The vitamin D and cancer conundrum: aiming at a moving target.

The case for the influence of vitamin D on health, including cancer prevention, is increasingly compelling. While some are calling for increases in the Tolerable Upper Intake Level, fortification, and dietary supplementation, questions regarding dose and individual response variability continue to merit attention. Colorectal cancer risk reduction with adequate vitamin D status is well documented. Protection has also been observed for cancer at all sites, skin, prostate, and breast. At the same time, some individuals may be adversely affected by elevated 25(OH)D concentrations with respect to risk of cancers of the prostate, breast, pancreas, and esophagus, and in some cases a U- or J-shaped association has been suggested. Future research should seek to clarify if and for whom there may be an increased risk for cancer at particular sites with high 25(OH)D concentrations, and the concentrations at which risk increases. Fundamentally, prospective longitudinal studies of these relationships are warranted. The health status, life stage, adiposity, estrogen exposure, and nutritional status of study participants should be taken into account. Continued investigation is necessary to ensure that vitamin D recommendations are appropriately targeted to individuals who stand to benefit most, while protecting vulnerable subgroups from risk of overexposure.