Nutrition, Metabolism & Cardiovascular Diseases

WHO Technical Report Series, No. 916 (TRS 916)

Nutritional Recommendations for Cardiovascular Disease Prevention
Mayo Clinic does not endorse companies or products. The effectiveness of folic acid and B vitamin supplementation was examined mainly in secondary prevention intervention studies. Vegetables and fruits, like other plants or plant-based foods, contain substances that may help prevent cardiovascular disease. The impact of garlic on lipid parameters: Featuring vegetables and fruits in your diet can be easy.

1. Introduction


Tea has been one of the most popular beverages for years. Brewed from the plant Camellia sinensis , tea is consumed in different parts of the world as green, black, or Oolong tea.

Green and black teas are processed differently during manufacturing. To produce green tea, freshly harvested leaves are steamed, yielding a dry, stable product.

Most of the beneficial effects of tea are attributed to its polyphenolic flavonoids, known as catechins. The major flavonoid is epigallocatechingallate EGCG. A population-based prospective cohort study the Ohsaki Study included 40, persons in Miyagi prefecture in northern Japan [ 74 ].

Within CVD mortality, the stronger inverse association was observed for stroke mortality. A meta-analysis of 18 studies included 13 studies on black tea and 5 studies on green tea.

For black tea, no significant association was seen with the risk for developing CAD. No randomized controlled trial studied the effects of tea consumption on CVD morbidity or mortality; however, many studies evaluated the effects of tea on CV risk factors. More than half of the randomized controlled trials have demonstrated the beneficial effects of green tea on CVD risk profiles.

These results suggest a plausible mechanism for the beneficial effects of green tea [ 75 ]. In a meta-analysis of trials, black tea consumption increased systolic 5. Other suggested mediators for the association between tea consumption and reduced CVD risks include anti-inflammatory, anti-oxidant, and anti-proliferative effects, as well as favorable effects on endothelial function [ 77 ]. There do not appear to be any significant side-effects or toxicity associated with green tea consumption.

In general, the stimulatory effect from green tea is considerably less than that from coffee [ 78 ]. However, tea extract may cause gastrointestinal irritation. Although there are a few case reports of liver toxicity resulting from the ingestion of large quantities of green tea or green tea extract, the incidence of this potential adverse effect appears extremely low. Since green tea may interfere with the absorption of iron supplements, iron supplements should not be ingested together with green tea components.

Possible interactions between green tea and other medications have also been reported [ 79 ]. Cocoa is rich in polyphenols, similar to those found in green tea. Chocolate and cocoa are two different things. Fat and sugar are major components of chocolate, which has high caloric content that needs to be taken into account when assessing possible risks and benefits of recommending chocolate consumption for health purposes.

However, the major fatty acids in chocolate are oleic, palmitic, and stearic acids; oleic and stearic acids may have a neutral effect on blood lipid levels [ 81 ]. Chocolate, especially of the milk variety, contains large amounts of sugar and has possible implications for dental health and diabetes if eaten in large quantities, although carbohydrates might play a role in improving uptake of polyphenols.

Cocoa itself is much easier to recommend on a health basis as it is not high in sugar and fat. A recent meta-analysis of seven observational studies reported a beneficial association between higher levels of chocolate consumption and the risk of CVD.

However, most of the studies did not adjust for socioeconomic factors, which may confound this association. Most of the existing evidence is on intermediate factors of CVD.

Recent studies both experimental and observational have suggested that chocolate consumption has a positive influence on human health, with antioxidant, antihypertensive, anti-inflammatory, anti-atherogenic, and anti-thrombotic effects as well as influence on insulin sensitivity, vascular endothelial function, and activation of nitric oxide [ 82 ]. Dietary flavanols have also been shown to improve endothelial function and to lower blood pressure by causing vasodilation in the peripheral vasculature and in the brain [ 83 ].

Despite this array of benefits, there is a lack of well-designed clinical studies demonstrating a CV benefit of chocolate. The high caloric content of chocolate, particularly of some less pure forms, should be considered before recommending uncontrolled consumption [ 84 ].

The bulk of the dry weight of garlic Allium sativum contains mainly fructose-containing carbohydrates, followed by sulfur compounds, protein, fiber, and free amino acids. It also contains high levels of saponins, a variety of minerals and vitamins A and C, and a high phenolic content. Garlic has been attributed with favorable CV effects due to its high content of thiosulfinates, including allicin, which is considered to be the active component of garlic.

Allicin is formed when alliin, a sulfur-containing amino acid, comes into contact with the enzyme alliinase when raw garlic is chopped, crushed, or chewed. Over the years, different garlic preparations have been investigated for their prevention and treatment of CV disease, including raw garlic, garlic powder tablets, oil of steam-distilled garlic, oil of oil-macerated garlic, ether-extracted oil of garlic, and aged garlic extract.

