Vitamins E and C in the prevention of prostate and total cancer in men: the Physicians' Health Study II randomized controlled trial.
BACKGROUND
Many individuals take vitamins in the hopes of preventing chronic diseases such as cancer, and vitamins E and C are among the most common individual supplements. A large-scale randomized trial suggested that vitamin E may reduce risk of prostate cancer; however, few trials have been powered to address this relationship. No previous trial in men at usual risk has examined vitamin C alone in the prevention of cancer.


OBJECTIVE
To evaluate whether long-term vitamin E or C supplementation decreases risk of prostate and total cancer events among men.


METHODS
The Physicians' Health Study II is a randomized, double-blind, placebo-controlled factorial trial of vitamins E and C that began in 1997 and continued until its scheduled completion on August 31, 2007. A total of 14,641 male physicians in the United States initially aged 50 years or older, including 1307 men with a history of prior cancer at randomization, were enrolled.


METHODS
Individual supplements of 400 IU of vitamin E every other day and 500 mg of vitamin C daily.


METHODS
Prostate and total cancer.


RESULTS
During a mean follow-up of 8.0 years, there were 1008 confirmed incident cases of prostate cancer and 1943 total cancers. Compared with placebo, vitamin E had no effect on the incidence of prostate cancer (active and placebo vitamin E groups, 9.1 and 9.5 events per 1000 person-years; hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.85-1.09; P = .58) or total cancer (active and placebo vitamin E groups, 17.8 and 17.3 cases per 1000 person-years; HR, 1.04; 95% CI, 0.95-1.13; P = .41). There was also no significant effect of vitamin C on total cancer (active and placebo vitamin C groups, 17.6 and 17.5 events per 1000 person-years; HR, 1.01; 95% CI, 0.92-1.10; P = .86) or prostate cancer (active and placebo vitamin C groups, 9.4 and 9.2 cases per 1000 person-years; HR, 1.02; 95% CI, 0.90-1.15; P = .80). Neither vitamin E nor vitamin C had a significant effect on colorectal, lung, or other site-specific cancers. Adjustment for adherence and exclusion of the first 4 or 6 years of follow-up did not alter the results. Stratification by various cancer risk factors demonstrated no significant modification of the effect of vitamin E on prostate cancer risk or either agent on total cancer risk.


CONCLUSIONS
In this large, long-term trial of male physicians, neither vitamin E nor C supplementation reduced the risk of prostate or total cancer. These data provide no support for the use of these supplements for the prevention of cancer in middle-aged and older men.


BACKGROUND
clinicaltrials.gov Identifier: NCT00270647.
Gaziano
J Michael
JM
Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02120, USA. jmgaziano@partners.org
Glynn
Robert J
RJ
Christen
William G
WG
Kurth
Tobias
T
Belanger
Charlene
C
MacFadyen
Jean
J
Bubes
Vadim
V
Manson
JoAnn E
JE
Sesso
Howard D
HD
Buring
Julie E
JE
D000368:Aged; D000975:Antioxidants / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000627:therapeutic use*; D019587:Dietary Supplements; D004311:Double-Blind Method; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology / Q000517:prevention & control*; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000517:prevention & control*; D016896:Treatment Outcome; D014810:Vitamin E / Q000627:therapeutic use*; D024502:alpha-Tocopherol / Q000627:therapeutic use
D000975:Antioxidants; D014810:Vitamin E; D024502:alpha-Tocopherol; D001205:Ascorbic Acid