Nicotinamide mononucleotide
Names
IUPAC name
3-Carbamoyl-1-(5-O-phosphono-β-D-ribofuranosyl)pyridin-1-ium
Systematic IUPAC name
[(2R,3S,4R,5R)-5-(3-Carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl hydrogen phosphate
Other names
  • Nicotinamide ribonucleoside 5′-phosphate
  • Nicotinamide D-ribonucleotide
  • β-Nicotinamide ribose monophosphate
  • Nicotinamide nucleotide
Identifiers
3D model (JSmol)
3570187
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.012.851
EC Number
  • 214-136-5
KEGG
UNII
  • InChI=1S/C11H15N2O8P/c12-10(16)6-2-1-3-13(4-6)11-9(15)8(14)7(21-11)5-20-22(17,18)19/h1-4,7-9,11,14-15H,5H2,(H3-,12,16,17,18,19)/t7-,8-,9-,11-/m1/s1
    Key: DAYLJWODMCOQEW-TURQNECASA-N
  • c1cc(c[n+](c1)[C@H]2[C@@H]([C@@H]([C@H](O2)COP(=O)(O)[O-])O)O)C(=O)N
Properties
C11H15N2O8P
Molar mass 334.221 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

Nicotinamide mononucleotide ("NMN" and "β-NMN") is a nucleotide derived from ribose, nicotinamide, nicotinamide riboside and niacin.[1] In humans, several enzymes use NMN to generate nicotinamide adenine dinucleotide (NADH).[1] In mice, it has been proposed that NMN is absorbed via the small intestine within 10 minutes of oral uptake and converted to nicotinamide adenine dinucleotide (NAD+) through the Slc12a8 transporter.[2] However, this observation has been challenged,[3] and the matter remains unsettled.[4]

Because NADH is a cofactor for processes inside mitochondria, for sirtuins and PARP, NMN has been studied in animal models as a potential neuroprotective and anti-aging agent.[5][6] The reversal of aging at the cellular level by inhibiting mitochondrial decay in presence of increased levels of NAD+ makes it popular among anti-aging products.[7] Dietary supplement companies have aggressively marketed NMN products, claiming those benefits.[8] However, no human studies to date have properly proven its anti-aging effects. Single-dose administration of up to 500 mg was shown safe in men in a study at Keio University.[9] One 2021 clinical trial found that NMN improved muscular insulin sensitivity in prediabetic women,[10] while another found that it improved aerobic capacity in amateur runners.[11] A 2023 clinical trial showed that NMN improves performance on a six-minute walking test and a subjective general health assessment.[12]

NMN is vulnerable to extracellular degradation by CD38 enzyme,[13] which can be inhibited by compounds such as CD38-IN-78c.[14]

Dietary sources

NMN is found in fruits and vegetables such as edamame, broccoli, cabbage, cucumber and avocado at a concentration of about 1 mg per 100g,[15][16][17] making these natural sources impractical to acquire the quantities needed to accomplish the dosing currently being investigated for NMN as a pharmaceutical.

Production

Production of nicotinamide mononucleotide has been redacted since the latter half of 2022 by the FDA because it is under investigation as a pharmaceutical drug.[18][19]

Different expressions of NMN across human organs

The synthesizing enzymes and consumption enzymes of NMN also exhibit tissue specificity: NMN is widely distributed in tissues and organs throughout the body and has been present in various cells since embryonic development.[19]

Potential benefits and risks

NMN is a precursor for NAD+ biosynthesis, and NMN dietary supplementation has been demonstrated to increase NAD+ concentration and thus has the potential to mitigate aging-related disorders such as oxidative stress, DNA damage, neurodegeneration and inflammatory responses.[20] The potential benefits and risks of NMN supplementation, as of 2023, are currently under investigation.[20]

