No Link Between Vitamins and Cancer Prevention

Two large randomized studies call into question the efficacy of various vitamins and dietary supplements in preventing cancer. Preliminary results from the Physician’s Health Study II (PHSII) show that taking vitamins C or E imparts no cancer-reducing benefits in men. A second report concluded that a combination of folic acid, vitamin B₆, and vitamin B₁₂ were no better than placebo at preventing breast and invasive cancers in women.

In the PHSII, 14,641 US men, consisting of physicians aged 50 years and older, were randomized into two groups. One group received either placebo or 400 IU of vitamin E every other day. The other group was given placebo or 500 mg of vitamin C every day.

“At the time we began this study [in 1997], there was still genuine uncertainty about the relative merits of taking individual supplements such as vitamin C or E,” said co-author Howard D. Sesso, ScD, assistant professor of medicine at Brigham and Women’s Hospital in Boston. “To address this, we initiated the PHSII to try to evaluate any potential risks and benefits associated with long-term supplementation with vitamin E and C on the risk of cancer.”

During the course of treatment and follow-up in PHSII, 1929 cancers were recorded, including 1013 cases of prostate cancer. “After a mean follow-up of 8 years, we found that neither vitamin E nor vitamin C supplementation had any effect on our primary end points of prostate cancer and total cancer,” Dr. Sesso said. “Despite the fact that people continue to take these supplements with the hope of getting benefits, our trial adds to the overall evidence, and we would not recommend the use of these supplements in the prevention of cancer.” Instead, he suggested focusing on the basic risk factors for cancer such as diet, smoking, exercising, and keeping body weight under control.

“In this study, there were no adverse effects, but neither were there beneficial ones,” said Michele Forman, PhD, professor of epidemiology at M. D. Anderson Cancer Center in Houston, Texas. “In those who have adequate dietary intake of vitamin C and E, I would say that it doesn’t look like it works,” he concluded.

Results may be limited by the fact that trial participants were of medical professionals. It is unclear whether the results would translate to the general population or individuals who have certain at-risk behaviors. “If your patient is nutritionally deficient, is a heavy smoker, drinks a lot of alcohol, then you might have different results,” said Somdat Mahabir, PhD, assistant professor of epidemiology at M. D. Anderson.

These preliminary results were presented as an abstract at last year’s American Association for Cancer Research Seventh Annual Frontiers in Cancer Prevention Research Conference.

Journal of the American Medical Association

The second report, based on data from the Women’s Antioxidant and Folic Acid Cardiovascular Study (WAFACS), found that a combination of folic acid, vitamin B₆, and vitamin B₁₂ had no significant effect on breast or other invasive cancers in women. “Observational studies, which were conducted mostly before folic acid fortification [in foods], in general supported an inverse relationship between high intake or blood level of folate, vitamin B₆, and vitamin B₁₂, and risk of cancer,” wrote the authors in the article appearing in a November issue of the . “Data from randomized trials of folic acid alone or in combination with B vitamins and cancer risk are limited, not entirely consistent, and 1 trial has even raised concerns about deleterious effects.”

WAFACS enrolled 5442 women, all of whom were health professionals with preexisting cardiovascular disease or at least 3 risk factors. Participants were randomized to receive a daily combination of 2.5 mg of folic acid, 50 mg of vitamin B₆, and 1 mg of vitamin B₁₂ or placebo. They were treated for 7.3 years, from April 1998 through July 2005.

A total of 379 women developed invasive cancers. Those in the active treatment group had a similar risk of total invasive cancer (101.1/ 10,000 person years) as those receiving the placebo (104.3/ 10,000 person years). Similar risk levels were also seen in those who developed breast cancer (37.8/10,000 person years and 45.6/10,000 person years, respectively) or died from cancer.

“In the WAFACS trial, up to 7.3 years of treatment with combined folic acid, vitamin B₆, and vitamin B₁₂ had no significant effect on overall risk of total invasive cancer, breast cancer, other individual cancers, or cancer death among women at high risk for cardiovascular disease,” wrote the authors. “There were no differences according to current use of multivitamin supplements, intake of total folate, vitamin B₆, vitamin B₁₂, or history of cancer at baseline. Lack of effect on total evasive cancer did not vary over time.”

Dr. Forman noted that this study took place during a time when dietary fortification of folic acid was occurring. Thus, both the controls and intervention groups were probably getting the 400 mg of recommended folic acid through fortified breads and cereals. In addition, WAFACS included only women with certain risk factors or a past history of cardiovascular disease, which limits its generalizability to the general population.

“In this particular study, they basically have a null result,” she said. “Meaning, no effect of any of the supplements on total, cancer, breast cancer, or cancer mortality. This is not surprising when the dietary fortification is included.”

“All of these women were getting folic acid in their food supply,” said Dr. Mahabir. “If a population has adequate levels of the nutrient already, additional supplementation would not be expected to have any big effect; that is why we are not seeing significant findings.”

Dr. Forman also thought that the timing of the study might have had an impact on its sensitivity to the kinds of cancers they were looking at. “Bear in mind that the average age of the women was 62 years when they entered the study,” she said. “Breast cancer incidence tends to rise in women in their 50s and colon cancer peaks in the seventh decade of life in women. For some of the cancer end points, they were not covering the years close to the peak.”

The bottom line for both experts is that, based on study results, there seems to be no effect on cancer end points in either series. “For oncologists, I would suggest they tell patients that in both of these trials there was no harm and no benefit, ” she noted. “So there is no reason to give [the vitamins].”

Buring JE, et al. A randomized factorial trial of vitamins E and C in the prevention of cancer in men. Abstract PR-1. Presented at Seventh Annual International Conference on Frontiers in Cancer Prevention Research; November 17, 2008; Washington, DC.

JAMA.

Zhang SM, et al. Effect of combined folic acid, vitamin B₆ and vitamin B12 on cancer risk in women. 2008;300:2012-2021.