Yoshinari O, Shiojima Y, Igarashi K. Anti-obesity effects of onion extract in Zucker diabetic fatty rats. Nutrients. 2012;**4**:1518-1526. DOI: 10.3390/ nu4101518

[213] Wang H, Kruszewki A, Brautigan DL. Cellular chromium activation of insulin receptor kinase. Biochemistry. 2005;**44**:8167-8175. DOI: 10.1021/ bi0473152

[214] Chau CF, Chen CH, Lee MH. Comparison of the characteristics, functional properties, and in vitro hypoglycemic effects of various carrot insoluble fiber-rich fractions. Lebensmittel-Wissenshaff und Technologie. 2004;**37**:155-160. DOI: 10.1016/j.lwt.2003.08.001

[215] Coyne T, Ibiebele TI, Baade PD. Diabetes mellitus and serum carotenoids: Findings of a populationbased study in Queensland, Australia. The American Journal of Clinical Nutrition. 2005;**82**:685-693

[216] Chen Q, Chan LLY, Li ETS. Bitter melon (*Momordica charantia*) reduces adiposity, lowers serum insulin and normalizes glucose tolerance in rats fed a high fat diet. The Journal of Nutrition. 2003;**133**:1088-1093

[217] Patil B, Jayaprakasha GK, Vikram A. Indigenous crops of Asia and Southeast Asia: Exploring healthpromoting properties. Hortscience. 2012;**47**:821-827

[218] Chao PM. One more support for recruiting bitter melon in therapeutic diet for diabetes and its comorbidity management—Bitter melon ameliorates hepatic steatosis related with hyperglycemia. BIT's 4th Annual World Congress of Diabetes–2015, Kaohsiung, Taiwania 2015; p. 236

[219] Ahmad N, Hassan M, Halder H, Bennoor K. Effect of *Momordica charantia* (Karolla) extracts on fasting and postprandial serum glucose levels in NIDDM patients. Bangladesh Medical Research Council Bulletin. 1999;**25**:11

[220] Yeh G, Eisenberg D, Kaptchuk T, Phillips R. Systematic review of herbs and dietary supplements for glycemic control in diabetes. Diabetes Care. 2003;**26**:1277. DOI: 10.2337/ diacare.26.4.1277

[221] Chen J, Tian R, Qiu M, Lu L, Zheng Y, Zhang Z. Trinorcucurbitane and cucurbitane triterpenoids from the roots of *Momordica charantia*. Phytochemistry. 2008;**69**:1043-1048. DOI: 10.1016/j.phytochem.2007.10.020

[222] Saxena A, Vikram N. Role of selected Indian plants in management of type 2 diabetes: A review. The Journal of Alternative and Complementary Medicine. 2004;**10**:369-378. DOI: 10.1089/107555304323062365

[223] Singh LW. Traditional medicinal plants of Manipur as anti-diabetics. Journal of Medicinal Plant Research. 2011;**5**:677-687

[224] Villegas R, Gao YT, Yang G, Li HL, Elasy TA, Zheng W, et al. Legume and soy food intake and the incidence of type 2 diabetes in the Shanghai women's health study. The American Journal of Clinical Nutrition, 2008;**87**:162-167. DOI: 10.1093/ajcn/87.1.162

**113**

**Chapter 7**

**Abstract**

**1. Introduction**

Sports Nutrition and Performance

Nutrition plays an essential role on sports performance. Following an adequate nutrition pattern determines winning the gold medal or failing in the attempt. That is why it is commonly referred to as "invisible training." However, regarding food and performance, it is not only referred to professional athletes. Nowadays, a large number of amateur athletes perform daily physical activity both recreationally and semiprofessionally. That population also seeks to achieve an improvement in their personal brands, which can be reached following proper nutritional guidelines. In athlete

population, nutrient requirements are incremented compared with nonathlete population. Therefore, it is essential to carry out a nutritional approach adapted to the athlete and training sessions. In addition, other advantages of adequate food intake in sports are related to changes in body composition, reduction of injuries, and prolongation of professional career length. The objective of this chapter is to determine the nutritional requirements of athlete population that allow to achieve their sporting goals. Nutritional strategies will be addressed in terms of macronutrients consumption, hydration, and timing depending on type and intensity of exercise.

**Keywords:** nutrition, sports performance, intake, nutrients, hydration

intake and thereby improve sports performance (SP).

rate, a factor that together makes the SP increase by itself.

Nutrition is strongly linked to health, especially when sports are concerned, due to the increase in energy and nutrient demands. It is necessary to know the physiology of the exercise in order to know the different metabolic pathways that coexist during sports practice. In this way, you can predict the changes that occur in the organism during physical effort, in order to achieve some dietary recommendations. The nutritional practices of athletes are multifactorial and depend on the habits, culture, or nutritional knowledge of the athlete. So the work of a sports nutritionist is to advise the athlete and his environment to make the necessary changes in his

Nutrition is determinant in achieving an adequate SP, which is defined by three variables: training, rest, and feeding. However, the main objective of sports nutrition must be preserving the health of the athlete, which can be achieved with an adequate intake adapted to the type of training performed. Optimal nutrition provides the energy necessary to perform physical exercise while reducing injury

Two of the aspects that can limit the SP are the state of hydration and the energy contribution. Hypohydration states produce alterations in homeostasis, decreased blood volume, increased heart rate, lower rate of sweating, increased organism

*Raúl Arcusa Saura, María Pilar Zafrilla Rentero* 

*and Javier Marhuenda Hernández*

#### **Chapter 7**

*Nutrition in Health and Disease - Our Challenges Now and Forthcoming Time*

of Alternative and Complementary Medicine. 2004;**10**:369-378. DOI: 10.1089/107555304323062365

[223] Singh LW. Traditional medicinal plants of Manipur as anti-diabetics. Journal of Medicinal Plant Research.

[224] Villegas R, Gao YT, Yang G, Li HL, Elasy TA, Zheng W, et al. Legume and soy food intake and the incidence of type 2 diabetes in the Shanghai women's health study. The American Journal of Clinical Nutrition, 2008;**87**:162-167.

2011;**5**:677-687

DOI: 10.1093/ajcn/87.1.162

**112**

## Sports Nutrition and Performance

*Raúl Arcusa Saura, María Pilar Zafrilla Rentero and Javier Marhuenda Hernández*

#### **Abstract**

Nutrition plays an essential role on sports performance. Following an adequate nutrition pattern determines winning the gold medal or failing in the attempt. That is why it is commonly referred to as "invisible training." However, regarding food and performance, it is not only referred to professional athletes. Nowadays, a large number of amateur athletes perform daily physical activity both recreationally and semiprofessionally. That population also seeks to achieve an improvement in their personal brands, which can be reached following proper nutritional guidelines. In athlete population, nutrient requirements are incremented compared with nonathlete population. Therefore, it is essential to carry out a nutritional approach adapted to the athlete and training sessions. In addition, other advantages of adequate food intake in sports are related to changes in body composition, reduction of injuries, and prolongation of professional career length. The objective of this chapter is to determine the nutritional requirements of athlete population that allow to achieve their sporting goals. Nutritional strategies will be addressed in terms of macronutrients consumption, hydration, and timing depending on type and intensity of exercise.

**Keywords:** nutrition, sports performance, intake, nutrients, hydration

#### **1. Introduction**

Nutrition is strongly linked to health, especially when sports are concerned, due to the increase in energy and nutrient demands. It is necessary to know the physiology of the exercise in order to know the different metabolic pathways that coexist during sports practice. In this way, you can predict the changes that occur in the organism during physical effort, in order to achieve some dietary recommendations.

The nutritional practices of athletes are multifactorial and depend on the habits, culture, or nutritional knowledge of the athlete. So the work of a sports nutritionist is to advise the athlete and his environment to make the necessary changes in his intake and thereby improve sports performance (SP).

Nutrition is determinant in achieving an adequate SP, which is defined by three variables: training, rest, and feeding. However, the main objective of sports nutrition must be preserving the health of the athlete, which can be achieved with an adequate intake adapted to the type of training performed. Optimal nutrition provides the energy necessary to perform physical exercise while reducing injury rate, a factor that together makes the SP increase by itself.

Two of the aspects that can limit the SP are the state of hydration and the energy contribution. Hypohydration states produce alterations in homeostasis, decreased blood volume, increased heart rate, lower rate of sweating, increased organism

temperature, and greater perception of effort which translates into SP deterioration. Likewise, a low energy consumption accentuates fatigue, immunosuppression, and predisposition for injuries, which can interfere in the development of SP.

Nowadays, an exponential increase in the population that performs physical activity has been reported. In the USA, the total number of runners endorsed in marathon events is 541,000 in 2013, which represents 27% more participants than observed in 2008 in the same trend observed in many countries. For example, in Spain the number of participants increased from 28,000 (2008) to 57,931 (2013), which represented an increase of 101%. These increases far from ceasing have continued growing in the last 5 years. Specifically, marathons of Sevilla and Valencia have reached 14,500 and 20,000 runners in 2018, which contrast with the previous participation observed in 2013 (5963 and 9653 participants, respectively).

Unfortunately, sports nutrition is often referenced to sports supplements or "magical" strange diets. In fact 40–70% of athletes use sports supplements without even analyzing if their use is really necessary.

#### **2. Body composition**

The body composition (BC) of the athletes is related to the SP, as it can be modified throughout the season. There is no single BC for each group of athletes; however, it can serve as a guide for athletes and coaches [1].

The season of the athlete will be divided into different phases throughout the competitive period. Competitive season can be divided in preseason, competitive period, transition period, and in the worst case injury period. Due to different intensities, timing, and types of training, the BC is normally different in the competitive season. Therefore, it is vital to know the BC of the athletes in order to determine the adequacy of the current season stage [2].

Apart from a higher body mass index (BMI), there are several methods for the evaluation of BC [2]. Dual-energy X-ray absorptiometry (DEXA) is considered the gold standard for the assessment of body fat, mainly due to its high reproducibility and accuracy. However, DEXA has high economic cost, is not portable, and also emits a small radiation, so its use is not very common [3].

Among the most used methods are bioelectrical impedance analysis (BIA) and anthropometry. Impedance is defined as the opposition shown by biological materials to the passage of an electric flow. Tissues with high impedance offer greater resistance (adipose tissue, bone, air in the lungs) and contain less amount of water [4]. The greater the amount of water, the better this electrical flow, will pass through. Therefore, the hydration sate of the individual is the determinant for the BC measurement by BIA. In addition, in order to standardize previous conditions and dismiss errors, certain protocols must be followed prior to the measurement of BC by BIA. That fact makes BIA a rather imprecise method [5].

Anthropometry allows the evaluation of different body dimensions and the overall composition of the body. It consists of the measurement of skinfolds, perimeters of the muscles, and bone diameters. This technique must be carried out by experts qualified by the International Society for the Advancement of Kinanthropometry (ISAK) [4]. It is the most widely used method in the sports field, from which the percentages of fat, muscle mass, and bone mass can be obtained by means of mathematic formulas [5]. The most effective way to monitor an athlete using this technique is performing a sum of six bodyfolds (triceps, subscapular, supraspinal, abdominal, thigh, and medial leg) that gives an absolute value [6]. In summary mode, the values for said summation of folds are estimated in physically active people (75 mm men and 100 mm in women), footballers (<50 mm men

**115**

*Sports Nutrition and Performance*

42 mm for women (**Table 1**).

**Table 1.**

ent oxidation) [1].

**4. Energy needs**

training and competitions.

that must be made in the athlete.

*Summary of summation folds of the athletes.*

**3. Metabolic pathways and exercise**

*DOI: http://dx.doi.org/10.5772/intechopen.84467*

and <65 mm women), and endurance athletes (<35 mm men and 50 mm women). The minimum values seen in the healthy sports population were 25 mm for men and

**Population Men (∑six skinfolds) Women (∑six skinfolds)**

Physically active people 75 10 Footballers <50 <65 Runners <35 50 Minimum value 25 42

However, it must be taken into account that BC is not the only thing that will measure sports performance, but it is one more parameter of the measurements

Prior to establishing requirements regarding quantity and timing of macronutrients, a brief approach about different metabolic pathways that provides energy during exercise is necessary. The energy systems are integrated by a set of metabolic pathways that come into operation during exercise, depending on the intensity and duration. In summary, they can be divided into non-oxidative pathways (phosphogenic and glycolytic pathways) and aerobic pathways (nutri-

Both pathways aim to generate ATP that will be consumed during the exercise. The non-oxidative pathways occur in the cellular cytosol, do not require oxygen, and are activated during short-time periods (seconds). Phosphagen route uses ATP and phosphocreatine, lasting between 1 and 10 s, and is a route that does not need oxygen and does not generate lactate. Glycolytic pathways metabolize glucose, muscle, and liver glycogen through glycolysis and occur in high-intensity exercises up to 3 min. These glycolytic pathways generate lactate and hydrogen bonds, generating an acidity in the muscle cell—this acidity being one of its limitations [7].

