Can Vitamin D Protect Against Breast Cancer?

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Correction Appended: Nov. 12, 2008

It was a powerful idea, and there was some intriguing early evidence suggesting that something as simple as popping vitamin D might hold off the second biggest cancer killer among American women — breast cancer. So researchers were expecting to see positive results from the Women's Health Initiative (WHI), the first controlled trial of the effects of vitamin D on breast cancer.

Unfortunately, that didn't happen. Reporting in the Journal of the National Cancer Institute, the study authors announce that taking vitamin D supplements does not affect breast-cancer rates. After a seven-year period, women who took 400 IUs of vitamin D daily had the same rates of breast cancer as those not taking the supplements. (See TIME's A-Z Health Guide.)

"It's a disappointment," says study author Dr. Rowan Chlebowski at Los Angeles Biomedical Research Institute and Harbor-UCLA Medical Center. "Basically we have an agent in vitamin D that is almost free and with little toxicity, and wouldn't it be great if it did substantially reduce the risk of breast cancer?"

Of the 36,000 women participating in the WHI — a multiyear government trial investigating a range of women's health issues, from hormone therapy to heart disease, cancer and fracture risk — half were given 1,000 mg of calcium and 400s IU of vitamin D daily, while the other half were not. After seven years, 528 women in the supplement group and 546 women in the control group had developed invasive breast cancer, an equivalent rate, indicating no effect from the vitamin D. Earlier observational trials had found positive links between women's taking higher amounts of supplemental vitamin D and lower breast-cancer rates, and animal studies had also suggested that the vitamin might prevent the disease. The WHI trial hints that the relationship may be more complicated, and despite the negative results, experts believe the connection is worth pursuing.

For one thing, the dose of vitamin D supplementation used in the trial, 400 IUs, was relatively low. In the years since the study began in 1993, nutritionists have learned much more about the critical role that vitamin D plays in a wide range of cellular functions, and many now recommend up to 2,000 IUs daily for adults. Most people get very little vitamin D from their diet — the richest sources of the vitamin are dairy products and green leafy vegetables — so supplementation is the only way to reach recommended levels. "Four hundred IUs is just not a lot," says Dr. Larry Norton, a breast-cancer specialist at Memorial Sloan-Kettering Cancer Center. "The supplementation wasn't adequate to raise blood levels enough in susceptible individuals to have a biological impact." Indeed, the women in the study who began with the highest blood levels of vitamin D's most active breakdown product, 25-hydroxyvitamin D, showed no change in their levels even after taking the 400 IUs daily.

Confounding the results even more is the fact that calcium and vitamin D supplementation is now routine therapy for postmenopausal women to protect against bone fractures. So about 15% of the women in the placebo group were allowed to continue taking their vitamin D supplements for bone health (some were taking up to 600 IUs per day), which could explain why there was little difference between the two groups in breast-cancer rates. "This is a potential problem that confounds the results of this particular trial," says Dr. Powel Brown, a professor of medicine at Baylor College of Medicine and author of an editorial accompanying the study. "But it's not really ethical to tell postmenopausal women not to take vitamin D or calcium, because we know it protects against hip fractures." Future studies, he says, might compare standard doses of vitamin D with higher doses to determine whether the supplements have any effect on the cancer process.

Those studies might expose other factors affecting vitamin D levels that the WHI trial was not designed to track. Exposure to sunlight, for example, boosts vitamin D production in the body, and in the WHI trial, the women with the highest levels of 25-hydroxyvitamin D tended to be the leanest and most physically active, suggesting that they might spend more time outdoors.

Experts wonder whether the trial lasted long enough to uncover any benefit on breast-cancer rates. Breast cancer typically develops over a long period, anywhere from five to 20 years, and researchers believe that vitamin D's effect on curbing cancer-cell growth may be most powerful in the disease's early stages. That means that the cancers picked up in the seven-year WHI study may have already progressed beyond any potential to be influenced by the vitamin D supplementation. "This is an important study, and a well-done study, but the major question of whether vitamin D is important in breast cancer remains to be answered," says Norton. "These results don't close the door on vitamin D research on breast cancer."

The original version of this story misstated that breast cancer is the No. 1 cancer killer among women. In fact, lung cancer is the deadliest.

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