All these preparations differ in their composition, which complicates comparison of studies [ 85 ]. Dried garlic preparations containing alliin and alliinase must be enteric coated to be effective because stomach acid inhibits alliinase. Because alliinase also is deactivated by heat, cooked garlic is less powerful medicinally [ 86 ]. Long-term observation studies are missing.

Intervention trials focused on CVD risk factors. However, in a later meta-analysis of 13 trials there was no significant difference in effects on all outcome measures examined when compared with placebo [ 88 ].

A review of trials assessing the effect of garlic on thrombotic risk showed modest but significant decreases in platelet aggregation with garlic compared with placebo [ 89 ].

The antihypertensive effects of garlic have been studied but remain controversial [ 88 ]. Proven adverse effects include malodorous breath and body odor. Other unproven effects included flatulence, esophageal and abdominal pain, allergic reactions, and bleeding [ 86 ]. The effective dose of garlic has not been determined. Dosages generally recommended in the literature for adults are 4 g one to two cloves of raw garlic per day, one mg dried garlic powder tablet standardized to 1.

During the past 40 years, the public had been warned against frequent egg consumption due to the high cholesterol content in eggs and the potential association with CVD [ 90 ].

This was based on the assumption that high dietary cholesterol consumption is associated with high blood cholesterol levels and CVD. However, subsequent research suggests that, in contrast to SFA and TFA, dietary cholesterol in general and cholesterol in eggs in particular have limited effects on the blood cholesterol level and on CVD [ 91 ].

Eggs are also a source for high biological value protein, as well as vitamins and minerals such as folic acid, vitamin B12, vitamins E and D, selenium, choline, zinc, etc.

Level of evidence and classes of recommendations for food items is summarized in Table 7. The epidemiologic evidence relating egg-consumption to coronary disease risk is not entirely consistent. Most large population studies did not find an association between egg consumption and CVD [ 93 , 94 , 95 ].

In several studies, consumption of at least 5 eggs per week was associated with CVD and mortality in people with diabetes [ 98 ]. In a meta-analysis of 17 intervention studies lasting at least 14 days, the addition of mg dietary cholesterol per day increased cholesterol levels by 2.

There is a great variation in the response of blood cholesterol levels to dietary cholesterol, possibly related to the large variability in intestinal absorption of cholesterol. A low-sodium diet fits all dietary strategies. Dietary sources for sodium include: On average, as dietary salt sodium chloride intake rises, so does BP. Evidence includes results from animal studies, epidemiological studies, clinical trials, and meta-analyses of trials.

Despite these results, the authors concluded that the sample size had insufficient power to exclude clinically important effects of reduced dietary salt on mortality or CV morbidity in normotensive or hypertensive populations.

Recently, the Institute of Medicine committee concluded that, although sodium restriction is recommended, evidence from studies on direct health outcomes is inconsistent and insufficient to conclude that lowering sodium intakes below mg per day either increases or decreases risk of CVD outcomes including stroke and CVD mortality or all-cause mortality in the general U. While being supported by observational studies, randomized controlled trials have not supported a role for vitamins in the primary or secondary prevention of CVD, and have in some cases even indicated increased mortality in those with pre-existing late-stage atherosclerosis.

In intervention trials including vitamins A, C, E, beta-carotene, and selenium, no beneficial effect was detected on all cause mortality in secondary prevention. Studies have also indicated that beta-carotene mediates pro-oxidant effects. The trials that used a combination of vitamins that include beta-carotene have been disappointing. Studies also suggest that vitamins would be beneficial to individuals who are antioxidant-deficient [ ]. A recent trial reported that consumption of a multivitamin had no effect on CVD risk in men [ ].

The association between vitamin D and bone disease is well established. However, vitamin D has many other functions and the use of vitamin D supplements to prevent and treat a wide range of illnesses has increased substantially over the last decade. Epidemiologic evidence links vitamin D deficiency to autoimmune disease, cancer, CVD, depression, dementia, infectious diseases, musculoskeletal decline, and more [ ].

A diet high in oily fish prevents vitamin D deficiency. Solar ultraviolet B radiation penetrates the skin and converts 7-dehydrocholesterol to pre-vitamin D3, which is rapidly converted to vitamin D3 [ ]. Fortified milk with vitamin D is also a source for vitamin D. In a meta-analysis of five prospective cohort studies, the RR for CV events was 1.

In a meta-analysis of osteoporosis intervention trials, four trials in five articles reported the effect of vitamin D supplementation on incident CVD. None reported a statistically significant effect of vitamin D supplementation with or without calcium on myocardial infarction, stroke, and other cardiac and cerebrovascular outcomes.

