Over the past month, the "anti-aging supplement" NMN has seen considerable progress in mechanism research and animal experiments, with remarkable findings. However, the latest clinical trial yielded underwhelming results. Why is that? Let TIMEPIE bring you the updates and analysis:
PART 01 Mechanism Research
Intravenous NMN Increases Brain NAD+ Levels
Professor Chao-Yu Miao’s team from the Department of Pharmacology, Naval Medical University, intravenously injected a high dose of 2g/kg NMN into normal mice and mice with ischemic stroke induced by middle cerebral artery occlusion. Key findings:
- After injection, NMN levels in mouse serum rose sharply but dropped rapidly within 15 minutes, while NAD+ levels remained stable over the 30-minute observation period.
- Over time, both NMN and NAD+ accumulated in various tissues and organs, including the brain, with the highest concentration in the kidneys—suggesting NMN may have potential as a "kidney-protective agent."
- For mice with ischemic stroke, cerebral infarction area shrank 24 hours after NMN injection; no acute toxicity was observed in mice even with high-dose NMN over 14 days.
Original article link: https://www.eurekaselect.com/article/123721
NMN Improves the Hepatic Protein Acetylome in Aged Mice
Professor Haiteng Deng’s team from Tsinghua University found that with aging, acetylation modification increases in multiple liver proteins, including those regulating fatty acid β-oxidation, tricarboxylic acid cycle, valine degradation, as well as NAD(P)+ transhydrogenase (NNT) and cytochrome 3a25 (Cyp3a25).
NMN treatment inhibited this age-related increase in protein acetylation. The study suggests NMN therapy can reprogram age-associated acetylation to reduce age-related functional impairments.
Original article link: https://www.mdpi.com/20734409/11/10/1654/htm
NMN Boosts AMPK Activity by Over 12-Fold!
Japanese scientist Takahiko Yamamoto and colleagues treated human MCF-7 breast cancer cells with 1mg/mL NMN. Key results:
- NMN more than doubled intracellular NAD+ levels.
- Compared to untreated cells, AMPK activity in NMN-treated cells increased by 1230.5% after 1 hour and remained 849.2% higher after 24 hours—indicating NMN has a long-lasting effect on enhancing AMPK activity, potentially promoting mitochondrial biogenesis and autophagy in cells.
Notably, this study used breast cancer cells, which have abnormal metabolic states. Whether NMN exerts similar effects on normal cells requires further investigation.
Original article link: https://www.jelsciences.com/articles/jbres1480.pdf
PART 02 Efficacy Research
NMN Protects Against Age-Related Decline in Intestinal Structure and Function
A research team from the Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, found that NMN supplements protect intestinal function in aged mice.
NMN supplementation has significant effects on intestinal morphology, gut microbiota, inflammation, oxidative stress resistance, and intestinal barrier function:
- After 4 months of NMN administration, NAD+ levels in the jejunum of aged mice increased significantly, jejunal structure improved (villus length increased, crypt depth decreased).
- NMN also reduced the expression of inflammatory factors, reactive oxygen species production, and senescence-induced cellular changes to a certain extent.
Original article link: https://pubs.rsc.org/en/content/articlelanding/2022/fo/d2fo00525e
NMN May Alleviate Symptoms in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Patients
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a severe, complex chronic rheumatic immune disease that leaves patients in a highly debilitated state.
Researchers Mona Dehhaghi and Gilles J. Guillemin from the University of New South Wales found that impaired tryptophan metabolism plays a key role in the pathophysiology of ME/CFS. Since tryptophan is a critical precursor for serotonin and NAD+, this suggests NAD+ levels may be closely linked to the disease.
The researchers proposed that supplementing with NAD+ precursors (e.g., NMN and NR) may alleviate ME/CFS symptoms and improve patients’ quality of life.
Original article link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9116917/
NMN Repairs Mitochondrial Function and Prevents Diabetic Peripheral Neuropathy
Axonal degeneration in the pathogenesis of diabetic peripheral neuropathy (DPN) is associated with impaired NAD+ metabolism.
A research team from the University of Maryland tested the efficacy of NAD+ precursors (NMN and NR) in preventing DPN in type 1 and type 2 diabetes models. Key results after 2 months of NMN/NR supplementation:
- Sensory function improved in diabetic rat and mouse models.
- Sciatic and caudal nerve conduction velocities normalized.
- Loss of intraepidermal nerve fibers in hind paw skin samples was reduced.
Notably, NAD+ precursor supplementation did not significantly improve glucose tolerance, insulin levels, or insulin resistance.
Original article link: https://www.mdpi.com/1422-0067/23/9/4887/htm