Re: Dietary Supplements and Cancer Prevention: Balancing Potential Benefits Against Proven Harms

Martínez et al. (1) recommended against vitamin D supplements for reducing the risk of cancer. However, the evidence that vitamin D reduces the risk of cancer is very strong despite reports to the contrary. There are several types of evidence: ecological, case–control, cohort, and randomized controlled trials. Each approach has its strengths and limitations. The strengths of the ecological approach include the large number of cases and the large number of data sets available for such studies. The limitations include assessing the role of confounding factors, but many cancer risk–modifying factors are included in most recent ecological studies. A recent review of ecological studies found strong support for solar ultraviolet-B in reducing the risk of 15 types of cancer, with weaker support for another nine types of cancer (2). No factor other than vitamin D production has been proposed to explain the link. Case–control studies have the strength of determining serum 25-hydroxyvitamin D [25(OH)D] concentrations near the time of cancer diagnosis. Although there is a concern that the disease state may affect serum 25(OH)D concentration, there does not seem to be evidence to support this concern. Case–control studies have found the strongest inverse associations between serum 25(OH)D concentration and breast and colorectal cancer incidence (3). Cohort studies are perceived to be the strongest observational approach. The advantage is that the risk-modifying factors are determined before disease outcome. However, a little-recognized disadvantage is that a single blood collection at the time of enrollment in the cohort study is used to determine serum 25(OH)D concentrations , and this value loses predictive ability with increasing follow-up time (3). A recent analysis of the regression coefficient for two serum 25(OH)D concentration measurements for a cohort as a function of interval found a decrease of −0.020/year for intervals ranging from 1 to 14 years (4). In cohort studies of breast and colorectal cancer, the relative risks increased toward unity at a rate of 0.03/year to 0.05/year (3), whereas the hazard ratios for all-cause mortality rate increased at a rate of 0.017/year (4). In addition, only cohort studies that find direct relationships between serum 25(OH) D concentration and cancer incidence rates, such as for pancreatic and prostate cancer, are mentioned in References 66 and 68 (1). Many randomized-controlled trials such as the Women's Health Initiative used only 400 IU/day vitamin D3. However, a rea-nalysis of the Women's Health Initiative restricted to women who had not taken …