Dietary nutrients in preventing cardiovascular diseases: a narrative review

Document Type: Review

Authors

1 Ph.D candidate of Persian Medicine, School of Persian and Complementary Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

2 Ph.D Candidate of Persian Cedicine, School of Persian and Complementary Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

3 Assistant Professor of Drug Control, Department of Traditional Persian Pharmacy, School of Persian and Complementary Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Abstract

Foods play an important role in preparing the health of body. Foods and nutrients are effective in increasing health and regulating the immune system as well as in prevention of different diseases such as cardiovascular diseases. In the past few years, the prevalence of cardiovascular disease is progressively increasing. Change in lifestyle and dietary pattern of the societies plays an important role in inducing cardiovascular diseases. Studies have shown that the risk of cardiovascular disease among people consuming more vegetables is lower. Recent findings suggest that foods rich in omega-3, vitamins, antioxidants and fibers are useful for the health of cardiovascular system and such nutrition, in addition to disease prevention, reduces the cost and side effects of chemical treatments. In this article, different clinical trials introducing beneficial dietary approaches in preventing cardiovascular diseases are reviewed.

Keywords


Introduction
WHO (World Health Organization) estimates that about 16.7 million people annually die of cardiovascular diseases (CVD), and it has been estimated that the mortality rate will reach 25 million people by 2020as a result of  CVD  (1). People now believe that changes in the dietary lifestyle has a major impact on cardiovascular diseases (2). Drugs that are usually administered to lower the cholesterol are useful to prevent CVD, but their side effects restricted their wide applications. When supplements combine with food, similar to statins drugs, they can reduce the risk of CVD. In many studies, the benefits of vegetarian diets on CVD have been emphasized (1,3). The term “Nutraceutical” (a food or part of a food that has medicinal and health benefits) may be effective in the prevention and treatment of congestive heart failure (CHF), arrhythmias, hypertension, angina and hyperlipidemia (4). In the following article, various nutraceuticals, which are used for the prevention and treatment of CVDs, are discussed. For this purpose, a review study was conducted on studies that introduce neutraceuticals used in the treatment and management of CVDs.

Literature Review
Possible dietary approaches towards reducing cardiovascular disease    
1) Type of fat
Several studies were conducted on the relationship between the intake of saturated fatty acids and CVDs. Change in the type of fat you eat, is very useful in this regard (1). There is a strong correlation between mortality as a result of coronary heart disease and consumption of saturated fatty acids (5). Saturated fatty acids increase plasma cholesterol, and unsaturated fatty acids reduce plasma cholesterol (6). First-line treatment of patients with moderate increases in cholesterol and triglyceride levels is the change in their diet to reduce the percentage of energy intake from fats to about 30%, which should not be more than 10% from saturated fat (7). In a research, it was shown that reducing energy derived from fats from 40 to 27 percent, reduces cholesterol and triglyceride levels more than 20% (8). In a study, it was found that exercise therapy, stress management and eating a diet consisting of 10% fat, have a positive impact on the health of cardiovascular system (9). This program caused the oxidized low density lipoprotein (LDL) to be changed and eliminated by the macrophages of the artery walls (9). The results of a cross- sectional study conducted in the North and South India showed a strong correlation between total cholesterol and meat consumption. This study showed that total cholesterol is reduced by eating fruits and vegetables (10).

1-1) Saturated fatty acid
Different saturated fatty acids have different effects on plasma lipids and lipoproteins. Among these fatty acids, myristic acid acts more powerfully in elevating cholesterol than lauric or palmitic acid. According to the study findings, stearic acid in contrast to myristic acid and palmitic acid, lowers LDL, although it reduces  high density lipoprotein (HDL) (6). In a study, middle-aged men who were at high risk for CVD were placed in the experimental group, who used grains, vegetables, fruits and some unsaturated fatty acids and fish oil in their diet, resulting in a 36% reduction in mortality, a 44% reduction in CVDs and a decrease in serum cholesterol by 13%. They were followed for more than 6 years with the control group (11).The study showed that stearic acid cannot increase serum cholesterol, but compared to mono or polyunsaturated fatty acid reduces HDL-C (12).