The aerobic pathway occurs inside the mitochondria, so it requires the presence of oxygen to metabolize fuels. It is typical of resistance exercises with medium-low intensity and long duration. It includes the oxidation of CHOs, fats, and to a lesser extent proteins. This route generates much more ATP than the anaerobic path but

The key to success for any athlete will be to adapt energy intake to energy expenditure, which allows the correct functioning of the organism while improving BC [1]. However, it can be complicated due to multiple changes in periodization of

The energy demands of athletes differ widely depending on the type of sport, duration, intensity, competitive level, and individual variability of each athlete. The more demanding the competitive levels of the athlete are, the greatest increase in the intensity of both training and competition occurs, which will result in a significant reduction energy reserves that must be replaced by an adequate diet [8].

more slowly, speed being the limitation of this path [7].


#### **Table 1.**

*Nutrition in Health and Disease - Our Challenges Now and Forthcoming Time*

predisposition for injuries, which can interfere in the development of SP.

participation observed in 2013 (5963 and 9653 participants, respectively).

even analyzing if their use is really necessary.

however, it can serve as a guide for athletes and coaches [1].

determine the adequacy of the current season stage [2].

emits a small radiation, so its use is not very common [3].

BC by BIA. That fact makes BIA a rather imprecise method [5].

**2. Body composition**

Unfortunately, sports nutrition is often referenced to sports supplements or "magical" strange diets. In fact 40–70% of athletes use sports supplements without

The body composition (BC) of the athletes is related to the SP, as it can be modified throughout the season. There is no single BC for each group of athletes;

The season of the athlete will be divided into different phases throughout the competitive period. Competitive season can be divided in preseason, competitive period, transition period, and in the worst case injury period. Due to different intensities, timing, and types of training, the BC is normally different in the competitive season. Therefore, it is vital to know the BC of the athletes in order to

Apart from a higher body mass index (BMI), there are several methods for the evaluation of BC [2]. Dual-energy X-ray absorptiometry (DEXA) is considered the gold standard for the assessment of body fat, mainly due to its high reproducibility and accuracy. However, DEXA has high economic cost, is not portable, and also

Among the most used methods are bioelectrical impedance analysis (BIA) and anthropometry. Impedance is defined as the opposition shown by biological materials to the passage of an electric flow. Tissues with high impedance offer greater resistance (adipose tissue, bone, air in the lungs) and contain less amount of water [4]. The greater the amount of water, the better this electrical flow, will pass through. Therefore, the hydration sate of the individual is the determinant for the BC measurement by BIA. In addition, in order to standardize previous conditions and dismiss errors, certain protocols must be followed prior to the measurement of

Anthropometry allows the evaluation of different body dimensions and the overall composition of the body. It consists of the measurement of skinfolds, perimeters of the muscles, and bone diameters. This technique must be carried out by experts qualified by the International Society for the Advancement of

Kinanthropometry (ISAK) [4]. It is the most widely used method in the sports field, from which the percentages of fat, muscle mass, and bone mass can be obtained by means of mathematic formulas [5]. The most effective way to monitor an athlete using this technique is performing a sum of six bodyfolds (triceps, subscapular, supraspinal, abdominal, thigh, and medial leg) that gives an absolute value [6]. In summary mode, the values for said summation of folds are estimated in physically active people (75 mm men and 100 mm in women), footballers (<50 mm men

temperature, and greater perception of effort which translates into SP deterioration. Likewise, a low energy consumption accentuates fatigue, immunosuppression, and

Nowadays, an exponential increase in the population that performs physical activity has been reported. In the USA, the total number of runners endorsed in marathon events is 541,000 in 2013, which represents 27% more participants than observed in 2008 in the same trend observed in many countries. For example, in Spain the number of participants increased from 28,000 (2008) to 57,931 (2013), which represented an increase of 101%. These increases far from ceasing have continued growing in the last 5 years. Specifically, marathons of Sevilla and Valencia have reached 14,500 and 20,000 runners in 2018, which contrast with the previous

**114**

*Summary of summation folds of the athletes.*

and <65 mm women), and endurance athletes (<35 mm men and 50 mm women). The minimum values seen in the healthy sports population were 25 mm for men and 42 mm for women (**Table 1**).

However, it must be taken into account that BC is not the only thing that will measure sports performance, but it is one more parameter of the measurements that must be made in the athlete.

#### **3. Metabolic pathways and exercise**

Prior to establishing requirements regarding quantity and timing of macronutrients, a brief approach about different metabolic pathways that provides energy during exercise is necessary. The energy systems are integrated by a set of metabolic pathways that come into operation during exercise, depending on the intensity and duration. In summary, they can be divided into non-oxidative pathways (phosphogenic and glycolytic pathways) and aerobic pathways (nutrient oxidation) [1].

Both pathways aim to generate ATP that will be consumed during the exercise. The non-oxidative pathways occur in the cellular cytosol, do not require oxygen, and are activated during short-time periods (seconds). Phosphagen route uses ATP and phosphocreatine, lasting between 1 and 10 s, and is a route that does not need oxygen and does not generate lactate. Glycolytic pathways metabolize glucose, muscle, and liver glycogen through glycolysis and occur in high-intensity exercises up to 3 min. These glycolytic pathways generate lactate and hydrogen bonds, generating an acidity in the muscle cell—this acidity being one of its limitations [7].

The aerobic pathway occurs inside the mitochondria, so it requires the presence of oxygen to metabolize fuels. It is typical of resistance exercises with medium-low intensity and long duration. It includes the oxidation of CHOs, fats, and to a lesser extent proteins. This route generates much more ATP than the anaerobic path but more slowly, speed being the limitation of this path [7].

#### **4. Energy needs**

The key to success for any athlete will be to adapt energy intake to energy expenditure, which allows the correct functioning of the organism while improving BC [1]. However, it can be complicated due to multiple changes in periodization of training and competitions.

The energy demands of athletes differ widely depending on the type of sport, duration, intensity, competitive level, and individual variability of each athlete. The more demanding the competitive levels of the athlete are, the greatest increase in the intensity of both training and competition occurs, which will result in a significant reduction energy reserves that must be replaced by an adequate diet [8].

The objectives of the athletes' diet are the following: provide the necessary energy for exercise, regulate body metabolism, and provide nutrients to maintain and repair tissues [9]. Due to variation among athletes, different available food options, and individual food patterns, there is no single feeding pattern for athletes, so there are a large number of strategies and options to assess [2].

Caloric intakes below the basal metabolic rate (BMR) are not recommended because it can compromise organism functions. Depending on the type of training energy requirement, the following recommendations for athletes can be approached: moderate training 1.7 × BMR, intense training 2.1 × BMR, extreme training 3 × BMR, and with the maximum recommended limit being 4 × BMR.

Athletes should bear in mind that it is not enough to pay attention to food only on the day of competition, but daily. Appropriate nutritional guidelines will optimize SP, improve recovery, and reduce the risk of injury and illness [2]. For example, in women daily intake below 30 kcal/kg body mass/day can induce damage to metabolic and hormonal functions that affect SP, growth, and health [10].

A varied diet is recommended, covering energetic requirements, and is based on foods as fruits, vegetables, legumes, cereals, dairy products, eggs, fish, and lean meat, in order to provide vitamins and minerals. A poor choice of foods cannot be compensated by the use of supplements [2].

#### **5. Macronutrients**

In order to establish recommendations for macronutrients, it is preferable taking into account the body weight (BW) of the athlete, instead of giving the typical percentages based on the total caloric intake of the diet [2]. For this purpose the recommendations will be provided by grams of nutrient/kg of BW.

Main energy substrates used for physical exercise are carbohydrates (CHO) and lipids, while proteins as energy substrate are reserved for extreme conditions. The use of energy substrate varies depending on the intensity and duration of the exercise, level of training of the athlete, and the state of pre-workout CHO stores. The use of CHO as energy substrate is produced mainly during highintensity and short-duration exercises. Meanwhile, less intense and long-term exercises use fats' main energy substrate [11]. However the use of CHO will also have a great impact on exercises of less intensity and longer duration such as resistance test, showing that depletion of CHO together with dehydration is a major limitation of the SP [12].

One of the big differences between CHO and lipids is their storage in the body. While CHOs have a limited reserve which leads to around 1600–2000 kcal, fats suppose a practically unlimited energy reserve close to 70,000 kcal (depending on fat mass) [7, 11].

#### **5.1 Carbohydrate**

Currently, there are a large number of myths related to nutrition, which causes great confusion in general population. One of the most widespread errors is the demonization suffered by the CHO, which has generated some carbophobia in society, including the athlete population [13]. This is a mistake, due to the importance of CHO as energy substrate for the brain and central nervous system. Moreover, they can also be used at different intensities both by anaerobic and aerobic pathways [1].

CHO are an energy fuel that provides 4 kcal/g of dry weight. They are stores in liver and muscle in the form of glycogen. Although, these deposits are limited to around 400-500 g, providing 1600- 2000 kcal, they can be depleted if the diet

**117**

*Sports Nutrition and Performance*

SP due to fatigue [15].

*DOI: http://dx.doi.org/10.5772/intechopen.84467*

try new things on competition days [14].

tive hypoglycemia that affects the SP [18].

tions of CHO during the exercise are [19, 20]:

liquid can promote hydration.

physical activity can be summarized as follows [1, 18]:

• 5–7 g/kg/d for moderate intensity training of 1 h duration

does not contain enough CHO. Glycogen stores in the organism are divided into 350–400 g in the muscle, 75–100 g in the liver, and around 5 g in the plasma [14]. In addition to size differences, the liver is really a store of glycogen, responsible for maintaining blood glucose. Meanwhile, the muscle can be considered a "false" store since it only uses glucose for its own needs. In other words, the liver can contribute to the replacement of muscle glycogen in the event of depletion, something that does not happen in reverse, which can lead to hypoglycemia and considerably affect

It is vitally important to maintain high levels of glycogen so as not to compromise the physical demands of physical activity, since low availability can be associated with loss of abilities and impaired decision-making and increases risk of injury and decreases SP. Therefore, it is essential to provide CHO before exercise, as well as

A good strategy in order to optimize increased glycogen reserves for a competition is the "CHO overload" in the hours or even days before. In athletes with good training status, it is not necessary to deplete these deposits previously, as was believed decades ago. In fact an intake or around 10 g CHO/kg/day during the previous 36–48 h would be enough [17]. Athletes are advised to test how many CHOs are able to inatek without gastric problems. On the other hand, it is also advisable not to

In general, the CHO recommendations based on the intensity and duration of

• 3–5 g/kg/d of low-intensity training such as recovery days or tactical skills

• 6–10 g/kg/d for moderate–high intensity exercises between 1 and 3 h

• 8–12 g/kg/d for workouts of more than 4–5 h of moderate-high intensity

During competition as well as during high-intensity training, a high intake of CHO between 3 and 4 h before the beginning of the exercise is convenient, in order to complete glycogen levels [14]. In case of CHO overload, the recommendation ranges from 200 g CHO to 300 g CHO of moderate glycemic index. The intake should be light, easily digestible, and low in fat, protein, and fiber, in order not to decrease glycemia. Also, an intake of 1–4 g/kg of CHO between the previous 1 and 4 h would be recommended. However, some athletes should be careful with the intake of simple CHOs in the hour before the competition, which can cause a reac-

The type of exercise, length, and provisioning are determinant factors for the physical exercise. Depending on all the variables, the nutritional strategies will be adapted to the athlete as personalized as possible. To summarize, the recommenda-

• In exercise lasting 45–75 min, it seems that the intake of CHOs is not necessary and it would be enough to perform mouth rinses. However, ingesting this

• In exercises lasting 1–2 h, the intake of 30 g/h seems to be sufficient, increasing

• In an exercise of less than 30 min, CHO intake is not necessary.

CHO intake up to 60 g/h in case of more delayed sports.

during, in order to improve the SP and delay the onset of fatigue [14, 16].

#### *Sports Nutrition and Performance DOI: http://dx.doi.org/10.5772/intechopen.84467*

*Nutrition in Health and Disease - Our Challenges Now and Forthcoming Time*

so there are a large number of strategies and options to assess [2].

compensated by the use of supplements [2].

**5. Macronutrients**

major limitation of the SP [12].

fat mass) [7, 11].

