NEW trial data have revealed that propionic acid supplementation can significantly reduce a key biomarker of nerve damage in people with multiple sclerosis (MS), supporting its potential as a safe and well-tolerated add-on treatment, according to a new phase 2b clinical trial.
Propionic acid, a microbial-derived short-chain fatty acid, has been recognised to contribute to intestinal barrier integrity, systemic immune regulation, and neuronal function. People with multiple sclerosis have been shown to have reduced propionic acid levels, and open-label data have suggested beneficial effects of supplementation, although randomised evidence has remained limited.
Phase 2b MADAI Trial Design
Researchers conducted the Multiple sclerosis And DisAbility Improvement (MADAI) trial, a randomised, double-blind, placebo-controlled, single-centre, phase 2b study evaluating propionic acid as an add-on therapy in adults with clinically stable multiple sclerosis. Between April and May 2024, 101 adults (64% women; mean age 45 years) were randomly assigned 2:1 to receive propionic acid 500 mg twice daily or matching placebo for 90 days.
The primary outcome was 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.
Propionic Acid Linked to Reduced Neuroaxonal Damage
Serum neurofilament light chain levels fell significantly in the propionic acid group, by 17.9%, from 9.77 pg/mL to 8.02 pg/mL (p=0.000025), with no significant change in the placebo group. The adjusted mean difference between groups at follow-up was 0.91 pg/mL (p=0.045). Reductions were also observed among participants 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 propionic acid group, and no serious adverse events related to the study medication occurred.
Groundwork for Larger Trials
These findings have suggested that propionic acid supplementation is well tolerated and associated with significant reductions in neurofilament light chain, indicating attenuation of neuroaxonal injury in multiple sclerosis. The authors have proposed that propionic acid could address an unmet need for agents that modulate immune responses while promoting neuroprotection, and have called for larger, longer-term phase 3 trials to confirm these findings.
Reference
Moser T et al. Propionic acid in multiple sclerosis: a phase 2b, double-blind, randomized placebo-controlled trial. Brain. 2026;149(7):2286-94.
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