Study participants were followed for 1, 5, or 7 years. In summary, at this time no recommendations can be made for vitamin D screening or treatment in populations without risk for bone fractures, for the sake of preventing CVD.

Further investigation is needed to find whether treatment for vitamin D deficiency can reduce CVD morbidity and mortality. Coenzyme Q10 CoQ10 is a naturally occurring, fat-soluble quinone that is localized in hydrophobic portions of cellular membranes and acts as an electron carrier in the mitochondrial respiratory chain [ ]. It also functions as an antioxidant, scavenging free radicals and inhibiting lipid peroxidation [ ].

Clinical studies have focused on three potential effects of CoQ10 supplementation: In different CVDs, including cardiomyopathy, relatively low levels of CoQ10 in myocardial tissue have been reported.

However, in a sub-analysis of patients with ischemic systolic heart failure enrolled in the CORONA study, rosuvastatin reduced CoQ10, but even in patients with a low baseline CoQ10, rosuvastatin treatment was not associated with a significantly worse outcome [ ]. Favorable short-term clinical and hemodynamic effects of oral CoQ10 supplementation have been observed in double-blind trials, especially in people with HTN and chronic heart failure.

There have been no important adverse effects reported from experiments using daily supplements of up to mg CoQ10 for 6—12 months and mg daily for up to 6 years [ ]. There was a 3. However, the long-term effect of this supplementation on clinical outcome is unknown. In a meta-analysis of five trials including patients, treatment with coenzyme Q10 significantly improved endothelial function as assessed peripherally by flow-mediated dilatation SMD 1.

However, the endothelial function assessed peripherally by nitrate-mediated arterial dilatation was not significantly improved [ ]. However, the authors conclude that due to the possible unreliability of some of the included studies, it is uncertain whether or not CoQ10 reduces blood pressure in the long-term management of primary HTN [ ]. Statins inhibit 3-hydroxymethylglutaryl coenzyme A HMG-CoA reductase, blocking cholesterol synthesis at a step that not only reduces cholesterol synthesis but also the production of other metabolites, including ubiquinone CoQ The effects of statins on skeletal muscle with CoQ10 supplementation were inconsistent.

Supplementation of CoQ10 increases these levels [ ]. However, the effect of CoQ10 supplementation on patients with statin myopathy is inconsistent, and recent randomized trials of coenzyme Q10 supplementation have shown conflicting results [ ]. Magnesium Mg is an abundant intracellular mineral in the body. Therefore, Mg status is difficult to determine from serum Mg measurements [ ].

Dietary sources of Mg are green leafy vegetables particularly spinach , nuts, avocados, whole grains, legumes beans and peas , soy beans, chocolate, and some seafood [ ]. Observational epidemiological studies have shown that the Mg content of drinking water and food is inversely related to morbidity and mortality from heart disease and stroke [ , , ]. Relatively small studies have shown a distinct advantage in providing Mg versus placebo on reducing mortality in patients with acute MI; however, two major studies published in recent years have failed to prove this [ ].

Intervention studies have indicated that Mg supplementation was effective in patients with heart failure receiving diuretic therapy that reduces both Mg and potassium levels [ ]. The effect of Mg on the primary and secondary prevention of CV morbidity and mortality as well as all-cause mortality remains unclear, and therefore it is not yet possible to give conclusive recommendations in this respect.

Homocysteine is an amino acid that contains sulfur and is produced in the body during the breakdown of the amino acid methionine. Part of the homocysteine formed in this process is recycled back to build methionine, while the rest is excreted in the urine. Folic acid, vitamin B12, and vitamin B6 regulate the metabolism of homocysteine. Deficiencies of one of these vitamins can lead to high blood homocysteine level. Major food sources of folic acid are: Food sources for vitamin B12 include animal products: The effectiveness of folic acid and B vitamin supplementation was examined mainly in secondary prevention intervention studies.

These studies failed to prove that reducing homocysteine level by folic acid and vitamin B supplements improves CVD incidence [ ]. The effect in primary and secondary prevention of stroke was minimal, as shown in a meta-analysis of 13 trials and 39, participants. A meta-analysis of folic acid supplementation in patients with chronic kidney disease also failed to show a beneficial effect in cardiovascular outcome [ ]. Polyunsaturated fatty acids are characterized according to the position of the first double bond.

Humans cannot synthesize short-chain fatty acids and therefore need to consume them in their diet. They include the plant-derived alpha-linolenic acid ALA, ALA is found in seeds, vegetable oils especially canola and flaxseed , green leafy vegetables, walnuts, and beans. Although some ALA can be transformed in the human body to EPA and DHA, such conversion appears to be inefficient [ ], and the majority of these fatty acids are consumed from cold water oily fish, such as salmon, herring, mackerel, anchovies, tuna, and sardines.

