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Related Experiment Video

Updated: Jul 7, 2026

Positron Emission Tomography Imaging for In Vivo Measuring of Myelin Content in the Lysolecithin Rat Model of Multiple Sclerosis
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Propionic acid in multiple sclerosis: a phase 2b, double-blind, randomized placebo-controlled trial.

Tobias Moser1, Wolfgang Hitzl2,3, Tiago Lerda-Casaccia1

  • 1Department of Neurology, Christian Doppler University Hospital, Paracelsus Medical University and Center for Cognitive Neuroscience, European Reference Network EpiCARE, Salzburg 5020, Austria.

Brain : a Journal of Neurology
|July 5, 2026
PubMed
Summary

Propionic acid (PA) supplementation significantly reduced neuroaxonal damage in multiple sclerosis patients. This study suggests PA may be a beneficial add-on therapy for multiple sclerosis, warranting further investigation.

Keywords:
add-on therapyclinical trialmultiple sclerosisneurofilament light chainneuroprotectionpropionic acid

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Area of Science:

  • Neuroscience
  • Immunology
  • Metabolic Research

Background:

  • Propionic acid (PA), a short-chain fatty acid, plays a role in intestinal barrier integrity, immune regulation, and neuronal function.
  • Reduced PA levels are observed in individuals with multiple sclerosis (MS).
  • Preliminary data suggest PA supplementation may have immunomodulatory and clinical benefits in MS.

Purpose of the Study:

  • To evaluate the efficacy and safety of PA as an add-on therapy in adults with clinically stable MS.
  • To assess the impact of PA on neuroaxonal damage, measured by serum neurofilament light chain (sNfL) concentration.
  • To investigate the effects of PA on physical, cognitive, and patient-reported outcomes.

Main Methods:

  • A randomized, double-blind, placebo-controlled, phase 2b study (MADAI trial) involving 101 adults with stable MS.
  • Participants received either PA (500 mg twice daily) or placebo for 90 days.
  • The primary outcome was the change in age, BMI, creatinine, and baseline sNfL-adjusted serum neurofilament light chain (sNfL) concentration.

Main Results:

  • PA supplementation led to a significant reduction in sNfL levels by 17.9% (P = 0.000025).
  • The adjusted mean difference in sNfL between PA and placebo groups was significant (P = 0.045).
  • Reductions in sNfL were also noted in participants on high-efficacy disease-modifying therapies, including anti-CD20 treatments.

Conclusions:

  • PA supplementation was well-tolerated and significantly reduced sNfL levels, indicating a potential attenuation of neuroaxonal injury in MS.
  • These findings support PA as a potential add-on treatment for MS.
  • Larger, long-term studies are warranted to further evaluate PA's role in MS management.