Abstract
The evidence that specific vitamins may be beneficial in the prevention of cardiovascular disease (CVD) is supported by mechanistic models of atherogenesis. We and others have published observational epidemiologic studies in support of vitamins in the primary prevention of CVD, but the results from intervention studies are mixed. This article summarizes the recent results for vitamin E, vitamin D, and the B vitamins, comparing study populations, study designs, and potential methodologic reasons for differences in findings. For vitamin E, observational data suggest benefit at doses of 100 to 400 IU/d. Results from recent large-scale trials are mixed, with some showing modest benefit but others suggesting no benefit, especially for secondary prevention. Results for B vitamins are also mixed and further complicated by the recent folate fortification of the flour supply. If greater B vitamin intake does reduce CVD, the benefits are likely to be greatest for primary prevention and in populations with intake below dietary reference standards. Research on vitamin D and CVD is just beginning to emerge, but current data suggest that if there is benefit it likely needs to be at intake levels much higher than the current reference intakes of 200 to 600 IU/d for American adults.
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References and Recommended Reading
Fraunfelder FW: The science and marketing of dietary supplements. Am J Ophthalmol 2005, 140:302–304.
US Food and Drug Administration: Dietary supplement enforcement report. Available at http://www.fda.gov/oc/nutritioninitiative/report.html. Accessed May 5, 2007.
Radimer K, Bindewald B, Hughes J, et al.: Dietary supplement use by US adults: data from the National Examination Survey. Am J Epidemiol 2004, 160:339–349.
Erwin RB, Wright JD, Reed-Gillette D: Prevalence of Leading Types of Dietary Supplements Used in the Third National Health and Nutrition Examination Survey, 1988–94. Advance Data from Vital and Health Statistics, Number 349. Hyattsville, Maryland: National Center for Health Statistics; 2004.
Rimm EB, Stampfer MJ, Ascherio A, et al.: Vitamin E consumption and the risk of coronary heart disease in men. N Engl J Med 1993, 328:1450–1456.
Stampfer MJ, Hennekens CH, Manson JE, et al.: Vitamin E consumption and the risk of coronary disease in women. N Engl J Med 1993, 328:1444–1449.
Rimm EB, Willett WC, Hu FB, et al.: Folate and vitamin B6 from diet and supplements in relation to risk of coronary heart disease among women. JAMA 1998, 279:359–364.
Giovannucci E: Tomatoes, tomato-based products, lycopene, and cancer: review of the epidemiologic literature. J Natl Cancer Inst 1999, 91:317–331.
Giovannucci E, Stampfer MJ, Colditz GA, et al.: Multivitamin use, folate, and colon cancer in women in the Nurses’ Health Study. Ann Intern Med 1998, 129:517–524.
He K, Merchant A, Rimm EB, et al.: Folate, vitamin B6, and B12 intakes in relation to risk of stroke among men. Stroke 2004, 35:169–174.
Kushi L H, Fee RM, Sellers TA, et al.: Intake of vitamin A, C, and E and postmenopausal breast cancer. Am J Epidemiol 1996, 144:165–174.
Yusuf S, Dagenais G, Pogue J, et al.: Vitamin E supplementation and cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 2000, 342:154–160.
The Heart Outcomes Prevention Evaluation (HOPE) 2 Investigators: Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med 2006, 354:1567–1577.
The HOPE and HOPE-TOO Trial Investigators: Effects of long-term vitamin E supplementation on cardiovascular events and cancer—a randomized controlled trial. JAMA 2005, 293:1338–1347.
Bonaa K, Njolstad I, Magne-Ueland P, et al.: Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med 2006, 354:1578–1588.
Lee IM, Cook NR, Gaziano JM, et al.: Vitamin E in the primary prevention of cardiovascular disease and cancer: the Women’s Health Study: a randomized controlled trial. JAMA 2005, 294:56–65.
Hodis HN, Mack WJ, LaBree L, et al.: Alpha-tocopherol supplementation in healthy individuals reduces low-density lipoprotein oxidation but not atherosclerosis. The Vitamin E Atherosclerosis Prevention Study (VEAPS). Circulation 2002, 106:1453–1459.
Toole JF, Malinow MR, Chambless LE, et al.: Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infarction, and death: The Vitamin Intervention for Stroke Prevention (VISP) randomized controlled trial. JAMA 2004, 291:565–575.
Bjelakovic G, Nikolova D, Gluud LL: Mortality in randomized trials of antioxidant supplements for primary and secondary prevention. JAMA 2007, 297:842–857.
Rothman KJ, Greenland S: Modern Epidemiology. Philadelphia: Lippincott-Raven Publishers; 1998.
Goodman GE, Thornquist MD, Balmes J, et al.: The Beta-Carotene and Retinol Efficacy Trial: incidence of lung cancer and cardiovascular disease mortality during 6-year follow-up after stopping beta-carotene and retinol supplements. J Natl Cancer Inst 2004, 96:1742–1750.
Lonn E, Bosch J, Yusuf S, et al.: Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial. JAMA 2005, 293:1338–1347.
Waters DD, Alderman EL, Hsia J, et al.: Effects of hormone replacement therapy and antioxidant vitamin supplements on coronary atherosclerosis in post-menopausal women: a randomized controlled trial. JAMA 2002, 288:2432–2440.
Brown BG, Zhao XQ, Chait A, et al.: Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med 2001, 345:1583–1592.
Rapola JM, Virtamo J, Ripatti S, et al.: Randomised trial of alpha-tocopherol and beta-carotene supplements on incidence of major coronary events in men with previous myocardial infarction. Lancet 1997, 349:1715–1720.
