Nicotinamide mononucleotide explained

Nicotinamide mononucleotide ("NMN" and "β-NMN") is a nucleotide derived from ribose, nicotinamide, nicotinamide riboside and niacin. 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 with proposed health benefits only suggested through research done in vitro or through animal models.[9] Single-dose administration of up to 500 mg was shown safe in men in a study at Keio University.[10] One 2021 clinical trial found that NMN improved muscular insulin sensitivity in prediabetic women,[11] while another found that it improved aerobic capacity in amateur runners.[12] A 2023 clinical trial showed that NMN improves performance on a six-minute walking test and a subjective general health assessment.[13]

NMN is vulnerable to extracellular degradation by CD38 enzyme,[14] which can be inhibited by compounds such as CD38-IN-78c.[15]

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,[16] [17] [18] 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.[19] [20]

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.

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.[21] The potential benefits and risks of NMN supplementation, as of 2023, are currently under investigation.[21]

Certain enzymes are sensitive to the intracellular NMN/NAD+ ratio, such as SARM1,[22] a protein responsible for initiating cellular degeneration pathways such as MAP kinase and inducing axonal loss and neuronal death.[23] [24] NMNAT is an enzyme with neurorescuing properties that functions to deplete NMN and produce NAD+, attenuating SARM1 activity and aiding neuronal survival in-vitro,[25] [26] an effect that is reversed by applying exogenous NMN which promptly resumed axon destruction. The similar molecule nicotinic acid mononucleotide (NaMN) opposes the activating effect of NMN on SARM1, and is a neuroprotector.[27]

