van den Heuvel · Advances in nutrition (Bethesda, Md.) 2024 · systematic review and meta-analysis of randomized controlled trials · n=20 studies

Comparison of the Effect of Daily Vitamin D2 and Vitamin D3 Supplementation on Serum 25-Hydroxyvitamin D Concentration (Total 25(OH)D, 25(OH)D2, and 25(OH)D3) and Importance of Body Mass Index: A Systematic Review and Meta-Analysis.

Cited 61 times in the scientific literature.

Level 1 - systematic review of randomized trials

Systematic review and meta-analysis of randomized controlled trials

PubMed 37865222 · doi:10.1016/j.advnut.2023.09.016 · record verified 2026-08-26

What was done

Authors searched PubMed, EMBASE, Cochrane, and Web of Science for randomized controlled trials comparing daily or once/twice weekly dosing of vitamin D2 versus vitamin D3. Meta-analyses were conducted to determine the weighted mean difference (WMD) or standardized mean difference in total 25(OH)D, 25(OH)D2, and 25(OH)D3, as well as to evaluate effect modification by factors such as body mass index (BMI).

What was found

Based on 20 comparative studies, vitamin D3 produced a larger increase in total 25(OH)D than vitamin D2, although both had comparable effects on their corresponding hydroxylated forms (25(OH)D2 and 25(OH)D3). In 12 daily-dosing trials measured via liquid chromatography-tandem mass spectrometry, the increase in total 25(OH)D was 10.39 nmol/L lower with vitamin D2 than with vitamin D3 (95% CI: -14.62 to -6.16; I² = 64%; P < 0.00001). BMI was the strongest modifier of heterogeneity, reducing I² to 0% in subgroups; the difference between D2 and D3 was not statistically significant in individuals with a BMI > 25 kg/m² (P = 0.99).

Why it matters

This review confirms that vitamin D3 is generally more potent than vitamin D2 on a daily basis, but demonstrates that body mass index strongly moderates this difference, nullifying the superiority of D3 in overweight and obese populations.

Limits

Information on BMI was missing for 4 of the 17 daily-dosed comparisons (available in only 13/17). The analysis examined surrogate biochemical markers rather than clinical outcomes, and unexplained heterogeneity was moderately high (I² = 64%) before stratifying by BMI.

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