What does NMN do

Published: 2:20 p.m. PST May 7, 2020 | Updated: 11:05 a.m. PST Oct 13, 2021

NMN has been shown to boost levels of an essential molecule with crucial roles in over 400 metabolic reactions called nicotinamide adenine dinucleotide (NAD+). Falling NAD+ levels with age have been linked to age-related conditions in animals like mice and rats and even humans, but increasing NAD+ with NMN improves these ailments.

Age-related NAD+ level reductions have been linked to a plethora of age-related human diseases, and some studies provide evidence that increasing NAD+ combats these conditions. For example, one study has shown that NMN supplementation increases muscle function in aged men while another indicates that it increases insulin sensitivity in older women.

NMN studies from institutes like Harvard University and Washington University have shown that supplementing with the molecule or enhancing NMN synthesis promotes longevity and health during aging in rodents. Sinclair and colleagues found that when aged mice drank NMN-infused water, their running endurance almost doubled. Further studies have demonstrated that injecting mice with NMN preserves cognition during aging. Moreover, a study from Imai and colleagues indicates that an upsurge in NMN synthesis more than doubles the remaining lifespan of mice.

(Das et al., 2018 | Cell) NMN substantially enhances running endurance in aged mice. Aged mice (20 months old) given 400 mg/kg/day of NMN in drinking water displayed significantly extended running times before they stopped running from exhaustion.

(Tarantini et al., 2019 | Redox Biology) NMN provides neuroprotective benefits to preserve cognition in aged mice. The heatmap showing the paths that mice took to escape from a water maze indicates that aged mice made more errors than young mice but that taking NMN ameliorated these mistakes. The graph to the right shows aged mice made significantly more memory errors than young mice in the water maze but that NMN rescued aged mouse memory. These findings support that NMN enhances cognition during aging.

(Yoshida et al., 2019 | Cell Metabolism) Injecting mice with an enzyme that drives NMN synthesis more than doubles the remaining lifespan of female mice. Injecting female mice with vesicles containing the NMN synthesis enzyme nicotinamide phosphoribosyltransferase (NAMPT) more than doubles their remaining lifespan (Figure J). The upsurge in NMN synthesis also improves overall fitness as seen by the health of the mice’s fur coat (top mouse injected with vesicles containing NAMPT in Figure K).

(Hong et al., 2021 | Frontiers in Cell and Developmental Biology) NMN ameliorates a number of age-related diseases by increasing NAD+ levels. NMN’s health-related benefits extend to tissues ranging from the heart to the eye to the brain.

Taking NMN may provide a promising means to combat age-related diseases and ailments. Below is a summary of major studies elucidating the potential benefits of NMN.

Research Category  and Summary / Conclusion

Bone Repair

• Doubles the presence of new bone-forming cells in mice.²

Cancer

• Increases the potency of PD-1-mediated immunotherapy to reduce tumor size two-fold in mice.³
• Enhances cognition measurements two-fold in mice after chemoteherapy.³²

Cardiovascular

• Doubles the heart's contractile capacity in a heart disease mouse model.⁴
• Enhances cognition measurements two-fold in mice after chemoteherapy.²³
• Doubles the flexibility and elasticity of blood vessels to reverse their functional decline in mice.²⁵

DNA Repair

• Doubles the length of liver cell telomeres in mice with liver fibrosis.⁵
• Doubles DNA-repairing PARP1 protein activation in older mice.¹⁸

Eye Protection

• Reduces eye cell (photoreceptor) death by four times after their detachment from the retina in mouse eyes.⁶
• Diminishes eye cell death more than three times in a mouse dry eye disease model.¹⁷
• Reduces the size of eye wounds by 25% after nerve fiber detachment.³¹

Immunity

• NMN cocktail therapy promotes recovery from CoVID-19.⁷

Longevity

• Boosting NMN synthesis in cells more than doubles remaining lifespan in mice.⁸
• Significantly restores cardiovascular, cognitive, and metabolic decline in mice.²⁰

Metabolism

• Substantially improves insulin sensitivity in older women.⁹
• More than doubles mitochondrial cell energy production in mice.²¹
• Significantly improves insulin sensitivity in mouse age-induced diabetes.²⁷
• Doubles the amount of cell energy-generating mitochondria in the livers of obese mice.²⁹

Neurological

• Significantly improves cognition and memory in rodents with Alzheimer's disease.¹⁰
• Reduces depressive behavior by half in a mouse depression model.¹¹
• Improves cognitive function by 50% following brain hemorrhage in mice.¹²
• More than doubles the average time spent stroke-free in rats fed diets high in salt.³³

Reproduction

• Significantly improves female fertility in mice.¹³
• Protects egg cells from cell death two-fold from environmental toxin exposure in pigs.¹⁹

Skin and Muscle

• Significantly promotes the activation of genes with roles in muscle remodeling in older women.⁹