1-2) Unsaturated fatty acid
1-2-1) Olive oil and soybean oil
Many studies have shown beneficial effects of vegetable oils rich in linoleic acid such as olive oil and soybean oil (13). Foods containing polyunsaturated fatty acids are structurally classified to n3 and n6. One of n6 fatty acid that is present in foods is alpha-linoleic acid (an essential fatty acid), which is a precursor of arachidonic acid and has essential biological effect in the body. Linoleic acid has clearly an effect on reducing cholesterol, LDL and HDL levels in the body. Arachidonic acid has little effect on plasma lipoproteins (14). Omega-6 polyunsaturated fatty acids have other benefits in addition to improving lipid profiles. Consumption of omega-6 polyunsaturated fatty acid is significantly associated with reduced incidence of type 2 diabetes (DM2)(15). Polyunsaturated fatty acid intake reduces the risk of coronary heart disease (CHD) (1).

1-2-2) Fish oil
The main part of these polyunsaturated fatty acids is marine resources. The omega-3 reduces mortality associated with myocardial infarction (MI). Eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) that are found in foods, rich in omega 3, could decrease the risk of CVDs. Randomized trial conducted on 2033 men after MI showed that consuming fish oil reduces mortality in a 2-year period by 29% (16). A landmark study conducted in Italy on 110,324 patients who were followed for 3 and a half years showed that consumption of fish oil has a significant impact on reducing sudden deaths due to CVDs (4). Marine lipid supplements have shown to improve coronary arteries in frequent angina (4). Clinical trials have suggested that omega-3 fatty acids reduce the risk of cardiac arrhythmia, hypertension and atherosclerosis (17). American Heart Association recommends omega-3 fatty acid intake by the consumption of fish and plant source oils for providing heart health (4). Alpha – linolenic acid (ALA, in fish oil) is an essential fatty acid for humans. Adequate intake of ALA and n-3 long-chain fatty acids is necessary for children and teenagers (13) and patients with nutrition through enteral parenteral (18). In a study conducted on French farmers, it was found that by changing the type of fat (replacing butter with canola oil and margarine rich in ALA), EPA of plasma lipids and their platelets’ phospholipids were dramatically increased and after two years of feeding, a large reduction was observed in platelet aggregation (19). In a study, it has been reported that the risk of death due to CHD decreased by 40% in people who have high usage of ALA (20). Flax seed as source of ALA is useful for prevention of CVD (21).

2) Proteins and fibers
Hypertension is an important risk factor for CVDs. Inhibitors of angiotensin converting enzyme (ACE) are one of the main routes in controlling high blood pressure. However, these inhibitors can lead to complications such as hypotension, hyperkalemia, decreased kidney function, cough, angioedema, rash and fetal abnormality (22). Amino acids are formed by full hydrolysis of proteins. Vegetable proteins are rich in L-arginine. Arginine is a non-essential amino acid that is a precursor for producing nitric oxide helping to sympathetic coronary response as a vasodilator. In the treatment of patients with hypertension who have micro-vascular angina, oral administration of L-arginine is useful for treatment (23).
Fibers are such components of the plants that are resistant against digestion and they are beneficial for digestive health. Fibers are divided into two groups of soluble and non-soluble (24). Insoluble fibers reduce colon cancers. Soluble fibers reduce blood cholesterol significantly, thus are useful in the prevention of CVDs (25). Wheat, rice and other grains contain more water-insoluble fibers. Soluble fibers are more derived from oat bran and fruit pectin. Its other sources are flaxseed and psyllium shell. Legumes, beans, peas, fruits and certain vegetables are excellent sources of soluble and insoluble fibers. Oats have more soluble fibers than other grains (26). Soy protein is an excellent source of dietary fiber (27). An analysis of 35-47 year-old men and women in 20 developed countries showed that consumption of vegetables, fruits, grains and legumes is significantly associated with reduced mortality caused by CHD (28). The relationship between fiber intake and ischemic heart disease among 859 men and women lived in southern California were also assessed and it was showed that every 6 grams  increased intake of fiber per day is associated with a 25 percent reduction in mortality from ischemic heart disease (29). Totally, the soluble fibers like psyllium, oat bran, guar gum and pectin, reduce cholesterol and LDL-C. They do not have an effect on triglycerides.

