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Anti-inflammatory effects of nicotinamide mononucleotide (NMN) in human skeletal muscle after BFR-exercise

Yang DL, Chao KC, Yang HT, Chen KH, Dewi L, Condello G, Ye M, Nicholls A, Liao YC, Huang CY, Kuo CH
Journal of the International Society of Sports Nutrition 2026 Volume 23, issue 1, article 2632284

Bibliography

PubMed
PMID 41705654
PubMed Central
PMC12918316
DOI
10.1080/15502783.2026.2632284
Funding
The present study is sponsored by National Science and Technology Council, Taiwan, Grant number: 108-2410-H-845-022-MY3.
Competing interests
No potential conflict of interest was reported by the author(s).

Study snapshot

DesignRandomized, placebo-controlled, counterbalanced crossover trial with participant and experimenter blinding. Muscle biopsies were obtained before, immediately after, and 24 h after BFR-exercise. The abstract reports a 3-week washout between conditions, while the Methods describes crossover after a 4-week washout.
ModelUntrained young men (22.8 ± 1.5 y) with prior weight-training experience; vastus lateralis muscle biopsies analysed for mRNA (RT-PCR) and immunofluorescence (TOM20, MPO, p16INK4a, COX4, DAPI).
Samplen=11 (15 enrolled, 4 withdrew for scheduling).
InterventionOral gelatin capsules containing 300 mg NMN (AbinoNutra) four times daily (total 1200 mg/d) or 300 mg cornstarch placebo, for 7 consecutive days before and including the BFR-exercise day. The paper reports the crossover washout inconsistently: 3 weeks in the abstract/study-design description and 4 weeks later in Methods. Pre-exercise stimulus: three cycles of 5-min thigh-cuff occlusion at 180 mmHg, then 4 × 8 back squats at 70% 1-RM.
DurationSeven days of supplementation per condition with a 24-hour post-exercise recovery window. The paper is internally inconsistent on crossover washout: 3 weeks in the abstract versus 4 weeks in the Methods.
EndpointsTNF-α mRNA in muscle (RT-PCR); IL-10 mRNA in muscle; p21 mRNA in muscle; Nucleated cell infiltration in necrotic regions (DAPI); Mitochondrial content in muscle tissue (TOM20 immunofluorescence); Rating of perceived exertion (RPE)

What the study showed, in plain terms

Blood-flow-restriction resistance exercise creates a deliberately stressful muscle-repair challenge. This randomized, placebo-controlled, counterbalanced crossover study tested whether short-term NMN changes that acute response in human skeletal muscle.

Eleven young non-athletic men with prior weight-training experience completed both conditions. They received 1,200 mg/day NMN or cornstarch placebo for seven days around the exercise challenge, with multiple vastus lateralis biopsies before and after exercise. The paper reports participants and experimenters were blinded to treatment assignment.

NMN attenuated the exercise-induced rises in TNF-α and IL-10 mRNA, delayed the rise in p21 mRNA, and delayed clearance of infiltrating cells from necrotic regions. In the placebo condition, TOM20 staining indicated a 171% increase in muscle mitochondrial content at 24 hours; this increase was absent with NMN.

The microscopy also showed mitochondria-rich MPO-positive phagocytes accumulating near disrupted myofibers. The authors interpret the spatial pattern as consistent with phagocyte-to-myofiber mitochondrial transfer, but the experiment did not directly track organelles moving between cells. The study therefore supports an anti-inflammatory effect of short-term NMN in this exercise model while leaving the long-term consequences for adaptation, hypertrophy, strength and performance unresolved.

Key findings

  • TNF-α mRNA in muscle rose 187% at 0 h post-exercise on placebo (p<0.01, d=1.58) and only 106% on NMN (p<0.01 vs baseline, and significantly lower than placebo at the same time point).
  • IL-10 mRNA rose 67% at 0 h on placebo (p<0.05, d=0.86); the rise was suppressed to a non-significant change on NMN.
  • p21 mRNA (myogenic terminal differentiation marker) rose 143% at 0 h and 338% at 24 h on placebo; the 24 h rise was reduced to 257% on NMN.
  • Nucleated cell infiltration in necrotic muscle regions returned to baseline by 24 h on placebo but stayed elevated at +142% at 24 h on NMN (p<0.05), consistent with a delayed resolution of inflammation.
  • Mitochondrial content in muscle tissue (TOM20 staining) rose 171% at 24 h post-exercise on placebo (p=0.02, d=2.60); this increase was completely abolished on NMN.
  • Immunofluorescence with TOM20, MPO and COX4 showed infiltrating neutrophils carrying substantially more mitochondria than the myofiber cytoplasm they were engaging with, with the densest mitochondrial signal at the necrotic disruption sites — consistent with a directional, immune-cell-mediated donation of mitochondria to damaged fibres within 24 hours.
  • NMN did not alter the participants' rated perceived exertion during the exercise session (8.1 AU on NMN vs 8.5 AU on placebo).

What this study can and cannot tell us

The sample is small (n=11) and homogeneous: young non-athletic men with prior weight-training experience. There is no direct read-out for older adults, women, trained athletes, or people with different baseline inflammatory states.

The dosing period was short—seven days of 1,200 mg/day. The trial cannot establish whether months or years of NMN use would produce the same acute response or whether muscle adapts over time.

The primary read-outs are muscle-biopsy mRNA and immunofluorescence at 0 and 24 hours. The trial did not follow participants through a training program and did not measure downstream hypertrophy, strength or performance, so the practical effect of dampening this inflammatory response is unknown.

The mitochondrial-transfer interpretation is inferential. Fixed-tissue staining showed mitochondria-rich phagocytes near damaged myofibers and a spatial gradient consistent with transfer, but no live-cell or tracer experiment directly demonstrated organelle movement from phagocytes into human myofibers.

The paper is internally inconsistent about the crossover washout: the abstract states a 3-week washout between conditions, whereas the Methods section describes crossing over after a 4-week washout. This reporting discrepancy does not change the measured acute outcomes but should be noted.

The study was funded by Taiwan's National Science and Technology Council and reported no potential conflict of interest. The NMN capsules were AbinoNutra-branded; the paper did not report a manufacturer role in funding or analysis.

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Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology