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In preclinical models, nicotinamide (NAM) and pyridoxine (PN) synergistically increased MuSC proliferation and differentiation, and accelerated muscle regeneration. Herein we tested if NAM\/PN could enhance MuSC activity and muscle regeneration in a randomized, placebo\u2010controlled clinical trial. Men aged 18\u201349 years were supplemented daily with 714\u00a0mg NAM and 19\u00a0mg PN, or placebo, for 9 days following one session of damaging unilateral eccentric muscle contractions. The primary endpoint was MuSC activity via immunohistofluorescence on biopsy sections from the vastus lateralis muscle. Histological markers of muscle regeneration constituted secondary outcomes, and muscle damage was validated with clinical markers. 39 out of 43 enrolled participants completed the study. Supplementation of NAM\/PN was well tolerated and increased blood concentrations of NAM and PN vitamers. 8 days after the contraction protocol, the number of Pax7, MyoD, and myogenin positive cells per damaged fiber was significantly higher in NAM\/PN vs placebo groups (+29%\u201367%). NAM\/PN also increased the proportion of regenerating fibers (+37%). Daily oral NAM\/PN supplementation after high intensity muscle contractions enhances MuSC activity and accelerates muscle regeneration and repair, providing new opportunities for therapeutic applications in muscle recovery and muscle wasting disorders.<\/jats:p>","DOI":"10.1002\/advs.202518471","type":"journal-article","created":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T19:15:29Z","timestamp":1774379729000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Nicotinamide and Pyridoxine Supplementation Enhances Muscle Stem Cell Activity and Muscle Regeneration in Humans: A Randomized Placebo\u2010Controlled Clinical Trial of High Force Eccentric Contraction Recovery in Healthy Young Men"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2962-8080","authenticated-orcid":false,"given":"Grith","family":"H\u00f8jfeldt","sequence":"first","affiliation":[{"name":"Institute of 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Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elham","family":"Pazirandeh\u2010Micol","sequence":"additional","affiliation":[{"name":"Translational Research Nestl\u00e9 Health Science Vevey Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Odd E.","family":"Johansen","sequence":"additional","affiliation":[{"name":"Translational Research Nestl\u00e9 Health Science Vevey Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonidas G.","family":"Karagounis","sequence":"additional","affiliation":[{"name":"Translational Research Nestl\u00e9 Health Science Vevey Switzerland"},{"name":"Mary MacKillop Institute for Health Research (MMIHR) Australian Catholic University  Melbourne Australia"},{"name":"Institute of Social and Preventive Medicine (ISPM) University of Bern  Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bj\u00f8rk W.","family":"Helge","sequence":"additional","affiliation":[{"name":"Institute of Sports Medicine Copenhagen Department of Orthopaedic Surgery Copenhagen University Hospital \u2013 Bispebjerg and Frederiksberg  Copenhagen Denmark"},{"name":"Department of Clinical Medicine Faculty of Health and Medical Sciences University of Copenhagen  Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Hagemann","sequence":"additional","affiliation":[{"name":"Institute of Sports Medicine Copenhagen Department of Orthopaedic Surgery Copenhagen University Hospital \u2013 Bispebjerg and Frederiksberg  Copenhagen Denmark"},{"name":"Department of Clinical Medicine Faculty of Health and Medical Sciences University of Copenhagen  Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4582-8755","authenticated-orcid":false,"given":"Michael","family":"Kjaer","sequence":"additional","affiliation":[{"name":"Institute of 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