Evidence map›Paper›PMID 39447576›Full record

Trial reportMed (New York, N.Y.)2025

Bile acid metabolites predict multiple sclerosis progression and supplementation is safe in progressive disease.

Dimitrios C Ladakis, Kimystian L Harrison, Matthew D Smith, Krista Solem, Sachin Gadani, Larissa Jank, Soonmyung Hwang, Farzaneh Farhadi, Blake E Dewey, Kathryn C Fitzgerald and 4 more

Abstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Med (New York, N.Y.), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing 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

23 citing papers in PubMed.

  1. The Gut Microbiome in Multiple Sclerosis.Neurology(R) neuroimmunology & neuroinflammation · 2026
    Review
  2. Article
  3. Review
  4. Article
  5. Tobacco smoking disrupts bile acid and tryptophan metabolism in multiple sclerosis.Multiple sclerosis (Houndmills, Basingstoke, England) · 2026
    Article
  6. Article
  7. Review
  8. Article
  9. Review
  10. Review
  11. Review
  12. Review
  13. Article
  14. Review
  15. Emerging Roles of Bile Acids in Neuroinflammation.International journal of molecular sciences · 2025
    Review
  16. Review
  17. Review
  18. Review
  19. Article
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Dimitrios C LadakisJohns Hopkins University School of Medicine, Department of Neurology, Baltimore, MD 21205, USA.
Kimystian L HarrisonJohns Hopkins University School of Medicine, Department of Neurology, Baltimore, MD 21205, USA.
Matthew D SmithJohns Hopkins University School of Medicine, Department of Neurology, Baltimore, MD 21205, USA.
Krista SolemJohns Hopkins University School of Medicine, Department of Neurology, Baltimore, MD 21205, USA.
Sachin GadaniJohns Hopkins University School of Medicine, Department of Neurology, Baltimore, MD 21205, USA.
Larissa JankJohns Hopkins University School of Medicine, Department of Neurology, Baltimore, MD 21205, USA.
Soonmyung HwangJohns Hopkins University School of Medicine, Department of Neurology, Baltimore, MD 21205, USA.
Farzaneh FarhadiJohns Hopkins University School of Medicine, Department of Neurology, Baltimore, MD 21205, USA.
Blake E DeweyJohns Hopkins University School of Medicine, Department of Neurology, Baltimore, MD 21205, USA.
Kathryn C FitzgeraldJohns Hopkins University School of Medicine, Department of Neurology, Baltimore, MD 21205, USA.
Elias S SotirchosJohns Hopkins University School of Medicine, Department of Neurology, Baltimore, MD 21205, USA.
Shiv SaidhaJohns Hopkins University School of Medicine, Department of Neurology, Baltimore, MD 21205, USA.
Peter A CalabresiJohns Hopkins University School of Medicine, Department of Neurology, Baltimore, MD 21205, USA.
Pavan BhargavaJohns Hopkins University School of Medicine, Department of Neurology, Baltimore, MD 21205, USA. Electronic address: pbharga2@jhmi.edu.

Funding

Imaging Neurodegeneration in Multiple SclerosisR01NS082347 · NINDS · JOHNS HOPKINS UNIVERSITY · PI PETER A CALABRESI, Shiv Saidha · 2013 to 2026
$7.0M
NINDS NIH HHS R01 NS082347
6 · The paper itself

Abstract

backgroundBile acid metabolism is altered in multiple sclerosis (MS) and tauroursodeoxycholic acid (TUDCA) supplementation ameliorated disease in mouse models of MS.

methodsGlobal metabolomics was performed in an observational cohort of people with MS, followed by pathway analysis to examine relationships between baseline metabolite levels and subsequent brain and retinal atrophy. A double-blind, placebo-controlled trial was completed in people with progressive MS (PMS), randomized to receive either TUDCA (2 g/day) or placebo for 16 weeks. Participants were followed with serial clinical and laboratory assessments. Primary outcomes were safety and tolerability of TUDCA, and exploratory outcomes included changes in clinical, laboratory, and gut microbiome parameters.

findingsIn the observational cohort, higher primary bile acid levels at baseline predicted slower whole-brain atrophy, brain substructure atrophy, and specific retinal layer atrophy. In the clinical trial, 47 participants were included in our analyses (21 in placebo arm, 26 in TUDCA arm). Adverse events did not differ significantly between arms (p = 0.77). The TUDCA arm demonstrated increased serum levels of multiple bile acids. No significant differences were noted in clinical or fluid biomarker outcomes. Central memory CD4

conclusionsBile acid metabolism in MS is linked to brain and retinal atrophy. TUDCA supplementation in PMS is safe, tolerable, and has measurable biological effects that warrant further evaluation in larger trials with a longer treatment duration.

fundingNational MS Society grant RG-1707-28601 to P.B., R01 NS082347 from the National Institute of Neurological Disorders and Stroke to P.A.C., and National MS Society grant RG-1606-08768 to S.S.

Indexed as

Bile Acids and SaltsMultiple SclerosisMultiple Sclerosis, Chronic ProgressiveTaurochenodeoxycholic AcidAdultAtrophyBrainDietary SupplementsDisease ProgressionDouble-Blind MethodFemaleGastrointestinal MicrobiomeHumansMaleMetabolomicsMiddle AgedBile Acids and SaltsTaurochenodeoxycholic Acidursodoxicoltaurinebile acidsclinical trialmultiple sclerosisprogressive MSTranslation to patientsTUDCA

Identifiers

PMID39447576
PMCPMC11911100

What OpenQuestion holds

Textmetadata
LicenceTDM
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 OpenQuestion graph.