Coronary Artery Disease in Asian Indians (CADI) Research Foundation, and University of Illinois, Chicago, USA
Transfatty acids (TRAFA)—the hardened fat that hardens arteries fast: TRAFA is formed during the partial hydrogenation of vegetable oils, a process that converts oils into solid or semisolid fats for subsequent use in food products. This process not only improves the texture and firmness but also markedly increases the shelf-life of food by minimizing oxidative spoilage.33 Elaidic acid (n-9 trans 18:1) is the principal TRAFA, although several other trans isomers are also formed.23 Such oils are used in commercial baked goods, and for cooking in most fast-food chains in western countries.34 Perhaps an equally important and often neglected cause of TRAFA formation is the spontaneous hydrogenation of vegetable oils during deepfrying. 35 Very small amounts of TRAFA are also found in beef and dairy products (Table 1).
Consumption of TRAFA has a greater adverse effect on lipoproteins than that of SAFA.36 Whereas both SAFA and TRAFA increase LDL levels considerably, TRAFA also decreases HDL levels, thereby increasing the TC/HDL ratio, the single best lipid-related risk factor for CAD.37 Replacing 9% of calories from SAFA with TRAFA results in a 20% decrease in HDL level.38 Other important adverse effects of TRAFA consumption include increases in lipoprotein(a) (Lp[a]), TG, and small, dense LDL levels,34,38–44 as well as increased platelet aggregation, endothelial dysfunction, and sudden death.34 TRAFA are stronger predictors of CAD and diabetes than SAFA and carbohydrates.1,45–47 In the Nurses’ Health Study, women in the highest versus the lowest quartile of TRAFA consumption had a 50% higher risk of CAD.48 It is estimated that a substitution of 2% of calories from TRAFA with MUFA and PUFA results in a 53% reduction in CAD risk—a risk double that of substitution of calories from SAFA.29 TRAFA consumption also markedly increases the postprandial insulin response in diabetic patients.49 Replacing 2% of energy from TRAFA with PUFA would lead to a 40% reduction in diabetes.45 SAFA calories should not be replaced by TRAFA calories; doing so is like jumping from the frying pan to the deep-fat fryer.50
The average consumption of TRAFA in the USA and Europe is low (<2% of energy or 11–27 g/day).51,52 However, TRAFA accounts for about 5% of fat in American diets, and 5% of fat stored in adipose tissue.33,50,53 Butter contains 60% SAFA, whereas stick margarine contains 16% TRAFA. The tub or soft margarine contains only 2 g of TRAFA per 15 ml. Therefore, the fat-spread of choice remains soft margarine;54 olive oil may be an even better substitute. Although many margarines and shortenings previously contained up to 50% of TRAFA, in most western countries, these products currently have a low TRAFA content due to recent manufacturing changes.47 However, frying fats used in fast-food outlets still contain over 30% of TRAFA. French fries sold in these outlets provide 7–8 g of TRAFA per portion. About one-third of TRAFA in the western diet comes from French fries, fried chicken, pizza, and cookies.
The TRAFA consumption is likely to be high in Asian Indians because deep-frying is a favorite mode of cooking at home as well as in restaurants. Deep-frying is associated with spontaneous hydrogenation and TRAFA formation, and repeated re-use of oils previously used for deep-frying may further increase the TRAFA content. These practices appear to be the norm rather than the exception, and may be of enormous public health importance, especially with regard to elevated Lp(a) levels, and high rates of CAD in this population. There is an urgent need to ascertain and disseminate the TRAFA content of vanaspathi (vegetable ghee) and frying oils used in India. As of today, we are not aware of any industrial manufacturing changes aimed at lowering the TRAFA content of Indian foods, as has been done in western countries.
