Vitamin D toxicity, policy, and science.

The serum 25-hydroxyvitamin D [25(OH)D] concentration that is the threshold for vitamin D toxicity has not been established. Hypercalcemia is the hazard criterion for vitamin D. Past policy of the Institute of Medicine has set the tolerable upper intake level (UL) for vitamin D at 50 mug (2000 IU)/d, defining this as "the highest level of daily nutrient intake that is likely to pose no risks of adverse health effects to almost all individuals in the general population." However, because sunshine can provide an adult with vitamin D in an amount equivalent to daily oral consumption of 250 mug (10,000 IU)/d, this is intuitively a safe dose. The incremental consumption of 1 mug (40 IU)/day of vitamin D(3) raises serum 25(OH)D by approximately 1 nM (0.4 ng/ml). Therefore, if sun-deprived adults are to maintain serum 25(OH)D concentrations >75 nM (30 ng/ml), they will require an intake of more than the UL for vitamin D. The mechanisms that limit vitamin D safety are the capacity of circulating vitamin D-binding protein and the ability to suppress 25(OH)D-1-alpha-hydroxylase. Vitamin D causes hypercalcemia when the "free" concentration of 1,25-dihydroxyvitamin D is inappropriately high. This displacement of 1,25(OH)(2)D becomes excessive as plasma 25(OH)D concentrations become higher than at least 600 nM (240 ng/ml). Plasma concentrations of unmetabolized vitamin D during the first days after an acute, large dose of vitamin D can reach the micromolar range and cause acute symptoms. The clinical trial evidence shows that a prolonged intake of 250 mug (10,000 IU)/d of vitamin D(3) is likely to pose no risk of adverse effects in almost all individuals in the general population; this meets the criteria for a tolerable upper intake level.