:Nicotinamide mononucleotide
{{Chembox
| ImageFile = Nicotinamide mononucleotide.svg
| ImageSize = 220px
| IUPACName = 3-Carbamoyl-1-(5-O-phosphono-β-D-ribofuranosyl)pyridin-1-ium
| SystematicName = [(2R,3S,4R,5R)-5-(3-Carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl hydrogen phosphate
| OtherNames = {{unbulleted list | Nicotinamide ribonucleoside 5′-phosphate | Nicotinamide D-ribonucleotide | β-Nicotinamide ribose monophosphate| Nicotinamide nucleotide }}
| Section1 = {{Chembox Identifiers
| CASNo = 1094-61-7
| CASNo_Ref = {{cascite|correct|CAS}}
| Beilstein = 3570187
| ChEBI = 16171
| ChEMBL = 610238
| EINECS = 214-136-5
| KEGG = C00455
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 2KG6QX4W0V
| PubChem = 16219737
| ChemSpiderID = 13553
| SMILES = c1cc(c[n+](c1)[C@H]2[C@@H]([C@@H]([C@H](O2)COP(=O)(O)[O-])O)O)C(=O)N
| StdInChI = 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
| StdInChIKey = DAYLJWODMCOQEW-TURQNECASA-N
}}
| Section2 = {{Chembox Properties
| C=11|H=15|N=2|O=8|P=1
| Appearance =
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| Section3 = {{Chembox Hazards
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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).{{cite journal |last=Roger Lee |first=Roger |date=2023 |title=Different Expressions of NMN Across Human Organs |url=https://www.nmnsupplier.com/what-is-nmn.html |journal=American Journal of Sociology |via=Frank Lee}} 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+){{Cite web |title=Nicotinamide Mononucleotide benefits, dosage, and side effects |url=https://examine.com/supplements/nicotinamide-mononucleotide/ |access-date=2025-05-09 |website=Examine.com |language=en}} through the Slc12a8 transporter.{{cite journal |last1=Grozio |first1=A |last2=Mills |first2=KF |last3=Yoshino |first3=J |last4=Bruzzone |first4=S |last5=Sociali |first5=G |last6=Tokizane |first6=K |last7=Lei |first7=HC |last8=Cunningham |first8=R |last9=Sasaki |first9=Y |last10=Migaud |first10=ME |last11=Imai |first11=SI |title=Slc12a8 is a nicotinamide mononucleotide transporter. |journal=Nature Metabolism |date=January 2019 |volume=1 |issue=1 |pages=47–57 |doi=10.1038/s42255-018-0009-4 |pmid=31131364|pmc=6530925 }} However, this observation has been challenged,{{cite journal |last1=Schmidt |first1=MS |last2=Brenner |first2=C |title=Absence of evidence that Slc12a8 encodes a nicotinamide mononucleotide transporter. |journal=Nature Metabolism |date=July 2019 |volume=1 |issue=7 |pages=660–661 |doi=10.1038/s42255-019-0085-0 |pmid=32694648|s2cid=203899191 }} and the matter remains unsettled.{{cite journal |last1=Chini |first1=CCS |last2=Zeidler |first2=JD |last3=Kashyap |first3=S |last4=Warner |first4=G |last5=Chini |first5=EN |title=Evolving concepts in NAD+ metabolism. |journal=Cell Metabolism |date=1 June 2021 |volume=33 |issue=6 |pages=1076–1087 |doi=10.1016/j.cmet.2021.04.003 |pmid=33930322|pmc=8172449 }}
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.{{cite journal | vauthors = Brazill JM, Li C, Zhu Y, Zhai RG | title = + synthase... It's a chaperone... It's a neuroprotector | journal = Current Opinion in Genetics & Development | volume = 44 | pages = 156–162 | date = June 2017 | pmid = 28445802 | pmc = 5515290 | doi = 10.1016/j.gde.2017.03.014 }}{{cite journal|title=Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice|journal=Cell Metabolism|date=13 December 2016|doi=10.1016/j.cmet.2016.09.013|last1=Mills|first1=Kathryn F.|last2=Yoshida|first2=Shohei|last3=Stein|first3=Liana R.|last4=Grozio|first4=Alessia|last5=Kubota|first5=Shunsuke|last6=Sasaki|first6=Yo|last7=Redpath|first7=Philip|last8=Migaud|first8=Marie E.|last9=Apte|first9=Rajendra S.|last10=Uchida|first10=Koji|last11=Yoshino|first11=Jun|last12=Imai|first12=Shin-Ichiro|volume=24|issue=6|pages=795–806|pmid=28068222|pmc=5668137}} The alleged anti-aging effect at the cellular level by inhibiting mitochondrial decay in presence of increased levels of NAD+ makes it popular among anti-aging products.