Evidence map›Paper›PMID 40456316›Full record

ArticleThe American journal of clinical nutrition2025

One-carbon metabolism-related compounds are associated with epigenetic aging biomarkers: results from the cross-sectional National Health and Nutrition Examination Survey 1999-2002.

Anne K Bozack, Dennis Khodasevich, Jamaji C Nwanaji-Enwerem, Nicole Gladish, Hanyang Shen, Saher Daredia, Mary Gamble, Belinda L Needham, David H Rehkopf, Andres Cardenas

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Article in The American journal of clinical nutrition, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
–field-weighted citation impact
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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Frontiers in immunology · 2026
    Article
  6. Article
  7. Article
  8. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Anne K BozackDepartment of Epidemiology and Population Health, Stanford University, Palo Alto, CA, United States. Electronic address: abozack@stanford.edu.
Dennis KhodasevichDepartment of Epidemiology and Population Health, Stanford University, Palo Alto, CA, United States.
Jamaji C Nwanaji-EnweremCenter for Excellence in Environmental Toxicology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States; Center for Health Justice, University of Pennsylvania, Philadelphia, PA, United States.
Nicole GladishDepartment of Epidemiology and Population Health, Stanford University, Palo Alto, CA, United States.
Hanyang ShenDepartment of Epidemiology and Population Health, Stanford University, Palo Alto, CA, United States.
Saher DarediaDepartment of Epidemiology, School of Public Health, University of California, Berkeley, Berkeley, CA, United States.
Mary GambleDepartment of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, United States.
Belinda L NeedhamDepartment of Epidemiology, University of Michigan, Ann Arbor, MI, United States.
David H RehkopfDepartment of Epidemiology and Population Health, Stanford University, Palo Alto, CA, United States; Department of Health Policy, Stanford University, Palo Alto, CA, United States; Department of Medicine - Primary Care and Population Health, Stanford University, Palo Alto, CA, United States; Department of Pediatrics, Stanford University, Palo Alto, CA, United States; Department of Sociology, Stanford University, Palo Alto, CA, United States.
Andres CardenasDepartment of Epidemiology and Population Health, Stanford University, Palo Alto, CA, United States; Department of Pediatrics, Stanford University, Palo Alto, CA, United States.

Funding

Race/Ethnicity, DNA Methylation, and Disparities in Cardiovascular Mortality: NHANES 1999-2002R01MD011721 · NIMHD · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI NEEDHAM, BELINDA L., REHKOPF, DAVID H · 2017 to 2021
$3.1M
Common and Distinct Influences of Prenatal and Postnatal Early-Life Adversity on Epigenomic Trajectories in Mexican American ChildrenR01MD016595 · NIMHD · UNIVERSITY OF CALIFORNIA BERKELEY · PI Andres Cardenas, Julianna Deardorff · 2022 to 2026
$3.0M
PRENATAL AND POSTNATAL EXPOSURE TO ENVIRONMENTAL MIXTURES: NEURODEVELOPMENT AND DNA METHYLATION BIOMARKERSR01ES031259 · NIEHS · UNIVERSITY OF CALIFORNIA BERKELEY · PI CARDENAS, ANDRES · 2020 to 2024
$1.9M
NIEHS NIH HHS R01 ES031259NIMHD NIH HHS R01 MD011721NIMHD NIH HHS R01 MD016595
6 · The paper itself

Abstract

backgroundOne-carbon metabolism (OCM), a biochemical pathway dependent on micronutrients including B vitamins, plays an essential role in aging-related physiological processes. DNA methylation-based aging biomarkers may be influenced by OCM.

objectivesThis study investigated associations of OCM-related biomarkers with epigenetic aging biomarkers in the cross-sectional National Health and Nutrition Examination Survey (1999-2002).

methodsBlood DNA methylation was measured in adults aged ≥50 y. The following epigenetic aging biomarkers were included: Horvath1, Horvath2, Hannum, PhenoAge, GrimAge2, Dunedin Pace-of-Aging (DunedinPoAm), and DNA methylation telomere length (DNAmTL). We tested for associations of serum folate, red blood cell folate, vitamin B12, homocysteine (Hcy), and methylmalonic acid (MMA) concentrations with epigenetic age deviation (EAD) among 2346 participants with epigenetic and nutritional status biomarkers using adjusted survey-weighted general linear regression models.

resultsA doubling of serum folate concentration was associated with -0.82 y (95% confidence interval: -1.40, -0.23) lower GrimAge2 EAD, -0.13 SDs (-0.22, -0.03) lower DunedinPoAm, and 0.02 kb (0.00, 0.04) greater DNAmTL EAD. Conversely, a doubling in Hcy concentration was associated with 1.05 y (0.06, 2.04) greater PhenoAge EAD, 1.93 y (1.16, 2.71) greater GrimAge2 EAD, and 0.26 SDs (0.10, 0.41) greater DunedinPoAm. Associations of serum folate with EAD were attenuated after adjusting for smoking status, alcohol intake, and estimated glomerular filtration rate. Furthermore, smoking modified the associations of Hcy with GrimAge2 EAD. Chronic kidney disease modified associations of B12 and MMA with Horvath1 and GrimAge2 EAD, respectively.

conclusionsIn a nationally representative sample of United States adults, higher concentration of folate, a carbon donor, was associated with lower EAD, and higher concentration of Hcys, an indicator of OCM deficiencies, was associated with greater EAD; however, some associations were influenced by smoking and renal function. Future research should focus on high-risk populations. Long-term randomized controlled trials are also needed to establish causality and investigate the clinical relevance of changes in EAD.

Indexed as

AgingCarbonEpigenesis, GeneticAgedBiomarkersCross-Sectional StudiesDNA MethylationFemaleFolic AcidHomocysteineHumansMaleMethylmalonic AcidMiddle AgedNutritional StatusNutrition SurveysBiomarkersCarbonFolic AcidHomocysteineMethylmalonic AcidVitamin B 12DNA methylationepigenetic agingfolatehomocysteineNational Health and Nutrition Examination Survey (NHANES)one-carbon metabolismvitamin B12

Identifiers

PMID40456316
PMCPMC12405778

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Registered trials

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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.