Physicians’ Health Study II: Multivitamins, Cancer & CVD

Background: Physicians’ Health Studies I & II

The landmark Physician’s Health Study I began in 1982 to test the benefits and risks of aspirin and beta-carotene in the primary prevention of cardiovascular disease (CVD) and cancer. This trial ended in 1995, and found that low-dose aspirin decreased the risk of a first myocardial infarction (MI) by 44%. It also didn’t find any benefit or harm from beta-carotene.

A second randomized trial, the Physicians’ Health Study II (PHS II), was started in 1997 to test the benefits and risks of vitamin C, vitamin E and a multi-vitamin/mineral supplement for the primary prevention of CVD, cancer, age-related eye disease, and cognitive decline. PHS II randomized 14,642 men, 50 years and older who had not taken part in PHS I. Each participant was assigned to daily intake of one of 16 possible combinations of vitamin C, vitamin E, beta-carotene, a multivitamin, or their placebos.

The vitamin C and vitamin E components of PHS II, which ended in 2007, found that these antioxidant vitamins did not prevent major cardiovascular events, cancer, or eye disease in this healthy population of male physicians.

The multivitamin component ended in mid-2011, and the results for cancer (1) and those for CVD (2) were published in the October and November issues of the Journal of the American Medical Association.

Multivitamins and Cancer

The physicians who took part in the trial were quite healthy, with good dietary and lifestyle habits. Over 2/3 of them exercised regularly and only 4% smoked (though 40% were former smokers). They were also fairly diligent about taking the supplements over time, as compliance was 76.8% (vitamin) and 77.1% (placebo) at 4 years, and remained high at the end of the follow-up period at 67.5% and 67.1%, respectively. The men were followed 11.2 years on average.

The PHS II investigators report a significant 8% decrease in total cancer occurrence. The reduction in total cancer rate was found to be 12% when prostate cancer was removed from the analysis (no effect was seen for prostate cancer). Regular multivitamin use also lessened the risk of dying from cancer, with a 12% reduction in cancer mortality. Though not quite statistically significant, this was a consistent finding.

The study’s findings are important both from a public health and an individual perspective. An 8% decrease in cancer risk may seem modest. But with more than 1.6 million new cancer cases diagnosed yearly in the US, this risk reduction would translate into about 130,000 cancers prevented every year.

The study also confirms that multivitamins are generally safe, as no major differences in adverse effects were seen between groups.

Multivitamins and CVD

In contrast to the findings on cancer, PHS II reports no significant reductions for major cardiovascular events, heart attack, stroke or death from CVD with multivitamin use. There were fewer total deaths among those in the multivitamin group; however the difference was not statistically significant.

Analysis showed that the small number of multivitamin users with CVD at the study’s start were significantly less likely to die from a heart attack, with a 44% reduction in risk. However, statistical power was limited, with only 9 cases of MI death occurring during the trial.

PHS II investigators acknowledge that multivitamins may play a role in populations with nutritional deficiencies, and that their study results don’t extend to the large number of population sub-groups with marginal intakes of various vitamins and minerals.

Multivitamins and Cataract, AMD, & Cognition

Publication of the main findings for the study’s multivitamin on eye disease component (cataract and macular degeneration), as well as early cognitive decline, is expected in the very near future.

References

1. Gaziano JM, et al. Multivitamins in the prevention of cancer in men—The Physicians’ Health Study II Randomized Controlled Trial. JAMA, online Oct, 2012.
2. Sesso HD, et al. Multivitamins in the prevention of CVD in men—The Physicians’ Health Study II Randomized Controlled Trial. JAMA, 308:1751-60, 2012.