To the Editor:
Drs. Wilson and Walton1 are to be congratulated for an excellent scientific review of free radicals/reactive oxygen species generation in an earlier issue of this journal and for the delightful manner in which it was written.
I concur with the authors' concern about “brute-force antioxidant therapy.” The ability of vitamin E to function as an antioxidant in destroying free radicals has been projected to extremes by nutritionists, the wellness press, and corporate-interest hype. It is fortunate that most vitamin E stereoisomers heretofore have had reduced biological activity.
I have discouraged the use of megadoses of vitamin E for its purported value in the prevention and treatment of coronary heart disease.2–5 Indeed, striking instances of prolonged angina, myocardial infarction, or both, have been encountered in observant patients who specifically related these events to the ingestion of vitamin E … including rechallenge.5 I concur with Rapola and colleagues6 that patients with myocardial infarction should not have vitamin E prescribed routinely.
Other groups7,8 have reported that hypervitaminosis E may actually increase mortality from ischemic heart disease. It is noteworthy that synthetic shelf-stable forms of vitamin E can function as a pro-oxidant to produce free radicals, and accelerate peroxidation with lipid damage.
There would be little concern about people's taking megadoses of vitamin E if hypervitaminosis E were innocuous. But this is not the case, especially when more than 150 units are taken daily. Indeed, it is estimated that half of the elderly population in our country now consume vitamin E supplements.
I have emphasized the potential adverse effects of excessive vitamin E relative to the initiation and aggravation of hypertension, thrombophlebitis, pulmonary embolism, painful and enlarged breasts, many alterations of metabolism (including the depletion of gamma-tocopherol), and perhaps breast cancer.2–5 Moreover, most of the recent randomized controlled trials have failed to indicate any cardiovascular benefit of vitamin E.9,10
Drug interaction also poses a sobering consideration. Cheung and associates11 found that vitamin E (400 IU twice daily) and other “antioxidant supplements” (beta-carotene, vitamin C, and selenium) block the rise of HDL-cholesterol in patients with coronary artery disease (CAD) and low HDL concentrations who are being given combined simvastatin-niacin therapy. They concluded: “This unexpected adverse interaction between antioxidants and lipid therapy may have important implications for the management of CAD.”11
A Latin expression is relevant for clinicians in this context: Falsus in uno, falsus in omnibus—Untrue in one thing, untrue in everything.
References
- 1.Wilson JM, Walton B. Lesions and lipids and radicals—O m! Tex Heart Inst J 2004;31:118–26. [PMC free article] [PubMed]
- 2.Roberts HJ. Perspective on vitamin E as therapy. JAMA 1981;246:129–31. [DOI] [PubMed]
- 3.Roberts HJ. Mega vitamin E: is it safe? West Palm Beach: Sunshine Sentinel Press; 1994. www.sunsentpress.com/vitamine.html
- 4.Roberts HJ. Thrombophlebitis associated with vitamin E therapy. With a commentary on other medical side effects. Angiology 1979;30:169–77. [DOI] [PubMed]
- 5.Roberts HJ. Does vitamin E precipitate angina? Chest 1994;106:1636–7. [DOI] [PubMed]
- 6.Rapola JM, Virtamo J, Ripatti S, Huttunen JK, Albanes D, Taylor PR, Heinonen OP. Randomized trial of alpha-tocopherol and beta-carotene supplements on incidence of major coronary events in men with previous myocardial infarction. Lancet 1997;349:1715–20. [DOI] [PubMed]
- 7.The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group. N Engl J Med 1994;330:1029–35. [DOI] [PubMed]
- 8.Enstrom JE, Pauling L. Mortality among health-conscious elderly Californians. Proc Natl Acad Sci U S A 1982;79: 6023–7. [DOI] [PMC free article] [PubMed]
- 9.Vivekananthan DP, Penn MS, Sapp SK, Hsu A, Topol EJ. Use of antioxidant vitamins for the prevention of cardiovascular disease: meta-analysis of randomised trials [published erratum appears in Lancet 2004;363:662]. Lancet 2003; 361:2017–23. [DOI] [PubMed]
- 10.Waters DD, Alderman EL, Hsia J, Howard BV, Cobb FR, Rogers WJ, et al. Effects of hormone replacement therapy and antioxidant vitamin supplements on coronary atherosclerosis in postmenopausal women: a randomized controlled trial. JAMA 2002;288:2432–40. [DOI] [PubMed]
- 11.Cheung MC, Zhao X, Chait A, Albers JJ, Brown BG. Antioxidant supplements block the response of HDL to simvastatin-niacin therapy in patients with coronary artery disease and low HDL. Arterioscler Thromb Vasc Biol 2001; 21:1320–6. [DOI] [PubMed]