**1. Introduction**

Human metabolism is influenced by dietary, lifestyle, environmental and genetic factors [1]. Analysis of plasma metabolites by groups showed significant differences between meat eaters, fish eaters, vegetarians, and especially vegans [2]. Randomized clinical studies have shown that plant-based diets are associated with reduced risk of mortality and morbidity from cardiovascular disease (CVD) [3]. The association of low CVD index and vegetarian dietary patterns are the result of the constant reduction of organisms' exposure to harmful substances contained in products of animal origin (for example: saturated fat, cholesterol, heme iron, N-glycolylneuramine acid, persistent organic pollutants, polycyclic aromatic hydrocarbons, heterocyclic amines and advanced glycation end products), in addition to the increased consumption of fibers and phytochemicals present in whole plant foods. Phytochemicals in plant-food include carotenoids (α- and β-carotene, lycopene, phenolic compounds, vitamin C, tocopherols, biogenic amines, among others [4], which can act synergistically by reducing inflammation and oxidative stress, providing protection against CVD [3, 5].

Biogenic amines are aliphatic organic bases of low molecular weight and have biological activity in microorganisms, plants and animals. Polyamines (putrescine, cadaverine, spermidine and spermine) and biogenic amines (serotonin, dopamine, histamine, tyramine, among others) are called bioactive amines (BAs) and are relevant for both shelf life and final product quality, as well as for human health [6]. Some polyamines play an important role in growth and can act as antioxidants [7–9], while other amines are neuroactive or vasoactive [6]. In addition, amines are also described as being indicators of plant-food safety and some countries already limit the amount of some BAs, mainly in fermented foods [10, 11].

Although many BAs, such as histamine, tyramine and putrescine are necessary for many functions in humans, consumption of foods containing large amounts of these amines can have toxicological effects. For example, excessive consumption of histamine can induce histaminic intoxication and is mainly related to heart disease (hypotension and palpitations) and headache [12]. Tyramine is also considered harmful to the body [13]. Even though some studies show the levels of amines in plant-based food [7–9, 14], the number of studies that establish legal limits in foodstuffs is still insufficient.

While histamine and tyramine can have adverse effects, the ingestion of foods rich in some amines, such as spermidine and spermine, has been linked to longevity, both in humans [15] and in plants [16]. Diamines such as putrescine and cadaverine have been described due to their occurrence in higher levels in contaminated foods or in senescent plant tissue. Besides these polyamines, monoamines such as serotonin and dopamine have important neurological and antioxidant functions in both animals and plants. These amines can be obtained by eating some foods plant-based (banana, cauliflower, grapes - *in natura* and byproducts) and/or animal (fish and meat). However, the synthesis and *turnover* of serotonin depends on the intake of the amino acid tryptophan for the formation of serotonin in the brain, since this neutrotransmitter does not cross the blood–brain barrier [17]. In mammals, serotonin is a neurotransmitter that acts on the central nervous system, affecting appetite, sleep, anxiety and mood. In addition to being an important precursor to the formation of serotonin in the brain, tryptophan is also a precursor to melatonin, an indolamine, which has antioxidant action, besides acting in physiological processes related to the regulation of circadian rhythm, mood and sleep. This chapter provides an overview of the presence of amines in plant-based diets, the impacts of food handling and processing on these molecules, in addition to the mechanisms by which these compounds are absorbed and affect physiological functions in humans.

## **2. Fruit, vegetables and their bioactive amines against human diseases**

Fruit and vegetables play an important role in human health, since they contain many essential nutrients and phytochemicals that are responsible for preventing or reducing the risk of various chronic diseases, including cardiovascular disease, diabetes, obesity, certain types of cancer, inflammation, heart attack, stroke and septic shock. Additionally, vegans, vegetarians and omnivores, consume fruits and vegetable by-products that contribute to significant levels of important health compounds, which have been extensively researched, in addition to being profitable raw materials and easily available to the food and pharmaceutical industries.

Cells are constantly exposed to oxidizing agents and a key point is the balance of the oxidative effect by antioxidant mechanisms. To reduce the risk of developing chronic diseases in humans and possibly delay the appearance of age-related problems,

**3**

*The Increase of Amines Content in the Intake of a Vegan Diet*

antioxidant potential of fruits and vegetables [7, 8].

nutritional recommendations are that young and old people eat at least seven portions a day of different fruits and vegetables. For a lowest risk of total cancer, studies showed that it is important to intake of 600 g/day (7.5 portions/day), however, for coronary heart disease, stroke, cardiovascular disease and all-cause mortality the lowest risk was observed at 800 g/day (10 portions/day) [18]. Many studies show a strong and positive correlation between the content of BAs and the

