**3. Macronutrient and lipoprotein**

#### **3.1. Total fat**

The Nutrition Committee of the American Heart Association (AHA) emphasises on that diets providing up to 40% of dietary energy as primarily unsaturated fat (20% MUFA, 10% SFA, 10% PUFA and 1% TFA) were as heart healthy as low-fat diets (<30% of dietary energy) [19]. The effects of different dietary fatty acids on lipid profiles should be considered in the evaluation of strategies for controlling of disturbances in lipoprotein concentrations. Changes in dietary fat composition are clearly associated with changes in lipoprotein concentrations. Types of dietary fatty acids include saturated fatty acids (SFAs), monounsaturated fatty acid (MUFAs), polyunsaturated fatty acid (PUFAs) and dietary cholesterol, the effects of which on lipoprotein concentrations will be discussed.

#### **3.2. Dietary saturated fatty acids (SFAs)**

Among the dietary fatty acids only dietary SFAs and *trans* fatty acids increase LDL cholesterol concentrations [18]. The major sources of dietary SFAs are fast foods, processed foods, high-fat dairy products (whole milk, cheese, butter, ice cream, and cream), high-fat red meats, tropical oils such as palm oil, coconut oil, and palm kernel oil, baked products and mixed dishes containing dairy fats, shortening, and tropical oils. Dietary SFAs increase LDL and total cholesterol concentrations, in comparison with all dietary fatty acids except *trans* fatty acids [20-21], by inhibiting LDL receptor activity and enhancing apolipoprotein (apo) β-containing lipoprotein production [22]. Every 1 percent increase of total energy from dietary SFAs raises the serum LDL cholesterol about 2 percent. Conversely, a 1 percent reduction in saturated fatty acids will reduce serum cholesterol by about 2 percent [23,24]. The LDL cholesterol–raising effect of dietary SFAs depends on the intake of dietary cholesterol and PUFAs. In high intakes of dietary cholesterol, dietary SFAs decreased LDL receptor activity and increased plasma LDL concentrations [25]. However, in the adequate of dietary PUFAs (5–10% of total energy), dietary SFAs have no effect on LDL clearance [22]. In addition different dietary SFAs have different effects on lipoprotein concentrations [29]. Short chain SFAs have been shown to have a stronger LDL cholesterol raising effect, such that lauric acid (12:0) raised LDL cholesterol the most, followed by myristic (14:0) and palmitic (16:0) acids. In contrast, stearic acid (18:0), as a long chain SFA, has no effect on LDL and HDL cholesterol or the TC: HDL cholesterol ratio, and even lowers serum cholesterol [27,28]. Finally, the effects of dietary SFAs can be modulated by the foods in which they are contained. Cheeses may have smaller effects on LDL cholesterol concentrations than butter, and fermented dairy foods, such as yogurt, have been associated with LDL reductions [29]. Reduced intakes of dietary SFAs and cholesterol are first steps for the purpose of achieving the LDL cholesterol goal (<100 mg/dl). To maximize LDL cholesterol lowering by reducing dietary SFAs, it will be necessary to lower intakes of dietary SFAs approximately to <7 percent of total energy [18]. However the replacement of dietary SFAs with other macronutrients is important. Although replacement of dietary SFAs with carbohydrate decrease total, LDL, and HDL cholesterol, it also increases triglycerides [20]; however replacement of dietary SFAs by PUFAs decreases concentrations of total, LDL, and the LDL/HDL cholesterol ratio by decreasing LDL cholesterol production and increasing LDL clearance [30]. Although replacement of dietary SFAs with PUFAs has been shown to decrease HDL cholesterol, it decreases LDL cholesterol even more substantially; thus, the HDL:LDL ratio is increased [23] and the TC:HDL cholesterol ratio is decreased [26]. Replacement of 5% of total energy from SFAs with PUFAs reduces CHD risk by 42% [31]. Replacement of dietary SFAs with MUFAs has also been associated with improving lipoprotein concentrations, although this effect is slightly less than when PUFAs are the replacement dietary fatty acid [23]. Replacement of dietary SFAs with both MUFAs and carbohydrate decrease LDL cholesterol; however replacement with MUFA was associated with lower reductions in HDL cholesterol and lower arises in triglyceride concentrations [32].

