Effect of cholecalciferol versus calcifediol on serum 25(OH)D concentrations: a systematic review with meta-analysis

Deficiency in vitamin D is widely prevalent around the world. Oral vitamin D supplementation is suggested for older adults to sustain appropriate 25-hydroxyvitamin D (25(OH)D) levels throughout the year. At present, cholecalciferol (vitamin D3) and ergocalciferol (vitamin D2) are the most commonly used compounds. Supplementation with calcifediol (25OHD3) rather than vitamin D itself should also be considered for the treatment. We performed a systematic review of the literature with a meta-analysis to assess the effects of cholecalciferol (vitamin D3) compared to calcifediol (25OHD3) on increasing serum 25(OH)D levels.

A search of online databases was performed electronically for all relevant observational published population-based studies until November 2023, without geographical restrictions. We included studies that directly compared the effects of cholecalciferol and calcifediol on increasing concentrations of serum 25(OH)D. Only papers in English or French languages were considered. Records were screened and data were retrieved through a standardized extraction process.

Seventeen studies including 1575 participants were reviewed. Twelve intervention trials showed that, in spite of the dosage or the frequency of administration, calcifediol supplementation was more efficacious in raising serum 25(OH)D concentrations compared with cholecalciferol. Two studies showed that calcifediol and cholecalciferol were identically potent. According to three studies, cholecalciferol was more effective than calcifediol in raising 25(OH)D concentrations. A meta-analysis including randomized controlled trials (RCTs) and non-randomized trials revealed that calcifediol supplementation had a better impact on elevating serum 25(OH)D concentrations compared with the effect of cholecalciferol.

This meta-analysis suggests that calcifediol is more effective in increasing serum 25(OH)D concentrations compared to cholecalciferol. Consequently, calcifediol may emerge as the preferred option for supplementation.