‘Reassuring’: Harvard’s large-scale randomized trial in men supports safety of vitamin C and E supplements

By Stephen Daniells contact

- Last updated on GMT

Related tags: Vitamin c, Prostate cancer

Vitamin E supplements did not affect cancer risk, says the new study from Brigham and Women’s Hospital and Harvard Medical School
Vitamin E supplements did not affect cancer risk, says the new study from Brigham and Women’s Hospital and Harvard Medical School
Long-term use of vitamin C and E supplements do not increase the risk of cancer, while vitamin C may offer some colorectal benefits, according to a new analysis from Harvard researchers.

Data from the Physicians’ Health Study II randomized trial, published in the American Journal of Clinical Nutrition​, ​indicated that there were no effects from vitamin C and E supplements on prostate cancer, total cancers, or other cancer endpoints.

 “Given the widespread use of vitamin supplements in the United States, knowledge of their benefits and risks remains of paramount public health importance,”​ wrote the researchers, led by Lu Wang, MD, PhD, from Brigham and Women’s Hospital and Harvard Medical School.

Our findings contrast with those from the SELECT​, which reported an increased risk of prostate cancer in men randomly assigned to receive vitamin E supplementation that emerged during post-trial follow-up.”

PHS II is the only large-scale, randomized, double-blind, placebo-controlled trial investigating the long-term effects of a common multivitamin (Centrum Silver), and individual vitamin C (500 mg synthetic ascorbic acid per day; BASF) and vitamin E supplements (400 IU synthetic alpha-tocopherol every other day; BASF) in the prevention of chronic disease.

Data from the multivitamin arm of the study, published in 2012 in JAMA​, indicated that the supplements may reduce the risk of cancer by a modest 8%.


Duffy MacKay, ND, senior vice president, scientific & regulatory affairs for the Council for Responsible Nutrition (CRN), told NutraIngredients-USA that the new paper is reassuring.

“The SELECT trial raised some concerns regarding the safety of long-term vitamin E consumption,” ​he explained. “SELECT showed that a dose of 400 IU vitamin E was not likely to provide benefit for preventing cancer, and the authors found an increased risk for developing prostate cancer. Interestingly, when vitamin E was combined with selenium, the risk was reduced to a non-significant statistic, perhaps even the result of chance.

“At the time SELCT was published, CRN reminded consumers that this study provides an important addition to the knowledge base, but we should be reminded it is one study that should be looked at in context with all of the evidence. Well, now we have another good intervention study that suggests no negative effect.”

“The results of the current study tilt the preponderance of evidence even further towards supporting the safety of long-term vitamin E consumption.”

Vitamin C and colorectal cancer

While the data from the PHS II indicated no significant effects for either vitamin on prostate cancer, total cancers, or other cancer endpoints, the Boston-based scientists reported that, during the intervention period of eight years, vitamin C was associated with a 21% reduction in colorectal cancer, but this result was not statistically significant. During the additional 3.8 years of follow-up, however, the reduction in colorectal cancer increased to 46%, said the researchers, and achieved statistical significance. This result suggested, “a possible late effect of vitamin C supplementation,”​ they said.

CRN’s Dr MacKay described this result as, “absolutely intriguing and should be followed up with additional investigations.”

“This study adds to the body of evidence supporting the safety of long-term consumption of anti-oxidant vitamins,”​ he added. “It is my hope that it is a reminder that the ​case is not closed and there is so much more to research and learn about the role of anti-oxidant in maintaining health.”

The study and some of the researchers were supported financially by grants from the NIH and BASF Corporation, while the supplements used in the study were provided by BASF Corporation, Pfizer, and DSM Nutritional Products Inc.

Source: American Journal of Clinical Nutrition
 Published online ahead of print, doi:10.3945/ajcn.114.085480
 “Vitamin E and C supplementation and risk of cancer in men: posttrial follow-up in the Physicians’ Health Study II randomized trial”
 Authors: L. Wang, H.D. Sesso, R.J. Glynn, W.G. Christen, V. Bubes, J.E. Manson, J.E. Buring, J.M. Gaziano

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