Comparison of vitamin D₂and vitamin D₃ supplementation in raising serum 25-hydroxyvitamin D status: A systematic review and meta-analysis

Background: Currently, there is a lack of clarity in the literature as to whether there is a definitive difference between the effects of vitamins D ₂ and D₃ in the raising of serum 25-hydroxyvitamin D [25(OH)D]. Objective: The objective of this article was to report a systematic review and meta-analysis of randomized controlled trials (RCTs) that have directly compared the effects of vitamin D₂ and vitamin D₃ on serum 25(OH)D concentrations in humans. Design: The ISI Web of Knowledge (January 1966 to July 2011) database was searched electronically for all relevant studies in adults that directly compared vitamin D₃ with vitamin D₂. The Cochrane Clinical Trials Registry, International Standard Randomized Controlled Trials Number register, and clinicaltrials.gov were also searched for any unpublished trials. Results: A meta-analysis of RCTs indicated that supplementation with vitamin D₃ had a significant and positive effect in the raising of serum 25(OH)D concentrations compared with the effect of vitamin D₂ (P = 0.001). When the frequency of dosage administration was compared, there was a significant response for vitamin D ₃ when given as a bolus dose (P = 0.0002) compared with administration of vitamin D₂, but the effect was lost with daily supplementation. Conclusions: This meta-analysis indicates that vitamin D ₃ is more efficacious at raising serum 25(OH)D concentrations than is vitamin D₂, and thus vitamin D₃ could potentially become the preferred choice for supplementation. However, additional research is required to examine the metabolic pathways involved in oral and intramuscular administration of vitamin D and the effects across age, sex, and ethnicity, which this review was unable to verify.