Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2025 Apr;79(4):296-305.
doi: 10.1038/s41430-024-01520-x. Epub 2024 Oct 9.

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

Affiliations
Meta-Analysis

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

Selma Bouden et al. Eur J Clin Nutr. 2025 Apr.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

PubMed Disclaimer

Conflict of interest statement

Competing interests: The authors declare no competing interests.

References

    1. Rosen CJ, Adams JS, Bikle DD, Black DM, Demay MB, Manson JE, et al. The nonskeletal effects of vitamin D: an endocrine society scientific statement. Endocr Rev. 2012;33:456–92. - DOI - PubMed - PMC
    1. Charoenngam N, Holick MF. Immunologic effects of vitamin D on human health and disease. Nutrients. 2020;12:2097. - DOI - PubMed - PMC
    1. Bouillon R, Marcocci C, Carmeliet G, Bikle D, White JH, Dawson-Hughes B, et al. Skeletal and extraskeletal actions of vitamin D: current evidence and outstanding questions. Endocr Rev. 2018;40:1109–51. - DOI - PMC
    1. Hilger J, Friedel A, Herr R, Rausch T, Roos F, Wahl DA, et al. A systematic review of vitamin D status in populations worldwide. Br J Nutr. 2014;111:23–45. - DOI - PubMed
    1. Dominguez LJ, Farruggia M, Veronese N, Barbagallo M. Vitamin D sources, metabolism, and deficiency: available compounds and guidelines for its treatment. Metabolites. 2021;11:255. - DOI - PubMed - PMC

MeSH terms

LinkOut - more resources