{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T09:29:04Z","timestamp":1791538144355,"version":"4.3.4"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T00:00:00Z","timestamp":1783296000000},"content-version":"vor","delay-in-days":5,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ZeinPharma"},{"DOI":"10.13039\/501100008833","name":"ZeinPharma Germany GmbH","doi-asserted-by":"publisher","award":["64569"],"award-info":[{"award-number":["64569"]}],"id":[{"id":"10.13039\/501100008833","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n                  <jats:p>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.<\/jats:p>\n                  <jats:p>sNfL levels were significantly reduced in the PA group {\u221217.9%; 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.<\/jats:p>\n                  <jats:p>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.<\/jats:p>","DOI":"10.1093\/brain\/awag099","type":"journal-article","created":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T12:20:18Z","timestamp":1773404418000},"page":"2286-2294","source":"Crossref","is-referenced-by-count":3,"title":["Propionic acid in multiple sclerosis: a phase 2b, double-blind, randomized placebo-controlled trial"],"prefix":"10.1093","volume":"149","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5397-5595","authenticated-orcid":false,"given":"Tobias","family":"Moser","sequence":"first","affiliation":[{"name":"Department of Neurology, Christian Doppler University Hospital, Paracelsus Medical University and Center for Cognitive Neuroscience, European Reference Network EpiCARE , Salzburg 5020 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Doppler University Hospital, Paracelsus Medical University and Center for Cognitive Neuroscience, European Reference Network EpiCARE , Salzburg 5020 ,","place":["Austria"]},{"name":"Department of Dermatology and Allergology, University Hospital Salzburg, Paracelsus Medical University , Salzburg 5020 ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Belinda","family":"B\u00f6hm","sequence":"additional","affiliation":[{"name":"Department for Health Sciences, Physiotherapy, Salzburg University of Applied Sciences , Puch\/Salzburg 5412 ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Hofbauer","sequence":"additional","affiliation":[{"name":"Landesapotheke Salzburg, Betrieb des Landes Salzburg , Salzburg 5020 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