{{cite journal |last1=Nadeeshani |first1=Harshani |last2=Li |first2=Jinyao |last3=Ying |first3=Tianlei |last4=Zhang |first4=Baohong |last5=Lu |first5=Jun |title=Nicotinamide mononucleotide (NMN) as an anti-aging health product – Promises and safety concerns |journal=Journal of Advanced Research |date=1 March 2022 |volume=37 |pages=267–278 |doi=10.1016/j.jare.2021.08.003 |pmid=35499054 |pmc=9039735 |s2cid=238647478 |language=en |issn=2090-1232|hdl=10292/15010 |hdl-access=free }} Dietary supplement companies have aggressively marketed NMN products, claiming those benefits.{{Cite web |date=2025-02-04 |title=NMN supplements are trending – experts explain whether they really work |url=https://www.womenshealthmag.com/uk/food/a63661595/nmn-supplement/ |access-date=2025-05-09 |website=Women's Health |language=en-GB}}{{cite news| vauthors = Stipp D |title=Beyond Resveratrol: The Anti-Aging NAD Fad|url=https://blogs.scientificamerican.com/guest-blog/beyond-resveratrol-the-anti-aging-nad-fad |work=Scientific American Blog Network |date=March 11, 2015|language=en}} 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.{{Cite journal |last1=Nadeeshani |first1=Harshani |last2=Li |first2=Jinyao |last3=Ying |first3=Tianlei |last4=Zhang |first4=Baohong |last5=Lu |first5=Jun |date=2022-03-01 |title=Nicotinamide mononucleotide (NMN) as an anti-aging health product – Promises and safety concerns |journal=Journal of Advanced Research |volume=37 |pages=267–278 |doi=10.1016/j.jare.2021.08.003 |pmid=35499054 |issn=2090-1232|pmc=9039735 }} Single-dose administration of up to 500 mg was shown safe in men in a study at Keio University.{{Cite journal |last1=Irie |first1=Junichiro |last2=Inagaki |first2=Emi |last3=Fujita |first3=Masataka |last4=Nakaya |first4=Hideaki |last5=Mitsuishi |first5=Masanori |last6=Yamaguchi |first6=Shintaro |last7=Yamashita |first7=Kazuya |last8=Shigaki |first8=Shuhei |last9=Ono |first9=Takashi |last10=Yukioka |first10=Hideo |last11=Okano |first11=Hideyuki |date=2020 |title=Effect of oral administration of nicotinamide mononucleotide on clinical parameters and nicotinamide metabolite levels in healthy Japanese men |url=https://www.jstage.jst.go.jp/article/endocrj/67/2/67_EJ19-0313/_article |journal=Endocrine Journal |language=en |volume=67 |issue=2 |pages=153–60 |doi=10.1507/endocrj.EJ19-0313 |pmid=31685720 |issn=0918-8959|doi-access=free }} One 2021 clinical trial found that NMN improved muscular insulin sensitivity in prediabetic women,{{cite journal |vauthors=Yoshino M, Yoshino J, Kayser BD, Patti GJ, Franczyk MP, Mills KF, Sindelar M, Pietka T, Patterson BW, Imai SI, Klein S |display-authors=5 |title=Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women |journal=Science |volume=372 |issue=6547 |pages=1224–29 |date=June 2021 |pmid=33888596 |pmc=8550608 |doi=10.1126/science.abe9985 }} while another found that it improved aerobic capacity in amateur runners.{{cite journal|title="Nicotinamide mononucleotide supplementation enhances aerobic capacity in amateur runners: a randomized, double-blind study"|year=2021 |pmc=8265078 |last1=Liao |first1=B |last2=Zhao |first2=Y |last3=Wang |first3=D |last4=Zhang |first4=X |last5=Hao |first5=X |last6=Hu |first6=M |journal=Journal of the International Society of Sports Nutrition |volume=18 |issue=1 |page=54 |doi=10.1186/s12970-021-00442-4 |pmid=34238308 |doi-access=free }} A 2023 clinical trial showed that NMN improves performance on a six-minute walking test and a subjective general health assessment.{{cite journal | display-authors = etal |author=Yi Lin | title = 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 | journal = Geroscience | date = Feb 2023 |volume=45 |issue=1 |pages=29–43 |doi=10.1007/s11357-022-00705-1 |pmid=36482258 |pmc=9735188 }}
