Vitamins and Mortality: In Defense of Supplements

Ayaz Virji, MD


February 01, 2012

The article by Mursu and colleagues[1] that was recently reported on in Medscape News indicates that ad libitum use of multivitamins does not reduce all-cause mortality in women; to the contrary, it may slightly increase it. This arm of the Iowa Women's Health Study consisted of 38,772 elderly white women with a mean age of 61.6 years who were followed over 20 years. This well-designed, observational cohort study adjusted for diverse confounders, including body mass index (BMI), physical activity, smoking status, and educational level.

When interpreting these results, as for any other nutraceutical intervention, it would be imprudent to make broad, imprecise statements about the "ineffectiveness" of dietary supplements, although it may be tempting to do so. It is important to consider the limitations of the study to help prevent unscientific conclusions. The authors themselves conceded, "It is not advisable to make a causal statement of excess risk based on these observational data."[1]

Mursu and colleagues' study, although well executed, has several methodological limitations. It used the Harvard Service Food Frequency Questionnaire, which was originally designed to assess the diets of low-income women and gather information on dietary supplements used. However, the dietary supplement portion of the questionnaire has not been independently validated. In addition, a certain subset of patients inappropriately substitutes dietary supplements for medications to manage chronic disease. This concerning, yet uncaptured, trend could potentially confound the results.

The study did not report on the specific doses, excluding calcium and iron, or source of the supplements used. Both of these factors play an important role in the net effect of supplements on patient health. Take vitamin E, for example. Recent studies show that supplemental vitamin E doses > 400 IU may increase risk for congestive heart failure and prostate cancer, although in aggregate the data are inconclusive.[2,3] The Nurses' Health Study found that women who consumed 100 IU of vitamin E daily had a 44% reduction in developing major coronary disease.[4] Of note, 4 times the therapeutic dose of an angiotensin-converting enzyme inhibitor is likely to result in a similar reversal of outcome. There would be little disagreement regarding the inappropriateness of a conclusion on the safety and efficacy of an angiotensin-converting enzyme inhibitor without considering the dose or the population using it. The same consideration was not given to dietary supplements in this assessment, however. A targeted, rational strategy for supplement use, developed in partnership with a medical provider, is likely to lead to a different outcome than that reported in the current study.

As is the case for pharmaceutical agents, various isomers of the same vitamin have different clinical effects. Considering vitamin E again, alpha-tocopherol (which is more commonly found in supplements) and gamma-tocopherol (which is more commonly found in food sources) have different anti-inflammatory properties and vary in bioavailability. It is likely that a healthy ratio of these 2 substances is more important to preventing coronary artery disease than is taking one isomer in excess, which may deplete the other.[5] In addition, unlike for pharmaceutical agents, the source of vitamin supplement plays an important role. Synthetic vitamin E (dl-alpha-tocopherol) is thought to be much less potent than its natural vitamin E (d-alpha-tocopherol) counterpart and may have a varying clinical effect.

Whether it's chromium and reduced carbohydrate cravings, carnitine and improved claudication symptoms, or green tea and greater life expectancy,[6,7,8] much remains unanswered regarding the net effect of a particular supplemental nutrient or group of nutrients on overall health. Perhaps advancements in the field of nutrigenomics will help light our way on their utility. Nonetheless, when comparing apples to apples, "polynutrient" is far less toxic than polypharmacy; the latter incurs 100,000 related deaths annually. A conventional multivitamin supplement should still be generally recognized as safe.


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