#### **3.3. Trans fatty acids**

304 Lipoproteins – Role in Health and Diseases

herbal and phytochemicals.

**2. Diet and lipoprotein** 

**3. Macronutrient and lipoprotein** 

**3.2. Dietary saturated fatty acids (SFAs)** 

**3.1. Total fat** 

the role of the following dietary determinants in lipoprotein concentrations and dyslipidemia: including 1) macronutrients (total fat, saturated fatty acids, trans fatty acids, n-6 polyunsaturated fatty acids, n-3 polyunsaturated fatty acids, dietary cholesterol, carbohydrate and protein), 2) food groups (grains and cereal, fruit and vegetables, dairy products, nuts, beans and legumes, and meat, fish, poultry and eggs), 3) dietary patterns (Mediterranean diet, Dietary to Stop Hypertension, western **diet** and healthy diet), and therapeutic life style change (TLC), 4) dietary **supplements**, (plant stanols and sterols),

Lipoprotein concentrations are affected by both genetic and environmental factors. Among environmental factors such as physical activity and smoking, diet is an important component in preventing and improving dyslipidemia. Diet intervention is recommended by the National Cholesterol Education Program (NCEP) guidelines as first-line therapy for the management of disturbances in lipoprotein concentrations. Also the Third report of the NCEP recommended that if dietary therapy do not improve disturbances in lipoprotein concentrations, non-pharmacologic therapeutic factors such as viscous fiber and plant

The Nutrition Committee of the American Heart Association (AHA) emphasises on that diets providing up to 40% of dietary energy as primarily unsaturated fat (20% MUFA, 10% SFA, 10% PUFA and 1% TFA) were as heart healthy as low-fat diets (<30% of dietary energy) [19]. The effects of different dietary fatty acids on lipid profiles should be considered in the evaluation of strategies for controlling of disturbances in lipoprotein concentrations. Changes in dietary fat composition are clearly associated with changes in lipoprotein concentrations. Types of dietary fatty acids include saturated fatty acids (SFAs), monounsaturated fatty acid (MUFAs), polyunsaturated fatty acid (PUFAs) and dietary

Among the dietary fatty acids only dietary SFAs and *trans* fatty acids increase LDL cholesterol concentrations [18]. The major sources of dietary SFAs are fast foods, processed foods, high-fat dairy products (whole milk, cheese, butter, ice cream, and cream), high-fat red meats, tropical oils such as palm oil, coconut oil, and palm kernel oil, baked products and mixed dishes containing dairy fats, shortening, and tropical oils. Dietary SFAs increase LDL and total cholesterol concentrations, in comparison with all dietary fatty acids except *trans* fatty acids [20-21], by inhibiting LDL receptor activity and enhancing apolipoprotein (apo) β-containing lipoprotein production [22]. Every 1 percent increase of total energy from

stanols and sterols should be recommended prior to advancing to drug therapy[18].

cholesterol, the effects of which on lipoprotein concentrations will be discussed.

