Comparison of vitamin D2 and vitamin D3 supplementation in raising serum 25-hydroxyvitamin D status: a systematic review and meta-analysis

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International Standard Randomized Controlled Trials Number register, and clinicaltrials.gov were also searched for any unpublished trials.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.

FIGURE 1.

QUOROM statement flow diagram (29) indicating numbers of articles reviewed and later excluded or included for the systematic review and meta-analysis. QUOROM, Quality of Reporting of Meta-analyses.

FIGURE 2.

Random-effects meta-analysis comparing the effects of daily and bolus supplementation of D3 with that of D2 on net changes in serum 25(OH)D concentrations. The forest plot indicates that the absolute change in 25(OH)D from baseline favored the D3 intervention. In the figure, “Δ25(OH)D” denotes the change in serum 25(OH)D concentrations from baseline (net change), squares denote mean differences [with 95% CIs (lines)], and “Total” denotes the cumulative n from all included studies. With the use of a random-effects model, overall, there was a significantly greater effect in the raising of serum 25(OH)D concentrations over time for D3 supplementation than for D2 supplementation (mean difference: 15.23; 95% CI: 6.12, 24.34; P = 0.001). D2, vitamin D₂; D3, vitamin D₃; IV, inverse variance; 25(OH)D, 25-hydroxyvitamin D.

FIGURE 3.

Random-effects meta-analysis comparing the effects of bolus supplementation of D3 with that of D2 on net changes in serum 25(OH)D concentrations. The forest plot indicates that the absolute change in 25(OH)D from baseline favored the D3 intervention when administered as a bolus dose. In the figure, “Δ25(OH)D” denotes the change in serum 25(OH)D concentrations from baseline (net change), squares denote mean differences [with 95% CIs (lines)], and “Total” denotes the cumulative n from all included studies. With the use of a random-effects model, overall, there was a significantly greater effect in the raising of serum 25(OH)D concentrations over time for D3 supplementation as a bolus dosage (single and multiple bolus) than for D2 supplementation (mean difference: 34.10; 95% CI: 16.38, 51.83; P = 0.0002). D2, vitamin D₂; D3, vitamin D₃; IV, inverse variance; 25(OH)D, 25-hydroxyvitamin D.

FIGURE 4.

Random-effects meta-analysis comparing the effects of daily supplementation of D3 with that of D2 on net changes in serum 25(OH)D concentrations. The forest plot indicates that the absolute change in 25(OH)D from baseline favored the D3 intervention as a daily supplement. “Δ25(OH)D” denotes the change in serum 25(OH)D concentrations from baseline (net change), squares denote mean differences [with 95% CIs (lines)], and “Total” denotes the cumulative n from all included studies. With the use of a random-effects model, overall, there was no significant difference between D2 and D3 interventions in the raising of serum 25(OH)D concentrations when taken as a daily supplement (mean difference: 4.83; 95% CI: −0.98, 10.64; P = 0.10). D2, vitamin D₂; D3, vitamin D₃; IV, inverse variance; 25(OH)D, 25-hydroxyvitamin D.