Notes and References

  1. Roger Lee . Roger . 2023 . Different Expressions of NMN Across Human Organs . American Journal of Sociology . 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 . Slc12a8 is a nicotinamide mononucleotide transporter. . Nature Metabolism . January 2019 . 1 . 1 . 47–57 . 10.1038/s42255-018-0009-4 . 31131364. 6530925 .
  3. Schmidt . MS . Brenner . C . Absence of evidence that Slc12a8 encodes a nicotinamide mononucleotide transporter. . Nature Metabolism . July 2019 . 1 . 7 . 660–661 . 10.1038/s42255-019-0085-0 . 32694648. 203899191 .
  4. Chini . CCS . Zeidler . JD . Kashyap . S . Warner . G . Chini . EN . Evolving concepts in NAD+ metabolism. . Cell Metabolism . 1 June 2021 . 33 . 6 . 1076–1087 . 10.1016/j.cmet.2021.04.003 . 33930322. 8172449 .
  5. Brazill JM, Li C, Zhu Y, Zhai RG . + synthase… It's a chaperone… It's a neuroprotector . Current Opinion in Genetics & Development . 44 . 156–162 . June 2017 . 28445802 . 5515290 . 10.1016/j.gde.2017.03.014 .
  6. Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice. Cell Metabolism. 13 December 2016. 10.1016/j.cmet.2016.09.013. 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. 24. 6. 795–806. 28068222. 5668137.
  7. Nadeeshani . Harshani . Li . Jinyao . Ying . Tianlei . Zhang . Baohong . Lu . Jun . Nicotinamide mononucleotide (NMN) as an anti-aging health product – Promises and safety concerns . Journal of Advanced Research . 1 March 2022 . 37 . 267–278 . 10.1016/j.jare.2021.08.003 . 35499054 . 9039735 . 238647478 . en . 2090-1232. 10292/15010 . free .
  8. News: Stipp D . Beyond Resveratrol: The Anti-Aging NAD Fad. Scientific American Blog Network . March 11, 2015. en.
  9. Nadeeshani . Harshani . Li . Jinyao . Ying . Tianlei . Zhang . Baohong . Lu . Jun . 2022-03-01 . Nicotinamide mononucleotide (NMN) as an anti-aging health product – Promises and safety concerns . Journal of Advanced Research . 37 . 267–278 . 10.1016/j.jare.2021.08.003 . 35499054 . 2090-1232. 9039735 .
  10. 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 . en . 67 . 2 . 153–60 . 10.1507/endocrj.EJ19-0313 . 31685720 . 0918-8959. free .
  11. Yoshino M, Yoshino J, Kayser BD, Patti GJ, Franczyk MP, Mills KF, Sindelar M, Pietka T, Patterson BW, Imai SI, Klein S . 5 . Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women . Science . 372 . 6547 . 1224–29 . June 2021 . 33888596 . 8550608 . 10.1126/science.abe9985 .
  12. "Nicotinamide mononucleotide supplementation enhances aerobic capacity in amateur runners: a randomized, double-blind study". 2021 . 8265078 . Liao . B . Zhao . Y . Wang . D . Zhang . X . Hao . X . Hu . M . Journal of the International Society of Sports Nutrition . 18 . 1 . 54 . 10.1186/s12970-021-00442-4 . 34238308 . free .
  13. etal . Yi Lin . 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 . Feb 2023 . 45 . 1 . 29–43 . 10.1007/s11357-022-00705-1 . 36482258 . 9735188 .
  14. Cambronne XA, Kraus WL . + Synthesis and Functions in Mammalian Cells . Trends in Biochemical Sciences . 45 . 10 . 858–73 . October 2020 . 32595066 . 7502477 . 10.1016/j.tibs.2020.05.010 .
  15. Tarragó MG, Chini CC, Kanamori KS, Warner GM, Caride A, de Oliveira GC, Rud M, Samani A, Hein KZ, Huang R, Jurk D, Cho DS, Boslett JJ, Miller JD, Zweier JL, Passos JF, Doles JD, Becherer DJ, Chini EN . 5 . A Potent and Specific CD38 Inhibitor Ameliorates Age-Related Metabolic Dysfunction by Reversing Tissue NAD+ Decline . Cell Metab . 27 . 5 . 1081–95.e10 . May 2018 . 29719225 . 5935140 . 10.1016/j.cmet.2018.03.016 .
  16. Mills . KF . Yoshida . S . Stein . LR . Grozio . A . Kubota . S . Sasaki . Y . Redpath . P . Migaud . ME . Apte . RS . Uchida . K . Yoshino . J . Imai . SI . Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice. . Cell Metabolism . 13 December 2016 . 24 . 6 . 795–806 . 10.1016/j.cmet.2016.09.013 . 28068222. 5668137 .
  17. Web site: Ryan. Finn. 2016-12-06. 5 Anti-Aging Food Types You Should Already Be Eating. 2022-01-20. Bicycling. en-US.
  18. Web site: 2019-01-07 . Scientists identify new fuel-delivery route for cells . 2022-01-20 . . en.
  19. nutraingredients-usa.com/Article/2023/02/16/Amazon-removing-NMN-dietary-supplements-citing-FDA-actions
  20. Web site: FDA Halts NMN Supplement Approval, Citing Pharmaceutical Potential .
  21. 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 . 14 . 6 . 1416–35 . November 2023 . 37619764 . 10721522 . 10.1016/j.advnut.2023.08.008 .
  22. Figley . Matthew D. . Gu . Weixi . Nanson . Jeffrey D. . Shi . Yun . Sasaki . Yo . Cunnea . Katie . Malde . Alpeshkumar K. . Jia . Xinying . Luo . Zhenyao . Saikot . Forhad K. . Mosaiab . Tamim . Masic . Veronika . Holt . Stephanie . Hartley-Tassell . Lauren . McGuinness . Helen Y. . Manik . Mohammad K. . Bosanac . Todd . Landsberg . Michael J. . Kerry . Philip S. . Mobli . Mehdi . Hughes . Robert O. . Milbrandt . Jeffrey . Kobe . Bostjan . DiAntonio . Aaron . Ve . Thomas . SARM1 is a metabolic sensor activated by an increased NMN/NAD+ ratio to trigger axon degeneration . Neuron . 7 April 2021 . 109 . 7 . 1118–1136.e11 . 10.1016/j.neuron.2021.02.009 . 33657413 . 8174188 .
  23. Di Stefano . M . Nascimento-Ferreira . I . Orsomando . G . Mori . V . Gilley . J . Brown . R . Janeckova . L . Vargas . M E . Worrell . L A . Loreto . A . Tickle . J . Patrick . J . Webster . J R M . Marangoni . M . Carpi . F M . Pucciarelli . S . Rossi . F . Meng . W . Sagasti . A . Ribchester . R R . Magni . G . Coleman . M P . Conforti . L . A rise in NAD precursor nicotinamide mononucleotide (NMN) after injury promotes axon degeneration . Cell Death and Differentiation . April 2015 . 22 . 5 . 731–742 . 10.1038/cdd.2014.164 . 25323584 . 4392071 . 11581/387761 . free .
  24. Zhao . Zhi Ying . Xie . Xu Jie . Li . Wan Hua . Liu . Jun . Chen . Zhe . Zhang . Ben . Li . Ting . Li . Song Lu . Lu . Jun Gang . Zhang . Liangren . Zhang . Li-he . Xu . Zhengshuang . Lee . Hon Cheung . Zhao . Yong Juan . A Cell-Permeant Mimetic of NMN Activates SARM1 to Produce Cyclic ADP-Ribose and Induce Non-apoptotic Cell Death . iScience . 4 May 2019 . 15 . 452–466 . 10.1016/j.isci.2019.05.001 . 31128467 . 6531917 .
  25. Brazill . Jennifer M. . Li . Chong . Zhu . Yi . Zhai . R. Grace . NMNAT: It's an NAD+ Synthase… It's a Chaperone… It's a Neuroprotector . Current Opinion in Genetics & Development . 26 April 2017 . 44 . 156–162 . 10.1016/j.gde.2017.03.014 . 28445802 . 5515290 .
  26. Gerdts . Josiah . Summers . Daniel W. . Milbrandt . Jeffrey . DiAntonio . Aaron . Axon self destruction: new links among SARM1, MAPKs, and NAD+ metabolism . Neuron . 3 February 2016 . 89 . 3 . 449–460 . 10.1016/j.neuron.2015.12.023 . 26844829 . 4742785 .
  27. Sasaki . Yo . Zhu . Jian . Shi . Yun . Gu . Weixi . Kobe . Bostjan . Ve . Thomas . DiAntonio . Aaron . Milbrandt . Jeffrey . Nicotinic acid mononucleotide is an allosteric SARM1 inhibitor promoting axonal protection . Experimental Neurology . November 2021 . 345 . 113842 . 10.1016/j.expneurol.2021.113842 . 34403688 . 8571713 . 10072/407468 . free .

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Nicotinamide mononucleotide".

Except where otherwise indicated, Everything.Explained.Today is © Copyright 2009-2024, A B Cryer, All Rights Reserved. Cookie policy.