Vitamins and Supplements: Ingest at Your Own Risk

Abstract & commentary

By Barbara A. Phillips, MD, MSPH, Professor of Medicine, University of Kentucky; Director, Sleep Disorders Center, Samaritan Hospital, Lexington. Dr. Phillips serves on the speakers bureaus for Cephalon, Resmed, and Respironics.

Synopsis: In a large community-based cohort of older women, those who self-reported use of multivitamins, vitamin B6, folate, iron, magnesium, zinc, and copper were more likely to die than those who do not. Calcium use, however, was associated with reduced risk.

Source: Mursu J, et al. Dietary supplements and mortality rate in older women: The Iowa Women’s Health Study. Arch Intern Med 2011;171:1625-1633.

The cohort studied here was the Iowa Women’s Health Study, which was actually designed to look at associations between diet, lifestyle, and cancer in older women. All data were based on self-report in a questionnaire at baseline in 1986, and follow-up questionnaires in 1997 and 2004. The primary outcome variable was death over the nearly 20-year period between the first and last questionnaires. The investigators adjusted for age, calorie intake, education, place of residence, diabetes, hypertension, body mass index (BMI), waist-to-hip ratio, hormone replacement therapy, physical activity, smoking, alcohol intake, and consumption of saturated fatty acids, whole grains, fruits, and vegetables.

The analysis included 38,772 women whose mean age was about 62 at enrollment in 1986. Mean BMI was 27.0; 36.8% of the respondents reported high blood pressure; 6.8% reported diabetes mellitus; and 15.1% were current smokers. At baseline, compared with nonusers, those who took vitamins were less likely to smoke, have diabetes or hypertension, were thinner, more educated, more active, more likely to take hormone replacement, and had healthier diets in general. In short, the vitamin users appeared healthier. This pattern of healthier lifestyle for vitamin takers persisted in the 2004 questionnaire.

Self-reported use of dietary supplements increased substantially between 1986 and 2004. In 1986, about 63% of women were taking at least one vitamin supplement a day; by 2004, more than 85% were. The most commonly used supplements were calcium, multivitamins, vitamin C, and vitamin E. The most common supplement combinations were calcium and multivitamins; calcium, multivitamins, and vitamin C; and calcium and vitamin C. Before adjustment for other lifestyle factors likely to affect mortality, self-reported use of vitamin B complex, vitamins C, D, and E, and calcium had significantly lower risk of total mortality compared with nonuse; only copper was associated with higher risk. However, after adjustment for the nutritional factors and lifestyle factors listed above, absolute risk increases for supplements were demonstrated. For multivitamins, the hazard ratio (HR) was 1.06 and the absolute risk increase was 2.4%. For vitamin B6, the HR was 1.10 and the absolute risk increase was 4.1%. For folic acid, the HR was 1.15 and the absolute risk increase was 5.9%. For iron, the HR was 1.10, with an absolute risk increase of 3.9%. For zinc, the HR was 1.08 with an absolute risk increase of 3%. However, there was a risk reduction for calcium (HR 0.91 and absolute risk reduction 3.8%). After excluding women who had cardiovascular disease or diabetes mellitus (n = 5772) or cancer (n = 3523) at baseline, the findings did not change much. There appeared to be an inverse dose-response association for calcium supplements, with its beneficial effects disappearing at the highest dose of more than 1300 mg/day.


The use of dietary supplements has increased rapidly in our lifetimes; in 2000, almost half of the adults in the United States were taking some kind of vitamin or supplement.1-3 Supplemental nutrient intake is beneficial for individuals with poor diets,4 but their benefits in well-nourished populations are unclear. Much of the recent explosion in supplement use has been driven by the notion that these agents can prevent chronic disease or cancers, but the evidence for this is less than clear. Randomized, controlled trials (RCTs) focused mainly on calcium and vitamins B, C, D, and E have not demonstrated reduced mortality rate with use of these agents.5,6 Further, some RCTs have suggested the possibility of harm.7,8 This well-done study of a large cohort designed to investigate outcomes of lifestyle supports the growing body of evidence that less is more when it comes to nutritional supplements. This appears to be the first study to sound the alarm about multivitamin use. Evidence about other supplemental nutrients has been inconsistent. In the accompanying editorial, Bjelakovic and Gluud note, "The belief that antioxidant supplements are beneficial seems likely to have resulted from a collective error. Perhaps oxidative stress is one of the keys to extension of our life span."9

Lest we be tempted to believe that these findings apply only to women, take note of the RCT published nearly simultaneously, demonstrating that supplemental vitamin E was associated with an increased risk of prostate cancer in men.10

All of this comes against the backdrop of the latest nutrient of interest, which is vitamin D. I cannot help but agree with Bjelakovic, who asserts, "We cannot recommend the use of vitamin and mineral supplements as a preventive measure, at least not in a well-nourished population. Those supplements do not replace or add to the benefits of eating fruits and vegetables and may cause unwanted health consequences. Consumption of a varied, healthful diet seems to be a prudent preventive strategy. Older women (and perhaps men) may benefit from intake of vitamin D3 supplements, especially if they have insufficient vitamin D supply from the sun and from their diet. The issue of whether to use calcium supplements may require further study." In short, we should probably focus on getting our nutrients from food.


1. National Institutes of Health State-of-the-Science Panel. National Institutes of HealthState-of-the-Science conference statement: Multivitamin/mineral supplements and chronic disease prevention. Ann Intern Med 2006;145:364-371.

2. Park K, et al. Trends in dietary supplement use in a cohort of postmenopausal women from Iowa. Am J Epidemiol 2009;169:887-892.

3. Radimer K, et al. Dietary supplement use by US adults: Data from the National Health and Nutrition Examination Survey, 1999-2000. Am J Epidemiol 2004;160:339-349.

4. Silver HJ. Oral strategies to supplement older adults’ dietary intakes: Comparing the evidence. Nutr Rev 2009;67:21-31.

5. Sesso HD, et al. Vitamins E and C in the prevention of cardiovascular disease in men: The Physicians’ Health Study II randomized controlled trial. JAMA 2008;300: 2123-2133.

6. Lee IM, et al. Beta-carotene supplementation and incidence of cancer and cardiovascular disease: The Women’s Health Study. J Natl Cancer Inst 1999;91: 2102-2106.

7. Albanes D, et al. Effects of alpha-tocopherol and beta-carotene supplements on cancer incidence in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study. Am J Clin Nutr 1995;62(6 Suppl):1427S-1430S.

8. Ebbing M, et al. Cancer incidence and mortality after treatment with folic acid and vitamin B12. JAMA 2009; 302:2119-2226.

9. Bjelakovic G, Gluud C. Vitamin and mineral supplement use in relation to all-cause mortality in the Iowa women’s health study. Arch Intern Med 2011;171: 1633-1634.

10. Klein EA, et al. Vitamin E and the risk of prostate cancer: The Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA 2011;306:1549-1556.