By Jeremy Appleton, ND, and Steve Austin, ND
Healthnotes Newswire —Does vitamin E supplementation prevent heart disease? Researchers continue to struggle with this question, and the most recent trial,1 in which vitamin E supplementation failed to protect against heart disease, does little to resolve the debate.
The new study observed 4,495 women and men, who were in their mid-sixties and were at high risk for heart disease, for 3.6 years. Participants were randomly assigned to take vitamin E (300 IU per day of synthetic vitamin E) or to take nothing. (A second arm of the trial involved treatment with aspirin. Those results are not reported in this article.) The trial was controlled, but not blinded, meaning that there was no placebo and participants knew what they were taking. Researchers tracked the occurrence of various cardiovascular conditions, including cardiovascular death, nonfatal heart attacks, nonfatal stroke, angina pectoris, and others. Those who took vitamin E fared no better in any category of cardiovascular disease than those who did not take the supplement.
Vitamin E Successes are the Foundation of Controversy
Previous studies in humans found that both men2 and women3 taking more than 100 IU per day of vitamin E for several years experienced a significant decrease in cardiovascular disease. These studies were followed by a report from the Cambridge Heart Antioxidant Study (CHAOS) in England—a double-blind trial confirming a dramatic reduction in nonfatal heart attacks in a group of people with coronary heart disease who supplemented with vitamin E.4 Approximately a quarter of the study participants received 400 IU of vitamin E per day; a quarter received 800 IU per day; and the remainder received placebo. The rates of nonfatal heart attacks and cardiovascular deaths in the combined vitamin E groups were significantly lower than in the placebo group. Curiously, the authors of the new trial dismiss the results of the CHAOS as “controversial” without further consideration.
In a previous Italian trial (the GISSI-Prevenzione trial), heart attack survivors received 850 mg of omega-3 fish oil, 300 IU of synthetic vitamin E, both, or neither for 3.5 years.5 Although vitamin E supplementation was reported as a failure by the researchers, important (though not statistically significant) reductions in death, nonfatal heart attack, and nonfatal stroke occurred in the vitamin E groups, and statistically significant reductions in specific subgroups of cardiovascular death did occur. Subsequent researchers, including the authors of the new study, have largely ignored these findings.
HOPE and Despair: Vitamin E Fails to Live Up to Its Promise
Last year, a double-blind prevention trial compared the effects of supplemental vitamin E (400 IU per day of natural vitamin E) with the effects of placebo.6 As widely discussed in the media, the HOPE study found that vitamin E did not reduce the incidence of nonfatal heart attacks in a large group of people with a history of diabetes or existing cardiovascular disease. In fact, cardiovascular events were slightly higher in the vitamin E group than in the placebo group. Not only was the HOPE study larger than CHAOS, but it also utilized a longer intervention period (4.5 years). In the HOPE study, natural vitamin E was used. No patients received 800 IU per day.
Success in the Midst of Doubts
A recent double-blind trial (known as the SPACE trial)7 turned the tables yet again in favor of vitamin E, if only for a select group of people. The researchers gave vitamin E supplements (800 IU of natural vitamin E per day) to a group of people considered to be at very high risk of heart attack (due to a combination of kidney failure, dependency on kidney dialysis machines, and a history of heart disease). Fatal heart attacks were reduced by 43% compared with a placebo group, but a higher number of deaths unrelated to heart disease and stroke in the vitamin E group resulted in no improvement in overall death rates.
No Easy Answers
What are we to make of these conflicting outcomes? Are people with heart disease wasting their money on 400–800 IU of vitamin E per day? The positive evidence for vitamin E and heart disease prevention and the many questions the negative trials have failed to answer leave the issue unresolved.
There is a plausible mechanism to explain how vitamin E could protect people from heart disease. LDL, the “bad” cholesterol, only causes trouble when it becomes damaged, and vitamin E prevents damage to LDL.8 9 10 Moreover, support from animal data11 12 and from previous human studies, have not vaporized as a result of the new study. Considering the remarkably positive results of the CHAOS report and the somewhat confirmatory clues hidden in the fine print of the GISSI-Prevenzione data, the SPACE trial, and elsewhere, many people with heart disease will likely continue to take vitamin E. Because of its lack of toxicity and its reasonable cost, there would be few adverse consequences if vitamin E turns out to be unhelpful for people with heart disease.
