Donald B. McCormick, Ph.D
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  EDITORIAL

                  The dubious use of vitamin-mineral supplements
                           in relation to cardiovascular disease1,2
Donald B McCormick
1 From the Department of Biochemistry and the Program in Nutrition and Health Sciences, Emory University, Atlanta, GA

2 Address reprint requests to DB McCormick, 2245 Deer Ridge Drive, Stone Mountain, GA 30087. E-mail: biocdbm@emory.edu .


Our knowledge of the essentiality of the micronutrients is derived largely from the isolation and identification of those dietary ingredients that prevent specific deficiency diseases. The occurrence, conversions to functional forms, and dynamics of physiologic routing of micronutrients have been compiled in periodically updated volumes on vitamins and trace elements, and such information is compacted in texts (1). Promulgations on Dietary Reference Intakes (DRIs) of vitamins and minerals and the ongoing Recommended Dietary Allowances (RDAs) are from the Food and Nutrition Board of the Institute of Medicine. It should be recalled that the RDA is set 20% above the Estimated Average Requirement (EAR), which is based on scientifically determined values. The intent of the RDA is to supply enough of a nutrient to meet the requirement of nearly all healthy persons.

Despite the relatively broad coverage of healthy humans (after infancy) by the RDAs, there are some who believe that even healthy people should try to achieve a state of "optimal nutrition" by taking a vitamin-mineral supplements that supplies 100% of the RDAs in addition to the foods eaten each day. Such is the recommendation from the Linus Pauling Institute, which at least recognizes that "the intake levels most likely to promote optimum health remain to be determined" (2), and from a workshop reputing to explore the evidence for supplements but also adding the caveat that "further research continues to be necessary" (3). On the basis of fairly recent estimates of the consumption of vitamin-mineral supplements in the United States (4), it seems that nearly 50% of our population may be spending 1.5 billion dollars each year in this practice of "securing" their health.

The presumption is held by some that vitamin-mineral supplements may have the potential to prevent and treat certain chronic diseases, such as some cancers and cardiovascular disease. This belief has been fostered by several reports on observational studies dealing with in vitro experimental animal and even clinical findings over the past couple of decades. An example of a "guide" to micronutrient supplementation for prevention and therapy indicates dosages that conform to practices but that allow for additional investigations to determine what (if any) benefit may accrue (5). Much of the thrust in such use has been based on the presumption of a special benefit from antioxidant nutrients (mainly vitamins C and E, ß-carotene, and selenium) and those B vitamins (mainly folate and vitamins B-6 and B-12) that in coenzyme forms are essential for the metabolism of sulfur amino acids, including homocysteine—an indirect plasma marker for the risk of ischemic heart disease. The expectation that these antioxidants and B vitamins may prevent or decrease damage that accompanies or causes heart disease is derived from in vitro studies or from studies that were generally observational and often marginal in statistical significance or control.

Many studies and reviews have appeared that do not support the use of such vitamin-mineral supplements to reduce the risk of cardiovascular disease. Neither ß-carotene nor vitamin E proved effective in large-scale, double-blind, placebo-controlled trials (6); in fact, high doses of vitamin E may increase all-cause mortality (7). Also, randomized controlled trials of vitamins A, C, and E and of folate have failed to show a consistent or significant effect of any single vitamin or combination of vitamins on the incidence of or death from cardiovascular disease (8, 9). A recent report that summarizes results from large-scale trials states that vitamins B-12 and B-6 and folic acid may not reduce the number of cardiovascular events (10). In addition, the risk of recurrent cardiovascular disease was not lowered by the use of such supplements after acute myocardial infarction; a harmful effect was even suggested (11).

The report by Bleys et al (12) in this issue of the Journal concludes that there is no evidence of a protective effect of antioxidant or B vitamin supplements on the progression of atherosclerosis and that these supplements had no effect on clinical cardiovascular disease. This study is a meta-analysis of randomized controlled trials that were previously reported. Of 2311 trials identified, only 16 met the inclusion criteria. Five of these 16 trials involved the use of percutaneous transluminal coronary angioplasty (PTCA): 3 evaluated the effects of antioxidants and 2 the effects of folate, vitamin B-6, and vitamin B-12. The remaining 11 trials did not involve the use of PTCA: 7 evaluated the effects of antioxidants and 4 the effects of the B vitamins. Size effects were used to obtain standardized measures of the difference in progression of atherosclerosis in comparisons of supplements and control treatments. In addition to the finding that supplements do not prevent the development of atherosclerosis, no evidence existed that vitamin-mineral supplements prevent restenosis after PTCA. The authors concluded, on the basis of their findings—which are now supported by other recent studies—that antioxidants and B vitamins should not be used to prevent cardiovascular disease. One can hope that the exuberant use of vitamin-mineral supplements may be tempered somewhat by such findings, which carefully separate fact from faith.

ACKNOWLEDGMENTS

The author had no conflict of interest.

REFERENCES


Shills ME, Shike M, Ross AC, Caballero B, Cousins RJ, eds. Modern nutrition in health and disease. 10th ed. Philadelphia, PA: Lippincott Williams & Wilkins, 2006.
Higdon J, ed. An evidence-based approach to vitamins and minerals. New York, NY: Thieme, 2003.
Blumberg J, Heber D, eds. Multivitamins & public health: exploring the evidence. Summary statement from multivitamins & public health: exploring the evidence. Washington, DC: BioScience Communications, 2004.
Balluz LS, Kieszak SM, Philen RM, Mulinare J. Vitamin and mineral supplement use in the United States: results from the third National Health and Nutrition Examination Survey. Arch Fam Med 2000;9:258–62.[Abstract/Free Full Text]
Zimmermann M. Pocket guide to micronutrients in health and disease. New York, NY: Thieme, 2001.
Steinberg D, Witztum JL. Is the oxidative modification hypothesis relevant to human atherosclerosis? Do the antioxidant trials conducted to date refute the hypothesis? Circulation 2002;105:2107–11.
Miller ER III, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Guallar E. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med 2005;142:37–46.[Abstract/Free Full Text]
Morris CD, Carson S. Routine vitamin supplementation to prevent cardiovascular disease: a summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 2003;139:56–70.
Davey Smith G, Ebrahim S. Folate supplementation and cardiovascular disease. Lancet 2005;366:1679–81.[Medline]
Barclay L, Vega C. B12, B6, and folic acid may not reduce cardiovascular events. 15 March 2006. Medscape Medical News. Internet: www.medscape.com/viewarticle/527591 (accessed 20 July 2006).
Bønaa KH, Njølstad I, Ueland PM, et al. Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med 2006;354:1578–88.[Abstract/Free Full Text]
Bleys J, Miller ER III, Pastor-Barriuso R, Appel LJ, Guallar E. Vitamin-mineral supplementation and the progression of atherosclerosis: a meta-analysis of randomized controlled trials. Am J Clin Nutr 2006;84:880–7.[Abstract/Free Full Text]


Related articles in AJCN:


Vitamin-mineral supplementation and the progression of atherosclerosis: a meta-analysis of randomized controlled trials
Joachim Bleys, Edgar R Miller, III, Roberto Pastor-Barriuso, Lawrence J Appel, and Eliseo Guallar
AJCN 2006 84: 880-887. [Abstract] [Full Text]