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

  1. Grith Højfeldt
  2. Joris Michaud
  3. Ann Damgaard
  4. Karoline Karlog
  5. Eugenia Migliavacca
  6. Sonia Karaz
  7. Elham P. Micol
  8. Odd E. Johansen
  9. Leonidas G. Karagounis
  10. Bjørk W. Helge
  11. William Hagemann
  12. Michael Kjaer
  13. Jerome N. Feige
  14. Pascal Stuelsatz
  15. Abigail L. Mackey
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Abstract

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.

Methods

This 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.

Results

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. 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%).

Conclusion

Daily 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 registration

NCT04874662

One Sentence Summary

Muscle regeneration is enhanced by nicotinamide and pyridoxine supplementation, accelerating recovery and offering therapeutic potential.

Article activity feed

  1. Version published to 10.1101/2025.03.24.25323226v1 on medRxiv