**5.1 Carbohydrate**

The objectives of the athletes' diet are the following: provide the necessary energy for exercise, regulate body metabolism, and provide nutrients to maintain and repair tissues [9]. Due to variation among athletes, different available food options, and individual food patterns, there is no single feeding pattern for athletes,

Caloric intakes below the basal metabolic rate (BMR) are not recommended because it can compromise organism functions. Depending on the type of training energy requirement, the following recommendations for athletes can be approached: moderate training 1.7 × BMR, intense training 2.1 × BMR, extreme training 3 × BMR, and with the maximum recommended limit being 4 × BMR. Athletes should bear in mind that it is not enough to pay attention to food only on the day of competition, but daily. Appropriate nutritional guidelines will optimize SP, improve recovery, and reduce the risk of injury and illness [2]. For example, in women daily intake below 30 kcal/kg body mass/day can induce damage to metabolic and hormonal functions that affect SP, growth, and health [10]. A varied diet is recommended, covering energetic requirements, and is based on foods as fruits, vegetables, legumes, cereals, dairy products, eggs, fish, and lean meat, in order to provide vitamins and minerals. A poor choice of foods cannot be

In order to establish recommendations for macronutrients, it is preferable taking

Main energy substrates used for physical exercise are carbohydrates (CHO) and lipids, while proteins as energy substrate are reserved for extreme conditions. The use of energy substrate varies depending on the intensity and duration of the exercise, level of training of the athlete, and the state of pre-workout CHO stores. The use of CHO as energy substrate is produced mainly during highintensity and short-duration exercises. Meanwhile, less intense and long-term exercises use fats' main energy substrate [11]. However the use of CHO will also have a great impact on exercises of less intensity and longer duration such as resistance test, showing that depletion of CHO together with dehydration is a

One of the big differences between CHO and lipids is their storage in the body. While CHOs have a limited reserve which leads to around 1600–2000 kcal, fats suppose a practically unlimited energy reserve close to 70,000 kcal (depending on

Currently, there are a large number of myths related to nutrition, which causes great confusion in general population. One of the most widespread errors is the demonization suffered by the CHO, which has generated some carbophobia in society, including the athlete population [13]. This is a mistake, due to the importance of CHO as energy substrate for the brain and central nervous system. Moreover, they can also be used at different intensities both by anaerobic and aerobic pathways [1]. CHO are an energy fuel that provides 4 kcal/g of dry weight. They are stores in liver and muscle in the form of glycogen. Although, these deposits are limited to around 400-500 g, providing 1600- 2000 kcal, they can be depleted if the diet

into account the body weight (BW) of the athlete, instead of giving the typical percentages based on the total caloric intake of the diet [2]. For this purpose the

recommendations will be provided by grams of nutrient/kg of BW.

**116**

does not contain enough CHO. Glycogen stores in the organism are divided into 350–400 g in the muscle, 75–100 g in the liver, and around 5 g in the plasma [14]. In addition to size differences, the liver is really a store of glycogen, responsible for maintaining blood glucose. Meanwhile, the muscle can be considered a "false" store since it only uses glucose for its own needs. In other words, the liver can contribute to the replacement of muscle glycogen in the event of depletion, something that does not happen in reverse, which can lead to hypoglycemia and considerably affect SP due to fatigue [15].

It is vitally important to maintain high levels of glycogen so as not to compromise the physical demands of physical activity, since low availability can be associated with loss of abilities and impaired decision-making and increases risk of injury and decreases SP. Therefore, it is essential to provide CHO before exercise, as well as during, in order to improve the SP and delay the onset of fatigue [14, 16].

A good strategy in order to optimize increased glycogen reserves for a competition is the "CHO overload" in the hours or even days before. In athletes with good training status, it is not necessary to deplete these deposits previously, as was believed decades ago. In fact an intake or around 10 g CHO/kg/day during the previous 36–48 h would be enough [17]. Athletes are advised to test how many CHOs are able to inatek without gastric problems. On the other hand, it is also advisable not to try new things on competition days [14].

In general, the CHO recommendations based on the intensity and duration of physical activity can be summarized as follows [1, 18]:


During competition as well as during high-intensity training, a high intake of CHO between 3 and 4 h before the beginning of the exercise is convenient, in order to complete glycogen levels [14]. In case of CHO overload, the recommendation ranges from 200 g CHO to 300 g CHO of moderate glycemic index. The intake should be light, easily digestible, and low in fat, protein, and fiber, in order not to decrease glycemia. Also, an intake of 1–4 g/kg of CHO between the previous 1 and 4 h would be recommended. However, some athletes should be careful with the intake of simple CHOs in the hour before the competition, which can cause a reactive hypoglycemia that affects the SP [18].

The type of exercise, length, and provisioning are determinant factors for the physical exercise. Depending on all the variables, the nutritional strategies will be adapted to the athlete as personalized as possible. To summarize, the recommendations of CHO during the exercise are [19, 20]:


• In exercises lasting more than 2.5 h, the intake of CHO should be 90 g/h. High CHO amounts can cause digestive problems; therefore, a previous intestine training is determinant to tolerate such CHO intake.

The rate of glucose oxidation is estimated at 60 g/h. Therefore, the CHO composition must be formed by a combination of CHOs that use different transporters and increase the oxidation rate, such as maltodextrin or sucrose, among others [20]. Consuming 90 g CHOs/h can cause gastrointestinal problems in sports such as continuous running. These gastrointestinal problems may be due to the redistribution of blood flow to the muscles during exercise. Therefore, strategies for bowel training have been proposed to increase the rate of gastric emptying as well as reduce possible discomfort [21]. When it is proposed to reach recommendations, it seems beneficial to alternate different types of drinks, gels, or bars, so that the taste is not monotonous.

The reposition of CHO is determinant in approaching the following training or competitive sessions. After the completion of physical activity, it is vitally important to replenish CHO stores after the training and competition sessions. These replacements of CHO levels can be approached by different methods, depending on the closeness and intensity of the next sporting event. It will be necessary to rehydrate and to ensure glycogen recovery as well as muscle tissue. The optimum approach is a recovery of 150% of BW lost and a CHO intake between 1 and 2 g/kg/h during the following 6 h after exercise. Moreover, it is advisable to take advantage of the first 2 h afterward where the glycogen resynthesis rate is maximum [14, 22].

The contribution of 1 g/kg BW of CHO after the first hour post-exercise has anticatabolic effect, increases insulin secretion, and increases muscle protein synthesis. Moreover, the addition of protein may also increase the glycogen resynthesis, so a less aggressive pattern can be reached by combining a consumption of 0.8 g kg BW/h of CHO together with protein intake of 0.2–0.4 g/kg BW/h [19].

The appropriate intake of CHO before, during and, after exercise ensures a satisfactory energy intake to face both training and competitions. Most CHOs are found in cereals, fruits, legumes, and vegetables and can be found in smaller quantities in dairy products, unless they could have added sugars. Given the importance of CHO, it is considered essential that athletes ingest enough CHO complexes during the course of the day, leaving simple CHOs during and after exercise [2].

However, in some circumstances in which physiological adaptations to training are the target, different strategies can be handled to those previously mentioned. For example, training with low availability of glycogen induces mitochondrial biogenesis (increase in the number of mitochondria) and thereby enhances lipid oxidation [23]. This strategy can make the athlete more profitable metabolically, allowing a saving of glycogen reserves during exercise and thereby delaying the onset of fatigue. Another purpose of this strategy can be to accustom the athlete to know the feeling of emptiness that can have at the end of a competition and know in advance how to deal with it [24].

Because a reduction in the availability of CHO will affect the quality of the training, these strategies should be carried out with extreme caution and under the supervision of nutritionist and coach. The performance of training under low availability of CHO will be done during low-intensity sessions due to the perception of effort is greater, the immune system can be affected, and the athlete is at greater risk of injury [24].

#### **5.2 Proteins**

The proteins are composed of amino acid (AA) chains. There are 20 types of AA, divide into nonessential AAs (can be synthetized by the organism) and

**119**

*Sports Nutrition and Performance*

oxidized to obtain energy [28].

cise, there is not such limitation.

presence of all essential AAs [30].

for its high content on AAs and leucine content.

subjects.

digestion [29].

*DOI: http://dx.doi.org/10.5772/intechopen.84467*

nent of muscle enzymes and play a large role in SP [14].

estimating an adequate protein intake for each given moment [1].

increase is to maintain maximum muscle mass integrity [26].

essential AAs (must be contributed by the diet) [2]. Within the essential AAs, there are three types of AAs called branched (leucine, valine, and isoleucine). Among them, leucine stands out as a stimulator of the mammalian target of rapamycin (mTOR) pathway, which is related to protein synthesis and hypertrophy [25]. Although proteins can contribute between 5 and 10% to the total energy used during physical activity, they are not considered as energy source. Proteins constitute the base of muscle tissue and of the immune system and are the major compo-

Regarding sedentary population, the estimated consumption rate is 0.8 g/ kg BW/day. In the athlete population, these requirements are increased to repair muscle damage caused by exercise, enhance metabolic adaptations to training, and avoid possible muscle catabolism [2]. The focus of protein consumption is on

The current recommendations for athlete population range between 1.2 and 2.0 g/kg BW/day depending on the type of sports performed [1]. Moreover, higher amounts may be reached at exceptional times such as injurious period, highintensity training, or weight loss plans with caloric restriction. The purpose of this

Although the most important factor in terms of protein consumption is the overall consumption throughout the day, it may be advisable to divide the protein intake into several intakes. For example, four doses of 0.4 g/kg BW ensuring a total of 1.6 g/kg BW a day [25]. Likewise, it is recommended to ensure a contribution of 3 g of leucine every meal [27]. The optimal timing seems to adjust the intake depending on the moment, type of training, as well as availability of the rest of nutrients and energy. It is important to have an adequate energy and CHO consumption, so that dietary amino acid are used for protein synthesis and not

Protein-rich diets are associated with increased risk of dehydration due to elimination of nitrogenous waste products, an increased cardiovascular disease risk due to the association of fat with protein products, or a shift of CHO [2]. However, even at high doses, no negative effects on renal function have been reported in healthy

Regarding timing of protein intake along with exercise, it seems that the most optimal time is the period after exercise. Better doses ranged between 0.25 and 0.3 g/protein/kg BW (approximately 15–25 g protein) [1]. However, high protein intake is discouraged close to physical exercise, due to possible digestive problems as a result of its long time of gastric emptying. However, in very long duration exer-

In order to stimulate muscle protein synthesis, the intake of 30–40 g of casein is beneficial prior to going to bed, promoting nocturnal recovery due to its slow

To choose protein sources, it is important that animal proteins may be of greater interest. In fact, animal proteins are considered as a complete protein due to the

The main protein sources are lean meat products, fish, eggs, dairy products, and

The use of protein supplements does not seem to be necessary because protein

legumes that provide vegetable protein and reduce animal consumption.

requirements are usually reached with diet in Western population. However, population that may find it difficult to reach such recommendations should be monitored. These groups includes: vegetarian athletes, young athletes in the growth phase, and athletes who restrict their diet due to religious or cultural reason. can be included [2]. If protein supplementation is chosen, the best option is whey protein

#### *Sports Nutrition and Performance DOI: http://dx.doi.org/10.5772/intechopen.84467*

*Nutrition in Health and Disease - Our Challenges Now and Forthcoming Time*

training is determinant to tolerate such CHO intake.

2 h afterward where the glycogen resynthesis rate is maximum [14, 22].

BW/h of CHO together with protein intake of 0.2–0.4 g/kg BW/h [19].

course of the day, leaving simple CHOs during and after exercise [2].

in advance how to deal with it [24].

risk of injury [24].

**5.2 Proteins**

The contribution of 1 g/kg BW of CHO after the first hour post-exercise has anticatabolic effect, increases insulin secretion, and increases muscle protein synthesis. Moreover, the addition of protein may also increase the glycogen resynthesis, so a less aggressive pattern can be reached by combining a consumption of 0.8 g kg

The appropriate intake of CHO before, during and, after exercise ensures a satisfactory energy intake to face both training and competitions. Most CHOs are found in cereals, fruits, legumes, and vegetables and can be found in smaller quantities in dairy products, unless they could have added sugars. Given the importance of CHO, it is considered essential that athletes ingest enough CHO complexes during the

However, in some circumstances in which physiological adaptations to training are the target, different strategies can be handled to those previously mentioned. For example, training with low availability of glycogen induces mitochondrial biogenesis (increase in the number of mitochondria) and thereby enhances lipid oxidation [23]. This strategy can make the athlete more profitable metabolically, allowing a saving of glycogen reserves during exercise and thereby delaying the onset of fatigue. Another purpose of this strategy can be to accustom the athlete to know the feeling of emptiness that can have at the end of a competition and know

Because a reduction in the availability of CHO will affect the quality of the training, these strategies should be carried out with extreme caution and under the supervision of nutritionist and coach. The performance of training under low availability of CHO will be done during low-intensity sessions due to the perception of effort is greater, the immune system can be affected, and the athlete is at greater

The proteins are composed of amino acid (AA) chains. There are 20 types of AA, divide into nonessential AAs (can be synthetized by the organism) and

• In exercises lasting more than 2.5 h, the intake of CHO should be 90 g/h. High CHO amounts can cause digestive problems; therefore, a previous intestine

The rate of glucose oxidation is estimated at 60 g/h. Therefore, the CHO composition must be formed by a combination of CHOs that use different transporters and increase the oxidation rate, such as maltodextrin or sucrose, among others [20]. Consuming 90 g CHOs/h can cause gastrointestinal problems in sports such as continuous running. These gastrointestinal problems may be due to the redistribution of blood flow to the muscles during exercise. Therefore, strategies for bowel training have been proposed to increase the rate of gastric emptying as well as reduce possible discomfort [21]. When it is proposed to reach recommendations, it seems beneficial to alternate different types of drinks, gels, or bars, so that the taste is not monotonous. The reposition of CHO is determinant in approaching the following training or competitive sessions. After the completion of physical activity, it is vitally important to replenish CHO stores after the training and competition sessions. These replacements of CHO levels can be approached by different methods, depending on the closeness and intensity of the next sporting event. It will be necessary to rehydrate and to ensure glycogen recovery as well as muscle tissue. The optimum approach is a recovery of 150% of BW lost and a CHO intake between 1 and 2 g/kg/h during the following 6 h after exercise. Moreover, it is advisable to take advantage of the first

**118**

essential AAs (must be contributed by the diet) [2]. Within the essential AAs, there are three types of AAs called branched (leucine, valine, and isoleucine). Among them, leucine stands out as a stimulator of the mammalian target of rapamycin (mTOR) pathway, which is related to protein synthesis and hypertrophy [25].

