Perspective: Vitamin D Deficiency Relationship to Initiation of Diseases.

Vitamin D is converted to a steroid hormone by 25-hydroxylation in the liver and then by 1-hydroxylation in the kidney to produce the circulating hormone 1,25-dihydroxy vitamin D [1,25(OHD]. This hormone then functions in cells of the intestinal mucosa and in bone to maintain whole-body calcium homeostasis. Classical vitamin D deficiency thus results in defective calcium homeostasis. Yet vitamin D deficiency is often reported in people with various diseases not associated with whole-body calcium homeostasis. Because of these associations with vitamin D deficiency, clinical trials have been undertaken to determine whether raising vitamin D status could be an effective treatment for such diseases. However, the results of such clinical trials have largely been inconclusive. The steroidal autocrine or paracrine role of locally produced 1,25(OH)D in many nonrenal cells throughout the body is protective against a range of pathological changes. In vitamin D deficiency such protection becomes defective. A disease process may thus be initiated, and then progress, while vitamin D status is inadequate, as in the months of winter in temperate regions of the world. The subsequent correction of vitamin D deficiency may no longer be able to protect patients when the disease process has already become established. To maintain the many protective roles of vitamin D against disease, it is important that public health strategies aim to maintain adequate vitamin D status throughout the year.