Organ Health

• Reduces blood test measurements for liver damage by half in a mouse chronic alcohol consumption model.¹⁴
• Reduces kidney cell death by 40% and significantly protects against kidney damage from ischemia injury.¹⁵
• Significantly inhibits liver scarring gene activity and subsequent liver scarring in mice.¹⁶
• Increases the number of intestinal stem cells by 20% in mice.³⁰

Mechanism

• An NMN-specific transporter in mammalian guts called SLC12A8 has been identified.¹

Reference Links

• Alessia Grozio, Kathryn F. Mills, Jun Yoshino, Santina Bruzzone, Giovanna Sociali, Kyohei Tokizane, Hanyue Cecilia Lei, Richard Cunningham, Yo Sasaki, Marie E. Migaud, Shin-ichiro Imai.  Slc12a8 is a nicotinamide mononucleotide transporter.  Nat Metab, 2019; DOI: 10.1038/s42255-018-0009-4.
• Huang RX, Tao J. Nicotinamide mononucleotide attenuates glucocorticoid-induced osteogenic inhibition by regulating the SIRT1/PGC-1α signaling pathway. Mol Med Rep. 2020;22(1):145-154. doi:10.3892/mmr.2020.11116
• Lv H, Lv G, Chen C, Zong Q, Jiang G, Ye D, Cui X, He Y, Xiang W, Han Q, Tang L, Yang W, Wang H. NAD+ Metabolism Maintains Inducible PD-L1 Expression to Drive Tumor Immune Evasion. Cell Metab. 2020 Nov 9. DOI: 10.1016/j.cmet.2020.10.021
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• Hisayuki Amano, Arindam Chaudhury, Cristian Rodriguez-Aguayo, Lan Lu, Viktor Akhanov, Andre Catic, Yury V. Popov, Eric Verdin, Hannah Johnson, Fabio Stossi, David A. Sinclair, Eiko Nakamaru-Ogiso, Gabriel Lopez-Berestein, Jeffrey T. Chang, Joel R. Neilson, Alan Meeker, Milton Finegold, Joseph A. Baur, Ergun Sahin.  Telomere dysfunction induces sirtuin repression that drives telomere-dependent disease.  Cell Metab, 2019; DOI: 10.1016/j.cmet.2019.03.001.
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• Xie X, Yu C, Zhou J, et al. Nicotinamide mononucleotide ameliorates the depression-like behaviors and is associated with attenuating the disruption of mitochondrial bioenergetics in depressed mice. J Affect Disord. 2020;263:166-174. doi:10.1016/j.jad.2019.11.147
• Liang Shu, Xiaolei Shen, Yaxue Zhao, Xinwei He, Jiawen Yin, Jingjing Su, Qiang Li, Jianren Liu.  Mechanisms of transformation of nicotinamide mononucleotides to cerebral infarction hemorrhage based on MCAO model.  Saudi J Biol Sci, 2020; DOI: 10.1016/j.sjbs.2019.12.023.
• Yang L, Lin X, Tang H, Fan Y, Zeng S, Jia L, Li Y, Shi Y, He S, Wang H, Hu Z, Gong X, Liang X, Yang Y, Liu X. Mitochondrial DNA mutation exacerbates female reproductive aging via impairment of the NADH/NAD+ redox. Aging Cell. 2020 Sep;19(9):e13206. doi: 10.1111/acel.13206.
• Assiri MA, Ali HR, Marentette JO, Yun Y, Liu J, Hirschey MD, Saba LM, Harris PS, and Fritz KS.  Investigating RNA expression profiles altered by nicotinamide mononucleotide therapy in a chronic model of alcoholic liver disease.  Hum Genomics, 2019; DOI: 10.1186/s40246-019-0251-1.
• Jia Y, Kang X, Tan L, Ren Y, Qu L, Tang J, Liu G, Wang S, Xiong Z and Yang L (2021) Nicotinamide Mononucleotide Attenuates Renal Interstitial Fibrosis After AKI by Suppressing Tubular DNA Damage and Senescence. Front. Physiol. 12:649547. doi: 10.3389/fphys.2021.649547
• Zong Z, Liu J, Wang N, Yang C, Wang Q, Zhang W, Chen Y, Liu X, Deng H. Nicotinamide mononucleotide inhibits hepatic stellate cell activation to prevent liver fibrosis via promoting PGE2 degradation. Free Radic Biol Med. 2020 Nov 19:S0891-5849(20)31626-9. doi: 10.1016/j.freeradbiomed.2020.11.014. Epub ahead of print. PMID: 33220424.
• Meng YF, Pu Q, Dai SY, Ma Q, Li X, Zhu W. Nicotinamide Mononucleotide Alleviates Hyperosmolarity-Induced IL-17a Secretion and Macrophage Activation in Corneal Epithelial Cells/Macrophage Co-Culture System. J Inflamm Res. 2021 Feb 22;14:479-493. doi: 10.2147/JIR.S292764. PMID: 33658825; PMCID: PMC7917392.
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