3) Inulin
Recent studies have shown that reduced secretion of very low density lipoprotein (VLDL) particles from the liver and also reduced enzyme activity and expression of gene regulating the production of fatty acids, can reduce serum triglycerides (30). Chicory fructans effects on triglycerides have been studied in mice. A number of studies showed that the effect of inulin on people with high cholesterol is low. But a study was conducted on volunteers who had a slight increase in blood cholesterol, which showed a significant decrease in total cholesterol and LDL_C with consuming inulin (31). Reduced triglycerides in mice feeding high doses of oligo fructose has also been impressive, although reduced cholesterol has been observed in long-term feeding (32). Inulin can help controlling food cholesterol by the following methods: 1. direct effect on serum lipids, 2. replacement of some fatty acids in food formulations, 3. reducing the accumulation of calories by replacing the fat or sugar in foods (33). Most recent randomized crossover trials, in the case of inulin, demonstrated a significant decrease in total cholesterol and LDL_C, but it had no impact on serum triglyceride and HDL_C (31).
4) Vitamins
A study in South India showed reduction of total cholesterol and LDL with high consumption of fruit and vegetables. The reason is that grains and vegetables contain low-fat and high amount of antioxidants such as vitamin C and folate (34). Antioxidant vitamins are present in some fixed oils, fruits, vegetables and fishes, which prevent the formation of oxygen free radicals, or trap them. These vitamins reduce LDL oxidation. Supplements containing antioxidants such as vitamins E and C are useful in the prevention of CHD (4).
Of all the carotenoids, beta-carotene particularly plays an important role in trapping the proxy radicals (35), and there is collaboration between beta-carotene and vitamin E. Beta-carotene and lycopene inhibit the oxidation of  LDL. Plasma carotenoids are lower in smokers (36). Taking 15-25 mg/d of this vitamin for groups that are at high risk of CVDs is necessary (36). Several epidemiological studies consider high intake of beta-carotene as a cause of reduced risk of heart attack (37).
Vitamin C acts as an antioxidant and inhibits hydroxyl, oxygen and peroxyl radicals to protect the cells. If accompanied by vitamin E, it prevents peroxidation reactions on LDL particles. Vitamin C supplements in addition to vitamin E, in heart transplant patients, prevent the progression of atherosclerosis and plaque formation (38). The proposed dose of vitamin C in high risk groups is 100-150 mg/d (39). Reduced blood pressure in people who are vegetarian can be attributed to consumption of more vitamin C and folate and less salt and fat. Beneficial effects of these foods and micro-foodstuff have been proven (40). In one study on 109 vegetarians, they showed that low vitamin C and folate causes hypertension (41).
Vitamin E, as an antioxidant, protects the cells against heart disease through two mechanisms:
1. It inhibits the oxidation of lipoproteins that play an important role in carrying cholesterol (42).
2. It inhibits the formation of the blood clot (43).
Epidemiological and biochemical studies showed that prevention of CVDs in risky people needs to consume 36-100 mg/d vitamin E (37). Alarge epidemiological study by Harvard researchers has found that middle-aged men and women who had received vitamin E supplements in the form of unit dose (SINGLE ENTITY) equal to or greater than 100 unit of vitamin E showed a lower risk of heart disease than those who consumed less vitamin E (25).  The results of this literature review are shown in Table 1.

Conclusion
Poor foodstuffs are an important risk factor for people who are at risk of CVDs. Consumption of  food containing useful components such as fibers and unsaturated fatty acids could be so effective in heart health and should be taken into consideration. It is hoped that awareness in this field will be increased and these products be used as preventive and alternative treatments.

Acknowledgement
This study was supported by a grant from the Mashhad University of Medical Sciences Research Council, Mashhad, Iran.

Conflict of Interest
The authors declare no conflict of interest.