Although proteins can contribute between 5 and 10% to the total energy used during physical activity, they are not considered as energy source. Proteins constitute the base of muscle tissue and of the immune system and are the major component of muscle enzymes and play a large role in SP [14].

Regarding sedentary population, the estimated consumption rate is 0.8 g/ kg BW/day. In the athlete population, these requirements are increased to repair muscle damage caused by exercise, enhance metabolic adaptations to training, and avoid possible muscle catabolism [2]. The focus of protein consumption is on estimating an adequate protein intake for each given moment [1].

The current recommendations for athlete population range between 1.2 and 2.0 g/kg BW/day depending on the type of sports performed [1]. Moreover, higher amounts may be reached at exceptional times such as injurious period, highintensity training, or weight loss plans with caloric restriction. The purpose of this increase is to maintain maximum muscle mass integrity [26].

Although the most important factor in terms of protein consumption is the overall consumption throughout the day, it may be advisable to divide the protein intake into several intakes. For example, four doses of 0.4 g/kg BW ensuring a total of 1.6 g/kg BW a day [25]. Likewise, it is recommended to ensure a contribution of 3 g of leucine every meal [27]. The optimal timing seems to adjust the intake depending on the moment, type of training, as well as availability of the rest of nutrients and energy. It is important to have an adequate energy and CHO consumption, so that dietary amino acid are used for protein synthesis and not oxidized to obtain energy [28].

Protein-rich diets are associated with increased risk of dehydration due to elimination of nitrogenous waste products, an increased cardiovascular disease risk due to the association of fat with protein products, or a shift of CHO [2]. However, even at high doses, no negative effects on renal function have been reported in healthy subjects.

Regarding timing of protein intake along with exercise, it seems that the most optimal time is the period after exercise. Better doses ranged between 0.25 and 0.3 g/protein/kg BW (approximately 15–25 g protein) [1]. However, high protein intake is discouraged close to physical exercise, due to possible digestive problems as a result of its long time of gastric emptying. However, in very long duration exercise, there is not such limitation.

In order to stimulate muscle protein synthesis, the intake of 30–40 g of casein is beneficial prior to going to bed, promoting nocturnal recovery due to its slow digestion [29].

To choose protein sources, it is important that animal proteins may be of greater interest. In fact, animal proteins are considered as a complete protein due to the presence of all essential AAs [30].

The main protein sources are lean meat products, fish, eggs, dairy products, and legumes that provide vegetable protein and reduce animal consumption.

The use of protein supplements does not seem to be necessary because protein requirements are usually reached with diet in Western population. However, population that may find it difficult to reach such recommendations should be monitored. These groups includes: vegetarian athletes, young athletes in the growth phase, and athletes who restrict their diet due to religious or cultural reason. can be included [2]. If protein supplementation is chosen, the best option is whey protein for its high content on AAs and leucine content.

#### **5.3 Lipids**

Along with the CHO, lipids are major energy substrates during exercise [27]. The difference is that fats are not as profitable per unit of time as CHO and high fat consumption is not associated with improvements in SP [31].

Lipid consumption is important for both energy intake and essential nutrients such as fat-soluble vitamins A, D, E, and K. Both quantity and quality of fats are determinant in the diet. The quality is often referred by its content on inflammatory fatty acids [2].

The recommendation regarding fat consumption in athletes is similar to that of the general population. It is advisable not to make restrictive consumption of fat, as it can lead to deficit of nutrients such as fat-soluble vitamins and omega-3 fatty acids [1].

Fatty acid requirements, according to the American College of Sports Medicine (ACSM), are 20–35% of the total kcal of the diet, where 7–10% should correspond to saturated fatty acids, 10% to polyunsaturated fatty acids, and 10–15% to monounsaturated fatty acids [32].

Adequate intake of omega-3 fatty acids should be ensured due to its antiinflammatory effects, improvements in the organism's coagulation, or increase in omega-3/omega-6 ratio [33].

In particular, food as avocado or olive oil is recommended, due to their high content on monounsaturated fatty acids, which have less susceptible to oxidation.

It is recommended to reduce the consumption of fatty meats, substituting them for lean meats, fish, and legumes. It is also advisable to eliminate the consumption of processed products such as sausages [2].

An excess of polyunsaturated fatty acids carries a risk of lipid peroxidation, so a joint intake with vitamin E is recommend. Moreover, the ratio omega-3/omega-6 series should be greater as possible, because of the greater pro-inflammatory character of omega-6. The recommendations regarding the omega-6/omega-3 range oscillate between 2 and 4/1 in favor of the omega-6, something that is far from the inflammatory level that this entails [33]. In order to reduce the omega-6/omega-3 ratio, it is advisable to reduce consumption of meats and increase consumption of blue fish such as sardines, salmon, tuna, anchovy, and mackerel.

#### **6. Hydration**

During exercise, increments of energy requirements are associated to larger production of metabolic heat [34]. Human organism dissipates that extra heat mainly by the mechanism of evaporation, which ultimately induces dehydration [35, 36].

One of the greatest limitations of SP is dehydration. It is estimated that each kg of BW lost during exercise corresponds to 1 L of sweat [35]. The sensitivity to dehydration is personal, but generally no losses greater than 2% of the BW are recommended in order not to compromise the SP [37]. In fact, 1% of BW lost leads to SP decrease by 10%. Some authors have raised the possibility of training dehydration, but there is some controversy about it [38, 39].

The consumption of water is the only method to prevent dehydration and will be essential before, during, and after exercise. However, a large number of athletes usually begin the exercise in a state of hypohydration [40]. Therefore, it is necessary to instruct the athlete to acquire correct hydration habits according to the type of sports, so that the SP is affected as little as possible [12].

Losses of electrolytes, especially sodium, occur along with water losses. It has been seen that well-trained athletes "sweat more but swear better," that is, they

**121**

death" [44].

**Figure 1.**

*How to calculate sweat rate? [43].*

characteristics [12]:

*Sports Nutrition and Performance*

*DOI: http://dx.doi.org/10.5772/intechopen.84467*

sweat more water, but the loss of electrolytes is lower [41]. Recent studies have compared both the rate of sweating and the concentration of sodium in tattooed people versus non-tattooed people, concluding that the most tattooed skin presented lower

It seems interesting to perform a sweat test to athletes, in order to know their rate of sweating (liters/hour). To accomplish it, weighing the athlete before and after the exercise session is enough. This data reveals the amount of sweat that is lost at the time, so it can serve to adjust the athlete's water intake (**Figure 1**). [43]. In general, the rate of sweating is usually greater than that of gastric emptying. However athletes can be trained to increase gastric emptying during workouts and thereby reduce dehydration as possible [21]. In conditions of higher temperature and humidity, this rate of sweating will rise higher. Another simpler way to determine the state of hydration in athletes is controlling the color of urine (darker colors

Wherein some cases, athletes must acclimatize to different temperatures they accustomed. It has been reported that among all factors, the most important factor

In healthy non-athlete population, the sensation of thirst is an ancestral mechanism that informs of the need to ingest liquid. However, in children, elderly people, and athletes, this mechanism is altered and liquid should be ingested before presenting thirst sensation. In the case of athletes, thirst appears when there is a deficit of 2% dehydration [27]. However, special care should be taken to amateur athletes, who increase their water intake above their needs, which can suffer dilutional hyponatremia "leading to serious problems and even lead to

Regarding the drink to be used for sports, it is advisable to use replacement drinks instead of water, due to the CHO and sodium content. Both salts and CHO improve intestinal transport, which facilitates the arrival of fluid in the blood. Prepositional beverages should present an isotonic composition, with the following

sweating rate and higher sodium concentration [42].

are associated with enhanced dehydration states) [2].

is the previous state of hydration.

*Nutrition in Health and Disease - Our Challenges Now and Forthcoming Time*

consumption is not associated with improvements in SP [31].

Along with the CHO, lipids are major energy substrates during exercise [27]. The difference is that fats are not as profitable per unit of time as CHO and high fat

Lipid consumption is important for both energy intake and essential nutrients such as fat-soluble vitamins A, D, E, and K. Both quantity and quality of fats are determinant in the diet. The quality is often referred by its content on inflammatory

The recommendation regarding fat consumption in athletes is similar to that of the general population. It is advisable not to make restrictive consumption of fat, as it can lead to deficit of nutrients such as fat-soluble vitamins and omega-3 fatty acids [1]. Fatty acid requirements, according to the American College of Sports Medicine (ACSM), are 20–35% of the total kcal of the diet, where 7–10% should correspond to saturated fatty acids, 10% to polyunsaturated fatty acids, and 10–15% to mono-

Adequate intake of omega-3 fatty acids should be ensured due to its antiinflammatory effects, improvements in the organism's coagulation, or increase in

In particular, food as avocado or olive oil is recommended, due to their high content on monounsaturated fatty acids, which have less susceptible to oxidation. It is recommended to reduce the consumption of fatty meats, substituting them for lean meats, fish, and legumes. It is also advisable to eliminate the consumption

An excess of polyunsaturated fatty acids carries a risk of lipid peroxidation, so a joint intake with vitamin E is recommend. Moreover, the ratio omega-3/omega-6 series should be greater as possible, because of the greater pro-inflammatory character of omega-6. The recommendations regarding the omega-6/omega-3 range oscillate between 2 and 4/1 in favor of the omega-6, something that is far from the inflammatory level that this entails [33]. In order to reduce the omega-6/omega-3 ratio, it is advisable to reduce consumption of meats and increase consumption of

During exercise, increments of energy requirements are associated to larger production of metabolic heat [34]. Human organism dissipates that extra heat mainly by the mechanism of evaporation, which ultimately induces dehydration [35, 36]. One of the greatest limitations of SP is dehydration. It is estimated that each kg of BW lost during exercise corresponds to 1 L of sweat [35]. The sensitivity to dehydration is personal, but generally no losses greater than 2% of the BW are recommended in order not to compromise the SP [37]. In fact, 1% of BW lost leads to SP decrease by 10%. Some authors have raised the possibility of training dehydration,

The consumption of water is the only method to prevent dehydration and will be essential before, during, and after exercise. However, a large number of athletes usually begin the exercise in a state of hypohydration [40]. Therefore, it is necessary to instruct the athlete to acquire correct hydration habits according to the type of

Losses of electrolytes, especially sodium, occur along with water losses. It has been seen that well-trained athletes "sweat more but swear better," that is, they

blue fish such as sardines, salmon, tuna, anchovy, and mackerel.

**5.3 Lipids**

fatty acids [2].

**6. Hydration**

unsaturated fatty acids [32].

omega-3/omega-6 ratio [33].

of processed products such as sausages [2].

but there is some controversy about it [38, 39].

sports, so that the SP is affected as little as possible [12].

**120**

sweat more water, but the loss of electrolytes is lower [41]. Recent studies have compared both the rate of sweating and the concentration of sodium in tattooed people versus non-tattooed people, concluding that the most tattooed skin presented lower sweating rate and higher sodium concentration [42].

It seems interesting to perform a sweat test to athletes, in order to know their rate of sweating (liters/hour). To accomplish it, weighing the athlete before and after the exercise session is enough. This data reveals the amount of sweat that is lost at the time, so it can serve to adjust the athlete's water intake (**Figure 1**). [43]. In general, the rate of sweating is usually greater than that of gastric emptying. However athletes can be trained to increase gastric emptying during workouts and thereby reduce dehydration as possible [21]. In conditions of higher temperature and humidity, this rate of sweating will rise higher. Another simpler way to determine the state of hydration in athletes is controlling the color of urine (darker colors are associated with enhanced dehydration states) [2].

Wherein some cases, athletes must acclimatize to different temperatures they accustomed. It has been reported that among all factors, the most important factor is the previous state of hydration.

