Evidence map›Paper›PMID 39900648›Full record

Trial reportNature aging2025

Individual and additive effects of vitamin D, omega-3 and exercise on DNA methylation clocks of biological aging in older adults from the DO-HEALTH trial.

Heike A Bischoff-Ferrari, Stephanie Gängler, Maud Wieczorek, Daniel W Belsky, Joanne Ryan, Reto W Kressig, Hannes B Stähelin, Robert Theiler, Bess Dawson-Hughes, René Rizzoli and 7 more

Abstract readRandomized Controlled Trial
In one paragraph

Trial report in Nature aging, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
95citing papers in PubMed, 3 pooled it
–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

95 citing papers in PubMed, 3 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Trial
  5. Trial
  6. Trial
  7. Trial
  8. Trial
  9. Review
  10. The Hallmarks of Aging: From Molecular Mechanisms to Clinical Translation.International journal of molecular sciences · 2026
    Review
  11. Article
  12. Review
  13. Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Review
  19. Review
  20. Epigenetic Mechanisms of Vitamin D in the Aging Process: A Narrative Review.International journal of molecular sciences · 2026
    Review

35 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

17 authors.

Heike A Bischoff-FerrariDepartment of Geriatrics and Aging Research, University of Zurich, Zurich, Switzerland. Heikea.bischoff-ferrari@uzh.ch.ORCID http://orcid.org/0000-0002-4554-658X
Stephanie GänglerDepartment of Geriatrics and Aging Research, University of Zurich, Zurich, Switzerland.ORCID http://orcid.org/0000-0002-7799-1514
Maud WieczorekDepartment of Geriatrics and Aging Research, University of Zurich, Zurich, Switzerland.ORCID http://orcid.org/0000-0002-4528-9923
Daniel W BelskyDepartment of Epidemiology, Butler Columbia Aging Center, Mailman School of Public Health, Columbia University, New York, NY, USA.
Joanne RyanBiological Neuropsychiatry & Dementia Unit, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.ORCID http://orcid.org/0000-0002-7039-6325
Reto W KressigUniversity Department of Geriatric Medicine Felix Platter, University of Basel, Basel, Switzerland.
Hannes B StähelinDepartment of Geriatrics, University of Basel, Basel, Switzerland.
Robert TheilerDepartment of Geriatrics and Aging Research, University of Zurich, Zurich, Switzerland.
Bess Dawson-HughesBone Metabolism Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA.
René RizzoliDivision of Bone Diseases, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland.
Bruno VellasIHU HealthAge, Toulouse, France.
Laure RouchCERPOP UMR1295, University of Toulouse III, Inserm, UPS, Toulouse, France.
Sophie GuyonnetIHU HealthAge, Toulouse, France.
Andreas EgliDepartment of Geriatrics and Aging Research, University of Zurich, Zurich, Switzerland.
E John OravDepartment of Health Policy and Management, Harvard University T.H. Chan School of Public Health, Boston, MA, USA.
Walter WillettDepartments of Nutrition and Epidemiology, Harvard TH Chan School of Public Health, Harvard University, Boston, MA, USA.
Steve HorvathAltos Labs Limited, Cambridge, UK.ORCID http://orcid.org/0000-0002-4110-3589

Funding

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation) 204452
6 · The paper itself

Abstract

While observational studies and small pilot trials suggest that vitamin D, omega-3 and exercise may slow biological aging, larger clinical trials testing these treatments individually or in combination are lacking. Here, we report the results of a post hoc analysis among 777 participants of the DO-HEALTH trial on the effect of vitamin D (2,000 IU per day) and/or omega-3 (1 g per day) and/or a home exercise program on four next-generation DNA methylation (DNAm) measures of biological aging (PhenoAge, GrimAge, GrimAge2 and DunedinPACE) over 3 years. Omega-3 alone slowed the DNAm clocks PhenoAge, GrimAge2 and DunedinPACE, and all three treatments had additive benefits on PhenoAge. Overall, from baseline to year 3, standardized effects ranged from 0.16 to 0.32 units (2.9-3.8 months). In summary, our trial indicates a small protective effect of omega-3 treatment on slowing biological aging over 3 years across several clocks, with an additive protective effect of omega-3, vitamin D and exercise based on PhenoAge.

Indexed as

AgingDNA MethylationExerciseFatty Acids, Omega-3Vitamin DAgedAged, 80 and overDietary SupplementsFemaleHumansMaleMiddle AgedFatty Acids, Omega-3Vitamin D

Identifiers

PMID39900648
PMCPMC11922767

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.