New Supplement Results Easy to Sensationalize, Not Highly Meaningful

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New research published in this month’s Archives of Internal Medicine has caused quite a stir amongst vitamin- and mineral-popping Americans [1]. Researchers report that over the course of a decades-long study, older women who regularly took vitamin and mineral supplements were more likely to die than those who did not.

This news may surprise those who look to vitamin and mineral supplements as a mechanism for maintaining — and even improving — health. However, while it would be easy to sensationalize the research findings, the reality is that there are many limitations that prevent drawing meaningful conclusions — ones that could be used to inform behavior — from the study.

The first limitation is that the study was neither randomized nor placebo-controlled.

These are major limitations, despite the fact that the study was strong elsewhere (it took place over a long period of time, and included tens of thousands of participants). Because the study was not randomized, there is no way to determine whether the multivitamin supplements were responsible for increased death rate, or whether women who took multivitamin supplements had another characteristic that made them more likely to die (but which was not effected by the supplements). For instance, perhaps women who feel ill, tired, or otherwise less fit than they once did are more likely to take supplements. Perhaps their perceptions of failing health are accurate. In such a hypothetical scenario, the very women most likely to die due to failing health would also be those most likely to start taking supplements in an effort to improve their quality (and quantity) of life.

Another major limitation associated with interpreting the results of this study in a broad sense (i.e. supplements increase risk of death) is that the study included both women who used supplements as recommended and those who used supplements in inappropriately high dosages. For instance, the researchers report that use of iron supplements leads to a risk of death (hazard ratio) of 1.10 (compared to a baseline risk of 1), or an absolute risk increase of 3.9%. However, these numbers do not isolate the women who were using iron in dosages recommended by the National Institutes of Health. Per the NIH, women age 51 and older should get 8 mg of iron a day from food or supplements. Many study participants were taking supplemental iron in quantities much greater than those recommended, with some participants taking upwards of 400 mg daily. Iron toxicity is a real risk, and increases the likelihood of heart disease and other organ failure. As might be expected, the women taking the highest doses of iron had the greatest hazard ratios (the greatest likelihood of dying). While the researchers did evaluate the hazard ratios of women on different iron doses separately, large ranges were clumped together for analytical purposes. For instance, all women taking low dose iron were analyzed as a single group, where “low dose” meant anywhere from 0 to 50 mg per day. This incorporates those taking iron per the NIH guidelines and those taking as much as 6-times the NIH-recommended quantity into the same group.

Current scientific evidence does not conclusively support the use of multivitamin and mineral supplements in otherwise healthy individuals to any conclusive extent, though there are certainly cases (such as calcium supplementation in older women and multivitamin supplementation in the case of chronic malabsorption) in which supplements are medically indicated and widely used. Further, even a cursory review of the literature reveals a multitude of inconsistencies and ambiguities in the field of supplement research. One study suggests that folic acid decreases risk of breast cancer [2], while another suggests it has no effect [3]. One suggests that selenium helps reduce risk of prostate cancer [4], while a later study refutes that assertion [5]. In a particularly boggling turn, one study suggests that vitamin E decreases risk of heart disease [6], while a second suggests it has no effect on heart disease [7], and a third notes that supplementation with vitamin E increases overall mortality rate, and should be avoided [8].

While it’s tempting — and in many cases, appropriate — to make personal health decisions on the basis of scientific research, it’s important to remember that a single study, taken alone, is never anything more than interesting. Those who are already taking multivitamin supplements shouldn’t stop on the basis of these data, though individuals taking “megadoses” of particular vitamins or minerals — meaning doses much larger than those recommended by the NIH — should discuss their supplementation decisions with a physician. Those considering starting a multivitamin supplement should bear in mind that the safest and best way to get vitamins and minerals is from food, in the context of a healthy, balanced diet.

References

1. Mursu et al. Dietary Supplements and Mortality Rate in Older Women: The Iowa Women’s Health Study. Arch Intern Med. 2011 Oct 10;171(18):1625-33.
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2. Rohan et al. Dietary folate consumption and breast cancer risk. J Natl Cancer Inst. 2000 Feb 2;92(3):266-9.
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3. Zhang et al. Effect of combined folic acid, vitamin B6, and vitamin B12 in women: a randomized trial. JAMA. 2008 Nov 5;300(17):2012-21.
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4. Duffield-Lillico et al. Selenium supplementation, baseline plasma selenium status and incidence of prostate cancer: an analysis of the complete treatment period of the Nutritional Prevention of Cancer Trial. BJU Int. 2003 May;91(7):608-12.
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5. Lippman et al. Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the selenium and vitamin E cancer prevention trial. JAMA. 2009 Jan 7;301(1):39-51. Epub 2008 Dec 9.
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6. Knekt et al. Antioxidant vitamin intake and coronary mortality in a longitudinal population study. Am J Epidemiol. 1994 Jun 15;139(12):1180-9.
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7. Lee et al. Vitamin E in the primary prevention of cardiovascular disease and cancer: the Women’s Health Study: a randomized con- trolled trial. JAMA. 2005 Jul 6;294(1):56-65.
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8. Miller et al. Meta-Analysis: High-Dosage Vitamin E Supplementation May Increase All-Cause Mortality. Ann Intern Med. 2005 Jan 4;142(1):37-46. Epub 2004 Nov 10.
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