Daily intake of propionic acid, a short-chain fatty acid produced when gut bacteria break down dietary fiber, significantly reduced blood levels of neurofilament light chain (NfL) in people with multiple sclerosis, according to data from a Phase 2b clinical trial published in the journal Brain. The findings indicate that the supplement, tested as an add-on to standard disease-modifying therapies, may help lower neuroaxonal injury in patients.
Phase 2b Trial Results and NfL Reductions
The trial, designated as the MADAI study (NCT06402487), evaluated 101 adults with clinically stable multiple sclerosis at a single medical center in Austria. Researchers defined stability as patients experiencing no relapses in the three months prior to enrollment. Participants had a mean age of 45, and 64% of the cohort were women.
Investigators randomly assigned 67 patients to receive 500 mg of propionic acid twice daily, while 34 participants received a matching placebo. Both groups maintained their existing multiple sclerosis medications throughout the 90-day trial period. According to published data, 95% of the total participants completed the study.
After 90 days, blood levels of NfL—a structural protein released into fluid compartments when nerve cell fibers, or axons, sustain damage—dropped by 17.9% in the propionic acid group. By contrast, NfL levels remained largely unchanged in the placebo group, yielding a statistically significant difference between the two cohorts at follow-up. Among a subgroup of participants who had not started or changed disease-modifying therapies within 12 months prior to the trial, NfL levels similarly decreased in the treatment arm but not in the placebo arm.
Understanding the Gut-Brain Mechanism in MS
Multiple sclerosis is an autoimmune condition characterized by chronic inflammation and damage to myelin, the protective sheath surrounding axons in the central nervous system. This pathological process results in lesion formation visible on MRI scans and gradual neurodegeneration over time.
While standard disease-modifying therapies effectively control acute inflammatory activity, clinical relapses, and new MRI lesions, study authors noted that these medications do not act directly within the central brain and spinal cord tissue. Consequently, some patients continue accumulating disability independently of overt inflammatory relapses. Researchers hypothesize that interventions targeting metabolic pathways, such as gut-derived short-chain fatty acids, may offer complementary neuroprotective effects.
Previous observational work indicates that individuals with multiple sclerosis often possess lower internal levels of propionic acid compared to healthy controls. Naturally generated by intestinal microbiota during the breakdown of dietary fibers and indigestible carbohydrates, propionic acid helps preserve intestinal barrier integrity, modulate immune system responses, and support cellular metabolism.
Trial Safety and Future Research Directions
Throughout the 90-day trial, the 500 mg twice-daily propionic acid regimen demonstrated a favorable safety profile and was generally well tolerated by participants. Secondary endpoints measured during the study included changes in patient walking speed, hand dexterity, cognitive function, fatigue, daytime sleepiness, and overall quality of life.
Despite the promising biochemical reduction in neuroaxonal injury markers, investigators emphasized that larger and longer-duration clinical trials are required. These subsequent studies must determine whether short-chain fatty acid supplementation translates into tangible, long-term clinical benefits for patients managing chronic neurodegenerative disease progression.
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