Vitamin D Supplements Don’t Reduce Cancer Incidence

December 13, 2018, by NCI Staff

In the largest-ever randomized clinical trial testing vitamin D for cancer prevention, the supplement did not reduce the risk of developing cancer.

A large body of epidemiology research had suggested that people with higher blood levels of vitamin D have a lower risk of cancer, said Barry Kramer, M.D., director of NCI’s Division of Cancer Prevention.

However, such studies can only highlight associations, not prove cause and effect, he added. “This is why it’s important to question intuitions and observational epidemiology studies, and fund large-scale trials,” Dr. Kramer continued; they can conclusively show whether a treatment—in this case, a dietary supplement—truly can help to prevent cancer.

Results from the trial, called the Vitamin D and Omega-3 Trial (VITAL), were published November 10 in the New England Journal of Medicine (NEJM).

Isolating the Effects of Vitamin D

The body produces vitamin D when the skin is exposed to sunlight. The vitamin is also found naturally in some foods, such as fatty fish and mushrooms, and is often added to others, including milk and some cereals.

For people with known vitamin D deficiencies, supplementation is recommended to maintain bone health and prevent fractures. “The main goal of VITAL was to see if there’s benefit to getting above the recommended dietary allowance, more than what is considered necessary for bone health,” explained JoAnn Manson, M.D., of Brigham and Women’s Hospital and Harvard Medical School, who led the study.

Observational studies have suggested that people who take vitamin D supplements may have a lower risk of many diseases. But “people who take vitamins may be very different in important ways from people who don’t take vitamins,” explained Dr. Kramer. They often have a higher income and are less likely to smoke, less likely to be overweight, and more likely to have health insurance, he added—all of which are strongly linked with a lower risk of a variety of chronic health conditions, including heart disease and many cancers.

Large randomized clinical trials with thousands of participants can avoid these biases by randomly assigning study participants to receive or not receive the treatment.

VITAL was designed so that it could study the effects of both vitamin D and omega-3 supplements. The trial’s primary endpoints—the key outcomes it measured—were the supplements’ impact on the risk of developing cancer and heart disease. It also had several secondary endpoints, including the risk of dying from cancer. VITAL was funded primarily by NCI and the National Heart, Lung, and Blood Institute.

Almost 26,000 participants with no history of invasive cancer or cardiovascular disease enrolled in the trial. Men had to be age 50 or older, and women age 55 or older, to enroll in the study. About half of the participants were women, and the participants were racially diverse, with about 20% being African American.

“The number of participants and the substantial proportion of black participants make this cohort a nationally representative sample,” wrote John Keaney, M.D., and Clifford Rosen, M.D., of the University of Massachusetts Medical School and the Maine Medical Center Research Institute, in an accompanying editorial.

Participants were randomly assigned to one of four groups: daily vitamin D plus a placebo, omega-3 supplements plus a placebo, both vitamin D and omega-3 supplements, or two placebos. The researchers followed the participants for a median of 5.3 years.

About 17,000 participants provided blood samples at the start of the trial, 1,600 provided a second sample a year into the study, another 5,000 provided follow-up blood samples at later time points. The researchers used these samples to measure blood levels of vitamin D and omega-3s in the different groups.