In healthy non-athlete population, the sensation of thirst is an ancestral mechanism that informs of the need to ingest liquid. However, in children, elderly people, and athletes, this mechanism is altered and liquid should be ingested before presenting thirst sensation. In the case of athletes, thirst appears when there is a deficit of 2% dehydration [27]. However, special care should be taken to amateur athletes, who increase their water intake above their needs, which can suffer dilutional hyponatremia "leading to serious problems and even lead to death" [44].

Regarding the drink to be used for sports, it is advisable to use replacement drinks instead of water, due to the CHO and sodium content. Both salts and CHO improve intestinal transport, which facilitates the arrival of fluid in the blood. Prepositional beverages should present an isotonic composition, with the following characteristics [12]:


As commented before, it is advisable to use drink with different CHOs as glucose, sucrose, and maltodextrinas, in order to facilitate the absorption of liquid due to the use of different intestinal transporters. Moreover, the fructose content should not be very high, due to quantities between 20 and 30% can cause intestinal problems [22].

The hydration guidelines indicated for performing physical exercise are [12, 14]:


In a situation where the environment is very hot and has high humidity, the recommendations of intake of liquid and sodium will be higher [22]. A good strategy can be to make salted snacks in the hours before the exercise or add more salt content to the meals before and after the exercise. Such increase of sodium has a double purpose, on the one hand to increase the intake of liquid through thirst and on the other to favor the retention of that liquid in the organism.

Finally, alcohol consumption is discouraged in both athletes and non-athletes. However, there seems to be a high consumption of this substance in team sports and greater consumption in men than women [45]. Among the harmful effects of alcohol consumption, the following can be highlighted: reduction of SP due to decrease in strength, power, speed, and resistance; diuretic effect that affects hydration [46]; diminution of sleep quality, mood, and immune system [47]; elevation of cortisol concentration; and reduction of muscle synthesis up to 24% even when consumed right at the end of the exercise [48].

#### **7. Diabetes in sports**

First, the effect of exercise between insulin-dependent (type 1) and insulindependent (type 2) diabetes should be differentiated. In type 2, you do the exercise

**123**

*Sports Nutrition and Performance*

*DOI: http://dx.doi.org/10.5772/intechopen.84467*

as well as adjust the dose of insulin used [49].

gon, cortisol, and catecholamines) [49].

**8. Supplements**

tice of physical exercise [50].

evidence to support their effect [50].

offense involuntarily by the athlete [51].

four groups, based on effectiveness and safety [52]:

to improve insulin resistance, while in type 1, you should adjust and modify the

Physical exercise is one of the most difficult activities to adapt to diabetes, due to the increase in the frequency of hypoglycemia. People with diabetes who perform physical activity on a regular basis have less need for insulin, but this does not ensure adequate glycemic control. The blood glucose value is of multifactorial origin, and one should take into account the CHO intake and type of sports performed

In order to avoid hypoglycemia, during the exercise the dose of insulin will be reduced but in no case will be completely eliminated, because the lack of insulin prevents the entry of a sufficient amount of glucose into the cells for obtaining energy. A greater use of fats as fuel can generate an accumulation of ketone bodies and cause ketoacidosis. In the presence of glucose values (>250 mg/dL), ketone levels should be checked, and if elevated (>0.5 mmol/l), postpone the activity [49]. The type of exercise performed by the athlete should be taken into account, since aerobic exercise increases the risk of hypoglycemia during and after exercise, while anaerobes cause hyperglycemia due to counterregulatory hormones (gluca-

Physical exercise has some ability to introduce glucose into the muscle cell without

the need for insulin action. This effect can occur during the 48 h after exercise, so there is a certain risk of suffering hypoglycemia in that period depending on the sports performed. This is due to the fact that during the physical exercise, the reserves of the muscle and liver glycogen have been emptied. Once the exercise is finished and after the intake of CHO, the glucose will be destined to replace the glycogen reserves instead of the blood, which can cause hypoglycemia, so that the high blood glucose value after a type of anaerobic exercise can be deceptive. Therefore, higher consump-

tion of CHO or decreased insulin dose can prevent such hypoglycemia [49].

An ergonomic aid is a product that contains a nutrient or a group of nutrients that improve the SP without taking into account the harmful effects in athletes, while a supplement is a nutritional aid to complete the diet associated with the prac-

When an athlete seeks to improve in the SP, his ability to tolerate intense workouts and hard competitions is crucial to avoid falling into injury or chronic fatigue. To achieve this purpose, an adequate supply of nutrients is essential. However, many times this does not happen, and the use of dietary supplements is resorted to [50]. These supplements must be prescribed individually according to the needs of each person (sex, age, fitness, intensity and duration of the exercise, season, etc.), in order to maintain both the state of health and the improvement of the SP. Dietary supplements must offer maximum possible safety and have a degree of scientific

Currently between 40 and 70% of athletes make use of supplements without previously analyzing if necessary. In addition, a large number of sports supplements have not shown empirical evidence to improve SP. Likewise, there is a certain legal vacuum with the labeling of these substances, where 80% of these products do not contain the quantities declared on the label. In addition, 10–15% of these contain prohibited substances, and this can generate a high risk of committing an

According to the Australian Institute of Sport, supplements are classified into

amount of insulin administered, along with the CHO intake.

#### *Sports Nutrition and Performance DOI: http://dx.doi.org/10.5772/intechopen.84467*

*Nutrition in Health and Disease - Our Challenges Now and Forthcoming Time*

• At least 75% of the kcal should be high glycemic index CHO

As commented before, it is advisable to use drink with different CHOs as glucose, sucrose, and maltodextrinas, in order to facilitate the absorption of liquid due to the use of different intestinal transporters. Moreover, the fructose content should not be very high, due to quantities between 20 and 30% can cause intestinal

The hydration guidelines indicated for performing physical exercise are [12, 14]:

• Ingest between 400 and 600 ml of water along the 4 h before the start of the

• Just at the beginning of the activity, ingest 200–400 ml of water with CHO (5–8%).

• During the exercise, ingest 100–200 ml of water every 15–20 min.

• The ideal temperature of drinks oscillates between 15 and 21°C

• The taste should be pleasant to the palate of the athlete.

on the other to favor the retention of that liquid in the organism.

right at the end of the exercise [48].

**7. Diabetes in sports**

• After physical activity consume 150% of the BW lost in the 6 h after.

• In low-intensity training and short-duration, the intake of water alone is

In a situation where the environment is very hot and has high humidity, the recommendations of intake of liquid and sodium will be higher [22]. A good strategy can be to make salted snacks in the hours before the exercise or add more salt content to the meals before and after the exercise. Such increase of sodium has a double purpose, on the one hand to increase the intake of liquid through thirst and

Finally, alcohol consumption is discouraged in both athletes and non-athletes. However, there seems to be a high consumption of this substance in team sports and greater consumption in men than women [45]. Among the harmful effects of alcohol consumption, the following can be highlighted: reduction of SP due to decrease in strength, power, speed, and resistance; diuretic effect that affects hydration [46]; diminution of sleep quality, mood, and immune system [47]; elevation of cortisol concentration; and reduction of muscle synthesis up to 24% even when consumed

First, the effect of exercise between insulin-dependent (type 1) and insulindependent (type 2) diabetes should be differentiated. In type 2, you do the exercise

• 80–35 kcal

problems [22].

exercise.

sufficient

• No more than 90 g CHO/liter

• Osmolality 200–330 mOsm/kg of water

• 460–1150 mg sodium/liter

**122**

to improve insulin resistance, while in type 1, you should adjust and modify the amount of insulin administered, along with the CHO intake.

Physical exercise is one of the most difficult activities to adapt to diabetes, due to the increase in the frequency of hypoglycemia. People with diabetes who perform physical activity on a regular basis have less need for insulin, but this does not ensure adequate glycemic control. The blood glucose value is of multifactorial origin, and one should take into account the CHO intake and type of sports performed as well as adjust the dose of insulin used [49].

In order to avoid hypoglycemia, during the exercise the dose of insulin will be reduced but in no case will be completely eliminated, because the lack of insulin prevents the entry of a sufficient amount of glucose into the cells for obtaining energy. A greater use of fats as fuel can generate an accumulation of ketone bodies and cause ketoacidosis. In the presence of glucose values (>250 mg/dL), ketone levels should be checked, and if elevated (>0.5 mmol/l), postpone the activity [49].

The type of exercise performed by the athlete should be taken into account, since aerobic exercise increases the risk of hypoglycemia during and after exercise, while anaerobes cause hyperglycemia due to counterregulatory hormones (glucagon, cortisol, and catecholamines) [49].

Physical exercise has some ability to introduce glucose into the muscle cell without the need for insulin action. This effect can occur during the 48 h after exercise, so there is a certain risk of suffering hypoglycemia in that period depending on the sports performed. This is due to the fact that during the physical exercise, the reserves of the muscle and liver glycogen have been emptied. Once the exercise is finished and after the intake of CHO, the glucose will be destined to replace the glycogen reserves instead of the blood, which can cause hypoglycemia, so that the high blood glucose value after a type of anaerobic exercise can be deceptive. Therefore, higher consumption of CHO or decreased insulin dose can prevent such hypoglycemia [49].

#### **8. Supplements**

An ergonomic aid is a product that contains a nutrient or a group of nutrients that improve the SP without taking into account the harmful effects in athletes, while a supplement is a nutritional aid to complete the diet associated with the practice of physical exercise [50].

When an athlete seeks to improve in the SP, his ability to tolerate intense workouts and hard competitions is crucial to avoid falling into injury or chronic fatigue. To achieve this purpose, an adequate supply of nutrients is essential. However, many times this does not happen, and the use of dietary supplements is resorted to [50].

These supplements must be prescribed individually according to the needs of each person (sex, age, fitness, intensity and duration of the exercise, season, etc.), in order to maintain both the state of health and the improvement of the SP. Dietary supplements must offer maximum possible safety and have a degree of scientific evidence to support their effect [50].

Currently between 40 and 70% of athletes make use of supplements without previously analyzing if necessary. In addition, a large number of sports supplements have not shown empirical evidence to improve SP. Likewise, there is a certain legal vacuum with the labeling of these substances, where 80% of these products do not contain the quantities declared on the label. In addition, 10–15% of these contain prohibited substances, and this can generate a high risk of committing an offense involuntarily by the athlete [51].

According to the Australian Institute of Sport, supplements are classified into four groups, based on effectiveness and safety [52]:

	- Useful and timely source of energy or nutrients in the diet of athlete
	- Scientifically proven their evidence for the improvement of the SP, when they are used with a protocol and specific situation

In this group we can find:

	- Some benefit in non-athlete population or have data that suggest possible benefit of SP.
	- Of particular interest to athletes and coaches.

In this group we can find (quercetin, HMB, glutamine, BCCA, CLA, carnitine).

	- Not proven improvement RD despite its widespread use.
	- Very little or no benefit, and sometimes they even affect the RD in a negative way.

In this group supplements of group A and B may be included when used without an individualized protocol and without a basis in scientific evidence.

	- Are prohibited or have risk of contamination with doping or positive substance by drug

In this group we can find glycerol, ephedrine, sibutramine, and tribulus terrestris.

Despite all this information, many athletes believe that supplements are the basis of the athlete's diet and believe that without that supplement, they will not reach their maximum level. This belief is one of the biggest mistakes in the world of sports nutrition, where the basic diet that is the true pillar on which sports nutrition is based is neglected.

### **9. Conclusions**

The basis of sports nutrition is a varied diet and individually tailored to the requirements and appetency of each athlete. The athlete should be instructed about

**125**

Spain

**Author details**

provided the original work is properly cited.

Raúl Arcusa Saura, María Pilar Zafrilla Rentero

\*Address all correspondence to: jmarhuenda@ucam.edu

and Javier Marhuenda Hernández\*

*Sports Nutrition and Performance*

*DOI: http://dx.doi.org/10.5772/intechopen.84467*

revisions through the sum of six skinfolds.

consumption of omega-3 compared to omega-6.

DEXA dual-energy X-ray absorptiometry BIA bioelectrical impedance analysis

mTOR mammalian target of rapamycin ACSM American College of Sports Medicine

patterns on the day of competition.

SP sports performance BC body composition BMI body mass index

**Acronyms and abbreviations**

CHOs carbohydrates BMR basal metabolic rate

BW body weight AA amino acid

the importance of diet, called "invisible training," which is not only important on competition day. Prior to establishing nutritional guidelines, it is necessary to know and adapt the BC of the athlete in the different periods of the season and make

It is necessary to know some physiology to know the different metabolic pathways that interact during the exercise. In this way depending on the type of sports performed, duration and intensity adapt dietary intake at expense. Macronutrient requirements will be established based on g/kg/BW. With respect to CHOs, recommendations vary between 3 and 12 g/kg/BW to avoid compromising the SP, and protein consumption can vary between 1.2 and 2.0 g/kg/BW, with the total daily intake being more important than the number of intakes. Regarding to fatty acids, quality will prevail, improving the inflammatory profile with an increase in the

It is essential to maintain a state of hydration before, during, and after exercise to avoid compromising SP, so it is necessary to instruct the athlete with proper hydration guidelines. It is advisable to train the digestive system during workouts, both for hydration and testing different CHOs doses. It is important not to try new

ISAK International Society for the Advancement of Kinanthropometry

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

Faculty of Health Sciences, Universidad Católica San Antonio de Murcia (UCAM),

#### *Sports Nutrition and Performance DOI: http://dx.doi.org/10.5772/intechopen.84467*

*Nutrition in Health and Disease - Our Challenges Now and Forthcoming Time*

• Group A: based on the evidence. Recommended for athletes.

they are used with a protocol and specific situation

○ Of particular interest to athletes and coaches.

