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Vitamin D₂ Is Much Less Effective than Vitamin D₃ in Humans

Creighton University (L.A.G.A., R.P.H.), Omaha, Nebraska 68131; and Medical University of South Carolina (B.W.H.), Charleston, South Carolina 29425

Address all correspondence and requests for reprints to: Robert P. Heaney, M.D., Creighton University, 601 North 30th Street, Suite 4841, Omaha, Nebraska 68131. E-mail: rheaney{at}creighton.edu.

Vitamins D₂ and D₃ are generally considered to be equivalent in humans. Nevertheless, physicians commonly report equivocal responses to seemingly large doses of the only high-dose calciferol (vitamin D₂) available in the U.S. market.

The relative potencies of vitamins D₂ and D₃ were evaluated by administering single doses of 50,000 IU of the respective calciferols to 20 healthy male volunteers, following the time course of serum vitamin D and 25-hydroxyvitamin D (25OHD) over a period of 28 d and measuring the area under the curve of the rise in 25OHD above baseline.

The two calciferols produced similar rises in serum concentration of the administered vitamin, indicating equivalent absorption. Both produced similar initial rises in serum 25OHD over the first 3 d, but 25OHD continued to rise in the D₃-treated subjects, peaking at 14 d, whereas serum 25OHD fell rapidly in the D₂-treated subjects and was not different from baseline at 14 d. Area under the curve (AUC) to d 28 was 60.2 ng·d/ml (150.5 nmol·d/liter) for vitamin D₂ and 204.7 (511.8) for vitamin D₃ (P < 0.002). Calculated AUC indicated an even greater differential, with the relative potencies for D₃:D₂ being 9.5:1.

Vitamin D₂ potency is less than one third that of vitamin D₃. Physicians resorting to use of vitamin D₂ should be aware of its markedly lower potency and shorter duration of action relative to vitamin D₃.

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