Various sources of omega-3 fatty acids are used as supplements for commercial use, including fish oil, flaxseed oil, and walnut oil. Most fish oil supplements undergo purification processes and do not appear to contain these substances in appreciable quantities.

Commonly used doses of omega-3 supplements up to 1 g daily do not appear to have significant side effects. However, larger doses may cause minor gastrointestinal upsets, worsening of glycemia control, and a rise in LDL-C levels [ ]. Most observational studies show an inverse correlation between fish consumption and cardiovascular CVD.

A review of 11 cohort studies involving , individuals suggested that fish consumption at 40—60 g daily is associated with markedly reduced CHD mortality in high-risk, but not in low-risk populations [ ]. A meta-analysis of intervention trials including individuals treated with omega-3 compared to controls found a significant decrease in mortality from MI but not in non-lethal MI [ ].

Recent meta-analyses of randomized controlled trials found little evidence of a protective effect of omega-3 supplementation on the incidence of CVD [ ], cerebrovascular disease [ ], or atrial fibrillation [ ]. In a meta-analysis of 20 studies of 68, patients 13 on secondary prevention , omega-3 PUFA supplementation was not associated with a lower risk of all-cause mortality, cardiac death, sudden death, myocardial infarction, or stroke based on relative and absolute measures of association.

The long-chain omega-3 fatty acids EPA and DHA compete with arachidonic acid a long chain omega-6 fatty acid in the synthesis of prostaglandins and leukotrienes involved in inflammation and thrombogenesis.

Omega-3 fatty acids have been shown to increase arrhythmic thresholds, reduce blood pressure, improve endothelial function, reduce inflammation and platelet aggregation, enhance plaque stabilization, and favorably affect autonomic tone [ ]. At high doses 2—6 g daily they can significantly reduce the serum triglyceride levels, but the long-term clinical outcome of such treatment in hypertriglyceridemic individuals has not been evaluated [ ].

Sterols constitute an important constituent of plant cellular membranes, in a manner similar to the role of cholesterol in human cells [ ]. They are found at low concentrations in most plant-derived nutrients but at somewhat higher concentrations in some grains. Despite their structural similarities to cholesterol, plant sterols are not synthesized in the human body and are only minimally absorbed from the human intestinal tract.

The average western diet contains approximately — mg of cholesterol, approximately — mg of plant sterols, and 20—50 mg of plant stanols. Amongst the best known plant sterols are sitosterol, campesterol, and stigmasterol. Those that are incorporated in food are usually esterified. Hydrogenation converts sterols into stanols e.

The optimal dose appears to be 1. Due to their biochemical similarity, plant sterols and stanols can displace cholesterol from mixed micelles in the intestine, thus reducing the absorption of dietary cholesterol [ ]. Although they have significant atherogenic potential, the intestinal absorption of sterols and stanols is poor, resulting in very low serum concentrations.

An exception to this rule is patients with sitosterolemia, a rare genetic disorder in which the absorption of sterols is enhanced, resulting in significant damage to various organs. Level of evidence and classes of recommendations for nutritional supplements is summarized in Table 8.

Sterol supplementation at the recommended doses is generally considered safe [ ]. However, several potential risks need to be considered. In addition to inhibiting cholesterol absorption, some though not all studies suggest that sterols and stanols can reduce the blood levels of antioxidants such as lycopene and beta-carotene.

This can be counteracted, at least partly, by the ingestion of a diet reach in vegetables and fruits [ ]. Despite the low serum concentration of sterols and stanols, some concern has been raised that even the slight increase associated with dietary supplementation of sterols might increase the risk for atherosclerosis [ ]. A healthy diet should include diversity of foods and to maintain a healthy weight.

It is preferable to eat fresh or frozen food without additional sugar, salt or high-calorie gravies, using cooking methods that retain the original nutrients undestroyed. It should contain a variety of vegetables and fruits, legumes, whole grains, whole wheat bread and high-fiber low-salt food items. Vegetable oils, especially olive and canola oils, excluding palm and coconut oils , should be preferred over animal fat. Additional elements that may confer health benefits include avocado, nuts, almonds and tahini, low-fat dairy products, green tea and 2 to 3 servings of fatty fish per week.

It is recommended to minimize consumption of high-fat meat especially processed meats that are high in fat and sodium , hard margarines and pastries with hydrogenated fat, and foods that are high in sodium and sugar. It is recommended to drink a lot of water, and reduce consumption of sweetened beverages as well as fresh juices. The Mediterranean diet has been shown to reduce cardiovascular morbidity and mortality in both primary and secondary prevention.

