From The North American Menopause Society (NAMS)
NAMS First to Know e-Newsletter

Effect of Multivitamins on Cancer and CVD in Postmenopausal Women

Robert P. Heaney, MD

Published: 06/04/2009

Summary

Neuhouser ML, Wassertheil-Smoller S, Thomson C, et al. Multivitamin use and risk of cancer and cardiovascular disease in the Women's Health Initiative cohorts. Arch Intern Med 2009;169:294-304. Level of evidence: II-2.

Abstract copyright © 2009 American Medical Association. All rights reserved. Used with permission.

Background: Millions of postmenopausal women use multivitamins, often believing that supplements prevent chronic diseases such as cancer and cardiovascular disease (CVD). Therefore, we decided to examine associations between multivitamin use and risk of cancer, CVD, and mortality in postmenopausal women.
Methods: The study included 161 808 participants from the Women's Health Initiative clinical trials (N=68 132 in 3 overlapping trials of hormone therapy, dietary modification, and calcium and vitamin D supplements) or an observational study (N=93 676). Detailed data were collected on multivitamin use at baseline and follow-up time points. Study enrollment occurred between 1993 and 1998; the women were followed up for a median of 8.0 years in the clinical trials and 7.9 years in the observational study. Disease end points were collected through 2005. We documented cancers of the breast (invasive), colon/rectum, endometrium, kidney, bladder, stomach, ovary, and lung; CVD (myocardial infarction, stroke, and venous thromboembolism); and total mortality.
Results: A total of 41.5% of the participants used multivitamins. After a median of 8.0 years of follow-up in the clinical trial cohort and 7.9 years in the observational study cohort, 9619 cases of breast, colorectal, endometrial, renal, bladder, stomach, lung, or ovarian cancer; 8751 CVD events; and 9865 deaths were reported. Multivariate-adjusted analyses revealed no association of multivitamin use with risk of cancer (hazard ratio [HR], 0.98, and 95% confidence interval [CI], 0.91-1.05 for breast cancer; HR, 0.99, and 95% CI, 0.88-1.11 for colorectal cancer; HR, 1.05, and 95% CI, 0.90-1.21 for endometrial cancer; HR, 1.0, and 95% CI, 0.88-1.13 for lung cancer; and HR, 1.07, and 95% CI, 0.88-1.29 for ovarian cancer); CVD (HR, 0.96, and 95% CI, 0.89-1.03 for myocardial infarction; HR, 0.99, and 95% CI, 0.91-1.07 for stroke; and HR, 1.05, and 95% CI, 0.85-1.29 for venous thromboembolism); or mortality (HR, 1.02, and 95% CI, 0.97-1.07).
Conclusion: After a median follow-up of 8.0 and 7.9 years in the clinical trial and observational study cohorts, respectively, the Women's Health Initiative study provided convincing evidence that multivitamin use has little or no influence on the risk of common cancers, CVD, or total mortality in postmenopausal women.

Commentary by Robert P. Heaney, MD

Two principal difficulties in many recent studies of nutrient effects are: 1) failure to include a low-intake control group and 2) failure to use (and validate) a nutrient dose sufficient to produce the desired effect. Both faults are exhibited in the paper by Neuhouser et al. Most nutrients exhibit a threshold (or plateau) characteristic, as manifested, for example, during iron supplementation (ie, iron raises hemoglobin in patients with iron deficiency, but only up to normal levels, above which further iron intake has no further effect on blood hemoglobin.) As many papers reported from WHI have clearly shown, the enrolled cohort of women exhibited substantial healthy volunteer bias as reflected, for example, in calcium intakes nearly twice what had been found in NHANES-III, and hip fracture rates approximately half what had been predicted from Medicare data. What the Neuhouser paper documented is that individuals in WHI, who were already getting enough of many key nutrients, exhibited no further benefit from getting more. It doesn't show that those nutrients have no benefit.

The second issue is the dosage question. Typical multivitamins contain, for example, 400 IU of vitamin D. This is usually enough to raise serum 25(OH)D by about 4 ng/ml. In several studies, this dose-evoked change in vitamin D status has been shown to be inadequate to produce appreciable benefit. All studies showing a benefit of vitamin D (including several randomized trials) used doses of 800 to 2,000 IU/d. WHI was designed nearly 20 years ago, and it would not be appropriate to criticize its designers for not knowing information that had not yet been developed. But neither is it appropriate to publish papers that presume adequacy of design and proceed to reach sweeping conclusions of "no benefit," such as did Neuhouser et al.

From the NAMS First to Know e-newsletter released April 28, 2009

For more, please visit http://www.menopause.org/news.aspx

[CLOSE WINDOW]

Authors and Disclosures

Robert P. Heaney, MD, John A. Creighton University Professor, Creighton University, Osteoporosis Research Center, Omaha, NE