VITAMINS

The biochemical, nutritional chemical and comparative biochemical studies on vitamin D were performed and the following results have been obtained. 1. Physiological activities of two kinds of novel vitamin D_3 derivatives, 22-oxa-1α,25(OH)_2D_3(OCT) and 2β-(3-hydroxy-propoxy)-1α,25(OH)_2D_3 (ED-71) have been studied. OCT, which has less calcemic and stronger cell differentiation activities than 1α,25(OH)_2D_3 was clarified to have the properties of weak binding affinity for vitamin D binding protein (DBP), rapid turn-over in the body and rapid excretion into bile. On the other hand, ED-71, which has stronger effects on intestinal calcium absorption and longer bone turn-over than 1α,25(OH)_2D_3 was clarified to have the properties of stronger binding affinity for DBP and longer half-life in blood than 1α,25(OH)_2D_3. 2. Assay of vitamin D in various kinds of Japanese foods revealed that fish generally contained high levels of vitamin D. 3. Assay of vitamin D and its metabolites in milk revealed that neither mother milk nor cow's milk contained enough amounts of vitamin D and its derivatives. 4. The origin of extremely high contents of vitamin D_3 in fish liver was confirmed to be a result of food chains originated from plankton. 5. The existence of 25-OH-D_3-1α-hydroxylase in the liver of fish was found. 6. Comparative studies on vitamin D metabolism in the liver and kidney of vertebrates (fish, amphibians, reptile and mammals) and fetal and mature rats support the thesis that ontogeny is a recapitulation of phylogeny.

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Alfacalcidol(1α-OH-D_3) is the prodrug of calcitriol(1α,25(OH)_2D_3), the active form of vitamin D. Sixteen years have passed since 1981 when alfacalcidol was first marketed as a therapeutic agent for bone disease associated with vitamin D metabolic disorders. In 1983, its indications were extended to include the treatment of osteoporosis. During this time, the usefulness of the active form of vitamin D for osteoporosis became accepted among Japanese clinicians, but internationally, researchers remained divided in their views. The positive outcome of the discussions that ensured regarding this issue is reflected directly in the consensus reports compiled at the symposia of 1993 and 1996 in Hong Kong and Amsterdam, respectively. Osteoporotic patients have intestinal calcium malabsorption and renal vitamin D activation dysfunction. Adequate results cannot be expected from the administration of nutritional supply of vitamin D (400-800 I.U.) or high doses of calcium agents. To bring about recovery of physiological function in such patients and maintain bone in normal condition, therefore, it is necessary to administer the active form of vitamin D. The consensus report of 1996 recognized that active vitamin D products are effective under vitamin D replete conditions and in Caucasians. In this review, we introduced the history of the debate surrounding the efficacy of the active form of vitamin D in osteoporosis, as well as the thinking behind the different views. Moreover, we explained how active vitamin D agents compare with the many other agents available for osteoporosis and proposed that their administration should become a basic therapeutic modality for osteoporotic patients.

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