Our Summary
There are two main forms of vitamin D available in supplements: vitamin D2 (ergocalciferol), which is derived from plants and fungi, and vitamin D3 (cholecalciferol), which is the form the human body produces naturally through sun exposure. Both are widely used in supplements and food fortification, and both have long been considered interchangeable by many clinicians and regulatory bodies. This 2012 systematic review and meta-analysis published in the American Journal of Clinical Nutrition by Tripkovic and colleagues set out to rigorously compare how effectively each form raises blood levels of 25-hydroxyvitamin D, the standard marker used to assess vitamin D status in the body. After analyzing the available studies, the review found that vitamin D3 was more effective than vitamin D2 at raising and maintaining total 25-hydroxyvitamin D levels overall, a finding that challenges the assumption that the two forms are equivalent. However, an important nuance emerged: the advantage of D3 was most pronounced in studies that used large, single or intermittent bolus doses of vitamin D, while at daily supplementation doses, the difference between D2 and D3 was less clear and not statistically definitive. The authors acknowledged high variability between the included studies and insufficient sample sizes to draw fully conclusive answers, calling for better-powered future research. Nonetheless, the overall weight of evidence pointed toward D3 as the superior form for raising vitamin D status, which has since influenced clinical preferences toward recommending D3 over D2 in supplementation protocols.
PMID: 22552031
PMCID: PMC3349454
Abstract
Background: Currently, there is a lack of clarity in the literature as to whether there is a definitive difference between the effects of vitamins D2 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International Standard Randomized Controlled Trials Number register, and clinicaltrials.gov were also searched for any unpublished trials.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 D3 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 D3 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.