In this group we can find:

bonate, beet juice)

benefit of SP.

protein)

protocol.

way.

terrestris.

is based is neglected.

**9. Conclusions**

stance by drug

○ Useful and timely source of energy or nutrients in the diet of athlete

○ Scientifically proven their evidence for the improvement of the SP, when

• Food for athletes (gels, bars, electrolytes, isotonic drinks, maltodextrins, whey

• Substances to improve SP (creatine monohydrate, caffeine, beta-alanine, bicar-

• Group B: more research deserved and advised under research or monitoring

○ Some benefit in non-athlete population or have data that suggest possible

In this group we can find (quercetin, HMB, glutamine, BCCA, CLA, carnitine).

○ Very little or no benefit, and sometimes they even affect the RD in a negative

In this group supplements of group A and B may be included when used without

○ Are prohibited or have risk of contamination with doping or positive sub-

In this group we can find glycerol, ephedrine, sibutramine, and tribulus

Despite all this information, many athletes believe that supplements are the basis of the athlete's diet and believe that without that supplement, they will not reach their maximum level. This belief is one of the biggest mistakes in the world of sports nutrition, where the basic diet that is the true pillar on which sports nutrition

The basis of sports nutrition is a varied diet and individually tailored to the requirements and appetency of each athlete. The athlete should be instructed about

• Group C: few tests of beneficial effect are not provided to athletes.

○ Not proven improvement RD despite its widespread use.

an individualized protocol and without a basis in scientific evidence.

• Group D: should not be used by athletes.

• Medical supplements (vitamin D, probiotics, iron/calcium supplements)

**124**

the importance of diet, called "invisible training," which is not only important on competition day. Prior to establishing nutritional guidelines, it is necessary to know and adapt the BC of the athlete in the different periods of the season and make revisions through the sum of six skinfolds.

It is necessary to know some physiology to know the different metabolic pathways that interact during the exercise. In this way depending on the type of sports performed, duration and intensity adapt dietary intake at expense. Macronutrient requirements will be established based on g/kg/BW. With respect to CHOs, recommendations vary between 3 and 12 g/kg/BW to avoid compromising the SP, and protein consumption can vary between 1.2 and 2.0 g/kg/BW, with the total daily intake being more important than the number of intakes. Regarding to fatty acids, quality will prevail, improving the inflammatory profile with an increase in the consumption of omega-3 compared to omega-6.

It is essential to maintain a state of hydration before, during, and after exercise to avoid compromising SP, so it is necessary to instruct the athlete with proper hydration guidelines. It is advisable to train the digestive system during workouts, both for hydration and testing different CHOs doses. It is important not to try new patterns on the day of competition.

#### **Acronyms and abbreviations**


### **Author details**

Raúl Arcusa Saura, María Pilar Zafrilla Rentero and Javier Marhuenda Hernández\* Faculty of Health Sciences, Universidad Católica San Antonio de Murcia (UCAM), Spain

\*Address all correspondence to: jmarhuenda@ucam.edu

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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[47] Barnes MJ. Alcohol: Impact on sports performance and recovery in male athletes. Sports Medicine.

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**131**

**Chapter 8**

**Abstract**

Increasing the Solubility and

Raw and Roasted Peanut

*Gary B. Smejkal, Srikanth Kakumanu* 

*and Amanda Cannady-Miller*

monly used ELISA-compatible reagents.

protein solubilization

**1. Introduction**

Recovery of Ara h3 Allergen from

Ara h3 belongs to the glycinin family of seed storage proteins and is one of the major peanut allergens. It comprises over 20% of the total peanut protein mass, making it a logical target for the detection of trace quantities of undeclared peanut contamination in foods. Both Ara h1 and Ara h3 are detected in lower quantities in cooked foods, either because of the failure to completely resolubilize the denatured proteins or because of the disruption of conformational epitopes required for monoclonal antibody recognition. A new reagent containing a proprietary nondetergent sulfobetaine (NDSB) is described which solubilizes more total protein and yields more Ara h3 protein from both raw and roasted peanut than other com-

**Keywords:** Ara h1, Ara h3, ELISA, non-detergent sulfobetaine, peanut allergy,

In the United States, an acute food allergy reaction sends someone to the emergency room every 3 minutes [1]. While over 170 foods are known to cause allergic reaction, only eight foods are responsible for over 90% of food allergies [2]. Between 1997 and 2008, the prevalence of peanut and tree nut allergies has more than tripled in the U.S. [3, 4]. Peanut allergies are a leading cause of fatal anaphylaxis [5, 6]. The U.S. Food and Drug Administration (FDA) and the European Union have imposed strict requirements for the labeling of food ingredients. However, warnings such as "May contain peanut" or "Manufactured in a facility that processes peanuts" are voluntary and considers the possibility of contamination with peanut residues [7]. Since traces of peanut may contaminate foods supposedly free of peanuts, methods capable of reliably detecting undeclared allergens are necessary to ensure food safety [8]. Highly sensitive enzyme-linked immunosorbent assays (ELISAs) can detect low nanogram quantities of contaminating allergens in foods and biologics, whereas the rapid lateral flow assays available for consumers to test their foods are less sensitive. For example, the recently described Ara h3 ELISA [9] is about 2000 times more sensitive than the NIMA Peanut Sensor, which also targets Ara h3 [10]. To put into perspective, the ELISA could detect roughly 14 peanuts dissolved in an Olympic size swimming pool, having a volume of 2,499,330 L of water.

#### **Chapter 8**

## Increasing the Solubility and Recovery of Ara h3 Allergen from Raw and Roasted Peanut

*Gary B. Smejkal, Srikanth Kakumanu and Amanda Cannady-Miller*

#### **Abstract**

Ara h3 belongs to the glycinin family of seed storage proteins and is one of the major peanut allergens. It comprises over 20% of the total peanut protein mass, making it a logical target for the detection of trace quantities of undeclared peanut contamination in foods. Both Ara h1 and Ara h3 are detected in lower quantities in cooked foods, either because of the failure to completely resolubilize the denatured proteins or because of the disruption of conformational epitopes required for monoclonal antibody recognition. A new reagent containing a proprietary nondetergent sulfobetaine (NDSB) is described which solubilizes more total protein and yields more Ara h3 protein from both raw and roasted peanut than other commonly used ELISA-compatible reagents.

**Keywords:** Ara h1, Ara h3, ELISA, non-detergent sulfobetaine, peanut allergy, protein solubilization

#### **1. Introduction**

In the United States, an acute food allergy reaction sends someone to the emergency room every 3 minutes [1]. While over 170 foods are known to cause allergic reaction, only eight foods are responsible for over 90% of food allergies [2]. Between 1997 and 2008, the prevalence of peanut and tree nut allergies has more than tripled in the U.S. [3, 4]. Peanut allergies are a leading cause of fatal anaphylaxis [5, 6].

The U.S. Food and Drug Administration (FDA) and the European Union have imposed strict requirements for the labeling of food ingredients. However, warnings such as "May contain peanut" or "Manufactured in a facility that processes peanuts" are voluntary and considers the possibility of contamination with peanut residues [7]. Since traces of peanut may contaminate foods supposedly free of peanuts, methods capable of reliably detecting undeclared allergens are necessary to ensure food safety [8]. Highly sensitive enzyme-linked immunosorbent assays (ELISAs) can detect low nanogram quantities of contaminating allergens in foods and biologics, whereas the rapid lateral flow assays available for consumers to test their foods are less sensitive. For example, the recently described Ara h3 ELISA [9] is about 2000 times more sensitive than the NIMA Peanut Sensor, which also targets Ara h3 [10]. To put into perspective, the ELISA could detect roughly 14 peanuts dissolved in an Olympic size swimming pool, having a volume of 2,499,330 L of water.

Proteins constitute 24–27% of the total peanut mass [11]. At least 13 different protein allergens have been identified in *Arachis hypogaea*. Of these, Ara h2 and Ara h6 are reportedly the most potent allergens [12, 13], whereas Ara h1 and Ara h3 are the two most abundant allergens, together comprising at least a third of the total peanut protein mass [14]. Ara h4 has 91.3% sequence homology with Ara h3 [8] and are considered to be the same allergen [15, 16].

Ara h3 exists as a trimer or hexamer consisting of identical 58.3 kDa subunits and having molecular masses of 180 and 360 kDa, respectively. Each subunit is derived from a single precursor which is posttranslationally cleaved to produce an acidic and a basic chain that are held together by a disulfide bond [17, 18]. Multiple subunits in the mature Ara h3 are associated via hydrophobic bonding.

The roasting of peanuts decreases the extractability of soluble protein by as much as 50% [19]. Upon heating, Ara h1 and Ara h3 may form aggregates, further decreasing their solubility [20]. Further, the denaturation of proteins drives conformational changes that can result in the loss of epitopes. Decreased antibody recognition in ELISA has been reported for both monoclonal and polyclonal antibodies [21, 22].

Lipid constitutes approximately 50% of the total peanut mass. There are conflicting reports on whether delipidation of peanuts increase protein recovery [22, 23]. Likewise, detergents such as Sarkosyl have been shown to increase protein solubility [24].

Sample preparation will be critical to the reliable quantitation of undeclared peanut allergens in foods by immunoassay, particularly in cooked foods where the denaturation of proteins renders them insoluble (e.g., imagine trying to resolubilize cooked egg whites). The failure to completely resolubilize target proteins results in their underestimation, a critical shortcoming where undeclared allergens may be present in only trace amounts.

This chapter reviews the solubility and the recovery of the Ara h3 allergen from raw and roasted peanuts extracted in several different buffers with consideration of ELISA compatibility. Since Ara h3 is one of the most abundant proteins, it is a logical target for the detection of trace quantities of peanut contamination in foods.

#### **2. Methods**

#### **2.1 Sample preparation of raw and roasted peanuts**

Raw Virginia peanuts (Hampton Farms, Severn, NC, USA) were dry roasted at 175°C for 20 minutes. Raw and roasted peanuts were shelled, and then course ground in a stainless steel coffee grinder. The resulting grounds were sifted through a 0.5 mm stainless steel mesh to provide uniform triturates.

The peanut triturates (53.9 ± 4.1 mg, n = 24) were weighed into the insert of a BioMasher centrifugal homogenizer (Omni International, Kennesaw, GA, USA). Biological replicates were extracted in 0.4 mL of each sample buffer. Sample buffers were (i) PBS pH 7.4, (ii) 0.05% Tween-20 in PBS pH 7.4, (iii), 8 M urea, 16 mM 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS) in 40 mM Tris-HCl pH 8.8, and (iv) a proprietary non-detergent sulfobetaine (NDSB) from ProdigY Biosciences (Louisville, KY, USA).

Each sample was homogenized in the BioMasher for 20 seconds and the extract was collected by centrifugation at 15,000 RCF for 1 minute. The BioMasher insert was removed and centrifugation was continued at 15,000 RCF for an additional 5 minutes. Both an insoluble pellet and a floating lipid layer were observed in all samples. The supernatant was carefully aspirated from below the lipid layer and

**133**

*Increasing the Solubility and Recovery of Ara h3 Allergen from Raw and Roasted Peanut*

of raw and roasted peanuts, and in 0.4 and 0.8 mL extraction volumes.

further clarified in an UltraFree MC centrifugal microfilter with 0.22 micron pore size (Millipore-Sigma, Burlington, MA, USA) at 12,000 RCF for 5 minutes.