*Trans* fatty acids contain at least one double bond in the *trans* configuration [40] and were the most harmful macronutrient that increase disturbances in lipoprotein concentrations [26,33,34]. Dietary *trans* fatty acids, produced during the hydrogenation of either vegetable or fish oils (industrial TFA**)**, are found in manufacturing products such as cookies, pastries, and salad dressings; *trans* fatty acids are also formed during anaerobic bacterial fermentation of unsaturated fatty acids that occurs in the rumen of polygastric animals such as cattle, sheep, and goats (natural trans fatty acids), and hence found in dairy products derived from the animals' milk and meat [33,35]. Industrial and natural *trans* fatty acids contain similar types of these fatty acids, but in different proportions. Industrial *trans* fatty acids contain trans isomers of oleic acid, the major ones being C18:1 trans-9 ( elaidic acid) and C18: 1 trans-10 [35]. Consumption of industrial *trans* fatty acids increases total, LDL cholesterol, and total to HDL cholesterol ratio and the LDL to HDL cholesterol ratio [33, 35- 37] and decrease HDL cholesterol [40]. Data on the effects of natural *trans* fatty acids on plasma lipoproteins in humans are inconsistent. An equivalent of 1% natural *trans* fatty acids of daily energy, has no significant effect on total cholesterol, LDL cholesterol, apo B, triglyceride concentrations but may be associated with a reduction in plasma HDL cholesterol concentrations [38]. However high intakes of natural *trans* fatty acids, but not low intakes, have adverse effects [39]. Therefore both natural and industrial *trans* fatty acids have detrimental effects on lipoprotein concentrations and their intakes should be limited [40]. The effects of *trans* fatty acids on lipid profiles are also variable, depending on their chain length; long chain *trans* fatty acids may have more adverse effect on lipid profiles. Partially hydrogenated fish oil or *trans* alpha-linolenic acid had more detrimental effect on lipoprotein compared with isocaloric amount of partially hydrogenated soy bean oil [37,41]. Effect of *trans* fatty acids on lipoprotein concentrations is a current topic of debate. *Trans* fatty acid intake increases lipoprotein a and triglycerides when substituted for dietary SFAs [42,43]. Issues related to the potential change in lipoprotein a levels induced by *trans* fatty acid intake and risk for disease need to be clarified.

Dietary guidelines for American 2010 emphasize that consumption of *trans* fatty acids should be reduced as much as possible by limiting foods that contain sources of these fatty acids [43]. On the basis of these data, it should be attempts to substitute unhydrogenated oil for hydrogenated or SFAs in diet.

#### **3.4. Monounsaturated fatty acids**

Monounsaturated fatty acids have received increased attention as being potentially beneficial for their association with low rates of CHD in olive-oil consuming populations of the Mediterranean style diet [18]. The most common form of dietary MUFAs is oleic acid (18:1 n-9), which occurs in the cis form. Olive oil, canola oil, and sunflower oil are the main sources of dietary MUFAs. Oleic acid is an effective hypocholesterolemic factor when substituted for dietary SFAs. MUFA-rich oil consumption has been one of the strategies recommended for modulating the plasma lipid profile in humans. Diets containing high MUFA-rich foods reduce plasma total and LDL cholesterol levels and enrich LDL particles with cholesteryl oleate, a change in LDL particle composition that has been shown to confer atherogenicity [23, 45-48]. Also compared with diets rich in saturated fat, MUFA-rich diets lower apolipoprotein β concentrations along with declines in LDL cholesterol level [49,50]. Consumption of MUFA-rich diets also induces lower triglycerides and higher HDL cholesterol concentrations compared with low-fat, high-carbohydrate diets [51]. Long term MUFA-rich diets result in an earlier postprandial peak in plasma triglyceride and apo β-48 concentrations [52,53]; this mechanism is not clear, however oleic acid has been shown to be preferentially esterified into triglycerides in the enterocyte [54], which may be result a faster entry rate of chylomicrons into the circulation, reflecting accelerated rates of digestion and absorption or upregulation of chylomicron synthesis and secretion [55]. However MUFArich diets increase clearance of plasma triglycerides compared with isocaloric SFA-rich or high complex carbohydrate diets and therefore decrease triglyceride concentrations [51,56,57]. MUFA substitution for dietary SFAs suggest an effective dietary strategy for improving disturbances of lipoprotein concentrations, which currently recommended in most national and international dietary guidelines [18].

#### **3.5. N-6 Polyunsaturated fatty acids**

306 Lipoproteins – Role in Health and Diseases

for hydrogenated or SFAs in diet.

