Nicotinamide and Pyridoxine Supplementation Enhances Muscle Stem Cell Activity and Muscle Regeneration in Humans: A Randomized Placebo-Controlled Clinical Trial of High Force Eccentric Contraction Recovery in Healthy Young Men.

2026-03-24
Advanced science (Weinheim, Baden-Wurttemberg, Germany) 13(28)
- Grith Højfeldt
- Joris Michaud
- Ann Damgaard
- Karoline Karlog
- Eugenia Migliavacca
- Sonia Karaz
- Elham Pazirandeh-Micol
- Odd E Johansen
- Leonidas G Karagounis
- Bjørk W Helge
- William Hagemann
- Michael Kjaer
- Jerome N Feige
- Pascal Stuelsatz
- Abigail L Mackey

PubMed: 41874466
DOI: 10.1002/advs.202518471

Study Design

Type: Randomized Controlled Trial (RCT)
Population: Men aged 18-49 years
Methods: Randomized, placebo-controlled clinical trial; daily supplementation with 714 mg NAM and 19 mg PN, or placebo, for 9 days following one session of damaging unilateral eccentric muscle contractions
Blinding: Double-blind
Duration: 9 days
Funding: Unclear

Muscle Stem Cells (MuSCs) drive muscle regeneration and slow pathological progression of muscle diseases. 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-controlled clinical trial. Men aged 18-49 years were supplemented daily with 714 mg NAM and 19 mg 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%-67%). 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.

Research Insights

Vitamin B3→Increased Muscle Stem Cell Activity
the number of Pax7, MyoD, and myogenin positive cells per damaged fiber was significantly higher in NAM/PN vs placebo groups (+29%-67%)
Effect
Beneficial
Effect size
Moderate
Dose
19 mg/day
Vitamin B3→Increased Muscle Stem Cell Count
the number of Pax7, MyoD, and myogenin positive cells per damaged fiber was significantly higher in NAM/PN vs placebo groups (+29%-67%)
Effect
Beneficial
Effect size
Moderate
Dose
19 mg/day
Vitamin B3→Increased Proportion of Regenerating Fibers
NAM/PN also increased the proportion of regenerating fibers (+37%)
Effect
Beneficial
Effect size
Moderate
Dose
19 mg/day
Vitamin B3→Increased Regenerating Fiber Count
NAM/PN also increased the proportion of regenerating fibers (+37%)
Effect
Beneficial
Effect size
Moderate
Dose
19 mg/day
Vitamin B6→Increased Muscle Stem Cell Activity
the number of Pax7, MyoD, and myogenin positive cells per damaged fiber was significantly higher in NAM/PN vs placebo groups (+29%-67%)
Effect
Beneficial
Effect size
Moderate
Dose
19 mg/day
Vitamin B6→Increased Muscle Stem Cell Count
the number of Pax7, MyoD, and myogenin positive cells per damaged fiber was significantly higher in NAM/PN vs placebo groups (+29%-67%)
Effect
Beneficial
Effect size
Moderate
Dose
19 mg/day
Vitamin B6→Increased Proportion of Regenerating Fibers
NAM/PN also increased the proportion of regenerating fibers (+37%)
Effect
Beneficial
Effect size
Moderate
Dose
19 mg/day
Vitamin B6→Increased Regenerating Fiber Count
NAM/PN also increased the proportion of regenerating fibers (+37%)
Effect
Beneficial
Effect size
Moderate
Dose
19 mg/day

Adverse Events Reported

Vitamin B3→Overall tolerability
Supplementation of NAM/PN was well tolerated.
Finding
Reported
Vitamin B6→Overall tolerability
Supplementation of NAM/PN was well tolerated.
Finding
Reported