The homogenizer bar was withdrawn from the BioMasher insert and an additional 0.4 mL of each reagent was added and the process was repeated a second time. This enabled estimates of extraction efficiency in first and second extractions

Total protein concentration was estimated using the Bradford protein assay (BioRad, Hercules, CA, USA) calibrated with a qualified BSA standard (Pierce

Ara h3 was quantified using the Ara h3 ELISA 2.0 Kit (Indoor Biotechnologies, Charlottesville, VA, USA) using the 1E8 and 4G9 monoclonal antibody pair and strep-

FASTA sequences of representative peanut proteins were procured from the UniProtKB Protein Knowledgebase [25, 26]. GRAVY values were based on amino acid hydropathy index [27] and calculated using the ProtParam software tools avail-

In every case, more total protein was recovered in raw than in roasted peanut. The NDSB buffer recovered more total protein in a single 0.4 mL extraction than all of the other buffers tested. NDSB replicates averaged 14.8% total protein recovery from raw peanut triturates, nearly twice as much protein than what was extracted with urea-CHAPS. On average, NDSB extracted seven times more total protein than

Lower total protein recoveries were observed from roasted peanut. NDSB yielded 4.0% total protein from roasted peanut, compared to 4.4% from urea-CHAPS. NDSB and urea-CHAPS yielded twice as much soluble protein from

NDSB yielded the highest recoveries of specific Ara h3 protein in both raw and roasted peanut as measured by ELISA. On average, NDSB yielded more than twice the measurable Ara h3 from raw peanut than PBS-Tween (**Figure 1**). From roasted peanut, NDSB yielded nearly seven times more Ara h3 than PBS-Tween (**Figure 2**). Ara h3 was not detected by ELISA in raw or roasted peanut samples extracted in urea-CHAPS. This is apparently due to the disruption of tertiary and secondary structure of the protein and the obliteration of conformational epitopes required for binding by the monoclonal antibodies used in the ELISA. While the urea-CHAPS was substantially diluted for ELISA, no restoration of antibody recognition was observed.

= 0.9998).

tavidin-HRP reporter. Calibration was linear over the 2–125 ng/mL range (r2

**2.3 Calculation of grand average of hydropathicity (GRAVY) values**

able from the ExPASy Bioinformatics Resource Portal [28].

**3.1 Total recoverable protein from raw peanut**

**3.2 Total recoverable protein from roasted peanut**

roasted peanut than PBS-Tween (**Figure 2**).

**3.3 Ara h3 yields from raw and roasted peanut**

*DOI: http://dx.doi.org/10.5772/intechopen.85236*

Biotechnology, Rockland, IL, USA).

**3. Results and discussion**

PBS-Tween (**Figure 1**).

**2.2 Analysis**

*Increasing the Solubility and Recovery of Ara h3 Allergen from Raw and Roasted Peanut DOI: http://dx.doi.org/10.5772/intechopen.85236*

further clarified in an UltraFree MC centrifugal microfilter with 0.22 micron pore size (Millipore-Sigma, Burlington, MA, USA) at 12,000 RCF for 5 minutes.

The homogenizer bar was withdrawn from the BioMasher insert and an additional 0.4 mL of each reagent was added and the process was repeated a second time. This enabled estimates of extraction efficiency in first and second extractions of raw and roasted peanuts, and in 0.4 and 0.8 mL extraction volumes.

#### **2.2 Analysis**

*Nutrition in Health and Disease - Our Challenges Now and Forthcoming Time*

are considered to be the same allergen [15, 16].

Proteins constitute 24–27% of the total peanut mass [11]. At least 13 different protein allergens have been identified in *Arachis hypogaea*. Of these, Ara h2 and Ara h6 are reportedly the most potent allergens [12, 13], whereas Ara h1 and Ara h3 are the two most abundant allergens, together comprising at least a third of the total peanut protein mass [14]. Ara h4 has 91.3% sequence homology with Ara h3 [8] and

Ara h3 exists as a trimer or hexamer consisting of identical 58.3 kDa subunits and having molecular masses of 180 and 360 kDa, respectively. Each subunit is derived from a single precursor which is posttranslationally cleaved to produce an acidic and a basic chain that are held together by a disulfide bond [17, 18]. Multiple

The roasting of peanuts decreases the extractability of soluble protein by as much as 50% [19]. Upon heating, Ara h1 and Ara h3 may form aggregates, further decreasing their solubility [20]. Further, the denaturation of proteins drives conformational changes that can result in the loss of epitopes. Decreased antibody recognition in ELISA has been reported for both monoclonal and polyclonal antibodies

Lipid constitutes approximately 50% of the total peanut mass. There are conflicting reports on whether delipidation of peanuts increase protein recovery [22, 23]. Likewise, detergents such as Sarkosyl have been shown to increase protein

Sample preparation will be critical to the reliable quantitation of undeclared peanut allergens in foods by immunoassay, particularly in cooked foods where the denaturation of proteins renders them insoluble (e.g., imagine trying to resolubilize cooked egg whites). The failure to completely resolubilize target proteins results in their underestimation, a critical shortcoming where undeclared allergens may be

This chapter reviews the solubility and the recovery of the Ara h3 allergen from raw and roasted peanuts extracted in several different buffers with consideration of ELISA compatibility. Since Ara h3 is one of the most abundant proteins, it is a logical target for the detection of trace quantities of peanut contamination in foods.

Raw Virginia peanuts (Hampton Farms, Severn, NC, USA) were dry roasted at 175°C for 20 minutes. Raw and roasted peanuts were shelled, and then course ground in a stainless steel coffee grinder. The resulting grounds were sifted through

The peanut triturates (53.9 ± 4.1 mg, n = 24) were weighed into the insert of a BioMasher centrifugal homogenizer (Omni International, Kennesaw, GA, USA). Biological replicates were extracted in 0.4 mL of each sample buffer. Sample buffers were (i) PBS pH 7.4, (ii) 0.05% Tween-20 in PBS pH 7.4, (iii), 8 M urea, 16 mM 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS) in 40 mM Tris-HCl pH 8.8, and (iv) a proprietary non-detergent sulfobetaine (NDSB)

Each sample was homogenized in the BioMasher for 20 seconds and the extract

was collected by centrifugation at 15,000 RCF for 1 minute. The BioMasher insert was removed and centrifugation was continued at 15,000 RCF for an additional 5 minutes. Both an insoluble pellet and a floating lipid layer were observed in all samples. The supernatant was carefully aspirated from below the lipid layer and

subunits in the mature Ara h3 are associated via hydrophobic bonding.

**132**

[21, 22].

solubility [24].

**2. Methods**

present in only trace amounts.

**2.1 Sample preparation of raw and roasted peanuts**

a 0.5 mm stainless steel mesh to provide uniform triturates.

from ProdigY Biosciences (Louisville, KY, USA).

Total protein concentration was estimated using the Bradford protein assay (BioRad, Hercules, CA, USA) calibrated with a qualified BSA standard (Pierce Biotechnology, Rockland, IL, USA).

Ara h3 was quantified using the Ara h3 ELISA 2.0 Kit (Indoor Biotechnologies, Charlottesville, VA, USA) using the 1E8 and 4G9 monoclonal antibody pair and streptavidin-HRP reporter. Calibration was linear over the 2–125 ng/mL range (r2 = 0.9998).

#### **2.3 Calculation of grand average of hydropathicity (GRAVY) values**

FASTA sequences of representative peanut proteins were procured from the UniProtKB Protein Knowledgebase [25, 26]. GRAVY values were based on amino acid hydropathy index [27] and calculated using the ProtParam software tools available from the ExPASy Bioinformatics Resource Portal [28].

#### **3. Results and discussion**

#### **3.1 Total recoverable protein from raw peanut**

In every case, more total protein was recovered in raw than in roasted peanut. The NDSB buffer recovered more total protein in a single 0.4 mL extraction than all of the other buffers tested. NDSB replicates averaged 14.8% total protein recovery from raw peanut triturates, nearly twice as much protein than what was extracted with urea-CHAPS. On average, NDSB extracted seven times more total protein than PBS-Tween (**Figure 1**).

#### **3.2 Total recoverable protein from roasted peanut**

Lower total protein recoveries were observed from roasted peanut. NDSB yielded 4.0% total protein from roasted peanut, compared to 4.4% from urea-CHAPS. NDSB and urea-CHAPS yielded twice as much soluble protein from roasted peanut than PBS-Tween (**Figure 2**).

#### **3.3 Ara h3 yields from raw and roasted peanut**

NDSB yielded the highest recoveries of specific Ara h3 protein in both raw and roasted peanut as measured by ELISA. On average, NDSB yielded more than twice the measurable Ara h3 from raw peanut than PBS-Tween (**Figure 1**). From roasted peanut, NDSB yielded nearly seven times more Ara h3 than PBS-Tween (**Figure 2**).

Ara h3 was not detected by ELISA in raw or roasted peanut samples extracted in urea-CHAPS. This is apparently due to the disruption of tertiary and secondary structure of the protein and the obliteration of conformational epitopes required for binding by the monoclonal antibodies used in the ELISA. While the urea-CHAPS was substantially diluted for ELISA, no restoration of antibody recognition was observed.

#### **Figure 1.**

*Normalized recovery of total protein and Ara h3 from biological triplicates of raw peanut (53.6 ± 4.9 mg, n = 12) extracted in 0.4 mL of PBS, PBS-Tween, NDSB, or urea-CHAPS. For extraction efficiency, total protein and Ara h3 mass are expressed in terms of their percentage of the total peanut biomass.*

#### **Figure 2.**

*Normalized recovery of total protein and Ara h3 from biological triplicates of roasted peanut (53.6 ± 4.9 mg, n = 12) extracted in 0.4 mL of PBS, PBS-Tween, NDSB, or urea-CHAPS. Total protein and Ara h3 mass are expressed in terms of their percentage of the total peanut biomass.*

#### **3.4 Increasing total protein yields by sequential extraction**

To investigate whether a second extraction would significantly improve total protein yields, an additional 0.4 mL of each buffer was added to the insoluble peanut triturate remaining in each homogenizer insert following the first extraction.

**135**

**Figure 3.**

*Increasing the Solubility and Recovery of Ara h3 Allergen from Raw and Roasted Peanut*

PBS extracted 50.4 and 45.3% of the total PBS soluble protein in the first extraction for raw and roasted peanut, respectively. PBS-Tween extracted 75.6 and 78.2% of the total PBS-Teen soluble protein in the first extraction for raw and roasted

NDSB extracted 83.7 and 92.0% of the total NDSB soluble protein in the first extraction for raw and roasted peanut, respectively. For raw peanut, mean efficiency of NDSB was 14.8% for the first extraction, which was increased to 17.7% when a second extraction was performed. For roasted peanut, mean efficiency of NDSB was 4.0 ± 0.3% for the first extraction, which was increased to 4.4 ± 0.3% when a second extraction was performed (**Figure 3**). In practical terms, only about 10% more protein is recovered when a second extraction is performed, but at the

Urea-CHAPS extracted 94.5 and 89.9% of the soluble protein in the first extraction for raw and roasted peanut, respectively. For raw peanut, mean efficiency

*Normalized recovery of total protein following sequential extractions in 0.4 mL of PBS, PBS-Tween, NDSB, or urea-CHAPS. Following an initial extraction in 0.4 mL, an additional 0.4 mL of buffer was added to the insoluble peanut triturate remaining in the BioMasher insert and the extraction process was repeated. Total* 

*protein is expressed in terms of its percentage of the total peanut biomass.*

*DOI: http://dx.doi.org/10.5772/intechopen.85236*

cost of doubling the sample volume of the isolate.

peanut, respectively.

*Increasing the Solubility and Recovery of Ara h3 Allergen from Raw and Roasted Peanut DOI: http://dx.doi.org/10.5772/intechopen.85236*

PBS extracted 50.4 and 45.3% of the total PBS soluble protein in the first extraction for raw and roasted peanut, respectively. PBS-Tween extracted 75.6 and 78.2% of the total PBS-Teen soluble protein in the first extraction for raw and roasted peanut, respectively.

NDSB extracted 83.7 and 92.0% of the total NDSB soluble protein in the first extraction for raw and roasted peanut, respectively. For raw peanut, mean efficiency of NDSB was 14.8% for the first extraction, which was increased to 17.7% when a second extraction was performed. For roasted peanut, mean efficiency of NDSB was 4.0 ± 0.3% for the first extraction, which was increased to 4.4 ± 0.3% when a second extraction was performed (**Figure 3**). In practical terms, only about 10% more protein is recovered when a second extraction is performed, but at the cost of doubling the sample volume of the isolate.

Urea-CHAPS extracted 94.5 and 89.9% of the soluble protein in the first extraction for raw and roasted peanut, respectively. For raw peanut, mean efficiency

#### **Figure 3.**

*Nutrition in Health and Disease - Our Challenges Now and Forthcoming Time*

*Normalized recovery of total protein and Ara h3 from biological triplicates of raw peanut (53.6 ± 4.9 mg, n = 12) extracted in 0.4 mL of PBS, PBS-Tween, NDSB, or urea-CHAPS. For extraction efficiency, total protein and Ara h3 mass are expressed in terms of their percentage of the total peanut biomass.*

**3.4 Increasing total protein yields by sequential extraction**

*expressed in terms of their percentage of the total peanut biomass.*

To investigate whether a second extraction would significantly improve total protein yields, an additional 0.4 mL of each buffer was added to the insoluble peanut triturate remaining in each homogenizer insert following the first

*Normalized recovery of total protein and Ara h3 from biological triplicates of roasted peanut (53.6 ± 4.9 mg, n = 12) extracted in 0.4 mL of PBS, PBS-Tween, NDSB, or urea-CHAPS. Total protein and Ara h3 mass are* 

**134**

extraction.

