Vitamin D₂Is Much Less Effective than Vitamin D₃in Humans

TLDR

Vitamins D₂ and D₃ are often regarded as equivalent, yet clinicians report inconsistent responses to high‑dose D₂. In a crossover study, 20 healthy men received single 50,000‑IU doses of D₂ or D₃, with serum vitamin D, 25‑hydroxyvitamin D, and area‑under‑the‑curve values tracked over 28 days. D₂ and D₃ showed similar absorption and initial 25‑hydroxyvitamin D rises, but D₃ maintained higher levels, yielding an AUC 3.4‑fold greater and a potency ratio of ~9.5:1, indicating D₂ is less than one‑third as potent and has a shorter duration of action.

Abstract

Vitamins D(2) and D(3) 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 D(2)) available in the U.S. market. The relative potencies of vitamins D(2) and D(3) 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 D(3)-treated subjects, peaking at 14 d, whereas serum 25OHD fell rapidly in the D(2)-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 D(2) and 204.7 (511.8) for vitamin D(3) (P < 0.002). Calculated AUC(infinity) indicated an even greater differential, with the relative potencies for D(3):D(2) being 9.5:1. Vitamin D(2) potency is less than one third that of vitamin D(3). Physicians resorting to use of vitamin D(2) should be aware of its markedly lower potency and shorter duration of action relative to vitamin D(3).