The daily use of multivitamins may reduce the risk for cancer in men, according to the results of a very large randomized trial.

After about 11 years, multivitamin use resulted in a modest but statistically significant reduction — specifically, an 8% reduction in total cancer incidence.

However, the investigators observed no effect of vitamin usage on prostate cancer, so they removed that cancer from all the other cancer types in another analysis. In that analysis, "there was a 12% reduction in total cancers which was significant," said lead author John Michael Gaziano, MD, MPH. He was speaking at a press briefing ahead of a presentation at the Annual American Association for Cancer Research (AACR) Frontiers in Cancer Prevention Research meeting.

The study has also been published early online in the Journal of the American Medical Association to coincide with the meeting.

Multivitamin use also lessened the risk of dying from cancer.

"Cancer mortality also went in the right direction — a 12% reduction which wasn't quite statistically significant but certainly a consistent finding," said Dr. Gaziano, a researcher at Brigham and Women's Hospital, Center for Older Adult Health, Boston, Massachusetts.

"Our main message is that the main reason to take a multivitamin is for nutritional deficiencies but it certainly appears that there may be a modest benefit in preventing cancer in men over the age of 50," he said.

A number of trials of individual vitamins, administered at high doses, have not shown any effect at preventing cancer, Dr. Gaziano explained.

Observational studies have also not provided evidence of an association between multivitamin use and a reduction in cancer incidence or mortality.

However, the current study is unique in a number of ways, the first being that it is the only large-scale placebo-controlled trial evaluating a multivitamin in the prevention of cancer.

It is also of long duration, he said. "This effort was 17 years in the making, from the time we wrote the first protocol and we have 11 years of follow up, with up to 14 years of treatment for some of the participants."

In addition, Dr. Gaziano pointed out that this study was well controlled. The participants who were randomized to the multivitamin arm were all taking the exact same brand and formulation (Centrum Silver), which has not necessarily been the case in other studies.

Conflicting Results

Previous studies have reported conflicting results. As reported by Medscape Medical News, 2 studies evaluating the association of multivitamins and breast cancer found opposite results — one study found an increased risk while the other found that multivitamins decreased the risk.

Another study reported more neutral results, in that multivitamin use had no influence on the risk for common cancers, cardiovascular disease, or overall mortality.

The lead author of that study, Marian L Neuhouser, MD, commented at that time that the "main message of our study is that postmenopausal women who take a multivitamin don't increase their risk for cancer or cardiovascular disease, but they don't decrease it either.

"These multivitamins are having no effect with regard to these particular disease outcomes," said Dr. Neuhouser, who is from the Fred Hutchinson Cancer Research Center, Seattle, Washington.

Reduction in Total Cancers

The data in the current study was drawn from the Physicians' Health Study II, a large-scale, randomized, double-blind, placebo-controlled trial that included 14, 641 male US physicians who were 50 years or older when the study began. The cohort included 1312 men with a history of cancer. The multivitamin study began in 1997, with treatment and follow-up that continued through June 1, 2011.

The cohort included a large proportion of former smokers (40.0%) and a very low proportion of current smokers (3.6%) with a high rate of current aspirin use (77.4%).

"This was a population of healthy physicians," Dr. Gaziano said. "Over two thirds of them exercised regularly and only 4% smoked."

Adherence to the protocol was high in both the multivitamin and placebo group. At 4 years, it was 76.8% (vitamin) and 77.1% (placebo), P = .71; and at 8 years, adherence was 72.3% (vitamin) and 70.7% (placebo), P = .15. It remained high even at the end of the follow-up period, at 67.5% and 67.1%, respectively (P = .70).

During the study period, a total of 2669 men developed cancer, including 1373 cases of prostate cancer and 210 cases of colorectal cancer. A total of 2757 participants (18.8%) died during follow-up, and this included 859 (5.9%) from cancer.

Their results showed that men taking a daily multivitamin had a statistically significant reduction in the incidence of total cancer, as compared with placebo (17.0 and 18.3 events, respectively, per 1000 person-years; hazard ratio [HR], 0.92; P = .04).

However, when the cancers were considered separately, there was no significant effect. There was no effect of the daily multivitamin on prostate cancer (multivitamin and placebo groups, 9.1 and 9.2 events per 1000 person-years; HR, 0.98; P = .76), colorectal cancer (1.2 and 1.4 events per 1000 person years; HR, 0.89; P = .39), or any other site-specific cancers.

Dr. Gaziano and colleagues noted that the total cancer rates in this cohort were probably influenced by the increased surveillance for prostate-specific antigen (PSA) and subsequent diagnoses of prostate cancer during the last 1990s.

"We had included participants with a prior history of cancer and we had prespecified an analysis that we would do, and there is an appearance of a stronger effect in those with a prior cancer," he said.

Among men with a baseline history of cancer, daily multivitamin use was associated with a reduction in total cancer (HR, 0.73; P = .02). However, this reduction was not significantly different from the cohort without a cancer history (HR, 0.94; P = .15; P for interaction = .07).

"We are continuing more analyses, looking at the nutritional status of the individuals," Dr. Gaziano said. "We hope to be able to continue following this cohort, some of whom we have been following for 30 years, so we can see the long term effects."

Researchers from the Linus Pauling Institute at Oregon State University, Corvallis, who have been studying related issues, commented that this data "conclusively shows that multivitamins are safe to take, help fill important nutritional gaps, reduce cancer risk and in turn will help cut health care costs."

"An 8 percent drop in overall cancer rates is not small," said Balz Frei, PhD, professor and director of the Linus Pauling Institute, in a statement.

"Given that more than 1.6 million new cancer cases are diagnosed in the U.S. each year, this translates into about 130,000 cancers prevented every year, and with it all the health care costs and human suffering," commented Dr. Frei, who was not involved in the study.

Dr. Frei also pointed out that the effect might be even higher in other population groups than seen in this study. "And it's worth noting that the research was done with 14,600 physicians," Dr. Frei said. "This highly-educated group has a better diet, knowledge base and health habits than the average person, so it's reasonable to believe that the impact of multivitamin use in the general population will be even greater."

11th Annual AACR International Conference on Frontiers in Cancer Prevention Research, Presented October 17, 2012.

The study was supported by grants from the National Institutes of Health and the BASF Corporation. Dr. Gaziano reports investigator-initiated research funding from the NIH, the Veterans Administration, and the BASF Corporation; assistance with study agents and packaging from BASF Corporation and Pfizer (formerly Wyeth, American Home Products, and Lederle); and assistance with study packaging provided by DSM Nutritional Products Inc. (formerly Roche Vitamins). Several other coauthors also report relationships with industry as noted in the paper.

JAMA. 2012. Published online October 17, 2012. Full text

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