NEJM: followup on vitamin D

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Vitamin D and Prevention of Cancer - Ready for Prime Time?

JoAnn E. Manson, M.D., Dr.P.H., T. Mayne, Ph.D., and K.

Clinton, M.D., Ph.D.

N Engl J Med 2011; 364:1385-1387April 14, 2011

Snips:

" The theory that vitamin D can help prevent cancer is biologically

plausible. The vitamin D receptor is expressed in most tissues. Studies in

cell culture and experimental models suggest that calcitriol promotes cell

differentiation, inhibits cancer-cell proliferation, and exhibits

antiinflammatory, proapoptotic, and antiangiogenic properties. "

" The committee's comprehensive review of the evidence regarding vitamin D's

role in preventing cancer, however, revealed that the research is

inconsistent and doesn't establish a cause-effect relationship.

Other recent reviews have reached similar conclusions.2,3

No large-scale randomized clinical trial of vitamin D has been completed

with cancer as the primary prespecified outcome.

Most evidence is derived from laboratory studies, ecologic correlations, and

observational investigations of serum 25-hydroxyvitamin D levels in

association with cancer outcomes.

Although this serum measure is a useful marker of current vitamin D

exposure, associational studies have important limitations. Specifically,

low serum 25-hydroxyvitamin D levels are also linked with confounding

factors related to higher cancer risk, including

-obesity (vitamin D becomes sequestered in adipose tissue),

-lack of physical activity (correlated with less time outdoors and less

solar exposure),

-dark skin pigmentation (less skin synthesis of vitamin D in response to

sun), and

-diet or supplementation practices.

Reverse-causation bias may also occur if poor health reduces participation

in outdoor activities and sun exposure or adversely affects diet, resulting

in lower vitamin D levels.

Association therefore cannot prove causation.

Many micronutrients that seemed promising in observational studies (e.g.,

beta carotene, vitamins C and E, folic acid, and selenium) were not found to

reduce cancer risk in randomized clinical trials, and some were found to

cause harm at high doses.4 "

" despite biologic plausibility and widespread enthusiasm, the IOM committee

found that the evidence that vitamin D reduces cancer incidence and related

mortality was inconsistent and inconclusive as to causality. New trials

assessing moderate-to-high-dose vitamin D supplementation for cancer

prevention are in progress and should provide additional information within

5 to 6 years. Although future research may demonstrate clear benefits of

vitamin D related to cancer and other nonskeletal health outcomes, and

possibly support higher intake requirements, the existing evidence falls

short. "

http://www.nejm.org/doi/full/10.1056/NEJMp1102022 (requires subscription)

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