Dietary Supplements and Mortality Rate in Older Women: The Iowa Women’s Health Study

Study Questions:

Are dietary supplements associated with long-term risk for adverse events?


Use of vitamin and mineral supplements was examined in relation to total mortality in older women enrolled in the Iowa Women’s Health Study. Women were excluded if they did not adequately complete a questionnaire including food frequency and supplement use at baseline in 1986. For the analyses starting in 1997, a total of 29,230 women who filled out the supplement use questionnaire were included. In the 2004 starting analysis, 19,124 women were included. Supplement use was queried in 1986, 1997, and 2004 and included the 15 supplements assessed at all three surveys: multivitamins; vitamins A, beta-carotene, B6, folic acid, B complex, C, D, and E; and minerals iron, calcium, copper, magnesium, selenium, and zinc. Different forms of vitamin D, cholecalciferol (D3) or ergocalciferol (D2), were not distinguished. The primary outcome of interest was deaths recorded through December of 2008, which were identified through the State Health Registry of Iowa and the National Death Index.


A total of 38,772 women (mean age 61.6 years at baseline [1986]) were included in this analysis. Over the mean follow-up time of 19 years, 15,594 deaths (40.2%) were identified. Mean body mass index was 27 kg/m2; 36.8% of the respondents reported high blood pressure; 6.8% had diabetes mellitus; and 15.1% were current smokers. At baseline, compared with nonusers, supplement users had a lower prevalence of diabetes mellitus, high blood pressure, and smoking status; a lower BMI and waist-to-hip ratio; and were less likely to live on a farm. Supplement users had a higher educational level, were more physically active, and were more likely to use estrogen replacement therapy. Self-reported use of dietary supplements increased significantly from 1986 to 2004. In 1986, 1997, and 2004, 62.7%, 75.1%, and 85.1% of the women, respectively, reported using at least one supplement daily. 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. In multivariable models, the use of multivitamins (hazard ratio [HR], 1.06; 95% confidence interval [CI], 1.02-1.10) was associated with an increased risk of total mortality compared with women who did not use supplements. Increased risk of total mortality was also observed for vitamin B6 (HR, 1.10; 95% CI, 1.01-1.21), folic acid (HR, 1.15; 95% CI, 1.00-1.32), iron (HR, 1.10; 95% CI, 1.03-1.17), magnesium (HR, 1.08; 95% CI, 1.01-1.15), zinc (HR, 1.08; 95% CI, 1.01-1.15), and copper (HR, 1.45; 95% CI, 1.20-1.75) for supplement users compared to nonusers. Use of calcium was inversely related (HR, 0.91; 95% CI, 0.88-0.94). Findings for iron and calcium were similar when shorter follow-up times were examined.


The authors concluded that among older women, several commonly used dietary vitamin and mineral supplements may be associated with increased total mortality. The association was strongest for supplemental iron, whereas calcium was associated with decreased risk.


Given the billion or so dollars that are spent each year on supplements, the data from this study suggest patients may wish to reallocate their health care spending to other evidence-based preventive therapies.

Clinical Topics: Dyslipidemia, Prevention, Lipid Metabolism, Nonstatins, Diet

Keywords: Iron, Magnesium, Follow-Up Studies, Vitamin E, Women's Health, Estrogen Replacement Therapy, Calcium, Zinc, Copper, Vitamin B 6, Body Mass Index, Folic Acid, Selenium, Dietary Supplements, Cardiology, Minerals, Cardiovascular Diseases, Iowa, Vitamin D, Diabetes Mellitus, Cholecalciferol, Ergocalciferols

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