BAs are involved in several physiological processes and can act as antioxidants [7, 8] and some studies relate polyamines to ion channel regulation, DNA methylation, histone acetylation, protein biosynthesis, RNA translation, apoptosis and regulation of the immune response [19], in addition to being considered a secondary messenger, mediating some growth factors in plants [20]. Studies indicate that the BAs present in fruits and vegetables are strong antioxidant compounds with more effective free radical scavenging properties, compared to some natural antioxidants, for example, phenolic compounds [8, 21] or well-accepted synthetic compounds, such as α-tocopherol, octyl gallate and palmitoyl-ascorbic acid [22]. In fruits and vegetables, around 22 BAs have already been described, and the most detected BAs are tyramine, putrescine, cadaverine, histamine, spermine and spermidine [10], while few studies report the detection of serotonin and

In addition to the ingestion of BAs by food, the body synthesizes endogenous amines by producing intestinal bacteria [19, 23], which can promote excess of these amines, facilitating the increase of diseases, mainly involving high cell proliferation. Amines such as spermidine have been described as being related to increased longevity. Spermidine - the most absorbed polyamine from the human gut - is most consumed by women and is related to the increase of survivability in humans [15], due to the capacity to restore or induce efficient autophagy [24], among others factors. However, ingestion of high levels can promote cancer development when critical immunoregulatory circuits are afflicted [25]. Studies demonstrate the lesser cytotoxic effect of spermine using an *in vitro* human intestinal cell model, compared to spermidine [26]. The cytotoxic level of spermidine ranges from 5 mM (NOAEL) to 10 mM (LOAEL), while for spermime, the levels are lower (NOAEL - 2.40 mM and LOAEL - 3.23 mM) [26]. Autophagy plays an important role in the prevention of several diseases [27], who demonstrated that spermidine may decrease the level of lipids and necrotic

In plants, putrescine is formed from ornithine or arginine by the action of ornithine decaborxylase (ODC, EC 4.1.1.17) or arginine decarboxylase (ADC, EC 4.1.1.19). The addition of aminopropyl groups from S-adenosylmethionine (SAM) to putrescine is catalyzed by S-adenosylmethionine (SAM) decarboxylase (SAMDC, EC 4.1.1.50) forming spermidine, through spermidine synthase. A new aminopropyl group is added to spermidine, forming spermine by the action of spermine synthase. In contrast, the action of 1-aminocyclopropane-1-carboxylate (ACC) synthase leads to the formation of 1-aminocyclopropane-1-carboxilic acid (ACC), a precursor to ethylene [16]. Thus, ethylene and the polyamines spermidine and spermine use the same precursor, that is, SAM. Several studies have shown that higher levels of spermidine and spermine indicate juvenility, and the Put/(Spd + Spm) > 1 ratio would indicate the formation of ethylene, related to senescence. Evidently, the levels of these amines affect post-harvest life and the action of ethylene may be an indicator of a decrease in the content of spermidine and spermine. Thus, juvenile fruits and vegetables contain higher levels of spermidine and spermine and their consumption can lead to improved

*DOI: http://dx.doi.org/10.5772/intechopen.94095*

dopamine [7, 8].

core formation.

### *The Increase of Amines Content in the Intake of a Vegan Diet DOI: http://dx.doi.org/10.5772/intechopen.94095*

*Veganism - a Fashion Trend or Food as a Medicine*

foodstuffs is still insufficient.

functions in humans.

Biogenic amines are aliphatic organic bases of low molecular weight and have biological activity in microorganisms, plants and animals. Polyamines (putrescine, cadaverine, spermidine and spermine) and biogenic amines (serotonin, dopamine, histamine, tyramine, among others) are called bioactive amines (BAs) and are relevant for both shelf life and final product quality, as well as for human health [6]. Some polyamines play an important role in growth and can act as antioxidants [7–9], while other amines are neuroactive or vasoactive [6]. In addition, amines are also described as being indicators of plant-food safety and some countries already

Although many BAs, such as histamine, tyramine and putrescine are necessary for many functions in humans, consumption of foods containing large amounts of these amines can have toxicological effects. For example, excessive consumption of histamine can induce histaminic intoxication and is mainly related to heart disease (hypotension and palpitations) and headache [12]. Tyramine is also considered harmful to the body [13]. Even though some studies show the levels of amines in plant-based food [7–9, 14], the number of studies that establish legal limits in

While histamine and tyramine can have adverse effects, the ingestion of foods rich in some amines, such as spermidine and spermine, has been linked to longevity, both in humans [15] and in plants [16]. Diamines such as putrescine and cadaverine have been described due to their occurrence in higher levels in contaminated foods or in senescent plant tissue. Besides these polyamines, monoamines such as serotonin and dopamine have important neurological and antioxidant functions in both animals and plants. These amines can be obtained by eating some foods plant-based (banana, cauliflower, grapes - *in natura* and byproducts) and/or animal (fish and meat). However, the synthesis and *turnover* of serotonin depends on the intake of the amino acid tryptophan for the formation of serotonin in the brain, since this neutrotransmitter does not cross the blood–brain barrier [17]. In mammals, serotonin is a neurotransmitter that acts on the central nervous system, affecting appetite, sleep, anxiety and mood. In addition to being an important precursor to the formation of serotonin in the brain, tryptophan is also a precursor to melatonin, an indolamine, which has antioxidant action, besides acting in physiological processes related to the regulation of circadian rhythm, mood and sleep. This chapter provides an overview of the presence of amines in plant-based diets, the impacts of food handling and processing on these molecules, in addition to the mechanisms by which these compounds are absorbed and affect physiological

**2. Fruit, vegetables and their bioactive amines against human diseases**

raw materials and easily available to the food and pharmaceutical industries.