**3.4. Monounsaturated fatty acids** 

acids contain trans isomers of oleic acid, the major ones being C18:1 trans-9 ( elaidic acid) and C18: 1 trans-10 [35]. Consumption of industrial *trans* fatty acids increases total, LDL cholesterol, and total to HDL cholesterol ratio and the LDL to HDL cholesterol ratio [33, 35- 37] and decrease HDL cholesterol [40]. Data on the effects of natural *trans* fatty acids on plasma lipoproteins in humans are inconsistent. An equivalent of 1% natural *trans* fatty acids of daily energy, has no significant effect on total cholesterol, LDL cholesterol, apo B, triglyceride concentrations but may be associated with a reduction in plasma HDL cholesterol concentrations [38]. However high intakes of natural *trans* fatty acids, but not low intakes, have adverse effects [39]. Therefore both natural and industrial *trans* fatty acids have detrimental effects on lipoprotein concentrations and their intakes should be limited [40]. The effects of *trans* fatty acids on lipid profiles are also variable, depending on their chain length; long chain *trans* fatty acids may have more adverse effect on lipid profiles. Partially hydrogenated fish oil or *trans* alpha-linolenic acid had more detrimental effect on lipoprotein compared with isocaloric amount of partially hydrogenated soy bean oil [37,41]. Effect of *trans* fatty acids on lipoprotein concentrations is a current topic of debate. *Trans* fatty acid intake increases lipoprotein a and triglycerides when substituted for dietary SFAs [42,43]. Issues related to the potential change in lipoprotein a levels induced by

Dietary guidelines for American 2010 emphasize that consumption of *trans* fatty acids should be reduced as much as possible by limiting foods that contain sources of these fatty acids [43]. On the basis of these data, it should be attempts to substitute unhydrogenated oil

Monounsaturated fatty acids have received increased attention as being potentially beneficial for their association with low rates of CHD in olive-oil consuming populations of the Mediterranean style diet [18]. The most common form of dietary MUFAs is oleic acid (18:1 n-9), which occurs in the cis form. Olive oil, canola oil, and sunflower oil are the main sources of dietary MUFAs. Oleic acid is an effective hypocholesterolemic factor when substituted for dietary SFAs. MUFA-rich oil consumption has been one of the strategies recommended for modulating the plasma lipid profile in humans. Diets containing high MUFA-rich foods reduce plasma total and LDL cholesterol levels and enrich LDL particles with cholesteryl oleate, a change in LDL particle composition that has been shown to confer atherogenicity [23, 45-48]. Also compared with diets rich in saturated fat, MUFA-rich diets lower apolipoprotein β concentrations along with declines in LDL cholesterol level [49,50]. Consumption of MUFA-rich diets also induces lower triglycerides and higher HDL cholesterol concentrations compared with low-fat, high-carbohydrate diets [51]. Long term MUFA-rich diets result in an earlier postprandial peak in plasma triglyceride and apo β-48 concentrations [52,53]; this mechanism is not clear, however oleic acid has been shown to be preferentially esterified into triglycerides in the enterocyte [54], which may be result a faster entry rate of chylomicrons into the circulation, reflecting accelerated rates of digestion and

*trans* fatty acid intake and risk for disease need to be clarified.

Dietary n-6 PUFAs such as linoleic acid (18:2) are widely found in a variety of vegetables and vegetables oils [58]. Conjugated linoleic acid (CLA), a group of naturally occurring fatty acids that are mainly present in foods from ruminant sources**,** is a collective term used to describe positional and geometric derivatives of linoleic acid containing conjugated double bonds [59].