Other dietary patterns that have been shown to confer advantage in specific medical situations include low-fat diet for individuals at high cardiovascular risk, DASH diet for people with hypertension, and low-carbohydrate diets for overweight people and for the metabolic syndrome. Sigal Eilat-Adar serves as a scientific consultant for the dairy industry and has given lectures on behalf of a number of companies in the food and pharmaceutical industry, including some on cereals, milk and milk products, tea, nuts, and nutritional supplements.

Yaakov Henkin serves as a scientific consultant, and has given lectures on behalf of a number of companies in the food and pharmaceutical industry, including some that are involved in the distribution of cereals, milk products, tea, chocolate, wine, and nutritional supplements. National Center for Biotechnology Information , U.

Journal List Nutrients v. Published online Sep This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license http: This article has been cited by other articles in PMC. Abstract Lifestyle factors, including nutrition, play an important role in the etiology of Cardiovascular Disease CVD. Introduction Lifestyle factors, including nutrition, play an important role in the etiology of Cardiovascular Disease CVD.

Table 1 Levels of evidence. Open in a separate window. Low-Fat Diets The consumption of a lower fat diet is generally accepted in all clinical guidelines on CV prevention, and will therefore not be discussed in detail in this manuscript.

Table 4 Level of evidence and classes of recommendations for food patterns. Food pattern Recommendations Strength Level of evidence Low-fat diet Low-fat diet with restricted calories may present a healthy alternative to the typical Western diet. It may improve quality and life expectancy in healthy people, as well as in patients with overweight, diabetes, and CVD. II a A Low-carbohydrate Diet In the short-run, low-carbohydrate diets lead to a greater weight loss compared to low-fat diets.

Some studies have shown that this advantage is retained at 2 years but not at longer follow-up periods II b A Low-carbohydrate diets are preferable to a low-fat diet in reducing TG levels and increasing HDL-C blood levels. It should be emphasized that carbohydrates should preferably be replaced by unsaturated vegetable fats. I A The diet should be accompanied by lifestyle changes such as: Conclusions All four dietary patterns described above are useful for reducing CVD risk factors, and some have also shown a favorable effect on plaque regression [ 19 ] and CVD mortality [ 16 ].

Individual Food Items 3. Whole Grains and Dietary Fiber Whole grains represent unprocessed grains that contain the endosperm; the bran the outer layer of the whole grain and the germ are in the same relative proportions as they exist in the intact grain. Nuts Nuts tree nuts and peanuts are nutrient-dense foods with complex matrices rich in unsaturated fatty acids and other bioactive compounds: Intervention Studies In 22 randomized trials, isolated soy protein with isoflavones was compared with casein or milk protein, wheat protein, or mixed animal proteins.

Dairy Products Dairy products are rich in minerals calcium, potassium, and magnesium , protein casein and whey , and vitamins riboflavin and vitamin B that can exert beneficial effects on CVD. Possible Mechanisms Suggested mechanisms for the blood-pressure lowering effects of dairy products include the high content of potassium, magnesium, and calcium. Conclusions Despite the contribution of dairy products to the saturated fatty acid composition of the diet, and given the diversity of dairy foods of widely differing fat composition, there is no clear evidence that dairy food consumption is consistently associated with a higher risk of CVD [ 48 ] and some evidence that low-fat products may have beneficial effects on blood pressure.

Alcoholic Drinks The consumption of alcohol ethanol is widely accepted in many social situations. Possible Mechanisms Numerous mechanisms have been proposed to explain the benefit of light-to-moderate alcohol intake on the heart, including an increase in HDL-C, reduction in plasma viscosity and fibrinogen concentration, increase in fibrinolysis, decrease in platelet aggregation, improvement in endothelial function, reduction in inflammation, and promotion of antioxidant effects [ 58 , 59 ]. Conclusions Despite the evidence from cohort studies on the inverse association between moderate alcohol drinking and CVD, current guidelines do not recommend to begin consuming alcohol for preventing CVD.

Table 5 Energy content and ethanol in alcoholic beverages [ 61 ]. Coffee and Caffeine Coffee is one of the most widely consumed beverages in the world.

Table 6 Caffeine content in selected food and drink products. Product Quantity Caffeine content mg Coffee, instant 1 glass, mL 75 Roasted, ground, perculated or filter, or espresso 1 glass, mL — Coffee, decaffeinated 1 glass, mL 4 Tea, green 1 glass, mL 24 Tea, black 1 glass, mL 15—24 Tea, leaf or bag 1 glass, mL 40— Cocoa drink 1 glass, mL 1.

