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Is Vitamin D a Wonder Pill?

May-June 2015


“In the case of religion, we put our faith in gods. And in nutrition, we have vitamins,” writes journalist Catherine Price in Vitamania, in which she traces vitamin crazes from the 1920s to the present. Today’s star is vitamin D, nicknamed “the sunshine nutrient” because ultraviolet-B radiation prompts the body to produce it. Long known to aid calcium absorption and play an essential role in bone health, it’s often added to dairy products. More recent studies, linking low levels of the nutrient to conditions ranging from multiple sclerosis to high blood pressure, led The New York Times to declare in 2010 that “Vitamin D promises to be the most talked-about and written-about supplement of the decade.”

Some of the excitement seems warranted: drawing on previous research into vitamin D’s immune and anti-inflammatory benefits, two new epidemiological studies by scientists at Dana-Farber Cancer Institute (DFCI) have found that it may also inhibit cancer. One study investigated the nutrient’s effect on colorectal cancer survival; the other examined its impact on colorectal cancer tumors and patient immune systems.

In the first study, the largest to date of metastatic colorectal cancer patients and vitamin D, researchers found that on average, those with the highest blood plasma levels of the vitamin saw a 35 percent decrease in their risk of dying, and lived 33 percent longer than those with the lowest levels: 32.6 months, versus 24.5 months. Previous studies had defined a consistent, strong association between high levels of the vitamin and lower colorectal cancer risk in healthy individuals, explains the lead author, DFCI oncologist and assistant professor of medicine Kimmie Ng, so she focused her research on whether vitamin D levels matter for patients who already have colon cancer. Even after controlling for different chemotherapy regimens, and for diet and lifestyle factors (people with high vitamin D levels also tend to be less obese and to exercise more, which can complicate studies), Ng and her colleagues found that higher levels of the vitamin were associated with significantly better survival. They are now pursuing randomized controlled trials with early-stage colon-cancer patients (collecting tumor tissue to understand the biological mechanisms behind this relationship), and with patients in the late stage of the disease (testing whether extra-high doses of vitamin D, in addition to chemotherapy, might improve survival and slow the advance of the disease).

They also found an association with delayed progression of the disease, Ng reports—which strongly suggests that vitamin D might have a direct effect on a tumor and its microenvironment, and might make chemotherapy more effective. One possible explanation is that, with “more vitamin D around, perhaps there would be less angiogenesis. Blood vessels wouldn’t form, tumors wouldn’t be able to feed themselves as much.” Other theories are that the nutrient prevents the inflammation that promotes cancer growth, or stimulates immunity against the tumor. “All of these pathways are active in the tumor microenvironment,” Ng explains, “and may affect how patients do.”

The second DFCI study, published in the journal Gut, probed that third possibility: that vitamin D boosts the immune system’s anti-cancer function, by means of immune cells such as lymphocytes. The senior author, professor of pathology Shuji Ogino, and his colleagues analyzed tumor tissue samples to see if vitamin D had a stronger effect on some types of cancer than on others; the results might give them a clearer sense of the nutrient’s influence in the body. The researchers determined that people with high levels of vitamin D reduced their risk for the kind of tumor permeated by immune cells; for cancers with fewer immune cells, vitamin D status seemed to have little effect. This difference implied that vitamin D affects the body’s ability to fight cancer via the immune system, thus bolstering the hypothesis that immune cells cooperate with the nutrient to promote a process called differentiation, in which the behavior of evolving tumor cells is altered.

These findings provide insight into the possible biological mechanism behind vitamin D’s benefits, but further study is needed to determine whether supplementing with vitamins heightens the protective effect. Health authorities have defined healthy vitamin D ranges according to levels known to promote bone health, but the optimal ranges for nonskeletal benefits are still unknown—prompting some experts to urge caution. “Clinical enthusiasm for supplemental vitamin D has outpaced available evidence on its effectiveness,” Bell professor of women’s health JoAnn Manson warned in an opinion paper published in the Journal of the American Medical Association last February. She has spearheaded a 26,000-person study, the Vitamin D and Omega-3 Trial (VITAL), designed to test whether those nutrients reduce the risk of cancer and cardiovascular events such as heart attacks and strokes; ancillary studies will analyze whether these supplements have an effect on diabetes, depression, and cognitive decline, among other health conditions.

Supplement sales and screening rates have soared in recent years, Manson notes, even though lab definitions of what constitutes a “normal” vitamin D range vary dramatically. “It’s been referred to as the wild, wild, West,” she says, adding that “widespread screening is feeding into megadose supplementation because clinicians are chasing a number.” When it comes to vitamins, she cautions, “It shouldn’t be assumed that more is automatically better.” Supplementation might be merely ineffective, but extremely large doses could be deleterious to health.

When results of Manson’s study are available in late 2017, medical professionals will have a better sense of whether recommended daily allowances should be revised upward. In the meantime, her paper characterized research and clinical practice as being “at a crossroads”: only when more light is shed on the sunshine nutrient will it be known whether the vitamin D craze rests on fact, or faith.

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