Fruit and vegetables play an important role in human health, since they contain many essential nutrients and phytochemicals that are responsible for preventing or reducing the risk of various chronic diseases, including cardiovascular disease, diabetes, obesity, certain types of cancer, inflammation, heart attack, stroke and septic shock. Additionally, vegans, vegetarians and omnivores, consume fruits and vegetable by-products that contribute to significant levels of important health compounds, which have been extensively researched, in addition to being profitable

Cells are constantly exposed to oxidizing agents and a key point is the balance of the oxidative effect by antioxidant mechanisms. To reduce the risk of developing chronic diseases in humans and possibly delay the appearance of age-related problems,

limit the amount of some BAs, mainly in fermented foods [10, 11].

**2**

nutritional recommendations are that young and old people eat at least seven portions a day of different fruits and vegetables. For a lowest risk of total cancer, studies showed that it is important to intake of 600 g/day (7.5 portions/day), however, for coronary heart disease, stroke, cardiovascular disease and all-cause mortality the lowest risk was observed at 800 g/day (10 portions/day) [18]. Many studies show a strong and positive correlation between the content of BAs and the antioxidant potential of fruits and vegetables [7, 8].

BAs are involved in several physiological processes and can act as antioxidants [7, 8] and some studies relate polyamines to ion channel regulation, DNA methylation, histone acetylation, protein biosynthesis, RNA translation, apoptosis and regulation of the immune response [19], in addition to being considered a secondary messenger, mediating some growth factors in plants [20]. Studies indicate that the BAs present in fruits and vegetables are strong antioxidant compounds with more effective free radical scavenging properties, compared to some natural antioxidants, for example, phenolic compounds [8, 21] or well-accepted synthetic compounds, such as α-tocopherol, octyl gallate and palmitoyl-ascorbic acid [22]. In fruits and vegetables, around 22 BAs have already been described, and the most detected BAs are tyramine, putrescine, cadaverine, histamine, spermine and spermidine [10], while few studies report the detection of serotonin and dopamine [7, 8].

In addition to the ingestion of BAs by food, the body synthesizes endogenous amines by producing intestinal bacteria [19, 23], which can promote excess of these amines, facilitating the increase of diseases, mainly involving high cell proliferation. Amines such as spermidine have been described as being related to increased longevity. Spermidine - the most absorbed polyamine from the human gut - is most consumed by women and is related to the increase of survivability in humans [15], due to the capacity to restore or induce efficient autophagy [24], among others factors. However, ingestion of high levels can promote cancer development when critical immunoregulatory circuits are afflicted [25]. Studies demonstrate the lesser cytotoxic effect of spermine using an *in vitro* human intestinal cell model, compared to spermidine [26]. The cytotoxic level of spermidine ranges from 5 mM (NOAEL) to 10 mM (LOAEL), while for spermime, the levels are lower (NOAEL - 2.40 mM and LOAEL - 3.23 mM) [26]. Autophagy plays an important role in the prevention of several diseases [27], who demonstrated that spermidine may decrease the level of lipids and necrotic core formation.

In plants, putrescine is formed from ornithine or arginine by the action of ornithine decaborxylase (ODC, EC 4.1.1.17) or arginine decarboxylase (ADC, EC 4.1.1.19). The addition of aminopropyl groups from S-adenosylmethionine (SAM) to putrescine is catalyzed by S-adenosylmethionine (SAM) decarboxylase (SAMDC, EC 4.1.1.50) forming spermidine, through spermidine synthase. A new aminopropyl group is added to spermidine, forming spermine by the action of spermine synthase. In contrast, the action of 1-aminocyclopropane-1-carboxylate (ACC) synthase leads to the formation of 1-aminocyclopropane-1-carboxilic acid (ACC), a precursor to ethylene [16]. Thus, ethylene and the polyamines spermidine and spermine use the same precursor, that is, SAM. Several studies have shown that higher levels of spermidine and spermine indicate juvenility, and the Put/(Spd + Spm) > 1 ratio would indicate the formation of ethylene, related to senescence. Evidently, the levels of these amines affect post-harvest life and the action of ethylene may be an indicator of a decrease in the content of spermidine and spermine. Thus, juvenile fruits and vegetables contain higher levels of spermidine and spermine and their consumption can lead to improved

health, in addition to the fact that diets with adequate levels of these polyamines can increase longevity.
