Nicotinamide and Pyridoxine supplementation stimulates muscle stem cells in a randomized clinical trial on muscle repair

Skeletal muscle regeneration is a cardinal feature of muscle pathologies and is crucial for post-exercise recovery and traumatic sports injuries. Regeneration of damaged muscle in humans is a prolonged process and is accompanied by pain and physical dysfunction, highlighting the unmet need for effective interventions to accelerate the regenerative process. Through cellular and preclinical models, we have previously identified nicotinamide (NAM) and pyridoxine (PN) as potent stimulators of Muscle Stem Cells (MuSCs). Herein we investigated if a combination of NAM and PN could enhance MuSC activity and improve muscle regeneration in healthy volunteers during recovery from eccentric contractions. MethodsThis randomized, double-blind, placebo-controlled trial enrolled male participants aged 18-50 years supplemented daily with 714mg NAM and 19mg PN (NAM/PN) or placebo for 8 days following unilateral eccentric muscle contractions using Neuromuscular Electrical Stimulation (NMES). MuSC was quantified by immunohistofluorescence on vastus lateralis muscle biopsies. Results39 out of 43 enrolled participants completed the study. Supplementation of NAM/PN was well tolerated and increased blood concentrations of NAM and PN vitamers. The NMES protocol caused myofiber necrosis and triggered a strong MuSC response. After 8 days, the number of Pax7, MyoD, and myogenin positive cells per damaged fiber was significantly higher in NAM/PN vs placebo groups (+29-67%). NAM/PN also increased the proportion of regenerating fibers re-expressing embryonic myosin (+37%). ConclusionDaily oral NAM/PN supplementation following eccentric muscle damaging contractions enhances MuSC activity and accelerates muscle regeneration. These findings provide new possibilities for targeted therapeutic interventions in muscle repair. Trial registrationNCT04874662 One Sentence SummaryMuscle regeneration is enhanced by nicotinamide and pyridoxine supplementation, accelerating recovery and offering therapeutic potential.