MUFA, the good fat that raises the good cholesterol: Diets high in MUFA (oleic acid C18:1) make LDL resistant to oxidation, restore LDL-receptor activity, and markedly lower LDL levels. Substitution of 20% of energy from carbohydrates with MUFA decreases TC by 10 mg/dl. The reduction in TC is 3-fold higher when MUFA replaces SAFA. For example, TC decreases by 40 mg/dl when 20% of energy from SAFA is replaced with MUFA.13, 25 The effect on small, dense LDL is even greater. Other beneficial effects of MUFA include the favorable influence on blood pressure, endothelial activation, inflammation, and thrombogenesis.
A higher intake of MUFA lowers insulin resistance and diabetes, unlike SAFA and TRAFA, which increase it.45,49,55–60 Consumption of MUFA offers the unique advantage of effectively lowering LDL levels without lowering HDL or raising TG levels. Individuals with low HDL levels have a high risk of CAD.61,62 Subjects with high TG, especially those with the metabolic syndrome and diabetes, are highly sensitive to the TG-raising effects of a high carbohydrate load. A high carbohydrate diet is associated with highly atherogenic, small, dense LDL particles, while high-fat diets are associated with less atherogenic, buoyant LDL particles. Thus, replacing SAFA with MUFA is more effective in preventing CAD than reducing the total fat intake, especially in Asian Indians, a population with high rates of prevalence of the metabolic syndrome and diabetes. The NCEP III has recommended up to 20% of total calories from MUFA (Table 1). This recommendation seems particularly appropriate for Asian Indians.32
In Mediterranean countries, the high intake of MUFA in the form of olive oil is inversely related to CAD.15 The Nurses’ Health Study and other studies of almost 300 000 Americans showed that a diet rich in MUFA in the form of canola oil also reduces the risk of CAD.29,63,64 Contrary to common belief, energy-controlled, high-MUFA diets do not promote weight gain, and are more acceptable than lowfat diets for weight loss in obese subjects. The addition of MUFA should be at the expense of SAFA and carbohydrates. Since all fats are high in calories (9 cal/g), failure to decrease the energy from carbohydrates and SAFA would invariably result in weight gain, and mitigate most of the beneficial effects of MUFA.
Meat and dairy products, which are also rich in SAFA, provide most of the MUFA in western diets. Olive oil and canola oil are good sources of MUFA (Table 3),65 canola oil appears to be even better as it contains less SAFA and more PUFA, especially alpha-linolenic acid (ALNA). Mustard oil is high in MUFA but also high in erucic acid, which is known to have toxic effects on the heart. Canola oil is genetically engineered mustard oil without erucic acid. Nuts and avocado are excellent sources of MUFA and are recommended, provided the quantity is no more than 50– 100 g/day.66 Groundnut (peanut) products are a rich source of MUFA; they are inexpensive and widely available in India.67
PUFA, another healthy substitute for SAFA: There are 2 series of PUFA that are deemed essential. Linoleic acid (C18:2 n-6) is the predominant omega-6 or n-6 PUFA. The predominant (parent) omega-3 or n-3 PUFA is linolenic acid (18:3 n-3).23 Linoleic acid increases the fecal excretion of steroids, and inhibits the hepatic synthesis of apo Bcontaining lipoproteins. Replacing SAFA with PUFA reverses the suppression of LDL-receptor activity by cholesterol-raising SAFA (similar to that of MUFA).6,68 Substituting 20% of energy from SAFA with PUFA decreases the TC level by 40 mg/dl. Most of the reduction is in LDL, and the number of apo B particles.23,25 PUFA does not raise the TG level, and sometimes lowers it.69 The two undesirable effects of PUFA are increased susceptibility for peroxidation, and lowering of the HDL level.10,70–72 HDL levels are reduced by about 1% for every 2% of MUFA or SAFA energy substituted with PUFA.6,70–72
