Nature 325, 62 - 65 (01 January 1987); doi:10.1038/325062a0

A new mechanism for induced vitamin D deficiency in calcium deprivation

M. R.  Clements^*, L. Johnson & D. R. Fraser

Dunn Nutritional Laboratory, University of Cambridge and Medical Research Council, Milton Road, Cambridge CB4 1XJ, UK
^* Present address: University Department of Medicine, Royal Infirmary, Manchester M13 9WL, UK.

Synthesis of vitamin D in the skin in response to ultraviolet light is the main determinant of vitamin D status in man¹ and it is therefore surprising that rickets and osteomalacia, clinical signs of vitamin D deficiency, remain common in tropical and subtropical countries². Skin pigmentation can reduce vitamin D formation³ but this is a negligible limitation in people exposed to abundant ultraviolet light^4,5. Earlier studies in animals⁶ and man⁷ suggested that another environmental factor, the low calcium/high cereal diet typical of susceptible populations², might affect the efficiency of vitamin D utilization. We show here in rats that the rate of inactivation of vitamin D in the liver is increased by calcium deprivation. The effect is mediated by 1,25-dihydroxyvitamin D, produced in response to secondary hyperparathyroidism^8,9, which promotes hepatic conversion of vitamin D to polar inactivation products that are excreted in bile. This finding has widespread implications both for understanding the pathogenesis of endemic rickets and in that it provides a unifying mechanism for the development of vitamin D deficiency in many clinical disorders.

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