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
- 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
Skin and Muscle
- 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
- 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
- Martin AS, Abraham DM, Hershberger KA, et al. Nicotinamide mononucleotide requires SIRT3 to improve cardiac function and bioenergetics in a Friedreich’s ataxia cardiomyopathy model. JCI Insight. 2017;2(14):e93885. Published 2017 Jul 20. doi:10.1172/jci.insight.93885
- 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.
- Chen X, Amorim JA, Moustafa GA, Lee JJ, Yu Z, Ishihara K, Iesato Y, Barbisan P, Ueta T, Togka KA, Lu L, Sinclair DA, Vavvas DG. Neuroprotective effects and mechanisms of action of nicotinamide mononucleotide (NMN) in a photoreceptor degenerative model of retinal detachment. Aging (Albany NY). 2020 Dec 29;12. doi: 10.18632/aging.202453. Epub ahead of print. PMID: 33373320.
- Omran HM, Almaliki MS. Influence of NAD+ as an ageing-related immunomodulator on COVID 19 infection: A hypothesis. J Infect Public Health. 2020 Sep;13(9):1196-1201. doi: 10.1016/j.jiph.2020.06.004. Epub 2020 Jun 7. PMID: 32534944; PMCID: PMC7275989.
- Yoshida M, Satoh A, Lin JB, et al. Extracellular Vesicle-Contained eNAMPT Delays Aging and Extends Lifespan in Mice. Cell Metab. 2019;30(2):329-342.e5. doi:10.1016/j.cmet.2019.05.015
- Yoshino M, Yoshino J, Kayser BD, Patti G, Franczyk MP, Mills KF, Sindelar M, Pietka T, Patterson BW, Imai SI, Klein S. Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science. 2021 Apr 22:eabe9985. doi: 10.1126/science.abe9985. Epub ahead of print. PMID: 33888596.
- Sanli Xing, Yiran Hu, Xujiao Huang, Dingzhu Shen, Chuan Chen. Nicotinamide phosphoribosyl transferase related signalling pathway in early Alzheimer’s disease mouse models.Shanghai Geriatric Institute of Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200031, P.R. China (2019) doi: 10.3892/mmr.2019.10782
- 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.
- Li J, Bonkowski MS, Moniot S, et al. A conserved NAD+ binding pocket that regulates protein-protein interactions during aging. Science. 2017;355(6331):1312-1317. doi:10.1126/science.aad8242
- Miao Y, Li X, Shi X, Gao Q, Chen J, Wang R, Fan Y, Xiong B. Nicotinamide Mononucleotide Restores the Meiotic Competency of Porcine Oocytes Exposed to Ethylene Glycol Butyl Ether. Front Cell Dev Biol. 2021 Feb 2;9:628580. doi: 10.3389/fcell.2021.628580.
- Mills et al., 2016, Cell Metabolism 24, 795–806, December 13, 2016 ª 2016 Elsevier Inc. DOI: doi.org/10.1016/j.cmet.2016.09.013
- Gomes AP, Price NL, Ling AJ, et al. Declining NAD(+) induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging. Cell. 2013;155(7):1624-1638. doi:10.1016/j.cell.2013.11.037
- Yamamoto T, Byun J, Zhai P, Ikeda Y, Oka S, et al. (2014) Nicotinamide Mononucleotide, an Intermediate of NAD+ Synthesis, Protects the Heart from Ischemia and Reperfusion. PLoS ONE 9(6): e98972. doi:10.1371/journal.pone.0098972
- de Picciotto NE, Gano LB, Johnson LC, et al. Nicotinamide mononucleotide supplementation reverses vascular dysfunction and oxidative stress with aging in mice. Aging Cell. 2016;15(3):522-530. doi:10.1111/acel.12461
- Keisuke Okabe, Keisuke Yaku, Kazuyuki Tobe, Takashi Nakagawa. Implications of altered NAD metabolism in metabolic disorders. J Biomed Sci, 2019; DOI: 10.1186/s12929-019-0527-8.
- Uddin GM, Youngson NA, Sinclair DA, Morris MJ. Head to Head Comparison of Short-Term Treatment with the NAD(+) Precursor Nicotinamide Mononucleotide (NMN) and 6 Weeks of Exercise in Obese Female Mice. Front Pharmacol. 2016;7:258. Published 2016 Aug 19. doi:10.3389/fphar.2016.00258
- Uchida R, Saito Y, Nogami K, et al. Epigenetic silencing of Lgr5 induces senescence of intestinal epithelial organoids during the process of aging [published correction appears in NPJ Aging Mech Dis. 2019 Mar 7;5:5]. NPJ Aging Mech Dis. 2018;5:1. Published 2018 Dec 1. doi: 10.1038/s41514-018-0031-5
- Li Y, Ma X, Li J, et al. Corneal denervation causes epithelial apoptosis through inhibiting NAD. biosynthesis. Invest Ophthalmol Vis Sci. 2019;60:3538–3546. https://doi.org/10.1167/iovs.19-26909
- Yoo KH, Tang JJ, Rashid MA, Cho CH, Corujo-Ramirez A, Choi J, Bae MG, Brogren D, Hawse JR, Hou X, Weroha SJ, Oliveros A, Kirkeby LA, Baur JA, Jang MH. Nicotinamide mononucleotide prevents cisplatin-induced cognitive impairments. Cancer Res. 2021 Mar 26:canres.3290.2020. doi: 10.1158/0008-5472.CAN-20-3290.
- Forte M, Bianchi F, Cotugno M, Marchitti S, De Falco E, Raffa S, Stanzione R, Di Nonno F, Chimenti I, Palmerio S, Pagano F, Petrozza V, Micaloni A, Madonna M, Relucenti M, Torrisi MR, Frati G, Volpe M, Rubattu S, Sciarretta S. Pharmacological restoration of autophagy reduces hypertension-related stroke occurrence. Autophagy. 2020 Aug;16(8):1468-1481. doi: 10.1080/15548627.2019.1687215. Epub 2019 Nov 12. PMID: 31679456; PMCID: PMC7469607.