References

  1. 1 2 Roger Lee, Roger (2023). "Different Expressions of NMN Across Human Organs". American Journal of Sociology – via Frank Lee.
  2. ↑ Grozio, A; Mills, KF; Yoshino, J; Bruzzone, S; Sociali, G; Tokizane, K; Lei, HC; Cunningham, R; Sasaki, Y; Migaud, ME; Imai, SI (January 2019). "Slc12a8 is a nicotinamide mononucleotide transporter". Nature Metabolism. 1 (1): 47–57. doi:10.1038/s42255-018-0009-4. PMC 6530925. PMID 31131364.
  3. ↑ Schmidt, MS; Brenner, C (July 2019). "Absence of evidence that Slc12a8 encodes a nicotinamide mononucleotide transporter". Nature Metabolism. 1 (7): 660–661. doi:10.1038/s42255-019-0085-0. PMID 32694648. S2CID 203899191.
  4. ↑ Chini, CCS; Zeidler, JD; Kashyap, S; Warner, G; Chini, EN (1 June 2021). "Evolving concepts in NAD+ metabolism". Cell Metabolism. 33 (6): 1076–1087. doi:10.1016/j.cmet.2021.04.003. PMC 8172449. PMID 33930322.
  5. ↑ Brazill JM, Li C, Zhu Y, Zhai RG (June 2017). "+ synthase… It's a chaperone… It's a neuroprotector". Current Opinion in Genetics & Development. 44: 156–162. doi:10.1016/j.gde.2017.03.014. PMC 5515290. PMID 28445802.
  6. ↑ Mills, Kathryn F.; Yoshida, Shohei; Stein, Liana R.; Grozio, Alessia; Kubota, Shunsuke; Sasaki, Yo; Redpath, Philip; Migaud, Marie E.; Apte, Rajendra S.; Uchida, Koji; Yoshino, Jun; Imai, Shin-Ichiro (13 December 2016). "Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice". Cell Metabolism. 24 (6): 795–806. doi:10.1016/j.cmet.2016.09.013. PMC 5668137. PMID 28068222.
  7. ↑ Nadeeshani, Harshani; Li, Jinyao; Ying, Tianlei; Zhang, Baohong; Lu, Jun (1 March 2022). "Nicotinamide mononucleotide (NMN) as an anti-aging health product – Promises and safety concerns". Journal of Advanced Research. 37: 267–278. doi:10.1016/j.jare.2021.08.003. hdl:10292/15010. ISSN 2090-1232. PMC 9039735. PMID 35499054. S2CID 238647478.
  8. ↑ Stipp D (March 11, 2015). "Beyond Resveratrol: The Anti-Aging NAD Fad". Scientific American Blog Network.
  9. ↑ Irie, Junichiro; Inagaki, Emi; Fujita, Masataka; Nakaya, Hideaki; Mitsuishi, Masanori; Yamaguchi, Shintaro; Yamashita, Kazuya; Shigaki, Shuhei; Ono, Takashi; Yukioka, Hideo; Okano, Hideyuki (2020). "Effect of oral administration of nicotinamide mononucleotide on clinical parameters and nicotinamide metabolite levels in healthy Japanese men". Endocrine Journal. 67 (2): 153–60. doi:10.1507/endocrj.EJ19-0313. ISSN 0918-8959. PMID 31685720.
  10. ↑ Yoshino M, Yoshino J, Kayser BD, Patti GJ, Franczyk MP, et al. (June 2021). "Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women". Science. 372 (6547): 1224–29. doi:10.1126/science.abe9985. PMC 8550608. PMID 33888596.
  11. ↑ Liao, B; Zhao, Y; Wang, D; Zhang, X; Hao, X; Hu, M (2021). ""Nicotinamide mononucleotide supplementation enhances aerobic capacity in amateur runners: a randomized, double-blind study"". Journal of the International Society of Sports Nutrition. 18 (1): 54. doi:10.1186/s12970-021-00442-4. PMC 8265078. PMID 34238308.
  12. ↑ Yi Lin; et al. (Feb 2023). "The efficacy and safety of β-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults: a randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial". Geroscience. 45 (1): 29–43. doi:10.1007/s11357-022-00705-1. PMC 9735188. PMID 36482258.
  13. ↑ Cambronne XA, Kraus WL (October 2020). "+ Synthesis and Functions in Mammalian Cells". Trends in Biochemical Sciences. 45 (10): 858–73. doi:10.1016/j.tibs.2020.05.010. PMC 7502477. PMID 32595066.
  14. ↑ Tarragó MG, Chini CC, Kanamori KS, Warner GM, Caride A, et al. (May 2018). "A Potent and Specific CD38 Inhibitor Ameliorates Age-Related Metabolic Dysfunction by Reversing Tissue NAD+ Decline". Cell Metab. 27 (5): 1081–95.e10. doi:10.1016/j.cmet.2018.03.016. PMC 5935140. PMID 29719225.
  15. ↑ Mills, KF; Yoshida, S; Stein, LR; Grozio, A; Kubota, S; Sasaki, Y; Redpath, P; Migaud, ME; Apte, RS; Uchida, K; Yoshino, J; Imai, SI (13 December 2016). "Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice". Cell Metabolism. 24 (6): 795–806. doi:10.1016/j.cmet.2016.09.013. PMC 5668137. PMID 28068222.
  16. ↑ Ryan, Finn (2016-12-06). "5 Anti-Aging Food Types You Should Already Be Eating". Bicycling. Retrieved 2022-01-20.
  17. ↑ "Scientists identify new fuel-delivery route for cells". Washington University School of Medicine. 2019-01-07. Retrieved 2022-01-20.
  18. ↑ nutraingredients-usa.com/Article/2023/02/16/Amazon-removing-NMN-dietary-supplements-citing-FDA-actions
  19. 1 2 https://www.nmn.com/news/fda-bans-labeling-nmn-as-a-supplement
  20. 1 2 Song Q, Zhou X, Xu K, Liu S, Zhu X, Yang J. The Safety and Antiaging Effects of Nicotinamide Mononucleotide in Human Clinical Trials: an Update. Adv Nutr. 2023 Nov;14(6):1416-1435. doi: 10.1016/j.advnut.2023.08.008. Epub 2023 Aug 22. PMID: 37619764; PMCID: PMC10721522
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