The substitution of PUFA for SAFA calories has played amajor role in reducing TC levels and CAD in the USA. The CAD mortality rate declined by 60% in the past 3 decades in the USA.73 About a third of the decline in CAD rates is attributed to a 6%–8% decrease in the serum TC level in the population; this, in turn, was due to an increase in the consumption of PUFA from 3% to 6%, and a decrease in SAFA consumption from 16% to 12% of the energy. The importance of PUFA is further underscored by the marked differences in PUFA consumption, which parallel the 4-fold difference in CAD rates between France and Finland.16 Vegetable oils, such as soybean, corn, safflower, sunflower, and cottonseed, are the primary sources of n-6 PUFA (Table 1). Their average consumption in the western diet is 6%–8% of energy, (17 g/day for men, and 12 g/day for women).74
Contrary to previous fears, n-6 PUFA do not antagonize the anti-inflammatory effects of n-3 PUFA nor do they raise the risks of breast, colorectal, or prostate cancer in humans.75,76 However, a very high n-6 PUFA to n-3 PUFA ratio may increase the thrombogenicity through increased production of arachidonic acid and thromboxane A2. This is because linoleic and linolenic acids use the same set of enzymes for desaturation and chain elongation.77 An n-6 PUFA to n-3 PUFA ratio of 3:1 appears to be optimum.78–80 Japan, which has one of the highest rates of fish consumption, has recently changed the recommendation of this ratio from 4:1 to 2:1;81 this ratio may be advisable for vegetarians).9
Fish, a tasty way to prevent sudden death: Fish do not die from myocardial infarction (MI), and populations that consume large amounts of marine foods have a low prevalence of CVD death.82–99 Replacing high-fat meat with fish is also associated with a decreased risk of CAD. The results of several large studies show that one or two fish meals per week are associated with a 30%–50% reduction in sudden death.84,95,98 In a meta-analysis of 11 prospective studies involving 116 764 individuals, fish consumption was inversely related to CAD death. This report suggests that 40–60 g/day of fish consumption is optimal, and results in a 40%–60% risk reduction.100 Greater intake has no additional benefits, and suggests a threshold effect.101,102 However, a recent large study of 5103 women with diabetes showed a dose–response relationship. Consumption of fish 1–3 times per month was associated with a 40% risk reduction, and a 64% risk reduction was seen among those who consumed fish >5 times per week.102,103 The benefit is seen in people with and without prior heart disease.104 These benefits persist as long as the fish consumption is continued.
Fish is a tasty food that contains many essential nutrients, such as selenium, iodine, vitamin D, and n-3 PUFA.97,105 The beneficial effects of fish are largely mediated through n-3 PUFA, which displace arachidonic acid from platelet phospholipid stores, thereby reducing the available substrate for thromboxane A2 synthesis.106,107 The principal effects of n-3 PUFA are antithrombogenic and antiarrhythmic, whereas that of n-6 PUFA is antiatherogenic.108–117 The serum levels of n-3 PUFA are inversely related to sudden death.66,82,89,93,95,118–121 The consumption of n-3 PUFA decreases blood pressure, and homocysteine level, increases HDL level, and improves hemostatic factors (Table 4).10,75,122–132 A 30%–50% reduction in TG can be achieved by taking 3–5 g/day of n- 3 PUFA.130
The major n-3 PUFA in fish oils are eicosapentaenoic acid (EPA) (20:5 n-3) and docosahexaenoic acid (DHA) (22:6 n-3); together they constitute 26% of fish oil fatty acids.23 The benefits from n-3 PUFA are greater with DHA and EPA found in fatty fish, shellfish, and marine mammals than with ALNA found in canola oil, soybean oil, and walnut.108 It is important to distinguish between lean and fatty fish for cardioprotection, because the content of n-3 PUFA is highest in fatty fish.119 Fatty fish, such as mackerel, sardine, and salmon, are widely available and inexpensive. Heating is associated with significant loss of n-3 PUFA.9 Frying fish is associated with an even greater loss of EPA and DHA, and may be particularly harmful if fried in SAFA.133 The current intake of DHA and EPA is only 200 mg/day, and needs to be increased 5-fold to meet the dietary goals.11
