Evidence map›Paper›PMID 34116393›Full record

Trial reportNutrition (Burbank, Los Angeles County, Calif.)2021

Magnesium treatment on methylation changes of transmembrane serine protease 2 (TMPRSS2).

Lei Fan, Xiangzhu Zhu, Yinan Zheng, Wei Zhang, Douglas L Seidner, Reid Ness, Harvey J Murff, Chang Yu, Xiang Huang, Martha J Shrubsole and 2 more

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

Trial report in Nutrition (Burbank, Los Angeles County, Calif.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04196803 (Methylomic Biomarkers, Magnesium Deficiency and Colon Neoplasia Prevention), which is not on this map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
2.1field-weighted citation impact, top 12% 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.

NCT04196803 nacompletednot on this map

Methylomic Biomarkers, Magnesium Deficiency and Colon Neoplasia Prevention

TypeinterventionalSponsorVanderbilt University Medical CenterRan2011 to 2023Enrolled250ConditionsColorectal CancerArmsMagnesium glycinate, Placebo
3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 20 citations in OpenAlex.

  1. Genomic medicine and personalized treatment: a narrative review.Annals of medicine and surgery (2012) · 2025
    Review
  2. Review
  3. Review
  4. Article
  5. Article
  6. Review
  7. Review
  8. Article
  9. The relevance of magnesium homeostasis in COVID-19.European journal of nutrition · 2022
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 4 institutions in 1 country.

Lei FanDepartment of Medicine, Division of Epidemiology, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Xiangzhu ZhuDepartment of Medicine, Division of Epidemiology, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Yinan ZhengDepartment of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
Wei ZhangDepartment of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
Douglas L SeidnerCenter for Human Nutrition, Department of Gastroenterology, Hepatology and Nutrition, Digestive Disease and Surgical Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Reid NessDepartment of Medicine, Division of Gastroenterology, Vanderbilt School of Medicine, Nashville, Tennessee, USA.
Harvey J MurffDivision of Geriatric Medicine, General Internal Medicine and Public Health, Vanderbilt University School of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Chang YuDepartment of Biostatistics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Xiang HuangDepartment of Medicine, Division of Epidemiology, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Martha J ShrubsoleDepartment of Medicine, Division of Epidemiology, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Lifang HouDepartment of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
Qi DaiDepartment of Medicine, Division of Epidemiology, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA. Electronic address: qi.dai@vanderbilt.edu.
Vanderbilt University Medical Center · USNorthwestern University · USVanderbilt University · USCleveland Clinic · US

Funding

Tumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Ben Ho Park · 1995 to 2026
$172.8M
VANDERBILT UNIVERSITY CTSA FOR PEDIATRIC RESEARCHUL1RR024975 · NCRR · VANDERBILT UNIVERSITY · PI BERNARD, GORDON RAPHAEL · 2007 to 2011
$45.7M
The Vanderbilt Institute for Clinical and Translational Research (VICTR)UL1TR000445 · NCATS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BERNARD, GORDON RAPHAEL · 2012 to 2016
$41.4M
Methylomic biomarkers for magnesium deficiency and colon neoplasia preventionR01CA202936 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI DAI, QI, HOU, LIFANG · 2016 to 2019
$2.5M
Personalized Prevention of Colorectal CancerR01CA149633 · NCI · VANDERBILT UNIVERSITY · PI DAI, QI, YU, CHANG · 2010 to 2014
$2.0M
NCATS NIH HHS UL1 TR000445NCI NIH HHS P30 CA068485NCI NIH HHS R01 CA149633NCI NIH HHS R01 CA202936NCRR NIH HHS UL1 RR024975
6 · The paper itself

Abstract

objectivesThe viral entry of SARS-CoV-2 requires host-expressed TMPRSS2 to facilitate the viral spike protein priming. This study aims to test the hypothesis that magnesium (Mg) treatment leads to DNA methylation changes in TMPRSS2.

methodsThis study is nested within the Personalized Prevention of Colorectal Cancer Trial, a double-blind 2 × 2 factorial randomized controlled trial, which enrolled 250 participants from Vanderbilt University Medical Center.

resultsWe found that 12 wk of personalized Mg treatment significantly increased 5-methylcytosine methylation at cg16371860 (TSS1500, promoter) by 7.2% compared to the placebo arm (decreased by 0.1%) in those ages < 65 y. The difference remained statistically significant after adjusting for age, sex, and baseline methylation as well as correction for false discovery rate (adjusted P = 0.014). Additionally, Mg treatment significantly reduced 5-hydroxymethylcytosine levels at cg26337277 (close proximity to TSS200 and the 5' untranslated region, promoter) by 2.3% compared to an increase of 7.1% in the placebo arm after adjusting for covariates in those ages < 65 y (P = 0.003). The effect remained significant at a false discovery rate of 0.10 (adjusted P = 0.088).

conclusionsAmong individuals ages < 65 y with calcium-to-magnesium intake ratios equal to or over 2.6, reducing the ratio to around 2.3 increased 5-methylcytosine modifications (i.e., cg16371860) and reduced 5-hydroxymethylcytosine modifications (i.e., cg26337277) in the TMPRSS2 gene. These findings, if confirmed, provide another mechanism for the role of Mg intervention in the prevention of COVID-19 and treatment of early and mild disease by modifying the phenotype of the TMPRSS2 genotype.

Indexed as

COVID-19MagnesiumDNA MethylationHumansPromoter Regions, GeneticSARS-CoV-2Serine EndopeptidasesMagnesiumSerine EndopeptidasesTMPRSS2 protein, humanCOVID-19MagnesiumMethylation changesSARS-CoV-2TMPRSS2

Identifiers

PMID34116393
PMCPMC8102075
OpenAlexW3163686739

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.