Effect of Vitamin D2 Supplementation on 25-Hydroxyvitamin D3 Status: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract:

Context: Researchers have identified differences in metabolic activity between vitamins D2 and D3. Moreover, it is suspected from randomized controlled trial data that vitamin D2 supplementation increases the metabolic clearance of 25-hydroxyvitamin D3 [25(OH)D3], but this effect has yet to be quantified.

Objective: This study sought to undertake a systematic review and meta-analysis of the effect of vitamin D2 supplementation on serum 25(OH)D3 concentrations.

Data sources: PUBMED was searched for articles published from January 1, 1975, to February 1, 2023. Of the 202 articles retrieved, 20 were included in this review, and of those, 11 were suitable for meta-analysis.

Data extraction: Randomized controlled trials reporting either baseline and postintervention serum 25(OH)D3 concentrations (nmol/L) or absolute changes in concentrations were included. Random-effects meta-analyses were calculated using Review Manager (version 5.3; The Cochrane Collaboration). Mean differences were reported with 95% CIs.

Data analysis: In meta-analyses there was a reduction in serum 25(OH)D3 after vitamin D2 supplementation compared with control for end-of-trial between-groups data (random weighted mean difference [WMD] = -17.99 nmol/L; 95% CI, -25.86 to -10.12; P < .00001) and absolute change over the trial (random WMD = -9.25 nmol/L; 95% CI, -14.40 to -4.10; P = .0004).

Conclusions: Study participants who received vitamin D2 supplementation showed statistically significant reductions in serum 25(OH)D3 concentrations, compared to controls without supplementation. An inverse relationship between vitamin D2 and D3 concentrations has been proposed in the literature. A regulatory mechanism that increases the disposal rate of 25(OH)D after an increase in vitamin D concentrations could explain these results. However, further research is needed to establish whether vitamins D2 and D3 elicit different changes in overall vitamin D metabolism that might influence clinical advice to recommend vitamin D3 supplements over vitamin D2 supplements, where appropriate.