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Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety^1,2

For adults, the 5-µg (200 IU) vitamin D recommended dietary allowance may prevent osteomalacia in the absence of sunlight, but more is needed to help prevent osteoporosis and secondary hyperparathyroidism. Other benefits of vitamin D supplementation are implicated epidemiologically: prevention of some cancers, osteoarthritis progression, multiple sclerosis, and hypertension. Total-body sun exposure easily provides the equivalent of 250 µg (10000 IU) vitamin D/d, suggesting that this is a physiologic limit. Sailors in US submarines are deprived of environmentally acquired vitamin D equivalent to 20–50 µg (800–2000 IU)/d. The assembled data from many vitamin D supplementation studies reveal a curve for vitamin D dose versus serum 25-hydroxyvitamin D [25(OH)D] response that is surprisingly flat up to 250 µg (10000 IU) vitamin D/d. To ensure that serum 25(OH)D concentrations exceed 100 nmol/L, a total vitamin D supply of 100 µg (4000 IU)/d is required. Except in those with conditions causing hypersensitivity, there is no evidence of adverse effects with serum 25(OH)D concentrations <140 nmol/L, which require a total vitamin D supply of 250 µg (10000 IU)/d to attain. Published cases of vitamin D toxicity with hypercalcemia, for which the 25(OH)D concentration and vitamin D dose are known, all involve intake of 1000 µg (40000 IU)/d. Because vitamin D is potentially toxic, intake of >25 µg (1000 IU)/d has been avoided even though the weight of evidence shows that the currently accepted, no observed adverse effect limit of 50 µg (2000 IU)/d is too low by at least 5-fold.

Key Words: Calciferol • calcidiol • cholecalciferol • calcitriol • vitamin D • 25-hydroxyvitamin D • 1,25-dihydroxyvitamin D • toxicity • safety • nutrition • environment • ultraviolet light • hyperparathyroidism • osteoporosis • osteomalacia • daily reference intake • 25(OH)D • 1,25(OH)₂D • no observed adverse effect level • NOAEL • LOAEL • lowest observed adverse effect level

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				D. Rucker, J. A. Allan, G. H. Fick, and D. A. Hanley Vitamin D insufficiency in a population of healthy western Canadians Can. Med. Assoc. J., June 1, 2002; 166(12): 1517 - 1524. [Abstract] [Full Text] [PDF]

				R. Vieth and D. Fraser Vitamin D insufficiency: no recommended dietary allowance exists for this nutrient Can. Med. Assoc. J., June 1, 2002; 166(12): 1541 - 1542. [Full Text] [PDF]