CLA have beneficial effects on lipoprotein disturbances. CLA reduced total, LDL and VLDL cholesterol, especially atherogenic apolipoprotein β-rich lipoproteins and triglycerides concentrations [60,61]. CLA increases the excretion of sterols and consequently decreases serum cholesterol concentration [86**].**

#### **3.6. N-3 Polyunsaturated fatty acids**

Dietary sources of n-3 PUFAs are limited. The shorter chain n-3 PUFAs FA, α-linolenic acid (ALA), is found in many plants, but the longer chains eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are produced almost exclusively by cold water algae, which are**,** in turn**,** ingested by fish. Humans cannot synthesize the n-3 double bond, but they do have the elongase and desaturase enzymes to convert ALA to EPA and DHA, a conversion, which however is an inefficient process. The conversion of ALA to EPA may be further reduced as a result of large amounts of n-6 FA in the diet, which compete for the same enzymes. Some studies however have found that ALA, irrespective of n-6 PUFAs, has a beneficial effect of lipid profiles [63]. Mechanism of actions of the medium- and long chain n-3 fatty acids appears to be independent. ALA exerts most of its effects by modulating lipoproteins, while EPA and DHA may reduce triglyceride synthesis [64]. Experts currently recommend the consumption of EPA and DHA, rather than ALA, to meet dietary goals for dietary n-3 PUFA [65]. Long-chain n-3 PUFA reduce triglyceride concentrations. An intake of 4 g EPA and DHA per day results in a 25–30% decrease of fasting triglyceride concentrations in both normolipidaemic and hypertriacylglycerolaemic subjects (66). Compares EPA and DHA, EPA-ethyl ester shows no change in triglyceride concentrations, suggesting that DHA is the active agent in fish oil, that decreases triglyceride concentrations. Therefore among long chain n-3 PUFAs, EPA may produce favourable effects on triglyceride and HDL cholesterol concentrations [67,68]. The hypotriglyceridaemic effect of long chain n-3 PUFAs, mediated by several mechanisms such as enhanced hepatic fatty acid oxidation [69], inhibition of fatty acid and triglyceride synthesis, reduced assembly and secretion of VLDL triglyceride concentrations [70], facilitates triglyceride rich lipoprotein removal through enhanced LPL activity in plasma [71]. Significant increases in HDL have been observed after DHA supplementation [67,68,72,73]; it may be related to decreased cholesteryl ester transfer protein activity that reduces the exchange from HDL cholesterol ester and VLDL, resulting in larger, more cholesterol-rich HDL cholesterol particles [74,75].

Inconsistent effects of DHA on total and LDL cholesterol levels have been shown; some investigators found a LDL cholesterol-raising effect [68,76] or no significant changes in total cholesterol or LDL cholesterol concentration [77,78]. After supplementation with n-3 Long chain PUFA, limited amounts of triglycerides are available for packaging into VLDL, which results in VLDL particles with low triglycerides that are readily converted to LDL, increases LDL cholesterol concentrations [79]. N-3 PUFAs could increase production of LDL via conversion of VLDL to LDL by increased lipolysis of VLDL and/or increased lipolytic activity or decreased clearance of LDL, by decreases in LDL receptor binding activity or reduced LDL receptor expression [80]. ALA, an n-3 polyunsaturated fatty acid found mainly in plant sources, including flaxseed oil, canola oil, and walnuts, is a metabolic precursor of DHA and EPA and any risk reduction may be mediated through conversion to these fatty acids; ALA cannot be synthesized by humans, and therefore, it is an essential fatty acid in diet [58]. Although evidence indicates that consumption of long chain n-3 PUFAs from seafood reduces the risk factors of cardiovascular disease, the effect of ALA intake in these risk factors is less well established. Daily supplementation with ALA-rich flaxseed is reported to reduce total cholesterol, LDL-cholesterol [81,82]. Weight of the evidence favors recommendations for modest dietary consumption of ALA (2 to 3 g per day) for primary and secondary prevention of CHD [58]. The relationship between ALA intake and CHD risk was seen among participants who consumed very little seafood; among men with limited seafood intake, each 1 g per day ALA intake was associated with 50% lower risk of CVDs; in contrast among subjects with some seafood intake, ALA intake was not associated with CHD risk. If benefits of ALA are greatest when EPA and DHA intakes are very low, the consumption of plant sources of n-3 fatty acids may be particularly important for CHD prevention among individuals who do not regularly consume fish [58].

