Vitamin D and Cancer Mini-Symposium: The Risk of Additional Vitamin D

Any benefit of vitamin D needs to be balanced against the risk of toxicity, which is characterized by hypercalcemia. Daily brief, suberythemal exposure of a substantial area of the skin to ultraviolet light, climate allowing, provides adults with a safe, physiologic amount of vitamin D, equivalent to an oral intake of about 10,000IU vitamin D₃ per day, with the plasma 25-hydroxyvitamin D (25(OH)D) concentration potentially reaching 220 nmol/L (88 ng/mL). The incremental consumption of 40IU/d of vitamin D₃ raises plasma 25(OH)D by about 1 nmol/L (0.4 ng/mL). High doses of vitamin D may cause hypercalcemia once the 25(OH)D concentration is well above the top of the physiologic range. The physiological buffer for vitamin D safety is the capacity of plasma vitamin D–binding protein to bind the total of circulating 25(OH)D, vitamin D, and 1,25-dihydroxyvitamin D [1,25(OH)2D]. Hypercalcemia occurs when the free concentration is inappropriately high because vitamin D and its other metabolites have displaced 1,25(OH)2D from vitamin D–binding protein. Evidence from clinical trials shows, with a wide margin of confidence, that a prolonged intake of 10,000IU/d of vitamin D₃ poses no risk of adverse effects for adults, even if this is added to a rather high physiologic background level of vitamin D.

Key Words: Vitamin D, Dosage, Risk Assessment, Calcidiol, Calcitriol, Toxicity, Adverse Effects, Vitamin D–Binding Protein, Hypercalcemia