ArticlePloS one2012
Vitamin D binding protein and monocyte response to 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D: analysis by mathematical modeling.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
52 citing papers in PubMed, 100 citations in OpenAlex.
- Randomized controlled trial of vitamin D supplementation in older people to optimize bone health.The American journal of clinical nutrition · 2019Trial
- Associations Between Change in Total and Free 25-Hydroxyvitamin D With 24,25-Dihydroxyvitamin D and Parathyroid Hormone.The Journal of clinical endocrinology and metabolism · 2018Trial
- Associations of vitamin D pathway genes with circulating 25-hydroxyvitamin-D, 1,25-dihydroxyvitamin-D, and prostate cancer: a nested case-control study.Cancer causes & control : CCC · 2015Trial
- 25(OH)D2 half-life is shorter than 25(OH)D3 half-life and is influenced by DBP concentration and genotype.The Journal of clinical endocrinology and metabolism · 2014Trial
- Vitamin D-binding protein haplotype is associated with hospitalization for RSV bronchiolitis.Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology · 2014Trial
- Vitamin D as a Lifespan Neuroimmune Signal in Psychiatry: From Developmental Risk to Precision Nutrition.Nutrients · 2026Review
- Review
- Modelling the influence of vitamin D and probiotics on inflammation and the intestinal microbiota in older adults.Scientific reports · 2025Article
- Review
- Impact of gene polymorphisms involved in the vitamin D metabolic pathway on the susceptibility to and severity of autism spectrum disorder.Scientific reports · 2024Article
- Associations of free, bioavailable and total 25-hydroxyvitamin D with neonatal birth anthropometry and calcium homoeostasis in mother-child pairs in a sunny Mediterranean region.The British journal of nutrition · 2024Article
- Associations between total, free and bioavailable 25-hydroxyvitamin D forms with adiponectin and irisin in maternal-neonatal pairs at birth from Greece.Frontiers in endocrinology · 2024Article
- Vitamin D, vitamin D-binding protein, free vitamin D and COVID-19 mortality in hospitalized patients.The American journal of clinical nutrition · 2022Observational
- Pre- and Postnatal Vitamin D Status and Allergy Outcomes in Early Childhood.Biomedicines · 2022Review
- Effects of immunosuppressants on T-cell dynamics: Understanding from a generic coarse-grained immune network model.Journal of biosciences · 2022Review
- Vitamin D insufficiency in COVID-19 and influenza A, and critical illness survivors: a cross-sectional study.BMJ open · 2021Article
- Review
- Macrophages Control the Bioavailability of Vitamin D and Vitamin D-Regulated T Cell Responses.Frontiers in immunology · 2021Article
- Perspective: Vitamin D deficiency and COVID-19 severity - plausibly linked by latitude, ethnicity, impacts on cytokines, ACE2 and thrombosis.Journal of internal medicine · 2021Review
- Association of prediagnostic vitamin D status with mortality among colorectal cancer patients differs by common, inherited vitamin D-binding protein isoforms.International journal of cancer · 2020Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Vitamin D binding protein (DBP) plays a key role in the bioavailability of active 1,25-dihydroxyvitamin D (1,25(OH)(2)D) and its precursor 25-hydroxyvitamin D (25OHD), but accurate analysis of DBP-bound and free 25OHD and 1,25(OH)(2)D is difficult. To address this, two new mathematical models were developed to estimate: 1) serum levels of free 25OHD/1,25(OH)(2)D based on DBP concentration and genotype; 2) the impact of DBP on the biological activity of 25OHD/1,25(OH)(2)D in vivo. The initial extracellular steady state (eSS) model predicted that 50 nM 25OHD and 100 pM 1,25(OH)(2)D), <0.1% 25OHD and <1.5% 1,25(OH)(2)D are 'free' in vivo. However, for any given concentration of total 25OHD, levels of free 25OHD are higher for low affinity versus high affinity forms of DBP. The eSS model was then combined with an intracellular (iSS) model that incorporated conversion of 25OHD to 1,25(OH)(2)D via the enzyme CYP27B1, as well as binding of 1,25(OH)(2)D to the vitamin D receptor (VDR). The iSS model was optimized to 25OHD/1,25(OH)(2)D-mediated in vitro dose-responsive induction of the vitamin D target gene cathelicidin (CAMP) in human monocytes. The iSS model was then used to predict vitamin D activity in vivo (100% serum). The predicted induction of CAMP in vivo was minimal at basal settings but increased with enhanced expression of VDR (5-fold) and CYP27B1 (10-fold). Consistent with the eSS model, the iSS model predicted stronger responses to 25OHD for low affinity forms of DBP. Finally, the iSS model was used to compare the efficiency of endogenously synthesized versus exogenously added 1,25(OH)(2)D. Data strongly support the endogenous model as the most viable mode for CAMP induction by vitamin D in vivo. These novel mathematical models underline the importance of DBP as a determinant of vitamin D 'status' in vivo, with future implications for clinical studies of vitamin D status and supplementation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.