#### **3.7. Dietary cholesterol**

The main source of dietary cholesterol is eggs, which contribute about one-third of the cholesterol in the diet; intake of dietary cholesterol has increased in recent year. Other sources of dietary cholesterol include animal products, dairy, meats, poultry, and shellfish [83]. High cholesterol intakes increase LDL cholesterol and the degree of rise varies from person to person. On average, the response of serum cholesterol to dietary cholesterol as revealed is approximately 10 mg/dL per 100 mg dietary cholesterol per 1000 kcal [84,85]. A recent meta-analysis showed that dietary cholesterol raises the ratio of total to HDL cholesterol, adversely affecting the serum cholesterol profile [86].

#### **3.8. Carbohydrate**

Recommendations to decrease fat and increase carbohydrate intake have come under scrutiny. Diets low in fat necessarily has a high proportion of carbohydrates, and high carbohydrate diet increase triglycerides, reduce HDL cholesterol concentrations, and increase LDL cholesterol concentrations [87]. In addition to carbohydrate intake, the type of carbohydrate, according to glycemic index, most likely influences lipid profiles [88]. Glycemic index refers to the value obtained by feeding a carbohydrate load and measuring the level of blood glucose. Using the glycemic index, carbohydrates with a low glycemic index may decrease triglyceride concentrations and increase HDL cholesterol [89]. Also substituting low-GI foods for high-GI foods lowers triglyceride concentrations by 15 to 25% [138]. High-carbohydrate diets increase triglyceride concentrations, compared to high-fat diets [91] via enhance hepatic lipogenesis [92] and decrease the synthesis of lipoprotein lipase [93]. A high carbohydrate diet also increases glucose and insulin concentrations, the latter increasing lipogenesis, leading to increases in triglyceride concentrations, triglycerideenriched VLDL particles, and increases the LDL cholesterol concentrations [94]. Therefore reductions in dietary carbohydrate have been associated with reduced concentrations of LDL cholesterol [95] and increase means LDL particle size [96].

High carbohydrate diets (>60 percent of total energy) are associated with lipoprotein disturbances; reduction in the content of carbohydrate have beneficial effects on lipid profiles. However substitution of carbohydrate with other macronutrients is important. When carbohydrates are substituted for SFAs, the fall in LDL cholesterol levels equals that with monounsaturated fatty acids, and however, compared with MUFAs, this substitution frequently causes a fall in HDL cholesterol and a rise in triglycerides [23,97]. When dietary carbohydrate is consumed along with high-fiber diets, however, the rise in triglycerides or fall in HDL cholesterol has been reported to be reduced [98,99]. Addition of n-3 PUFA to low-fat, high-carbohydrate diets decreases the adverse effects of carbohydrate on blood lipids [51,100]. Also refined- and whole grains, as sources of carbohydrate, have an essential role in the metabolism of lipid profiles, that will be discussed in the section on food groups. In a relatively short period of time, dietary consumption of fructose has increased several fold above the amount present in natural foods, because of the use of high fructose corn sweeteners and sucrose in manufactured foods [101]. In human diets approximately onethird of dietary fructose comes from fruit, vegetables, and other natural sources and twothirds is added to beverages and food in the diet (e.g. soft drinks, fruit-flavored drinks, candies, jams, syrups, and bakery products). Although there is little evidence that modest amounts of fructose have detrimental effects on carbohydrate and lipid metabolism, larger doses have been associated with numerous metabolic abnormalities, suggesting that high fructose consumption adversely affects health. High levels of plasma triacylglycerols are a well-established consequence of dietary fructose intake [101]. Numerous mechanisms have been suggested to explain this phenomenon [102,103], e.g. enhanced hepatic lipogenesis**,**  and therefore overproduction of VLDL [102,104].

#### **3.9. Protein**

308 Lipoproteins – Role in Health and Diseases

**3.7. Dietary cholesterol** 

**3.8. Carbohydrate** 

more cholesterol-rich HDL cholesterol particles [74,75].

prevention among individuals who do not regularly consume fish [58].

cholesterol, adversely affecting the serum cholesterol profile [86].