Both plant-based (ALNA), and fish-based (EPA and DHA) supplements have shown benefits in secondary prevention.89,90,134,135 In one such trial of 605 French men recovering from an MI, there was a 70% reduction in total and cardiac death during a follow-up of 27 months in those who received an experimental "Mediterranean diet" using canola oil-based margarine, enriched with n-3 PUFA.136 In another large randomized study of 11 324 survivors of a recent MI, there was a 20% reduction in total deaths, 30% reduction in CVD deaths, and 45% reduction in sudden deaths among those who received n-3 PUFA 1g/day.90 The totality of the data suggest that n-3 PUFA can be considered as the best antiarrhythmic agent and antifibrillatory treatment.106,117,133,135 Cardiologists and their patients should pay serious attention to this new paradigm in the diet–heart hypothesis, and increase the intake of fish and fish oil.133,137
The amount of n-3 PUFA necessary for cardioprotection is surprisingly low. The current recommendation is to take 2–3 fish meals per week (200–300 g/week of fish). A less attractive alternative is to consume 1000 mg/day of n-3 PUFA (contained in 3000 mg of fish oil capsules).10,11,74,96,133 The current intake of n-3 PUFA in the US is 1600 mg/day or 0.7% of the calories, which is about half the recommendation.11 Fish is more beneficial than fish oil, but the latter may be required in most patients with CAD to obtain the required amount of n-3 PUFA.90 Patients with CAD should consume about 1800 mg/day of n-3 PUFA (DHA and EPA) as the best insurance against sudden death.
Alpha-Linoleic acid (ALNA)—the n-3 PUFA of the plant kingdom: There is no DHA and EHA in a vegetarian diet. Vegetarians derive their n-3 PUFA almost exclusively from ALNA, which is also the major type of n-3 PUFA in omnivores.138 There is increasing evidence for the cardioprotective effects of ALNA, albeit less than EPA and DHA.139 In a large study involving 43 700 men, increased intake of ALNA reduced the risk of MI by 60%.64 A similar risk reduction was also observed in the Nurses’ Health Study and Multiple Risk Factor Intervention Trial (MRFIT).93,140 Some vegetable oils are high in ALNA (flaxseed oil 50%, canola oil 10%, mustard oil 10%, soybean oil 7%) while others are low (groundnut oil <0.5%).141 Walnuts are a rich source of ALNA; small concentrations are found in green leafy vegetables, corn oil, almonds, hazelnuts, cereals, pulses, millets, and spices.78,142 Walnuts and canola oil account for most of the ALNA in the western diets.78,101 The recommended intake of ALNA is 2% of energy but the current intake in the USA is 0.6% of energy.11,74
ALNA is readily converted to EPA, and more slowly to DHA; the latter being the major component of phospholipid membranes of the brain and retina.78 The beneficial effects of ALNA are less than half that of DHA and EPA, because the conversion of ALNA to the more active longer-chain metabolites is inefficient: <5%–10% for EPA, and 2%–5% for DHA.80,141,143 This explains why vegetarians have lower levels of n-3 PUFA than omnivores, and also higher platelet aggregability.77 Since the biological effects of plant n-3 PUFA are significantly lower than marine n-3 PUFA, the requirements may be higher (3% of energy) for vegetarians than for nonvegetarians.9,74,77
Protein: Americans eat 80–90 g/day of protein, which is twice the daily requirement, and most of this comes from meat, which is also high in SAFA. Up to 25% of daily energy from protein (but not more than 100 g/day) is permissible if the major source of protein is plant-based. Nuts are important sources of plant protein along with soy, bran, beans, and legumes. Substituting protein for carbohydrates increases HDL and lowers TG levels.144,145 In a meta-analysis of 38 controlled human clinical trials, consumption of soy protein (47 g/day) was associated with a significant 13% decrease in LDL, 10% decrease in TG, and a 2% increase in HDL levels.146 This led to FDA approval for the use of food labels for the health claim that soy protein can reduce the risk of heart disease.
