Correspondence
What Vitamins Should I Be Taking?
N Engl J Med 2002; 346:1914-1916June 13, 2002
- Article
To the Editor:
Willett and Stampfer state in their Clinical Practice article (Dec. 20 issue)1 that “assuming a low probability that vitamin E will eventually be proved efficacious [against coronary disease] (and we view the probability as fairly high), the likelihood of benefit would still outweigh the very low probability of harm.” Brown et al. (Nov. 29 issue)2 reported that, among patients with established coronary disease, the combination of antioxidants (800 IU of vitamin E, 25 mg of natural beta carotene, and 100 μg of selenium) with simvastatin and niacin resulted in less benefit than simvastatin and niacin alone. The adverse interactions between antioxidants and lipid-lowering medications were significant in analyses of angiographic end points, although not in analyses of clinical end points. In view of the fact that many patients take a statin because of hypercholesterolemia, there are potential risks in taking supplemental vitamin E. Therefore, the recommendation of Willett and Stampfer with regard to taking vitamin E is not warranted.
2 ReferencesBurton T. Blackman, M.D.
6621 Moore Dr., Los Angeles, CA 90048
eblack66221@aol.com 1
Willett WC ,Stampfer MJ . What vitamins should I be taking, doctor? N Engl J Med 2001;345:1819-1824
Full Text | Web of Science | Medline2
Brown BG ,Zhao X-Q ,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
Full Text | Web of Science | Medline
To the Editor:
Beauty is in the eyes of the beholder; so, it seems, is evidence of a benefit of vitamin E. Willett and Stampfer conclude that vitamin E supplementation is “reasonable” for Americans who are at increased risk of coronary disease, despite the overwhelmingly negative data from randomized clinical trials.1 A meta-analysis of clinical trials involving 56,591 patients showed no effect of vitamin E supplementation on mortality from cardiovascular causes (odds ratio for death associated with vitamin E supplementation, 0.98; 95 percent confidence interval, 0.92 to 1.06).1 By contrast, observational studies involving 79,542 subjects suggested that mortality from cardiovascular causes was reduced by 33 percent (95 percent confidence interval, 17 to 46) in users of vitamin E supplements.1 The findings of observational studies may be confounded by socioeconomic and lifestyle-related factors associated with the use of supplements.
The Nutrition Committee of the American Heart Association does not favor population-wide vitamin E supplementation because data on efficacy and safety from randomized trials are lacking.2 Equivocal evidence of the benefit of vitamin E contrasts with clear evidence of the protection provided by angiotensin-converting–enzyme inhibitors3 and statins4 in persons with an increased risk of coronary disease. These are the agents that physicians should be using to achieve cardiovascular protection.
4 ReferencesLionel H. Opie, M.D., D.Phil.
University of Cape Town Medical School, Cape Town 7925, South Africa
opie@capeheart.uct. ac. za 1
Hooper L ,Ness AR ,Smith GD . Antioxidant strategy for cardiovascular diseases. Lancet 2001;357:1705-1705
CrossRef | Web of Science | Medline2
Krauss RM ,Eckel RH ,Howard B , et al. AHA dietary guidelines: revision 2000: a statement for healthcare professionals from the Nutrition Committee of the American Heart Association. Circulation 2000;102:2284-2299
Web of Science | Medline3
Heart Outcomes Prevention Evaluation Study Investigators
Full Text | Web of Science | Medline4
Downs JR ,Clearfield M ,Weis S , et al. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels. JAMA 1998;279:1615-1622
CrossRef | Web of Science | Medline
To the Editor:
Consideration of individual decisions to take vitamin or mineral supplements also raises the question of a broader public health approach of fortification of foods. Food fortification established in the private sector (Morton's Iodized Salt) in the United States in the 1920s led to control of iodine deficiency and goiter. In the 1930s state-mandated fortification of flour helped to eradicate a major epidemic of pellagra in the southern United States.1 More recently, the Food and Drug Administration mandated the addition of folic acid to “enriched” flour, which led to a reduction in the incidence of neural-tube defects and decreased homocysteine levels.2
In Canada, fortification of foods (milk, salt, and flour) has been mandatory since 1979.3 Conditions involving micronutrient deficiencies are a major public health concern in many developed countries and even more so in developing countries.4 Yet many other countries have not adopted such strategies. Food fortification must be considered as another vital element of national nutrition policy.