  1. Thompkinson DK, Bhavana V, Kanika P. Dietary approaches for management of cardio-vascular health-a review. J Food Sci Technol. 2014;51:2318-2330.
  2. Wrick KL. Consumer issues and expectations for functional foods. Crit Rev Food Sci Nutr. 1995;35:167-173.
  3. Mann JI. Diet and risk of coronary heart disease and type 2 diabetes. Lancet. 2002;360:783-789.
  4. Ramaa CS, Shirode AR, Mundada AS, et al. Nutraceuticals-an emerging era in the treatment and prevention of cardiovascular diseases. Curr Pharm Biotechnol. 2006;7:15-23.
  5. Kromhout D, Bosschieter EB, de Lezenne Coulander C. The inverse relation between fish consumption and 20-year mortality from coronary heart disease. N Engl J Med. 1985;312:205-209.
  6. Kris-Etherton PM, Yu S. Individual fatty acid effects on plasma lipids and lipoproteins: human studies. Am J Clin Nutr. 1997;65:1628S-1644S.
  7. Oh K, Hu FB, Manson JE, et al. Dietary fat intake and risk of coronary heart disease in women: 20 years of follow-up of the nurses’ health study. Am J Epidemiol. 2005;161:672-679.
  8. Lewis B, Hammett F, Katan M, et al. Towards an improved lipid-lowering diet: additive effects of changes in nutrient intake. Lancet. 1981;2:1310-1313.
  9. Parks EJ, German JB, Davis PA, et al. Reduced oxidative susceptibility of LDL from patients participating in an intensive atherosclerosis treatment program. Am J Clin Nutr. 1998;68:778-785.
  10. Shridhar K, Dhillon PK, Bowen L, et al. The association between a vegetarian diet and cardiovascular disease (CVD) risk factors in India: the Indian Migration Study. PLoS One. 2014;9:e110586.
  11. Hjermann I, Velve Byre K, Holme I, et al. Effect of diet and smoking intervention on the incidence of coronary heart disease: report from the Oslo Study Group of a randomised trial in healthy men. Lancet. 1981;2:1303-1310.
  12. Ostlund RE Jr, Racette SB, Okeke A, et al.  Phytosterols that are naturally present in commercial corn oil significantly reduce cholesterol absorption in humans. Am J Clin Nutr. 2002;75:1000-1004.
  13. Hu FB, Manson JE, Willett WC. Types of dietary fat and risk of coronary heart disease: a critical review. J Am Coll Nutr. 2001;20:5-19.
  14. Nelson GJ, Schmidt PC, Bartolini G, et al. The effect of dietary arachidonic acid on plasma lipoprotein distributions, apoproteins, blood lipid levels, and tissue fatty acid composition in humans. Lipids. 1997;32:427-433.
  15. Salmerón J, Hu FB, Manson JE, et al. Dietary fat intake and risk of type 2 diabetes in women. Am J Clin Nutr. 2001;73:1019-1026.
  16. Rimm EB, Ascherio A, Giovannucci E, et al. Vegetable, fruit, and cereal fiber intake and risk of coronary heart disease among men. JAMA. 1996;275:447-451.
  17. Lee KW, Lip GY. The role of omega-3 fatty acids in the secondary prevention of cardiovascular disease. QJM. 2003;96:465-480.
  18. Holman RT, Johnson SB, Hatch TF.  A case of human linolenic acid deficiency involving neurological abnormalities. Am J Clin Nutr. 1982;35:617-623.
  19. Renaud S, Nordøy A. “Small is beautiful”: alpha-linolenic acid and eicosapentaenoic acid in man. Lancet. 1983;1:1169.
  20. Dolecek TA. Epidemiological evidence of relationships between dietary polyunsaturated fatty acids and mortality in the multiple risk factor intervention trial. Proc Soc Exp Biol Med. 1992;200:177-182.
  21. Connor WE. α-Linolenic acid in health and disease. Am J Clin Nutr. 1999;69:827-828.
  22. Roush GC, Ernst ME, Kostis JB, et al.  Not just chlorthalidone: evidence-based, single tablet, diuretic alternatives to hydrochlorothiazide for hypertension. Curr Hypertens Rep. 2015;17:540.
