Vitamin D Nutrition and its Potential Health Benefits for Bone, Cancer and Other Conditions

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Abstract
Because humans evolved at equatorial latitudes, without modern clothing and shelter, their vitamin D supply would have been equivalent to at least 100 l g day2 1 (4000 units day2 1). Thus, the human genome was selected for under conditions where the circulating 25-hydroxyvitamin D (25(OH)D) concentration was greater than 100 nmol l2 1. This contrasts with modern humans in whom serum 25(OH)D is typically half that. This review poses the question of whether our genome was optimized for higher levels of vitamin D nutrition than are prevalent today. Many tissues possess 25(OH)D-1-hydroxylase and they can produce 1,25-dihydroxyvitamin D (1,25(OH)2D) for local, paracrine use. Furthermore, the activity of existing 1-hydroxylase depends upon the 25(OH)D concentration in a manner different from the substrate relationships for other hormone-producing systems. The functional, in vivo Km for 1,25(OH)2D production is higher than the concentration of substrate, 25(OH)D. That is, a doubling in 25(OH)D concentration will double the capacity for 1,25(OH)2D production in vivo. This applies not only to the kidney, but also to every tissue that possesses 1-hydroxylase. So far, there is little direct evidence for the health implications of this unique substrate relationship. The amounts of vitamin D that have been used in randomized clinical studies were small and do show some effect. Vitamin D supplementation with 20 l g day2 1 (800 IU day 2 1) is now recognized as preventing bone loss, reducing fracture risk, lowering blood pressure, and lowering circulating parathyroid hormone concentrations. However, the beneéts of a higher vitamin D supply are implicated by the circumstantial evidence of epidemiological studies that reèect differences in the sun exposure that produces vitamin D in skin. These potential beneéts of greater vitamin D nutrition include a reduction in the occurrence of breast, prostate, and bowel cancers and the autoimmune conditions of multiple sclerosis and insulin-dependent diabetes. Random- ized clinical trials into these conditions should focus on the higher, physiological doses of nutritional vitamin D whose consumption has recently been shown to be safe for adults. Unfortunately, the term 'vitamin D' is so commonly misapplied to analogs of its hormonal form that research and side-effects relating to those analogs can be misinterpreted as being somehow related to nutrition.