Vitamin D3 “could potentially become the preferred choice for supplementation,” the authors conclude in a paper online May 2 in the American Journal of Clinical Nutrition.
However, they say additional research is needed to examine the metabolic pathways involved in oral and intramuscular administration of vitamin D and the effects across age, sex, and ethnicity, which their review was unable to verify.
First author Laura Tripkovic, from the Department of Nutrition and Metabolism, University of Surrey, Guildford, the United Kingdom and colleagues say there is a “widespread perception” that both vitamins D2 and D3 are equally efficacious in raising serum 25(OH)D levels, when, in fact, there is a “lack of clarity” in the literature on this issue.
They performed a comprehensive literature search for relevant studies in adults that directly compared vitamin D2 with vitamin D3, eventually selecting 10 studies (1016 subjects total) for review, seven of which were included in their meta-analysis.
In these studies, vitamins D2 and D3 were used in varying dosages and treatment time periods. One study used a single bolus orally of 50,000 IU; one study used a single large bolus of vitamin D2 or D3 (300,000 IU) and compared intramuscular with oral administration. Six studies tested daily oral supplementation strategies by using dosages between 1000 and 4000 IU. One study chose a weekly intervention of 50,000 IU, and another study chose a daily compared with monthly intervention by using 1600 and 50,000 IU, respectively. The final study compared a single intramuscular injection of 300,000 IU of vitamin D2 compared with a single oral dose of 300,000 IU of vitamin D3.
Treatment follow-up times varied from 28 days to 24 weeks for the bolus-intervention studies, whereas the daily and weekly study designs had intervention periods that ranged from 14 days to 12 months. The researchers say a “concern for all studies” was the lack of consensus in the analysis of serum 25(OH)D concentrations.
With these caveats in mind, the researchers report that vitamin D3 supplementation produced a significantly greater absolute increase from baseline of serum 25(OH)D in eight studies, no matter what the dose, frequency or route of administration. Two studies found vitamin D2 and D3 equally efficacious.
Likewise, in the seven-study meta-analysis, vitamin D3 supplementation had a significantly greater effect in raising serum 25(OH)D concentrations over time compared with vitamin D2 supplementation, with a weighted mean difference of 15.23 (p=0.001).
“When the frequency of dosage administration was compared, there was a significant response for vitamin D3 when given as a bolus dose (p=0.0002) compared with administration of vitamin D2, but the effect was lost with daily supplementation,” the authors report.
Nevertheless, they say “regardless of whether supplementation with vitamin D was in small daily doses or in larger and more infrequent bolus dosages, the favoring toward cholecalciferol was still evident.”
Based on their findings, the authors say “it is clear that there are stark differences in the metabolic fates of ergocalciferol and cholecalciferol that should not be ignored. When the evidence from the studies that focused on vitamin D metabolism at the cellular level is compared with the evidence from clinical trials, it is clear that, overall, there was consistency in the results that shows cholecalciferol appears to have advantageous biological qualities that allow it to sustain its systemic influences for far longer and at far greater concentrations than does ergocalciferol.”
Limitations of the analysis include the small number of studies available for review and the “high” heterogeneity between studies. The investigators also point out that all studies used doses of ergocalciferol and cholecalciferol “far above” the amount currently recommended daily allowance of 600 IU for males and females aged 1 to 70 years. These factors “limit the ability to extrapolate the outcomes of this review toward realistic public health recommendations when referring to ergocalciferol and cholecalciferol supplementation,” the authors say.