Specifically, NMN supplementation was reported to have lowered inflammatory cytokine mRNA expression, such as TNF-α, in skeletal muscle after blood flow restriction-resistance exercise.
Writing in the Journal of the International Society of Sports Nutrition, researchers said that this was the first human study to report the findings.
“We were quite surprised by the findings. They showed that NMN has very strong anti-inflammatory action,” Professor Chia-Hua Kuo from The Education University of Hong Kong’s Department of Health and Physical Education and corresponding author on the new paper, told NutraIngredients.
The pilot study involved 11 men aged 20 to 30.
They were randomized to receive either a capsule containing 300mg of NMN each or a placebo four times per day for six days.
They then underwent blood flow restriction (BFR) before undergoing resistance exercise 10 minutes later.
“Blood flow restriction-resistance exercise is actually very inflammatory-inducing. Resistance exercise itself can cause muscle damage. In this study, we performed blood flow restriction before resistance exercise, which restricts the amount of blood going in a particular direction in the muscle,” said Prof Kuo. “This causes ischemia in the muscles and when you release the pressure all of a sudden, you are going to have a huge amount of inflammatory response. Combining blood flow restriction and resistance exercise will produce a lot of inflammation and we are using this model to see whether NMN can lower inflammation.”
Muscle biopsy was performed at baseline, post-exercise and during the recovery period, which was the first 24 hours post-exercise, or the seventh day of the study, when they also took an NMN or placebo capsule four times per day.
As this was a crossover study, the participants underwent the same protocol but had swapped their intervention after a three-week washout period.
The NMN used in this study was a trademarked ingredient known as AbinoNutra provided by Connecticut-based company Albinopharm.
Inflammation reduced
One of the key findings of the study was how the inflammatory marker TNF-α was reduced when participants took NMN.
Specifically, TNF-α had increased by 187% after BFR-exercise and returned to baseline within 24 hours.
However, this response was attenuated by NMN supplementation, which led to a significantly lower increase of TNF-α by 106%.
Another inflammatory marker, interleukin-10 (IL-10), also increased by 67% immediately after BFR-exercise and normalizing after 24 h. The IL-10 mRNA response was also minimized when NMN was supplemented.
NMN supplementation also significantly suppressed P21 mRNA expression in skeletal muscle following BFR-exercise at the 24th hour of the BFR-exercise.
P21 is a marker for muscle differentiation. The delayed rise in P21 mRNA expression also meant a slower myogenic differentiation - the process leading to muscle tissue formation.
Balancing the amount of inflammation
While inflammation is essential for muscle growth after injurious challenges, Prof Kuo said that in practice, the inflammation should be put under control.
This is important to prevent the overexertion of immune cells and their source, the bone marrow stem cells. Since immune cells are needed for clearing inflammation-induced senescent muscle cells, the higher the inflammation, the higher the number of immune cells needed to clear senescent cells.
Also, a bigger body size signals higher basal inflammation, which also means a higher rate of cell renewal and bone marrow stem cells required.
In the long term, bone marrow stem cell exhaustion can lead to issues such as shrinking bones and osteoporosis, said Prof Kuo.
“Muscle hypertrophy is driven by inflammation, but in practice, you do not want to induce it too much,” he said. “When the muscle cells are unhealthy, they will continuously lead to the withdrawal of bone marrow stem cells, which can cause bone shrinkage, and if you want to prevent the exhaustion of bone marrow stem cells, then you need to suppress the inflammation.”
“Exercise helps you to activate inflammation, and the NNM helps you to lower inflammation, and now you have the two opposing tools to help you to manipulate the system,” he added.
Having established NMN as possessing strong anti-inflammatory properties, he said that the next step would be to identify the amount of inflammation to suppress and the optimal dose of NMN needed through response studies.
“Dosage and timing of NMN supplementation are going to be the major scientific questions for the future,” he said.
NMN reduces mitochondria in exercised muscle
The study also showed that NMN supplementation can prevent BFR exercise-induced increases in the mitochondrial content within muscle tissue.
Specifically, BFR exercise had increased the mitochondrial content in exercised muscle by 171% after 24 hours of recovery. However, this exercise response was prevented by NMN supplementation.
According to the researchers, mitochondrial gains are generally considered as a favorable adaptation after exercise training, as more mitochondria allow efficient ATP production in cells.
However, in this study, the researchers could not conclude whether the lack of mitochondrial increase in BFR-exercised muscle by NMN supplementation should be considered a malignant metabolic outcome for humans.
This is because, as shown in a 2007 animal study, reducing mitochondrial content in skeletal muscle through genetic manipulation can substantially increase longevity in mice.
“The balance between the preservation of quiescent stem cells (low mitochondria, high cell renewal) in the bone marrow niche and activated stem cells (high mitochondria, mobilizable) for tissue regeneration may be more important to function and health in vivo,” the researchers added. “The underlying mechanism explaining the inhibitory effect of NMN on mitochondrial gain requires further investigation.”
New role of immune cell uncovered
The study also found that the immune cell neutrophils are a rich source of mitochondria and are able to donate mitochondria to damaged myofibers.
This is because the researchers found that in some of the damaged myofibers, or muscle fibers, mitochondria have spread from myofiber-engaged neutrophils by forming web-like structures.
This observation, along with evidence of mitochondria being projected from myofiber-engaged neutrophils onto disrupted myofibers following BFR exercise, suggests a new function for neutrophils in rejuvenating post-exercise muscle.
“We normally think the mitochondria are produced inside the myofiber, which is not correct. The mitochondria within the myofiber actually come from bone marrow cells, which include immune cells,” said Prof Kuo. “For myofiber to receive mitochondria, the only way to do so is through muscle fiber damage, which will attract immune cells and bone marrow stem cells to get into the damaged site and donate their mitochondria.”
Source: Journal of the International Society of Sports Nutrition. doi: 10.1080/15502783.2026.2632284. “Anti-inflammatory effects of nicotinamide mononucleotide (NMN) in human skeletal muscle after BFR-exercise.” Authors: D-L. Yang, et al.