The new trial puts at least one issue to rest: less than 400 IU per day of synthetic vitamin E does indeed appear to be useless for the prevention of heart disease. Still, further research is needed to answer other questions. Most important, future studies should examine the effects of 800 IU per day of natural vitamin E to confirm or refute the positive findings of CHAOS, findings the authors of the new study have neglected to examine.
Vitamin E is available in a variety of forms. Natural vitamin E, as used in the successful CHAOS and SPACE trials as well as the unsuccessful HOPE trial, can be identified by the letter “d” without the letter “l”, as in “d-alpha tocopherol.” The synthetic form, as used in most unsuccessful trials studying heart disease, can be identified by the combination of letters “dl”, as in “dl-alpha tocopherol.” Half of the synthetic form is identical to the natural form, but the other half is not. Milligram for milligram, natural vitamin E is more powerful than synthetic vitamin E. To compensate for this difference in potency, pills containing synthetic vitamin E contain a little more vitamin E than found in natural supplements. This is done in an attempt to achieve the same activity as found with natural vitamin E. However, some research suggests that natural vitamin E is twice as potent as the synthetic form.13
References1. Collaborative Group of the Primary Prevention Project (PPP). Low-dose aspirin and vitamin E in people at cardiovascular risk: a randomized trial in general practice. Lancet 2001;357:89–95.
2. 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;328:1450–6.
3. Stampfer MJ, Hennekens CH, Manson JE, et al. Vitamin E consumption and the risk of coronary disease in women. N Engl J Med 1993;328:1444–9.
4. 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;347:781–6.
5. GISSI-Prevenzione Investigators. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico. Lancet 1999;354:447–55.
6. Heart Outcomes Prevention Evaluation Study Investigators. Vitamin E supplementation and cardiovascular events in high-risk patients. N Engl J Med 2000;342:154–60.
7. 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;356:1213–8.
8. Belcher JD, Balla J, Balla G, et al. Vitamin E, LDL, and endothelium: Brief oral vitamin supplementation prevents oxidized LDL-mediated vascular injury in vitro. Arterioscler Thromb 1993;13:1779–89.
9. Jialal I, Grundy SM. Effect of combined supplementation with alpha-tocopherol, ascorbate, and beta carotene on low-density lipoprotein oxidation. Circulation 1993;88:2780–6.
10. Fuller CJ, Chandalia M, Garg A, et al. RRR-alpha-tocopheryl acetate supplementation at pharmacologic doses decreases low-density-lipoprotein oxidative susceptibility but not protein glycation in patients with diabetes mellitus. Am J Clin Nutr 1996;63:753–9.
11. Carr AC, Zhu BZ, Frei B. Potential antiatherogenic mechanisms of ascorbate (vitamin C) and alpha-tocopherol (vitamin E). Circ Res 2000;87:349–54 [review].
12. Pryor WA. Vitamin E and heart disease: basic science to clinical intervention trials. Free Radic Biol Med 2000;28:141–64 [review].
13. Acuff RV, Thedford SS, Hidiroglou NN, et al. Relative bioavailability of RRR- and all-rac-alpha-tocopheryl acetate in humans: studies using deuterated compounds. Am J Clin Nutr 1994;60:397–402. Jeremy Appleton, ND, is a licensed naturopathic physician, writer, and educator in the field of evidence-based complementary and alternative medicine. Dr. Appleton is Chair of Nutrition at the National College of Naturopathic Medicine and Senior Science Editor at Healthnotes.
Steve Austin, ND, is the Chief Science Officer for Healthnotes, Inc. He is a former Professor of Nutrition at the National College of Naturopathic Medicine in Portland, Oregon. Dr. Austin has also headed the nutrition department at Bastyr University.