Physiological significance of vitamin D produced in skin compared with oral vitamin D

Abstract

Since the discovery of vitamin D, it has been accepted that its physiological supply is either from food or by endogenous synthesis in skin exposed to solar UV light. Yet vitamin D is a component of very few foods and its supply as a natural nutrient is unable to maintain good vitamin D status for human populations. One aspect of vitamin D physiology that has been ignored is that the mechanisms for its transport and processing from these two sources are quite different. Excess intake of vitamin D causes hypercalcaemic toxicity. However, experiments with different animal species have shown that long-term supply of oral vitamin D in apparently non-toxic amounts causes atherosclerosis in large arteries. A mechanism for this toxicity is proposed. Alternative strategies for addressing widespread vitamin D deficiency by food fortification should be considered in light of the angiotoxicity caused by oral vitamin D in animal experiments.

Keywords: 25(OH)D, 25-hydroxy vitamin D; 25-hydroxyvitamin D production; 25-hydroxyvitamin D toxicity; 7-DHC, 7-dehydrocholesterol; Angiotoxicity; DBP, vitamin D-specific-binding protein; Vitamin D transport.

Fig. 1.

Pig aortic endothelial cells grown in culture: (a) control cells and (b) cells exposed for 24 h to 300 nm 25(OH)D₃. Reproduced from Levene and Lawson⁽³¹⁾.

Fig. 2.

Aortic lesions in squirrel monkeys given daily oral doses of vitamin D. Adult squirrel monkeys weighing 750–1000 g were given daily oral doses of 12·5 μg vitamin D₃ for 10–18 months with diets containing 0·5 % cholesterol. Histological sections of the aorta of these animals showed (a) intimal thickening with proliferation of myointimal cells and (b) atheromatous plaques. No aortic lesions were reported in animals on control diets containing 0·5 % cholesterol and providing 2·5 μg vitamin D₃ per day. Reproduced with permission from Peng et al. ⁽³²⁾.