Vitamin D Supplementation, 25-hydroxyvitamin D Concentrations, and Safety

Am J Clin Nutr. 1999 May;69(5):842-56. doi: 10.1093/ajcn/69.5.842.

Abstract

For adults, the 5-microg (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 microg (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 microg (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 microg (10000 IU) vitamin D/d. To ensure that serum 25(OH)D concentrations exceed 100 nmol/L, a total vitamin D supply of 100 microg (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 microg (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 > or = 1000 microg (40000 IU)/d. Because vitamin D is potentially toxic, intake of >25 microg (1000 IU)/d has been avoided even though the weight of evidence shows that the currently accepted, no observed adverse effect limit of 50 microg (2000 IU)/d is too low by at least 5-fold.

Publication types

  • Review

MeSH terms

  • Age Factors
  • Dietary Supplements*
  • Dose-Response Relationship, Drug
  • Humans
  • Hyperparathyroidism / etiology
  • No-Observed-Adverse-Effect Level
  • Nutritional Physiological Phenomena*
  • Nutritional Requirements
  • Osteomalacia / prevention & control
  • Sunlight
  • Vitamin D / administration & dosage*
  • Vitamin D / adverse effects
  • Vitamin D / analogs & derivatives*
  • Vitamin D / blood
  • Vitamin D / standards*

Substances

  • Vitamin D
  • 25-hydroxyvitamin D