Possible Mechanisms Several mechanisms have been proposed to explain the harmful as well as protective effects that certain components of coffee may have on the development of CHD. Conclusions Although regular consumption of moderate quantities of coffee seems to be associated with a small protection against CAD, results from randomized clinical trials about its beneficial effects are lacking. Tea Tea has been one of the most popular beverages for years.

Possible Mechanisms Most of the beneficial effects of tea are attributed to its polyphenolic flavonoids, known as catechins. Observational Studies A population-based prospective cohort study the Ohsaki Study included 40, persons in Miyagi prefecture in northern Japan [ 74 ]. Intervention Studies No randomized controlled trial studied the effects of tea consumption on CVD morbidity or mortality; however, many studies evaluated the effects of tea on CV risk factors.

Adverse Effects There do not appear to be any significant side-effects or toxicity associated with green tea consumption. Chocolate Cocoa is rich in polyphenols, similar to those found in green tea. Observation Studies A recent meta-analysis of seven observational studies reported a beneficial association between higher levels of chocolate consumption and the risk of CVD. Garlic The bulk of the dry weight of garlic Allium sativum contains mainly fructose-containing carbohydrates, followed by sulfur compounds, protein, fiber, and free amino acids.

Adverse Effects Proven adverse effects include malodorous breath and body odor. Dosage The effective dose of garlic has not been determined. Eggs During the past 40 years, the public had been warned against frequent egg consumption due to the high cholesterol content in eggs and the potential association with CVD [ 90 ].

Table 7 Level of evidence and classes of recommendations for food items. Food item Recommendations Strength Level of evidence Whole grains and dietary fiber The recommended dietary fiber intake is 14 g per kcal, or 25 g for adult women and 38 g for adult men.

I A Vegetables and fruits It is recommended to consume at least 8 portions of vegetables and fruits a day. Preferably root vegetables and deep-colored fruits such as spinach, carrot, peach, and blueberries since they usually contain more micronutrients compared to other vegetables and fruits.

II a B It is recommended to eat the whole fruit rather than fruit juice because of the fiber content and the satiation. II a A It is recommended to use cooking techniques such as sautéing or simmering that preserve the micronutrients in the vegetables and fruits without additional calories, SFA, TFA, salt or sugar.

II a A In cases of disease influenced by dietary carbohydrates, sodium, or potassium diabetes, kidney, coagulation , vegetables and fruits quantity should be personally adjusted.

II a B Milk and dairy products It is recommended to include dairy products preferably low-fat and without added sugar as part of a balanced diet. II a B Low-fat milk and dairy products lower blood pressure. I A There is epidemiologic data to suggest an association between dairy product consumption and reduced CVD.

III C Alcohol Due to the absence of interventional controlled studies of moderate alcohol consumption with clinical endpoints, there is no recommendation to start drinking alcohol for health benefits.

III C In individuals who regularly drink a moderate amount of alcohol 1 drink a day in women and 2 drinks per day in men with meals, there is an associated reduced CVD incidence. Larger amounts should be discouraged. Healthy adults without caffeine sensitivity: However, the causal effect and the dose needed for this effect is unknown. III C Dark chocolate, with a high cocoa percent, has abundant antioxidants and therefore preferable over milk chocolate.

II a B Garlic Eating 2 garlic cloves a day may marginally reduce blood cholesterol levels. It is recommended to limit egg consumption to 3—4 per week, including eggs contained in other foods.

Observational Studies The epidemiologic evidence relating egg-consumption to coronary disease risk is not entirely consistent. Intervention Studies In a meta-analysis of 17 intervention studies lasting at least 14 days, the addition of mg dietary cholesterol per day increased cholesterol levels by 2. Biological Mechanisms There is a great variation in the response of blood cholesterol levels to dietary cholesterol, possibly related to the large variability in intestinal absorption of cholesterol.

Salt and Sodium A low-sodium diet fits all dietary strategies. Antioxidant Vitamins E and C While being supported by observational studies, randomized controlled trials have not supported a role for vitamins in the primary or secondary prevention of CVD, and have in some cases even indicated increased mortality in those with pre-existing late-stage atherosclerosis.

Vitamin D The association between vitamin D and bone disease is well established. Randomized Trials In a meta-analysis of osteoporosis intervention trials, four trials in five articles reported the effect of vitamin D supplementation on incident CVD.

Coenzyme Q10 Coenzyme Q10 CoQ10 is a naturally occurring, fat-soluble quinone that is localized in hydrophobic portions of cellular membranes and acts as an electron carrier in the mitochondrial respiratory chain [ ].

Intervention Studies Favorable short-term clinical and hemodynamic effects of oral CoQ10 supplementation have been observed in double-blind trials, especially in people with HTN and chronic heart failure.