  23. Fosset S, Tome D. Dietary protein-derived peptides with antithrombotic activity. Bull Int Dairy Fed.  2000; 353:65- 8.
  24. Liu RH. Health benefits of fruit and vegetables are from additive and synergistic combinations of phytochemicals. Am J Clin Nutr. 2003;78:517S-520S.
  25. Gey KF, Puska P, Jordan P, et al. Inverse correlation between plasma vitamin E and mortality from ischemic heart disease in cross-cultural epidemiology. Am J Clin Nutr. 1991;53:326S-334S.
  26. Bagger M, Andersen O, Nielsen JB, et al. Dietary fibres reduce blood pressure, serum total cholesterol and platelet aggregation in rats. Br J Nutr. 1996;75:483-493.
  27. Hermansen K, Dinesen B, Hoie LH, et al. Effects of soy and other natural products on LDL: HDL ratio and other lipid parameters: a literature review. Adv Ther. 2003;20:50-78.
  28. Liu K, Stamler J, Trevisan M, et al. Dietary lipids, sugar, fiber and mortality from coronary heart disease. Bivariate analysis of international data. Arteriosclerosis. 1982;2:221-227.
  29. Khaw KT, Barrett-Connor E. Dietary fiber and reduced ischemic heart disease mortality rates in men and women: a 12-year prospective study. Am J Epidemiol. 1987;126:1093-1102.
  30. Kok N, Roberfroid M, Robert A, et al. Involvement of lipogenesis in the lower VLDL secretion induced by oligofructose in rats. Br J Nutr. 1996;76:881-890.
  31. Davidson MH, Maki KC, Kong JC, et al. Effects of dietary inulin on serum lipids in men and women with hypercholesterolemia. Am J Clin Nutr. 1998;67:367-376.
  32. Delzenne NM, Kok N, Fiordaliso MF, et al. Dietary fructooligosaccharides modify lipid metabolism in rats. Am J Clin Nutr. 1993;57:820S.
  33. Roberfroid M, Gibson GR, Delzenne N. The biochemistry of oligofructose, a nondigestible fiber: an approach to calculate its caloric value. Nutr Rev. 1993;51:137-146.
  34. Radhika G, Sudha V, Mohan Sathya R, et al. Association of fruit and vegetable intake with cardiovascular risk factors in urban south Indians. Br J Nutr. 2008;99:398-405.
  35. Burton GW. Antioxidant action of carotenoids. J Nutr. 1989;119:109-111.
  36. Chow CK, Thacker RR, Changchit C, et al. Lower levels of vitamin C and carotenes in plasma of cigarette smokers. J Am Coll Nutr. 1986;5:305-312.
  37. Gey KF, Stähelin HB, Eichholzer M. Poor plasma status of carotene and vitamin C is associated with higher mortality from ischemic heart disease and stroke Basel prospective study. Clin Investig. 1993;71:3-6.
  38. Gey KF, Stähelin HB, Puska P, et al. Relationship of plasma level of vitamin C to mortality from ischemic heart disease. Ann N Y Acad Sci. 1987;498:110-123.
  39. Esterbauer H, Gebicki J, Puhl H, et al. The role of lipid peroxidation and antioxidants in oxidative modification of LDL. Free Radic Biol Med. 1992;13:341-390.
  40. Berkow SE, Barnard ND. Blood pressure regulation and vegetarian diets. Nutr Rev. 2005;63:1-8.
  41. Chiplonkar SA, Agte VV, Tarwadi KV, et al. Micronutrient deficiencies as predisposing factors for hypertension in lacto-vegetarian Indian adults. J Am Coll Nutr. 2004;23:239-247.
  42. Reaven PD, Khouw A, Beltz WF, et al. Effect of dietary antioxidant combinations in humans. Protection of LDL by vitamin E but not by beta-carotene. Arterioscler Thromb. 1993;13:590-600.
  43. Calzada C, Bruckdorfer KR, Rice-Evans CA. The influence of antioxidant nutrients on platelet function in healthy volunteers. Atherosclerosis. 1997;128:97-105.