Relative Efficacy of Vitamin D2 and Vitamin D3 in Improving Vitamin D Status: Systematic Review and Meta-Analysis

Nutrients

Sep 2021

DOI: 10.3390/nu13103328

Citations:78

Influential Citations:0

Systematic Reviews / Meta-Analyses

Enhanced Details

Methods

Randomized and non-randomized controlled trials comparing ergocalciferol and cholecalciferol in apparently healthy humans. Participants included adults of various ages (including older adults) and subgroups such as hip fracture patients and pre-pubertal children; no dosing details provided here.

Intervention

Regimens varied; cholecalciferol (D3) vs ergocalciferol (D2) administered in diverse schedules, including daily, weekly, fortnightly, monthly, and single bolus doses, via oral, intramuscular injections, or fortified foods (orange juice, malt drinks, biscuits, bread). Doses ranged from about 400–2000 IU per day to large bolus doses of 300,000–600,000 IU; durations spanned about 2 weeks up to 1 year.

Results

Cholecalciferol yields greater improvements in vitamin D status than ergocalciferol, increasing total 25(OH)D by about 15.69 nmol/L (95% CI 9.46–21.93) and more effectively suppressing parathyroid hormone. Cholecalciferol raises 25(OH)D3 more; ergocalciferol raises 25(OH)D2 more; higher doses and bolus regimens show larger differences; daily dosing reduces the difference. Both vitamers raise their respective metabolites but no functional outcomes were reported in the analyzed studies. For fortification-level dosing, the advantage of cholecalciferol may be modest.

Limitations

Heterogeneous study designs, populations, dosing regimens, durations, and analytical methods; many studies lacked detailed methodological reporting and were of moderate quality; few reported 25(OH)D2/25(OH)D3 separately; most data come from high-income regions; underrepresentation of children and tropical LMICs; no functional outcomes consistently reported.

Abstract

Background: Widespread prevalence of vitamin D deficiency has been documented globally. Commonly used interventions to address this deficiency include supplementation and/or fortification with either ergocalciferol (vitamin D2) or cholecalciferol (vitamin D3), but the relative efficacy of these two vitamers is unclear. The current study aimed to evaluate the relative efficacy of ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3) for raising the serum levels of vitamin D metabolites and functional indicators including serum parathyroid (PTH) levels, isometric muscle strength, hand grip strength and bone mineral density. Methods: Randomized and non-randomized controlled studies evaluating relative efficacy of ergocalciferol and cholecalciferol were systematically reviewed to synthesize quantitative and qualitative evidence as per the recommendations of according to “Preferred Reporting Items for Systematic reviews and Meta-analysis” guidelines. Search terms were constructed on the basis of the “participants”, “intervention”, “control”, “outcome” and “study type” (PICOS) strategy to systematically search the popular electronic databases. Relevant data from studies meeting inclusion and exclusion criteria were extracted and analyzed. Meta-regression, subgroup and sensitivity analyses were performed to investigate the influence of study-level characteristics including intervention dosage, frequency of dosing, interval between the last dose and test for outcome assessment, participant characteristics and analytical methods. Results: Apparently healthy human participants (n = 1277) from 24 studies were included for meta-analysis. The quantitative analysis suggested higher efficacy of cholecalciferol than ergocalciferol in improving total 25(OH)D (mean difference: 15.69, 95%CI: 9.46 to 21.93 nmol/L) and reducing PTH levels, consistently across variable participant demographics, dosage and vehicle of supplementation. Meta-regression suggested smaller differences in the efficacy of cholecalciferol and ergocalciferol at lower doses. Average daily dose was the single significant predictor of effect size, as revealed by multivariate meta-regression analysis. Conclusions: Compared to ergocalciferol, cholecalciferol intervention was more efficacious in improving vitamin D status (serum levels of total 25(OH)D and 25(OH)D3) and regulating PTH levels, irrespective of the participant demographics, dosage and vehicle of supplementation. show less