Roxanne Nelson

November 18, 2008

November 18, 2008 — Supplementation with vitamins C and E does not have any effect on cancer risk, according to new results from the Physician's Health Study, which also found no affect from these supplements on risk for cardiovascular disease.

The cancer results were presented recently at the Seventh Annual American Association for Cancer Research International Conference on Frontiers in Cancer Prevention Research, held in Washington, DC. They show no beneficial effect of vitamin E supplementation on either prostate or total cancer, and no beneficial effect of vitamin C supplementation on total cancer.

"Vitamins E and C are very commonly used supplements, and basic science and observational studies have supported a potential role of antioxidants, including vitamins E and C, in the prevention of cancer," said study author Howard D. Sesso, ScD, MPH, an assistant professor of medicine at Harvard University and an associate epidemiologist at Brigham and Women's Hospital, in Boston, Massachusetts, during a press briefing.

There have been more studies focused on the potential benefits of vitamin E than vitamin C, explained Dr. Sesso. In fact, there have been very few long-term trials that have evaluated vitamin C alone for cancer prevention.

The current study involved 14,461 male physicians who participated in the Physicians' Health Study II. Study participants, who were 50 years and older, were given 400 IU of vitamin E every other day or placebo, and 500 mg of vitamin C daily or placebo.

"The participants were followed for a mean of 8 years, with a maximum of about 10 years," said Dr. Sesso. "We adjusted for confounders such as age, history of cancer, and smoking status, but after 8 years, we did not see any effect of vitamin E on the incidence of prostate cancer. We also did not see any effect from vitamin C on total cancers or on specific cancers, such as colorectal, lung, or prostate."

The primary end point of the vitamin E component was prostate cancer, with total cancer as a secondary end point. For vitamin C, the primary end point was total cancer. At baseline, there were 1274 (8.7%) men with prevalent cancer at randomization.

To date, the researchers report 1929 cases of cancer among the participants, including 1013 cases of prostate cancer. Based on preliminary results, men who received vitamin E had a relative risk for prostate cancer of 0.95 (490 events in the active group vs 523 in the placebo group), and a relative risk for total cancer of 1.04 (978 vs 951 in the placebo group). For those who received vitamin C, the relative risk for total cancer was 1.00 (964 events in the active group vs 965 in the placebo group).

"In this population of middle-aged men, we do not see vitamins E and C as part of a comprehensive cancer-prevention program," said Dr. Sesso. "In the absence of any clear benefit, it's hard to recommend more trials with vitamin E, but vitamin C is more of an open book."

Dr. Sesso pointed out that 1 group of the trial is still ongoing, in which they are evaluating the effect of multivitamin supplementation. In a normal diet, a person consumes a combination of vitamins and minerals, and that is where the multivitamin component of the trial comes into play. "It is perhaps the interaction of vitamins and minerals, even at lower doses, that leads to the preventive nature," he said.

These are a very-well-designed series of trials, and the conclusions are not what everyone has hoped for, commented Robert C. Young, MD, chancellor of Fox Chase Cancer Center, in Philadelphia, Pennsylvania. "The final arm of the study is about the effect of multivitamins on cancer risk, and this is one of the first trials that is looking at multivitamin use."

Dr. Young is a participant in the Physicians' Health Study II, but is not involved in running the trial.

One caveat to these results may be the population participating in the trial, he pointed out. "This is a group of healthy individuals who eat well and have access to healthcare and screening, and they are very compliant with study protocols. But the question is whether this is a population where you are likely to see a benefit from vitamin supplementation."

However, the Physicians' Health Study I found that daily low-dose aspirin use reduces the risk for cardiovascular disease. "They saw a huge impact from aspirin, so if the effect is significant enough, we'll see it," said Dr. Young.

The bulk of studies to date have not shown a benefit for vitamin supplements. "Despite data from epidemiological and preliminary studies, the sum total of these papers has been negative," he said. "Vitamin supplementation has, for the most part, not demonstrated a benefit."

"It may be that synthetic supplements differ from the natural presentation of vitamins in food, but that is unresolved question," Dr. Young added.

American Association for Cancer Research's Seventh Annual International Conference on Frontiers in Cancer Prevention Research. Abstract PR-1. Presented November 16, 2008.


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