Vitamin E and C supplementation and risk of cancer in men: posttrial follow-up in the Physicians' Health Study II randomized trial

Abstract

Background: Recent posttrial analysis of a completed randomized trial found an increased risk of prostate cancer among healthy men taking high-dose vitamin E supplements. Trials that examined the effect of vitamin C supplements on cancer risk are few.

Objective: We examined whether vitamin E or vitamin C supplementation affects the risk of cancer events during posttrial follow-up of the Physicians' Health Study II.

Design: Beginning in 1997, a total of 14,641 US male physicians aged ≥50 y were randomly assigned to receive 400 IU of vitamin E every other day, 500 mg of vitamin C daily, or their respective placebos. The vitamin E and vitamin C treatment ended in 2007, and observational follow-up continued through June 2011.

Results: This study included an additional 356 cases of incident prostate cancer and 771 total cancers that developed during a mean (maximum) of 2.8 (3.8) y of posttrial observation. During an overall mean of 10.3 (13.8) y, there were a total of 1373 incident prostate cancers and 2669 total cancers documented. In comparison with placebo, vitamin E supplementation had no effect on the incidence of prostate cancer (HR: 0.99; 95% CI: 0.89, 1.10) or total cancers (HR: 1.02; 95% CI: 0.95, 1.10). There was also no effect of vitamin C supplementation on total cancers (HR: 1.02; 95% CI: 0.94, 1.10) or incident prostate cancer (HR: 1.03; 95% CI: 0.93, 1.15). Neither vitamin E nor vitamin C supplementation had effects on other site-specific cancers overall. Stratification by known cancer risk factors, history of cancer, other randomized treatment, and follow-up time showed no significant interactions.

Conclusion: In this large-scale randomized trial in men, vitamin E and C supplementation had no immediate or long-term effects on the risk of total cancers, prostate cancer, or other site-specific cancers.

Trial registration: ClinicalTrials.gov NCT00270647.

FIGURE 1.

Flow diagram of participants from random assignment through the end of the vitamin E and vitamin C interventions and posttrial observation in the Physicians’ Health Study II.

FIGURE 2.

Cumulative incidence rate of cancer by random assignment during overall follow-up (active intervention plus posttrial observation) in the Physicians’ Health Study II. A: Cumulative incidence rate of prostate cancer by randomized vitamin E assignment. B: Cumulative incidence rate of total cancer by randomized vitamin C assignment.