The main source of dietary cholesterol is eggs, which contribute about one-third of the cholesterol in the diet; intake of dietary cholesterol has increased in recent year. Other sources of dietary cholesterol include animal products, dairy, meats, poultry, and shellfish [83]. High cholesterol intakes increase LDL cholesterol and the degree of rise varies from person to person. On average, the response of serum cholesterol to dietary cholesterol as revealed is approximately 10 mg/dL per 100 mg dietary cholesterol per 1000 kcal [84,85]. A recent meta-analysis showed that dietary cholesterol raises the ratio of total to HDL

Recommendations to decrease fat and increase carbohydrate intake have come under scrutiny. Diets low in fat necessarily has a high proportion of carbohydrates, and high

activity in plasma [71]. Significant increases in HDL have been observed after DHA supplementation [67,68,72,73]; it may be related to decreased cholesteryl ester transfer protein activity that reduces the exchange from HDL cholesterol ester and VLDL, resulting in larger,

Inconsistent effects of DHA on total and LDL cholesterol levels have been shown; some investigators found a LDL cholesterol-raising effect [68,76] or no significant changes in total cholesterol or LDL cholesterol concentration [77,78]. After supplementation with n-3 Long chain PUFA, limited amounts of triglycerides are available for packaging into VLDL, which results in VLDL particles with low triglycerides that are readily converted to LDL, increases LDL cholesterol concentrations [79]. N-3 PUFAs could increase production of LDL via conversion of VLDL to LDL by increased lipolysis of VLDL and/or increased lipolytic activity or decreased clearance of LDL, by decreases in LDL receptor binding activity or reduced LDL receptor expression [80]. ALA, an n-3 polyunsaturated fatty acid found mainly in plant sources, including flaxseed oil, canola oil, and walnuts, is a metabolic precursor of DHA and EPA and any risk reduction may be mediated through conversion to these fatty acids; ALA cannot be synthesized by humans, and therefore, it is an essential fatty acid in diet [58]. Although evidence indicates that consumption of long chain n-3 PUFAs from seafood reduces the risk factors of cardiovascular disease, the effect of ALA intake in these risk factors is less well established. Daily supplementation with ALA-rich flaxseed is reported to reduce total cholesterol, LDL-cholesterol [81,82]. Weight of the evidence favors recommendations for modest dietary consumption of ALA (2 to 3 g per day) for primary and secondary prevention of CHD [58]. The relationship between ALA intake and CHD risk was seen among participants who consumed very little seafood; among men with limited seafood intake, each 1 g per day ALA intake was associated with 50% lower risk of CVDs; in contrast among subjects with some seafood intake, ALA intake was not associated with CHD risk. If benefits of ALA are greatest when EPA and DHA intakes are very low, the consumption of plant sources of n-3 fatty acids may be particularly important for CHD

> Plant sources of protein are predominantly legumes, dry beans, nuts, and, to a lesser extent, grain products and vegetables, which are low in saturated fats and cholesterol. Animal sources of protein include dairy products, egg whites, fish, poultry, and meats. Dietary

protein in general has little effect on lipoprotein profiles. However, substituting plant protein including wheat gluten, soy proteins for animal protein decrease serum cholesterol [104,105]. Advice on the use of soy foods to displace animal products is consistent with the AHA advisory on soy [107**],** which states that 50 g/d soy protein consumption reduces approximate 3% LDL-C with no apparent dose-response effect [108]. Maximum reduction in LDL cholesterol was achieved when ~50 g of soy protein when was replaced meat or dairy protein [109]. Soy is a complex protein with a globulin fraction to which its cholesterollowering effect has been attributed; this fraction digested to peptides with inhibitory effects on cholesterol synthesis [110]. Isoflavones or the saponins found in soy, are also responsible for the cholesterol-lowering effect of soy [111,112]. Soy and other vegetable proteins also reduce oxidized LDL due to antioxidant activity [112,113].
