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(OH₂D]. 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)₂D 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.