Evidence map›Paper›PMID 26681795›Full record

ReviewPhysiological reviews2016

Vitamin D: Metabolism, Molecular Mechanism of Action, and Pleiotropic Effects.

Sylvia Christakos, Puneet Dhawan, Annemieke Verstuyf, Lieve Verlinden, Geert Carmeliet

Registry-linked trialOpen access · greenAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Physiological reviews, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03384121 (Rifampin to Reduce Elevated Levels of Blood and Urine Calcium in Patients With Idiopathic Infantile Hypercalcemia), which is not on this map. Cited by 950 papers, 8 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
950citing papers in PubMed, 8 pooled it
68.9field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

NCT03384121 phase1unknown statusnot on this mapstarted 2018, after this paper: background citation

Rifampin to Reduce Elevated Levels of Blood and Urine Calcium in Patients With Idiopathic Infantile Hypercalcemia

TypeinterventionalSponsorThe Hospital for Sick ChildrenRan2018 to 2021Enrolled5ConditionsIdiopathic Infantile Hypercalcemia - Mild FormArmsRifampin 150 mg, 300 mg capsules and 25 mg/mL oral suspension
3 · Its place in the literature

Who cites it

950 citing papers in PubMed, 8 syntheses or guidelines pooled it, 1,843 citations in OpenAlex.

  1. Pooled it
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  9. Trial
  10. Kinetics and concentrations of circulating 25-hydroxyvitamin D using different vitamin D repletion regimens.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2026
    Trial
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890 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 2 countries.

Sylvia ChristakosDepartment of Microbiology, Biochemistry and Molecular Genetics, Rutgers, The State University of New Jersey, New Jersey Medical School, Newark, New Jersey; and Laboratory of Clinical and Experimental Endocrinology, KU Leuven, Leuven, Belgium.
Puneet DhawanDepartment of Microbiology, Biochemistry and Molecular Genetics, Rutgers, The State University of New Jersey, New Jersey Medical School, Newark, New Jersey; and Laboratory of Clinical and Experimental Endocrinology, KU Leuven, Leuven, Belgium.
Annemieke VerstuyfDepartment of Microbiology, Biochemistry and Molecular Genetics, Rutgers, The State University of New Jersey, New Jersey Medical School, Newark, New Jersey; and Laboratory of Clinical and Experimental Endocrinology, KU Leuven, Leuven, Belgium.
Lieve VerlindenDepartment of Microbiology, Biochemistry and Molecular Genetics, Rutgers, The State University of New Jersey, New Jersey Medical School, Newark, New Jersey; and Laboratory of Clinical and Experimental Endocrinology, KU Leuven, Leuven, Belgium.
Geert CarmelietDepartment of Microbiology, Biochemistry and Molecular Genetics, Rutgers, The State University of New Jersey, New Jersey Medical School, Newark, New Jersey; and Laboratory of Clinical and Experimental Endocrinology, KU Leuven, Leuven, Belgium.
Rutgers, The State University of New Jersey · USKU Leuven · BE

Funding

VITAMIN D HORMONE--FUNCTION AND MECHANISM OF ACTIONR01DK038961 · NIDDK · UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL · PI CHRISTAKOS, SYLVIA S · 1987 to 2010
$3.2M
Vitamin D and Innate Immunity in Respiratory InfectionsR21AI100379 · NIAID · UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL · PI CHRISTAKOS, SYLVIA S, DIAMOND, GILL · 2012 to 2013
$431k
Osteoporosis and Molecular Targets of Vitamin DR21AG044552 · NIA · RBHS-NEW JERSEY MEDICAL SCHOOL · PI CHRISTAKOS, SYLVIA S · 2014 to 2015
$354k
NIAID NIH HHS AI100379NIA NIH HHS AG044552NIA NIH HHS R21 AG044552NIDDK NIH HHS DK38961-22NIDDK NIH HHS R01 DK038961
6 · The paper itself

Abstract

1,25-Dihydroxvitamin D3 [1,25(OH)2D3] is the hormonally active form of vitamin D. The genomic mechanism of 1,25(OH)2D3 action involves the direct binding of the 1,25(OH)2D3 activated vitamin D receptor/retinoic X receptor (VDR/RXR) heterodimeric complex to specific DNA sequences. Numerous VDR co-regulatory proteins have been identified, and genome-wide studies have shown that the actions of 1,25(OH)2D3 involve regulation of gene activity at a range of locations many kilobases from the transcription start site. The structure of the liganded VDR/RXR complex was recently characterized using cryoelectron microscopy, X-ray scattering, and hydrogen deuterium exchange. These recent technological advances will result in a more complete understanding of VDR coactivator interactions, thus facilitating cell and gene specific clinical applications. Although the identification of mechanisms mediating VDR-regulated transcription has been one focus of recent research in the field, other topics of fundamental importance include the identification and functional significance of proteins involved in the metabolism of vitamin D. CYP2R1 has been identified as the most important 25-hydroxylase, and a critical role for CYP24A1 in humans was noted in studies showing that inactivating mutations in CYP24A1 are a probable cause of idiopathic infantile hypercalcemia. In addition, studies using knockout and transgenic mice have provided new insight on the physiological role of vitamin D in classical target tissues as well as evidence of extraskeletal effects of 1,25(OH)2D3 including inhibition of cancer progression, effects on the cardiovascular system, and immunomodulatory effects in certain autoimmune diseases. Some of the mechanistic findings in mouse models have also been observed in humans. The identification of similar pathways in humans could lead to the development of new therapies to prevent and treat disease.

Indexed as

AnimalsCalcitriolCholestanetriol 26-MonooxygenaseCytochrome P450 Family 2Dietary SupplementsDisease Models, AnimalGenetic Predisposition to DiseaseHumansMice, TransgenicPhenotypeProtein ConformationReceptors, CalcitriolSignal TransductionStructure-Activity RelationshipVitamin DVitamin D3 24-HydroxylaseCalcitriolCholestanetriol 26-MonooxygenaseCYP2R1 protein, humanCytochrome P450 Family 2Receptors, CalcitriolVDR protein, humanVitamin DVitamin D3 24-Hydroxylase

Identifiers

PMID26681795
PMCPMC4839493
OpenAlexW2254563264

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.