Vitamin D and cancer mini-symposium: the risk of additional vitamin D

Ann Epidemiol. 2009 Jul;19(7):441-5. doi: 10.1016/j.annepidem.2009.01.009. Epub 2009 Apr 11.


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 10,000 IU vitamin D(3) per day, with the plasma 25-hydroxyvitamin D (25(OH)D) concentration potentially reaching 220 nmol/L (88 ng/mL). The incremental consumption of 40 IU/d of vitamin D(3) 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 10,000 IU/d of vitamin D(3) poses no risk of adverse effects for adults, even if this is added to a rather high physiologic background level of vitamin D.

Publication types

  • Review

MeSH terms

  • Adult
  • Congresses as Topic
  • Contraindications
  • Humans
  • Hypercalcemia / chemically induced*
  • Neoplasms / etiology*
  • Risk Assessment
  • Vitamin D / administration & dosage
  • Vitamin D / adverse effects*
  • Vitamin D / analogs & derivatives*
  • Vitamin D / blood
  • Vitamin D / pharmacology
  • Vitamin D-Binding Protein / metabolism
  • Vitamins / administration & dosage
  • Vitamins / pharmacology


  • Vitamin D-Binding Protein
  • Vitamins
  • Vitamin D
  • 25-hydroxyvitamin D