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

Am J Clin Nutr. 2014 Sep;100(3):915-23. doi: 10.3945/ajcn.114.085480. Epub 2014 Jul 9.

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.

Publication types

  • Comparative Study
  • Observational Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antioxidants / adverse effects
  • Antioxidants / therapeutic use*
  • Ascorbic Acid / adverse effects
  • Ascorbic Acid / therapeutic use*
  • Cohort Studies
  • Dietary Supplements* / adverse effects
  • Double-Blind Method
  • Follow-Up Studies
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Neoplasms / chemically induced
  • Neoplasms / epidemiology
  • Neoplasms / prevention & control*
  • Physicians
  • Prostatic Neoplasms / chemically induced
  • Prostatic Neoplasms / epidemiology
  • Prostatic Neoplasms / prevention & control
  • Risk Factors
  • United States / epidemiology
  • Vitamin E / adverse effects
  • Vitamin E / therapeutic use*

Substances

  • Antioxidants
  • Vitamin E
  • Ascorbic Acid

Associated data

  • ClinicalTrials.gov/NCT00270647