The case against ergocalciferol (vitamin D2) as a vitamin supplement

Supplemental vitamin D is available in 2 distinct forms: ergocalciferol (vitamin D-2) and cholecalciferol (vitamin D-3). Pharmacopoeias have officially regarded these 2 forms as equivalent and interchangeable, yet this presumption of equivalence is based on studies of rickets prevention in infants conducted 70 y ago. The emergence of 25-hydroxyvitamin D as a measure of vitamin D status provides an objective, quantitative measure of the biological response to vitamin D administration. As a result, vitamin D-3 has proven to be the more potent form of vitamin D in all primate species, including humans. Despite an emerging body of evidence suggesting several plausible explanations for the greater bioefficacy of vitamin D-3, the form of vitamin D used in major preparations of prescriptions in North America is vitamin D-2. The case that vitamin D-2 should no longer be considered equivalent to vitamin D-3 is based on differences in their efficacy at raising serum 25-hydroxyvitamin D, diminished binding of vitamin D-2 metabolites to vitamin D binding protein in plasma, and a nonphysiologic metabolism and shorter shelf life of vitamin D-2. Vitamin D-2, or ergocalciferol, should not be regarded as a nutrient suitable for supplementation or fortification.