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Vitamin D Metabolism, Mechanism of Action, and Clinical Applications
Open accessAbstract
Vitamin D3 is made in the skin from 7-dehydrocholesterol under the influence of UV light. Vitamin D2 (ergocalciferol) is derived from the plant sterol ergosterol. Vitamin D is metabolized first to 25 hydroxyvitamin D (25OHD), then to the hormonal form 1,25-dihydroxyvitamin D (1,25(OH)2D). CYP2R1 is the most important 25-hydroxylase; CYP27B1 is the key 1-hydroxylase. Both 25OHD and 1,25(OH)2D are catabolized by CYP24A1. 1,25(OH)2D is the ligand for the vitamin D receptor (VDR), a transcription factor, binding to sites in the DNA called vitamin D response elements (VDREs). There are thousands of these binding sites regulating hundreds of genes in a cell-specific fashion. VDR-regulated transcription is dependent on comodulators, the profile of which is also cell specific. Analogs of 1,25(OH)2D are being developed to target specific diseases with minimal side effects. This review will examine these different aspects of vitamin D metabolism, mechanism of action, and clinical application.
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“Vitamin D3 is modified through the mitochondria in the liver and kidney to assume its active form, 1,25 vitamin D (Bikle, 2014).”
From Comprehensive Multi-omics Analysis Reveals Mitochondrial Stress as a Central Biological Hub for Spaceflight Impact (2020) · cites this paper as Bikle, 2014
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“supplementation effects depend strongly on baseline status, assay standardization, dose, formulation, adherence, and population context [1,2,3,4,5,6].”
From Vitamin D Supplementation, Total Testosterone, and Androgen Bioavailability Markers in Adult Men: A Systematic Review and Meta-Analysis of Randomized Controlled Trials (2026) · cites this paper as [2]
Experimental — accuracy not yet measuredIn the citing paper
“3-Epi-1α,25(OH)2D3 generally has reduced biological activity compared to 1α,25(OH)2D3 [14, 73–75] and is discussed further in Sections 2.1.3 and 3.6.”
From The serum vitamin D metabolome: what we know and what is still to discover (2019) · cites this paper as [14]
In the citing paper
“Many other tissues express CYP27B1 too which can modulate the local level of this hormone utilizing plasma 25(OH)D as substrate [10, 14, 51].”
From The serum vitamin D metabolome: what we know and what is still to discover (2019) · cites this paper as [14]
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“Serum 1α,25(OH)2D3 and 1α,25(OH)2D2 are produced in the kidney by the action of CYP27B1 on 25(OH)D obtained from the circulation [14].”
From The serum vitamin D metabolome: what we know and what is still to discover (2019) · cites this paper as [14]
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Metadata
- Authors
- Bikle, D. D.
- Affiliations
- San Francisco VA Medical Center (US)
- Corresponding author
- Bikle, Daniel D.
- ORCID
- Bikle, Daniel D.
- Venue
- Chemistry & Biology
- Publisher
- Elsevier BV
- Published
- 2014-03
- Volume
- 21
- Issue
- 3
- Pages
- 319-329
- ISSN
- 1074-5521 (ISSN-L)
- PMC
- PMC3968073
- OpenAlex
- W1976776496
- Cited by
- 1,933
- References
- 133
- Citations by year
- 2026: 148 · 2025: 189 · 2024: 196 · 2023: 272 · 2022: 219 · 2021: 211 · 2020: 228 · 2019: 142 · 2018: 135 · 2017: 84 · 2016: 60 · 2015: 37 · 2014: 10
- FWCI
- 9.02
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Chemistry & Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- U.S. Department of Defense
- National Institutes of Health (AR050023)
- National Cancer Institute (CA110338)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR038386, R01AR050023, P01AR039448)
- National Center for Research Resources (P41RR001614)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Vitamin D Research Studies
- Health Sciences › Medicine › Nephrology › Parathyroid Disorders and Treatments
- Health Sciences › Nursing › Nutrition and Dietetics › Vitamin K Research Studies
- Keywords
- vitamin D metabolism, vitamin D3, vitamin D2, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, CYP2R1, CYP27B1, CYP24A1, vitamin D receptor, vitamin D response element, transcriptional regulation, vitamin D analogs, 7-dehydrocholesterol, ergosterol
- MeSH terms
- Cytochrome P-450 Enzyme System, DNA, Humans, Immune System, Metabolic Diseases, Neoplasms, Vitamin D, Receptors, Calcitriol, Response Elements
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