4 ReferencesT.H. Tulchinsky, M.D., M.P.H
Hebrew University–Hadassah, Jerusalem 91120, Israel
tedt@hadassah.org. il Dorit Nizan-Kaluski, M.D., M.P.H., R.D.
Ministry of Health, Jerusalem 91120, Israel1
Safer and healthier foods. MMWR Morb Mortal Wkly Rep 1999;48:905-913
Medline2
Honein MA ,Paulozzi LJ ,Mathews TJ ,Erickson JD ,Wong LYC . Impact of folic acid fortification of the US food supply on the occurrence of neural tube defects. JAMA 2001;285:2981-2986[Erratum, JAMA 2001;286:2236.]
CrossRef | Web of Science | Medline3
Cheney M . Canadian experience with food fortification. Public Health Rev 2000;28:171-177
Medline4
Tulchinsky TH . Vitamin enrichment of basic foods: the case-for-action in Israel. Isr J Med Sci 1993;29:58-61
Medline
Author/Editor Response
The authors reply:
To the Editor: Dr. Blackman is concerned that vitamin E supplements may reduce the effectiveness of statins against coronary atherosclerosis, as Brown et al. reported when our article was in the late stages of publication. However, preliminary results of a much larger randomized trial conducted by Collins and colleagues1 in patients with existing coronary heart disease or diabetes have not supported any inhibition by vitamin E of the effectiveness of statins in reducing the rate of clinical end points. Also, in a recent trial involving transplant recipients, reduced progression of atherosclerosis was found among those randomly assigned to receive vitamins E and C, as compared with those taking statins alone.2 It remains uncertain whether the findings of Brown et al. might be due to the other constituents of the antioxidant combination they used or to chance.
Dr. Opie refers to overwhelmingly negative data from randomized trials on the benefits of vitamin E. As we noted, the randomized trials (which are not entirely consistent) have been conducted almost entirely among patients with existing coronary heart disease, whereas such persons were excluded from the observational studies. For this reason, we concluded that the weight of evidence is against an important short-term benefit of vitamin E supplementation among patients with existing cardiovascular disease, but that the long-term benefits of vitamin E supplementation for primary prevention remain unclear. A large trial of vitamin E supplementation for primary prevention is currently under way,3 and we suggest that judgment be reserved. During a period of uncertainty, which is common in medical practice, we believe that a reasonable approach is to use all available evidence to weigh the likelihood of benefit against the likelihood of harm, while also considering the cost. Simply invoking the lack of data from randomized trials is insufficient, given that even advice to avoid smoking, control weight, and exercise regularly would not meet the criterion of proof of benefit from randomized trials. The scope of our commentary did not include other means of achieving cardioprotection, but we would strongly advocate avoiding smoking, exercising regularly, controlling one's weight, and following a healthy diet.4
Food fortification was also beyond the scope of our commentary, but we fully agree with Tulchinsky and Nizan-Kaluski that the fortification of foods with micronutrients can have a powerful role in public health. The failure of most countries to fortify foods with folic acid represents a major lost opportunity for improving health.
4 ReferencesWalter C. Willett, M.D., Dr.P.H.
Meir J. Stampfer, M.D., Dr.P.H.
Harvard School of Public Health, Boston, MA 021151
Collins R ,Peto R ,Armitage J . The MRC/BHF Heart Protection Study: preliminary results. Int J Clin Pract 2002;56:53-56
Web of Science | Medline2
Fang JC ,Kinlay S ,Beltrame J , et al. Effect of vitamins C and E on progression of transplant-associated arteriosclerosis: a randomised trial. Lancet 2002;359:1108-1113
CrossRef | Web of Science | Medline3
Buring JE ,Hennekens CH . Randomized trials of primary prevention of cardiovascular disease in women: an investigator's view. Ann Epidemiol 1994;4:111-114
CrossRef | Medline4
Stampfer MJ ,Hu FB ,Manson JE ,Rimm EB ,Willett WC . Primary prevention of coronary heart disease in women through diet and lifestyle. N Engl J Med 2000;343:16-22
Full Text | Web of Science | Medline
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