Evidence map›Paper›PMID 42402345›Full record

ArticleBrain : a journal of neurology2026

Propionic acid in multiple sclerosis: a phase 2b, double-blind, randomized placebo-controlled trial.

Tobias Moser, Wolfgang Hitzl, Tiago Lerda-Casaccia, Michael Unterhofer, Rina Demjaha, Maria Martinez-Serrat, Michael Khalil, Andrea Harrer, Belinda Böhm, Peter Hofbauer and 4 more

Abstract read
In one paragraph

Article in Brain : a journal of neurology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
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

14 authors.

Tobias MoserDepartment of Neurology, Christian Doppler University Hospital, Paracelsus Medical University and Center for Cognitive Neuroscience, European Reference Network EpiCARE, Salzburg 5020, Austria.ORCID 0000-0002-5397-5595
Wolfgang HitzlDepartment of Ophthalmology and Optometry, Paracelsus Medical University Salzburg, Salzburg 5020, Austria.
Tiago Lerda-CasacciaDepartment of Neurology, Christian Doppler University Hospital, Paracelsus Medical University and Center for Cognitive Neuroscience, European Reference Network EpiCARE, Salzburg 5020, Austria.
Michael UnterhoferDepartment of Neurology, Christian Doppler University Hospital, Paracelsus Medical University and Center for Cognitive Neuroscience, European Reference Network EpiCARE, Salzburg 5020, Austria.
Rina DemjahaDepartment of Neurology, Medical University of Graz, Graz 8036, Austria.
Maria Martinez-SerratDepartment of Neurology, Medical University of Graz, Graz 8036, Austria.
Michael KhalilDepartment of Neurology, Medical University of Graz, Graz 8036, Austria.
Andrea HarrerDepartment of Neurology, Christian Doppler University Hospital, Paracelsus Medical University and Center for Cognitive Neuroscience, European Reference Network EpiCARE, Salzburg 5020, Austria.
Belinda BöhmDepartment for Health Sciences, Physiotherapy, Salzburg University of Applied Sciences, Puch/Salzburg 5412, Austria.
Peter HofbauerLandesapotheke Salzburg, Betrieb des Landes Salzburg, Salzburg 5020, Austria.
Janne CadamuroDepartment of Laboratory Medicine, Paracelsus Medical University, Salzburg 5020, Austria.ORCID 0000-0002-6200-9831
Ursula Huber-SchönauerDepartment of Nuclear Medicine and Endocrinology, University Hospital Salzburg, Paracelsus Medical University, Salzburg 5020, Austria.
Eugen TrinkaDepartment of Neurology, Christian Doppler University Hospital, Paracelsus Medical University and Center for Cognitive Neuroscience, European Reference Network EpiCARE, Salzburg 5020, Austria.
Peter WipflerDepartment of Neurology, Christian Doppler University Hospital, Paracelsus Medical University and Center for Cognitive Neuroscience, European Reference Network EpiCARE, Salzburg 5020, Austria.

Funding

ZeinPharmaZeinPharma Germany GmbH 64569
6 · The paper itself

Abstract

Propionic acid (PA), a microbial-derived short-chain fatty acid, contributes to intestinal barrier integrity, systemic immune regulation, and neuronal function. Individuals with multiple sclerosis show reduced PA levels, and open-label data have suggested beneficial immunomodulatory and clinical effects of supplementation. The Multiple sclerosis And DisAbility Improvement (MADAI) trial was a randomized, double-blind, placebo-controlled, single-centre, phase 2b study designed to evaluate the efficacy and safety of PA as an add-on therapy in adults with clinically stable multiple sclerosis. Between April 5 and 29 May 2024, 101 adults (64% women; mean age 45 years) were randomly assigned in a 2:1 ratio to receive PA 500 mg twice daily or matching placebo for 90 days. The primary outcome was the change in serum neurofilament light chain (sNfL) concentration, a biomarker of neuroaxonal damage, adjusted for age, body mass index, creatinine, and baseline sNfL. Secondary outcomes included physical and cognitive performance measures and patient-reported outcomes, including fatigue and quality of life scores. sNfL levels were significantly reduced in the PA group {-17.9%; from 9.77 pg/ml [95% confidence interval (CI) 9.00 to 10.60] to 8.02 pg/ml (95% CI 7.36 to 8.73); mean difference 1.75 pg/ml (95% CI 0.9 to 2.6); P = 0.000025}, while no significant change was observed in the placebo group. The adjusted mean difference in sNfL levels between the PA and placebo groups at follow-up was 0.91 pg/ml (95% CI 0.02 to 1.79; P = 0.045). Reductions in sNfL were also observed among participants in the PA arm receiving moderate-to-high efficacy disease-modifying therapies (n = 41; P = 0.0001), including those on anti-CD20 treatment (n = 27; P = 0.0005). There was a trend towards improvement in motor fatigue in the PA group. No serious adverse events related to the study medication occurred. PA supplementation was well tolerated and associated with significant reductions in sNfL, suggesting attenuation of neuroaxonal injury in multiple sclerosis. These findings support further evaluation of PA as an add-on treatment in larger, long-term studies.

Indexed as

add-on therapyclinical trialmultiple sclerosisneurofilament light chainneuroprotectionpropionic acid

Identifiers

PMID42402345
PMCPMC13337218

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.