Effect of vitamin D2 supplementation on 25-hydroxyvitamin D3 status: a systematic review and meta-analysis of randomised controlled trials

Abstract

There are known differences in biological functionality between vitamin D2 and D3. It is suspected from randomised control trial (RCT) data that vitamin D2 supplementation causes a reduction in serum 25-hydroxyvitamin D3 (25(OH)D3) concentrations (1), but the size of the effect has yet to be fully assessed across multiple studies. The aim of this study was to undertake a systematic review and meta-analysis of the effect of vitamin D2 supplementation on serum 25(OH)D3 concentrations.PUBMED was searched for publications from 1st January 1975 to 1st February 2023. Of the 182 papers retrieved, 29 were included in the systematic review, and of those, 18 were suitable for meta-analysis.The meta-analysis found significant reductions in serum D3 after vitamin D2 supplementation compared with control, for both end of trial between groups data (weighted mean difference (WMD) (random) = −13.51 nmol/L; 95% CI: −20.14, −6.89; P < 0.0001) and absolute change over the trial (WMD (random) = −9.25 nmol/L; 95% CI: −14.40, −4.10; P = 0.0004). Similar results were found when D2 supplementation was compared to D3 supplementation, although as expected, the magnitude of the difference was larger, with WMD (random) = −46.20 nmol/L (95% CI: −60.80, −31.60; P < 0.00001) for end of trial data, and WMD (random) = −56.23 nmol/L (95% CI: -69.17, −43.28; P < 0.00001) for absolute change.Overall, we found that vitamin D2 supplementation produces significant reductions in serum 25(OH)D3 concentrations, when compared to either control or vitamin D3 supplementation. An inverse relationship between vitamin D2 and D3 concentrations has been proposed in the literature (2). A regulatory mechanism that disposes of 25(OH)D after an increase in vitamin D concentrations could explain our results (3). Moreover, supplementation with vitamins D2 and D3 has differential effects on gene expression (4). However, longer-term research is needed to establish whether clinical advice should recommend vitamin D3 supplements over vitamin D2 supplements, where appropriate.