Magnesium Magnesium Mg is an abundant intracellular mineral in the body. Observational Studies Observational epidemiological studies have shown that the Mg content of drinking water and food is inversely related to morbidity and mortality from heart disease and stroke [ , , ].

Intervention Studies Relatively small studies have shown a distinct advantage in providing Mg versus placebo on reducing mortality in patients with acute MI; however, two major studies published in recent years have failed to prove this [ ]. Conclusions The effect of Mg on the primary and secondary prevention of CV morbidity and mortality as well as all-cause mortality remains unclear, and therefore it is not yet possible to give conclusive recommendations in this respect.

Homocysteine-Reducing Agents Homocysteine is an amino acid that contains sulfur and is produced in the body during the breakdown of the amino acid methionine. Intervention Studies The effectiveness of folic acid and B vitamin supplementation was examined mainly in secondary prevention intervention studies.

Omega-3 and Fish Oil Polyunsaturated fatty acids are characterized according to the position of the first double bond. Dietary Sources ALA is found in seeds, vegetable oils especially canola and flaxseed , green leafy vegetables, walnuts, and beans.

Omega-3 Supplements Various sources of omega-3 fatty acids are used as supplements for commercial use, including fish oil, flaxseed oil, and walnut oil. Observational Studies Most observational studies show an inverse correlation between fish consumption and cardiovascular CVD. Intervention Studies A meta-analysis of intervention trials including individuals treated with omega-3 compared to controls found a significant decrease in mortality from MI but not in non-lethal MI [ ].

Possible Mechanisms The long-chain omega-3 fatty acids EPA and DHA compete with arachidonic acid a long chain omega-6 fatty acid in the synthesis of prostaglandins and leukotrienes involved in inflammation and thrombogenesis. Phytosterols Sterols constitute an important constituent of plant cellular membranes, in a manner similar to the role of cholesterol in human cells [ ]. Possible Mechanisms Due to their biochemical similarity, plant sterols and stanols can displace cholesterol from mixed micelles in the intestine, thus reducing the absorption of dietary cholesterol [ ].

Table 8 Level of evidence and classes of recommendations for nutritional supplements. Supplement Recommendations Strength Level of evidence Sodium It is recommended to limit salt intake to 2. It is recommended to substitute salt with other spices and herbs. It is recommended to use food labels for information of sodium content in foods. I B It is recommended to reduce as much as possible the use of industrial pre-prepared food, as well as salted snacks and vegetables.

I B Efforts should be put into reducing sodium content in industrial foods through legislation. I B Omega-3 General population primary prevention Eat a variety of fish, preferably fat, at least twice a week.

II a A It is recommended not to exceed g daily of fish that contain a high level of mercury such as mackerel, sword fish or shark or g of other fish. Removing the skin off the fish before preparation can reduce the amount of contaminants.

I B For children and pregnant women it is recommended to avoid eating fish with potentially high levels of contaminants. However, no long-term studies have been conducted to evaluate the clinical outcome in these individuals II b B Phytosterols Plant phytosterols can be considered for the reduction of LDL cholesterol in mildly hypercholesterolemic individuals at intermediate to high risk who do not wish to use, or cannot tolerate, other cholesterol-lowering medications.

II b A Antioxidant-vitamin supplementation Based on data from intervention controlled trials, it is not recommended to use antioxidant vitamins supplementation to prevent or treat CVD.

Therefore it is not recommended to use CoQ10 supplementation in these patients. II a A It is not recommended to use magnesium supplements in order to prevent CVD in people with normal magnesium levels.

I A Folic acid and vitamin B supplements are not effective for primary, nor for secondary prevention of CVD and stroke. Safety Sterol supplementation at the recommended doses is generally considered safe [ ]. Conclusions A healthy diet should include diversity of foods and to maintain a healthy weight. Conflicts of Interest Sigal Eilat-Adar serves as a scientific consultant for the dairy industry and has given lectures on behalf of a number of companies in the food and pharmaceutical industry, including some on cereals, milk and milk products, tea, nuts, and nutritional supplements.

Tali Sinai and Chaim Yosefy declare no conflicts of interest. Guidelines on diabetes, pre-diabetes, and cardiovascular diseases: American Heart Association Nutrition Committee. Diet and lifestyle recommendations revision Reduced or modified dietary fat for preventing cardiovascular disease. Effects of low-carbohydrate vs.

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This occurred without any change in the activity of the glutathione-related antioxidant enzymes superoxide dismutase and catalase Because these fatty acids also apparently compete for different intracellular phospholipid pools, the effects of oleate and DHA can be additive 5 , Pretreatment with DHA also reduces the adhesion of human monocytes and of monocytic U cells to the endothelial cells in response to stimulation It therefore appears that there is a down-regulation of the intracellular mechanisms that lead to the expression of proatherogenic genes.

