Moderate doses of vitamin D2 as effective as D3 in maintaining serum 25-hyd
Holick MF, Biancuzzo RM, Chen TC, et al. Vitamin D2 is as effective as vitamin D3 in maintaining circulating concentrations of 25-hydroxyvitamin D. J Clin Endocrinol Metab 2008;93:677-681.

A daily dose of 1,000 IU vitamin D₂ is as effective as 1,000 IU vitamin D₃ in maintaining levels of serum 25-hydroxyvitamin D (25[OH]D), found this randomized, double-blind, placebo-controlled study conducted in 68 healthy US adults, aged 18 to 84 years, for 11 weeks at the end of winter. Participants received, in one capsule daily, either placebo, 1,000 IU vitamin D₂ (ergocalciferol), 1,000 IU vitamin D₃ (cholecalciferol), or 500 IU vitamin D₂ plus 500 IU vitamin D₃. The purpose of the study was to evaluate in healthy adults the effect of these supplements on the circulating levels of 25(OH)D, 25(OH)D₂, and 25(OH)D₃.

Participants gradually increased circulating levels of 25(OH)D to the same extent: vitamin D₂—baseline 16.9 ± 10.5 ng/mL, 11 weeks 26.8 ± 9.6 mg/mL; vitamin D₃—baseline 19.6 ± 11.1 ng/mL, 11 weeks 28.9 ± 11.0 ng/mL; combination D₂/D₃ group—baseline 20.2 ± 10.4 ng/mL, 11 weeks 28.4 ± 7.7 ng/mL. In addition, 25(OH)D₃ levels did not change in those participants who received 1,000 IU vitamin D₂. The results contrast with those of recent studies that suggested vitamin D₂ in high doses is less effective than D₃ in maintaining circulating levels of 25(OH)D, or that it even enhances degradation of 25(OH)D₃, the paper states. Notably, 60% of participants were vitamin D deficient at the start of the study; however, supplementation did not raise any of the participants' 25(OH)D levels above 30 ng/mL, suggesting that more than 1,000 IU vitamin D is necessary to maintain sufficient serum levels when the sun provides no vitamin D, the authors conclude.

This paper is an important addition to our current knowledge of the relative effectiveness of vitamin D₂ versus vitamin D₃. Prior studies have indicated that vitamin D₃ is more effective than vitamin D₂ in maintaining serum 25(OH)D levels. In one study by Armas et al, a single dose of 50,000 IU of D₂ versus 10 tablets of 5,000 IU of D₃ were given to 30 males aged 33 years and the subjects were followed for 28 days. The conclusion was that vitamin D₂ potency was less than one third that of vitamin D₃ based on the 28 day area under the curve. In another study by Trang et al, 24 men and 48 women (mean age, 38 y) were given 4,000 IU vitamin D₂ (n = 17) or 4,000 IU of vitamin D₃ (n = 55) (both dissolved in ethanol) daily for 14 days. The authors concluded that, on a per mole basis, vitamin D₃ was 1.7 times more effective in maintaining serum 25(OH)D than vitamin D₂ at 14 days.

This new study by Holick et al was well designed, methodologically sound, and clearly raises questions regarding the relative effectiveness of vitamin D₂ versus vitamin D₃. The discrepant findings could have several potential explanations, including different formulations of the vitamin D compounds and the medium used (lactose vs ethanol), different doses, a single versus daily, and different lengths of follow-up (2, 4, or 11 weeks).

In each of the three studies, the endpoint of serum 25(OH)D was also determined differently. In the Holick study, serum 25(OH)D₂ and 25(OH)D₃ were determined by liquid chromatography tandem mass spectroscopy. In the Trang study, serum 25(OH)D was determined by using the Incstar radioimmunoassay (RIA) kit. And, in the Armas study, serum 25(OH)D₂ and 25(OH)D₃ were determined by reverse-phase high performance liquid chromatography and serum 25(OH)D was measured by RIA using both the Nichols and Diasorin kits. This further highlights the need for standardization of methods of testing serum 25(OH)D.

At this point, we need to consider all the findings and reevaluate whether we can clearly state which vitamin D compound would be ideal. It is not clear that one form of vitamin D is better at maintaining serum 25(OH)D levels than another. In addition, more research is needed to clarify the relative potency of these compounds at the cellular or postreceptor level.

Another important message here is that supplementation with 1,000 IU daily of either D₂ or D₃ is not enough to bring population serum levels above 30 ng/mL. Much of the US population has suboptimal levels of serum 25(OH)D—even individuals getting the current recommended amount of vitamin D. Given all the potential health benefits of higher serum 25(OH)D levels, we need to work toward increasing recommendations of vitamin D intake, clarifying whether vitamin D₃ or vitamin D₂ are equivalent in potency, and standardizing laboratory measurements of serum 25(OH)D.

From the NAMS First to Know e-newsletter released March 25, 2008

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