Monday, February 12, 2007

The Women’s Health Study and Vitamin E: Probable Benefits Lost in Study’s Conclusion

The Women’s Health Study and Vitamin E: Probable Benefits Lost in Study’s Conclusion In a new publication(1), researchers concluded that, “Long-term use of vitamin E supplements did not provide cognitive benefits among generally healthy older women.” Reading the details of the study, I find this conclusion to be a very inaccurate summation of the data. Vitamin E did show benefits in the women who were actually taking the vitamin, which many in the group who were supposed to be taking it failed to do. Including non-compliant study subjects in the data resulted in a misleading conclusion. The Women's Health Study is a randomized, double-blind, placebo-controlled trial of vitamin E supplementation (600 IU [ -tocopherol acetate], on alternate days) begun between 1992 and 1995 among 39,876 healthy US women. This study included about 5,000 women from the original Women's Health Study. Ignoring the complexity of the data and even the researchers’ own cautions about the robustness of their conclusions in order to produce a brief written or broadcast “sound bite” for a news report frequently results in over-simplistic and inaccurate reporting. It is also all too common that a careful analysis of the research data may even contradict a study’s main conclusions, making the ensuing media reports all the more misleading. This appears to be the case with this particular study. The researchers’ own data has elements that contradict the conclusion stated above. My concern about how the conclusion in this study may be sending the wrong message can be summed up in these contradictions to that conclusion (all quotations are from this study): · When results were adjusted to exclude non-compliant women (23-25% of the study population), there were benefits noted for those taking vitamin E: “…our secondary analyses including only compliant subjects suggested some potential cognitive benefits of vitamin E supplementation.” · Cognitive testing only was done for the last 4 years of a 9.6 year-long study, ignoring any possible improvements in the vitamin E group over the initial 5.6 year period: “Cognitive testing began a mean of 5.6 years after randomization; thus, we were unable to evaluate change in cognitive performance from randomization.” · Previous successful models were for mice given vitamin E from a young age, but not for mice given the vitamin only when elderly. Most women were in their 60’s when this trial began: “…in a transgenic mouse model of AD, a significant reduction in amyloid deposition in the brain was observed only when vitamin E supplementation was provided at young ages (5-13 months) but not at older ages (14-20 months).” · Previous successful human trials lasted over 10 years, but this study admittedly did not: “…2 observational studies of cognitive function both found that less than 10 years of vitamin E use was not strongly associated with better cognitive performance.” · There was a significantly lower risk of substantial decline in at least one cognitive measure for the people taking vitamin E: “For the verbal memory score, the vitamin E group had a borderline significant 15% lower risk of substantial decline compared with the placebo group (RR, 0.85; 95% CI, 0.71 to 1.02).” · Women who eat less dietary vitamin E did have less cognitive decline if they were in the group taking it as a supplement: “We observed that the vitamin E group experienced less adverse cognitive change compared with the placebo group among women with dietary intake below the median of 6.1 mg/d.” · There was also a benefit shown for vitamin E among the women who did not exercise: “Also among women who exercised less than once per week, the vitamin E group experienced a more favorable cognitive change than did the placebo group: the difference in mean change in global score over time was 0.06 (95% CI, 0.03 to 0.10).” · Another group that benefited from taking vitamin E was non-diabetic women: “We also observed that vitamin E treatment appeared beneficial among women without diabetes (mean difference, 0.03; 95% CI, 0.00 to 0.06) but not among women with diabetes (mean difference, –0.15; 95% CI, –0.31 to 0.01).” · The researchers admit that the dose used in this study is lower than was used in previous trials, making positive results more unlikely: “It is possible that the dose used in this study was not high enough.” · The authors also admit that other forms of vitamin E were not measured in this study, nor levels of other supporting antioxidants other than dietary vitamin E: “It has been suggested that tocopherols such as gamma-tocopherol that is found in foods rather than in supplements may be more important for delaying brain aging. Although alpha-tocopherol has stronger antioxidant properties, gamma-tocopherol has important additional anti-inflammatory effects that may enhance neuroprotection.” The researchers even caution against putting too much reliance on their own analysis: “However, these analyses themselves may be inherently biased and thus should be interpreted with caution.” It appears that the researchers were correct in cautioning that their conclusions may be questionable. It is dangerous to base health decisions on a one-line conclusion from a study without looking at the details of the study which may find benefits for specific populations, or without considering the admitted limitations of the study. In this particular case, the populations that benefited from taking vitamin E include non-diabetic women and women who eat diets low in the vitamin. Another section of the population also showed a benefit: those women who actually took the vitamin. That’s right, the data actually showed significant benefits for that portion of the study population that complied with the study protocol and properly took the vitamin, which about a quarter of the women failed to do. When non-compliant subjects were included in the total, vitamin E’s benefits as a whole were mostly insignificant; but if these subjects are excluded, the benefits become significant. If I were the researcher, my conclusion for this study would have reflected that taking vitamin E was shown to be protective to those women who took it; a far different conclusion than was written. People deserve more careful discussions and analysis of research data in order to be able to make informed health choices. Sadly, this study - and the subsequent reporting on the study - have failed to convey some useful and accurate information, and may even lead women away from taking an essential vitamin that showed evidence of being protective of mental function when taken as directed. REFERENCE: 1. Kang JH, et al. A Randomized Trial of Vitamin E Supplementation and Cognitive Function in Women. Arch Intern Med. 2006;166:2462-2468.

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