A critical analysis of the (near) legendary status of vitamin D.

Labels such as food constituent, nutrient and supplement do not convey a sense of being essential. Yet these rather mundane descriptors, even if correct, belie the true significance of vitamin D. Long believed to be merely a functioning cofactor akin to vitamin C, deficiency of this secosteroid hormone is clearly associated with morbid complications of calcium and bone mineral metabolism, and because the hormonal effects are mediated by nuclear receptors that regulate the expression of many subordinate genes, the vitamin's pleiotropic mode of action can influence numerous metabolic pathways and, possibly, a number of different diseases. Although the vitamin is under intensive investigation, much still remains unknown, even in bone health, as the identity of osteoporosis susceptibility genes remains uncertain. This article focuses on various aspects of the basic science and molecular biology of the vitamin D endocrine system. The primary goal is to critically examine the evidence supporting its role in bone metabolism, diabetes and cancer.