Virtamo J, Rapola JM, Ripatti S, et al.: Effect of vitamin E and beta carotene on the incidence of primary nonfatal myocardial infarction and fatal coronary heart disease. Arch Intern Med 1998, 158:668–675.
Stephens NG, Parsons A, Schofield PM, et al.: Randomised controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study (CHAOS). Lancet 1996, 347:781–786.
GISSI-Prevenzione Investigators: Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Lancet 1999, 354:447–455.
The Heart Outcomes Prevention Evaluation Study Investigators: Vitamin E supplementation and cardiovascular events in high-risk patients. N Engl J Med 2000, 342:154–160.
Collaborative Group of the Primary Prevention Project: Low-dose aspirin and vitamin E in people at cardiovascular risk: a randomised trial in general practice. Collaborative Group of the Primary Prevention Project. Lancet 2001, 357:89–95.
Boaz M, Smetana S, Weinstein T, et al.: Secondary prevention with antioxidants of cardiovascular disease in endstage renal disease (SPACE): randomised placebo-controlled trial. Lancet 2000, 356:1213–1218.
Blot WJ, Li JY, Taylor PR, et al.: Nutrition intervention trials in Linxian, China: supplementation with specific vitamin/mineral combinations, cancer incidence, and disease-specific mortality in the general population. J Natl Cancer Inst 1993, 85:1483–1492.
Salonen JT, Nyyssonen K, Salonen R, et al.: Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) study: a randomized trial of the effect of vitamins E and C on 3-year progression of carotid atherosclerosis. J Intern Med 2000, 248:377–386.
Brown MS, Goldstein JL: Lipoprotein metabolism in the macrophage: implications for cholesterol deposition in atherosclerosis. Annu Rev Biochem 1983, 52:223–261.
Steinberg D, Pathasarathy S, Carew TE, et al.: Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med 1989, 320:915–924.
Cook NR, Albert CM, Gaziano JM, et al.: A randomized factorial trial of vitamins C and E and beta carotene in the secondary prevention of cardiovascular events in women: Results from the Women’s Antioxidant Cardiovascular Study. Arch Intern Med 2007, 167:1610–1618.
The Homocysteine Studies Collaboration: Homocysteine and risk of ischemic heart disease and stroke: a meta-analysis. JAMA 2002, 288:2015–2022.
Wald DS, Law M, Morris JK: Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. BMJ 2002, 325:1202.
Jacques PF, Selhub J, Bostom AG, et al.: The effect of folic acid fortification on plasma folate and total homocysteine concentrations. N Engl J Med 1999, 340:1449–1454.
Hsia J, Heiss G, Hong R: Calcium/vitamin D supplementation and cardiovascular events. Circulation 2007, 115:846–854.
B-Vitamin Treatment Trialists’ Collaboration: Homocysteine-lowering trials for prevention of cardiovascular events: a review of the design and power of the large randomized trials. Am Heart J 2006, 151:282–287.
Wang X, Qin X, Demirtas H, et al.: Efficacy of folic acid supplmentation in stroke prevention: a meta-analysis. Lancet 2007, 369:1876–1882.
Food and Nutrition Board, Institute of Medicine: Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline—a Report of the Standing Committee on the Scientific Evaluation of Dietary Reference Intakes and Its Panel on Folate, Other B Vitamins, and Choline and Subcommittee on Upper Reference Levels of Nutrients. Washington, DC: The National Academies Press; 2000.
Troen AM, Mitchell B, Sorensen B, et al.: Unmetabolized folic acid in plasma is associated with reduced natural killer cell cytotoxicity among postmenopausal women. J Nutr 2006, 136:189–194.
Chiuve SE, Giovannucci EL, Hankinson SE, et al.: Alcohol intake and methylenetetrahydrofolate reductase polymorphism modify the relation of folate intake to plasma homocysteine. Am J Clin Nutr 2005, 82:155–162.
Giovannucci E, Liu Y, Willett WC: Cancer incidence and mortality and vitamin D in black and white male health professionals. Cancer Epidemiol Biomarkers Prev 2006, 15:2467–2472.
Giovannucci E, Liu Y, Rimm EB, et al.: Prospective study of predictors of vitamin D status and cancer incidence and mortality in men. J Natl Cancer Inst 2006, 98:451–459.
Munger KL, Levin LI, Hollis BW, et al.: Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA 2006, 296:2832–2838.
Zittermann A, Schleithoff SS, Koerfer R: Putting cardiovascular disease and vitamin D insufficiency into perspective. Br J Nutr 2005, 94:483–492.
Holick MF: The influence of vitamin D on bone health across the life cycle. J Nutr 2005, 135:2739S–2748S.
Zittermann A: Vitamin D and disease prevention with special reference to cardiovascular disease. Progress Biophysics Molecular Biol 2006, 92:39–45.
Lappe JM, Travers-Gustafson D, Davies KM, et al.: Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Am J Clin Nutr 2007, 85:1586–1591.
Chiuve SE, McCullough ML, Sacks FM, Rimm EB: Healthy lifestyle factors in the primary prevention of coronary heart disease among men: benefits among users and nonusers of lipid-lowering and antihypertensive medications. Circulation 2006, 114:160–167.
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Moats, C., Rimm, E.B. Vitamin intake and risk of coronary disease: Observation versus intervention. Curr Atheroscler Rep 9, 508–514 (2007). https://doi.org/10.1007/s11883-007-0068-6
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DOI: https://doi.org/10.1007/s11883-007-0068-6