**Figure 2.**

**Figure 1.**

*Normalized recovery of total protein following sequential extractions in 0.4 mL of PBS, PBS-Tween, NDSB, or urea-CHAPS. Following an initial extraction in 0.4 mL, an additional 0.4 mL of buffer was added to the insoluble peanut triturate remaining in the BioMasher insert and the extraction process was repeated. Total protein is expressed in terms of its percentage of the total peanut biomass.*

#### **Figure 4.**

*Relative hydrophobicity of 37 published protein sequences including 10 known allergens from Arachis hypogaea. Grand average of hydropathicity (GRAVY) values were calculated from FASTA sequences where the sum of the hydropathy index values for each amino acid is divided by the total number of residues.*

of urea-CHAPS was 9.0 ± 0.9% for the first extraction which was increased to 9.6 ± 0.8% when a second extraction was performed. For roasted peanut, mean efficiency of urea-CHAPS was 4.4 ± 0.8% for the first extraction which was increased to 4.9 ± 0.6% when a second extraction was performed. While the total protein recovered from roasted peanut extracted in urea-CHAPS or NDSB were similar, the chaotrope rendered the samples incompatible with the capture ELISA used in these studies (**Figures 3** and **4**).

#### **4. Concluding remarks**

Of the reagents tested, the NDSB reagent yielded the highest recovery of Ara h3, on average yielding seven times more allergen from roasted peanut than PBS-Tween. While the overall solubility of proteins is significantly diminished in roasted peanut, NDSB recovered nearly identical amounts of Ara h3 from both raw and roasted peanut.

ELISA and total protein values obtained from this cultivar indicated that Ara h3 comprised 34.9 ± 1.4% (CV = 0.039, n = 3), of the soluble protein derived from raw peanut and 34.6 ± 3.0% (CV = 0.085, n = 3) of the soluble protein from roasted peanut. Seed storage proteins may be overexpressed in response to growing conditions and can vary considerably between cultivars. This suggests that some cultivars may be more hyperallergenic than others. Moreover, the recovery of total soluble protein varies between cultivars, and extraction efficiencies as low as 9% based on the initial peanut mass have been reported for boiled runner peanuts [29]. The calculation of extraction efficiency, however, is influenced by variable water content. In these experiments, the NDSB reagent yielded 17.7 and 4.4% of the initial peanut mass as soluble protein from raw and dry roasted peanuts, respectively.

The described sample preparation method may be positively biased toward the solubility of this particular allergen. Further work is needed to investigate the solubility of other peanut proteins, particularly other clinically important peanut allergens.

**137**

**Author details**

Gary B. Smejkal1

provided the original work is properly cited.

\*, Srikanth Kakumanu1

\*Address all correspondence to: info@focusproteomics.com

1 Focus Proteomics, Hudson, New Hampshire, USA

2 ProdigY Biosciences, Louisville, Kentucky, USA

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

and Amanda Cannady-Miller2

*Increasing the Solubility and Recovery of Ara h3 Allergen from Raw and Roasted Peanut*

CHAPS 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate

*DOI: http://dx.doi.org/10.5772/intechopen.85236*

NDSB non-detergent sulfobetaine PBS phosphate buffered saline.

ELISA enzyme-linked immunosorbent assay

**Abbreviations**

*Increasing the Solubility and Recovery of Ara h3 Allergen from Raw and Roasted Peanut DOI: http://dx.doi.org/10.5772/intechopen.85236*

#### **Abbreviations**

*Nutrition in Health and Disease - Our Challenges Now and Forthcoming Time*

of urea-CHAPS was 9.0 ± 0.9% for the first extraction which was increased to 9.6 ± 0.8% when a second extraction was performed. For roasted peanut, mean efficiency of urea-CHAPS was 4.4 ± 0.8% for the first extraction which was increased to 4.9 ± 0.6% when a second extraction was performed. While the total protein recovered from roasted peanut extracted in urea-CHAPS or NDSB were similar, the chaotrope rendered the samples incompatible with the capture ELISA used in these

*hydropathy index values for each amino acid is divided by the total number of residues.*

*Relative hydrophobicity of 37 published protein sequences including 10 known allergens from Arachis hypogaea. Grand average of hydropathicity (GRAVY) values were calculated from FASTA sequences where the sum of the* 

Of the reagents tested, the NDSB reagent yielded the highest recovery of Ara h3, on average yielding seven times more allergen from roasted peanut than PBS-Tween. While the overall solubility of proteins is significantly diminished in roasted peanut, NDSB recovered nearly identical amounts of Ara h3 from both raw and

ELISA and total protein values obtained from this cultivar indicated that Ara h3 comprised 34.9 ± 1.4% (CV = 0.039, n = 3), of the soluble protein derived from raw peanut and 34.6 ± 3.0% (CV = 0.085, n = 3) of the soluble protein from roasted peanut. Seed storage proteins may be overexpressed in response to growing conditions and can vary considerably between cultivars. This suggests that some cultivars may be more hyperallergenic than others. Moreover, the recovery of total soluble protein varies between cultivars, and extraction efficiencies as low as 9% based on the initial peanut mass have been reported for boiled runner peanuts [29]. The calculation of extraction efficiency, however, is influenced by variable water content. In these experiments, the NDSB reagent yielded 17.7 and 4.4% of the initial peanut mass as soluble protein from raw and dry roasted

The described sample preparation method may be positively biased toward the solubility of this particular allergen. Further work is needed to investigate the solubility of other peanut proteins, particularly other clinically important peanut

**136**

allergens.

studies (**Figures 3** and **4**).

**4. Concluding remarks**

roasted peanut.

**Figure 4.**

peanuts, respectively.


### **Author details**

Gary B. Smejkal1 \*, Srikanth Kakumanu1 and Amanda Cannady-Miller2

1 Focus Proteomics, Hudson, New Hampshire, USA

2 ProdigY Biosciences, Louisville, Kentucky, USA

\*Address all correspondence to: info@focusproteomics.com

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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*DOI: http://dx.doi.org/10.5772/intechopen.85236*

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[15] Koppelman SJ, Knol EF, Vlooswijk RA, Wensing M, Knulst AC, Hefle SL, et al. Peanut allergen Ara h3: Isolation from peanuts and biochemical characterization. Allergy. 2003;**58**:1144-1151

[16] Boldt A, Fortunato D, Conti A, Petersen A, Ballmer-Weber B, Lepp U, et al. Analysis of the composition of an immunoglobulin E reactive high molecular weight protein complex of peanut extract containing Ara h1 and Ara h3/4. Proteomics. 2005;**5**: 675-686

[17] Beardslee TA, Zeece MG, Sarath G, Markwell JP. Soybean glycinin G1 acidic chain shares IgE epitopes with peanut allergen Ara h3. International Archives of Allergy and Immunology. 2000;**123**:299-307

[18] Yusnawan E, Marquis CP, Lee NA. Purification and characterization of Ara h1 and Ara h3 from four peanut market types revealed higher order oligomeric structures. Journal of Agricultural and Food Chemistry. 2012;**60**:10352-10358

[19] Koppelman S, Apostolovic D, Warmenhoven H, Verbart D, Taylor S, Isleib T, et al. The content of allergens Ara h1, Ara h2, Ara h3, and Ara h6 in different peanut cultivars commonly consumed in Europe and the USA. Allergy. 2012;**67**:548

[20] Koppelman SJ, Smits M, Tomassen M, De Jong GAH, Baumert J, Taylor SL, et al. Release of major peanut allergens from their matrix under various pH and simulated saliva conditions: Ara h2 and Ara h6 are readily bio-accessible. Nutrients. 2018;**10**:1281

[21] Iqbal A, Shah F, Hamayun M, Ahmad A, Hussain A, Waqas M, et al. Allergens of *Arachis hypogaea* and the effect of processing on their detection by ELISA. Food and Nutrition Research. 2016;**60**:28945

[22] Comstock SS, Maleki SJ, Teuber SS. Boiling and frying peanuts decreases soluble peanut (*Arachis Hypogaea*) allergens Ara h1 and Ara h2 but does not generate hypoallergenic peanuts. PLoS One. 2016;**11**:0157849

[23] Walczyk NE, Smith PMC, Tovey ER, Roberts TH. Peanut protein extraction conditions strongly influence yield of allergens Ara h1 and 2 and sensitivity of immunoassays. Food Chemistry. 2017;**221**:335-344

[24] Lin HY, Huang CH, Park J, Pathania D, Castro CM, Fasano A, et al. Integrated magneto-chemical sensor for on-site food allergen detection. ACS Nano. 2017;**11**:10062-10069

[25] UniProt Consortium. UniProt: The universal protein knowledgebase. Nucleic Acids Research. 2018;**46**:2699

[26] Pundir S, Martin MJ, O'Donovan C. UniProt protein knowledgebase. Methods in Molecular Biology. 2017;**1558**:41-55

[27] Kyte J, Doolittle RF. A simple method for displaying the hydropathic character of a protein. Journal of Molecular Biology. 1982;**157**:105-132

[28] Gasteiger E, Hoogland C, Gattiker A, Duvaud S, Wilkins MR, Appel RD, et al. Protein identification and analysis tools on the ExPASy server. In: The Proteomics Protocols Handbook. New York, NY: Humana Press; 2005. pp. 571-607

[29] Yusnawan E. Study of variation in Ara h1 and Ara h3 expression in Australian and Indonesian peanut genotypes, based on the antibody-based phenotyping assays [thesis]. School of Chemical Engineering, University of New South Wales. 2012. Available from: https://www. unsworks.unsw.edu. au/fapi/datastream/unsworks:10654/ SOURCE01

**138**

*Nutrition in Health and Disease - Our Challenges Now and Forthcoming Time*

detection of peanut contamination in food products. Comprehensive Reviews in Food Science and Food Safety.

[9] Hoyt AEW, Chapman MD, King EM, Platts-Mills TAE, Steinke JW. Food allergen component proteins are not detected in early-childhood vaccines. The Journal of Allergy and Clinical Immunology. In Practice.

[10] NIMA Labs. The Science behind NIMA: Understanding the device. 2018. Available from: https://nimasensor.com/ science-nima-understanding-device/

[11] Koppelman SJ, Vlooswijk RAA, Knippels LMJ, Hessing M, Knol EF, van Reijsen FC, et al. Quantification of major peanut allergens Ara h1 and Ara h2 in the peanut varieties runner, Spanish, Virginia, and Valencia, bred in different parts of the world. Allergy.

[12] Zhuang Y, Dreskin SC. Redefining

Immunologic Research. 2013;**55**:125-134

the major peanut allergens.

Allergy. 2004;**34**:583-590

2016;**88**:5689-5695

[14] Johnson PE, Sayers RL, Gethings LA, Balasundaram A, Marsh JT, Langridge JI, et al. Quantitative

proteomic profiling of peanut allergens in food ingredients used for oral food challenges. Analytical Chemistry.

[13] Koppelman SJ, Wensing M, Ertmann M, Knulst AC, Knol EF. Relevance of Ara h1, Ara h2 and Ara h3 in peanut-allergic patients as determined by immunoglobulin E Western blotting, basophilhistamine release and intracutaneous testing: Ara h2 is the most important peanut allergen. Clinical and Experimental

2007;**6**:47-58

2018;**6**:677-679

2001;**56**:132-137

**References**

2010;**126**:S1-S58

1999;**103**:559-562

2010;**125**:1322-1326

2013;**43**:1333-1341

[1] Clark S, Espinola J, Rudders SA, Banerji A, Camargo CA. Frequency of US emergency department visits for food-related acute allergic reactions. The Journal of Allergy and Clinical Immunology. 2011;**127**:682-683

[2] NIAID-Sponsored Expert Panel. Guidelines for the diagnosis and management of food allergy in the United States: Report of the NIAIDsponsored expert panel. The Journal of Allergy and Clinical Immunology.

[3] Sicherer SH, Muñoz-Furlong A, Burks AW, Sampson HA. Prevalence of peanut and tree nut allergy in the US determined by a random digit dial telephone survey. The Journal of Allergy and Clinical Immunology.

[4] Sicherer SH, Muñoz-Furlong A, Godbold JH, Sampson HA. US prevalence of self-reported peanut, tree nut, and sesame allergy: 11-year follow-up. The Journal of Allergy and Clinical Immunology.

[5] Umasunthar T, Leonardi-Bee J, Hodes M, Turner PJ, Gore C, Habibi P, et al. Incidence of fatal food

[6] Finkelman FD. Peanut allergy and anaphylaxis. Current Opinion in Immunology. 2010;**22**:783-788

[7] Taylor SL, Hefle SL. Food allergen labeling in the USA and Europe.

Immunology. 2006;**6**:186-190

[8] Wen HW, Borejsza-Wysocki W, DeCory TR, Durst RA. Peanut allergy, peanut allergens, and methods for the

Current Opinion in Allergy and Clinical

anaphylaxis in people with food allergy: A systematic review and meta-analysis. Clinical and Experimental Allergy.

**141**

Section 4

Undernutrition in Elderly

People

Section 4