Meat: Although meat contains a significant amount of SAFA, almost half the SAFA is stearic acid, which does not raise TC levels. In addition, meat contains up to 45% of cholesterol-lowering MUFA. Furthermore, lean meat has much less SAFA than fatty cuts of meat (Table 5).6,147 Lean beef is an excellent source of protein and MUFA, and has less SAFA than chicken (dark meat); 6 oz of lean beef contains 3.0 g of SAFA v. a chicken thigh which contains 5.2 g of SAFA (the term loin or round signifies lean meat whereas prime or rib signifies fat cuts with very high SAFA in the USA). Chicken and lean beef (not fatty meat) have similar effects on plasma lipoproteins, and are interchangeable in a healthy diet.30,148,149
Glycemic Load: A Potent Predictor of the Metabolic Syndrome and Diabetes
The source, nature, and amount of carbohydrates have a profound influence on postprandial glycemia, which in turn is directly associated with the risk of CAD in patients with diabetes.6,150,151 Foods containing the same amount of carbohydrate (carbohydrate exchange) may have up to a 5-fold difference in glycemic impact, depending on the differences in the digestion and absorption.152,153 The glycemic index is an extension of the fiber hypothesis, and was proposed in 1981 as a physiological system for the classification of carbohydrate-containing foods.154,155 Carbohydrate classified by glycemic index, in contrast to its traditional classification as either simple or complex, is a better predictor of CAD in epidemiological studies.156 The glycemic index is a scientific measure of the glycemic response to various foods, and is obtained from published food tables. The hierarchy of the glycemic index begins with beans, lentils, rice, spaghetti, potatoes, white bread (with refined flour), and refined grain cereals.150 A high glycemic index indicates a lower quality of carbohydrate associated with low HDL levels, and low rates of satiety. 157,158 Fruits, nonstarchy vegetables, parboiled rice, and legumes have a low glycemic index.159 The glycemic index of potato is 102%, white bread 100%, whereas that of apple is 55%, and broccoli 13%. Glycemia observed after consuming dried peas is only one-third that of an equivalent amount of potatoes. Since peas are also high in fiber, their consumption needs to be encouraged, especially in patients with diabetes.153,160
Glycemic load is the product of the glycemic value of the food and its carbohydrate content (per serving) divided by 100. For example, carrot has a high glycemic index but a low glycemic load (Table 6).152,161 The overall daily dietary glycemic load is calculated by adding the glycemic loads of all the different foods consumed in a given day. Accordingly, the glycemic load can be decreased by reducing the amount of carbohydrate intake and/or by consuming foods with a low glycemic index.162 In addition to the quality and quantity of carbohydrates consumed, the glycemic load also represents diet-induced insulin demand.163,164 PAI-1 levels are significantly increased with high glycemic load, and decreased with low glycemic load.165
Dietary carbohydrates drive TG much more than dietary fat.6 A high glycemic load produces only mild increments in TG levels in individuals with normal TG levels but marked elevation in those with fasting lipemia and/or obesity.6,166–168 A low HDL level is a strong risk factor for CAD, even when the TC level is not elevated.169,170 A high glycemic load produces a low HDL, particularly when substituted for MUFA or PUFA.23,157,166,171–179 In a prospective study of 75 521 women followed up for 10 years, those in the highest quintile of glycemic load had double the risk of CAD after adjustment for age, smoking status, total energy intake, and other risk factors (p<0.0001).156
More importantly, a glycemic load promotes diabetes, especially in those with insulin resistance.156,161,180–183 (Fig. 2)183 This is particularly true for refined carbohydrates, sweets, white bread, and potatoes.45,156,183,184 Thus, a high glycemic load may be considered a risk factor of equal importance as high SAFA diet in precipitating diabetes. A ,low glycemic load can reduce insulin secretion in patients with type 2 diabetes, decrease insulin requirements in type 1 diabetes, and improve glycemic control in both types of diabetes. The incremental benefit from low glycemic load is similar to that offered by pharmacological agents that also target postprandial hyperglycemia, such as alphaglycosidase inhibitors.185,186 The benefit of low glycemic load on the development of diabetes is similar to MUFA, PUFA, whole grains, fiber fruits, and vegetables.
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