Arachidonic acid, a fatty acid present in phospholipids, is a substrate for 5-lipoxygenase in white blood cells and other bone-marrow-derived cells. The enzyme 5-lipoxygenase catalyzes the conversion of arachidonic acid into leukotriene A 4 , which is then in turn enzymatically converted into either leukotriene B 4 or the cysteinyl leukotrienes. Leukotriene B 4 is a potent nonspecific chemoattractant for inflammatory cells and induces the chemokinesis and adhesion of these cells to the vascular endothelium.

Cysteinyl leukotrienes can increase vascular permeability. Leukotrienes may be involved in atherosclerosis Figure 4 ; 8 , and there are clues that genetic variants of 5-lipoxygenase are related to susceptibility to cardiovascular disease. Indeed, individuals carrying deletions or insertions in a region of the promoter of the 5-lipoxygenase gene exhibit increased atherosclerosis in the carotid artery, and this risk can be modulated by diet.

The increase in carotid artery intima-media thickness among persons with the variant genotype was similar in this cohort to that associated with diabetes, the strongest common cardiovascular disease risk factor.

Plasma concentrations of CRP were higher by a factor of 2 among individuals with the variant genotype than in carriers of the common allele. The main roles of 5-lipoxygenase 5-LO in atherosclerosis.

Early development of lesions is caused by invasion of the intima by monocytes, followed by the transformation of monocyte-derived macrophages into foam cells through the uptake of minimally modified mm or oxidized ox LDL.

Leukotrienes LTs may contribute to atherosclerosis by promoting nonspecific leukocyte chemotaxis LTB 4 and by increasing vascular permeability cysteinyl leukotrienes. The activation and gene expression of 5-LO, the enzyme responsible for the initiation of the leukotriene biosynthetic pathway from arachidonic acid AA , can be increased by various cytokines in inflammatory conditions.

Resident macrophages perpetuate a vicious circle of local inflammation by releasing inflammatory cytokines, matrix-degrading metalloproteinases contributing to plaque rupture , and tissue factor TF; increasing plaque thrombogenicity , as well as by producing more LTs. See also reference 8. The atherosclerotic risk in individuals carrying the proatherogenic variants of the 5-lipoxygenase gene is a function of dietary arachidonic acid intake, and progressively increases across tertiles of arachidonic acid intake, as measured by h recalls of food intake.

This is compatible with the biological notion that the higher the arachidonic acid intake with the diet, the higher the production of leukotrienes. Thus, increased dietary arachidonic acid significantly enhances the proatherogenic effect of the variant genotype. The observed diet-gene interaction is a further example of how dietary nutrients are a potent environmental factor allowing or denying the manifestations of a specific genotype.

Diet can affect the vast majority of modifiable risk factors for cardiovascular disease, which are now identified as explaining a very large part of the variability in the occurrence of a first acute myocardial infarction. Diet offers incredible opportunities for prevention of cardiovascular disease. Modulation of vascular inflammation is likely the most relevant common pathogenetic step by which nutritional factors influence cardiovascular disease.

Implementing relevant and successful dietary changes is the greatest challenge for preventive cardiovascular medicine after the turn of the century. A more complete understanding of how dietary changes may work will likely lead to a beneficial exploitation of such current knowledge. RDC conceived and wrote the largest part of this review. AZ reviewed and wrote the section on leukotriene biology.

RM reviewed and wrote the section on the general regulation of gene expression by nutrients. MM reviewed and wrote the section on the intracellular quenching of reactive oxygen species by polyunsaturated fatty acids.

Oxford University Press is a department of the University of Oxford. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide. Sign In or Create an Account. Close mobile search navigation Article navigation. Nutritional mechanisms that influence cardiovascular disease Raffaele De Caterina. View large Download slide. From asthma to atherosclerosis—5-lipoxygenase, leukotrienes, and inflammation.

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Hyperinsulinemia as an independent risk factor for ischemic heart disease. Insulin enhances vascular cell adhesion molecule-1 expression in human cultured endothelial cells through a pro-atherogenic pathway mediated by p38 mitogen-activated protein-kinase.

Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. Long-term calorie restriction is highly effective in reducing the risk for atherosclerosis in humans.

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The omega-3 fatty acid docosahexaenoate reduces cytokine-induced expression of proatherogenic and proinflammatory proteins in human endothelial cells. Structural requirements for inhibition of cytokine-induced endothelial activation by unsaturated fatty acids.

Arachidonate 5-lipoxygenase promoter genotype, dietary arachidonic acid, and atherosclerosis. Email alerts New issue alert. Receive exclusive offers and updates from Oxford Academic.

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Nutrition, Metabolism & Cardiovascular Diseases