NMN is vulnerable to extracellular degradation by CD38 enzyme,{{cite journal | vauthors = Cambronne XA, Kraus WL | title = + Synthesis and Functions in Mammalian Cells | journal = Trends in Biochemical Sciences | volume = 45 | issue = 10 | pages = 858–73 | date = October 2020 | pmid = 32595066 | pmc = 7502477 | doi = 10.1016/j.tibs.2020.05.010 | url = https://www.jbc.org/content/294/52/19831.long }} which can be inhibited by compounds such as CD38-IN-78c.{{cite journal |vauthors=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 |display-authors=5 |title=A Potent and Specific CD38 Inhibitor Ameliorates Age-Related Metabolic Dysfunction by Reversing Tissue NAD+ Decline |journal=Cell Metab |volume=27 |issue=5 |pages=1081–95.e10 |date=May 2018 |pmid=29719225 |pmc=5935140 |doi=10.1016/j.cmet.2018.03.016 }}
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,{{cite journal |last1=Mills |first1=KF |last2=Yoshida |first2=S |last3=Stein |first3=LR |last4=Grozio |first4=A |last5=Kubota |first5=S |last6=Sasaki |first6=Y |last7=Redpath |first7=P |last8=Migaud |first8=ME |last9=Apte |first9=RS |last10=Uchida |first10=K |last11=Yoshino |first11=J |last12=Imai |first12=SI |title=Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice. |journal=Cell Metabolism |date=13 December 2016 |volume=24 |issue=6 |pages=795–806 |doi=10.1016/j.cmet.2016.09.013 |pmid=28068222|pmc=5668137 }}{{Cite web|last=Ryan|first=Finn|date=2016-12-06|title=5 Anti-Aging Food Types You Should Already Be Eating|url=https://www.bicycling.com/health-nutrition/g20011748/5-anti-aging-food-types-you-should-already-be-eating/|access-date=2022-01-20|website=Bicycling|language=en-US}}{{Cite web |date=2019-01-07 |title=Scientists identify new fuel-delivery route for cells |url=https://medicine.wustl.edu/news/scientists-identify-new-fuel-delivery-route-for-cells/ |access-date=2022-01-20 |website=Washington University School of Medicine |language=en}} 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.nutraingredients-usa.com/Article/2023/02/16/Amazon-removing-NMN-dietary-supplements-citing-FDA-actions{{cite web | url=https://www.nmn.com/news/fda-bans-labeling-nmn-as-a-supplement | title=FDA Halts NMN Supplement Approval, Citing Pharmaceutical Potential }}
Different expressions of NMN across human organs
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.{{cite journal |vauthors=Song Q, Zhou X, Xu K, Liu S, Zhu X, Yang J |title=The Safety and Antiaging Effects of Nicotinamide Mononucleotide in Human Clinical Trials: an Update |journal=Adv Nutr |volume=14 |issue=6 |pages=1416–35 |date=November 2023 |pmid=37619764 |pmc=10721522 |doi=10.1016/j.advnut.2023.08.008 }} The potential benefits and risks of NMN supplementation, as of 2023, are currently under investigation.
Certain enzymes are sensitive to the intracellular NMN/NAD+ ratio, such as SARM1,{{cite journal |last1=Figley |first1=Matthew D. |last2=Gu |first2=Weixi |last3=Nanson |first3=Jeffrey D. |last4=Shi |first4=Yun |last5=Sasaki |first5=Yo |last6=Cunnea |first6=Katie |last7=Malde |first7=Alpeshkumar K. |last8=Jia |first8=Xinying |last9=Luo |first9=Zhenyao |last10=Saikot |first10=Forhad K. |last11=Mosaiab |first11=Tamim |last12=Masic |first12=Veronika |last13=Holt |first13=Stephanie |last14=Hartley-Tassell |first14=Lauren |last15=McGuinness |first15=Helen Y. |last16=Manik |first16=Mohammad K. |last17=Bosanac |first17=Todd |last18=Landsberg |first18=Michael J. |last19=Kerry |first19=Philip S. |last20=Mobli |first20=Mehdi |last21=Hughes |first21=Robert O. |last22=Milbrandt |first22=Jeffrey |last23=Kobe |first23=Bostjan |last24=DiAntonio |first24=Aaron |last25=Ve |first25=Thomas |title=SARM1 is a metabolic sensor activated by an increased NMN/NAD+ ratio to trigger axon degeneration |journal=Neuron |date=7 April 2021 |volume=109 |issue=7 |pages=1118–1136.e11 |doi=10.1016/j.neuron.2021.02.009 |pmid=33657413 |pmc=8174188 }} a protein responsible for initiating cellular degeneration pathways such as MAP kinase and inducing axonal loss and neuronal death.{{cite journal |last1=Di Stefano |first1=M |last2=Nascimento-Ferreira |first2=I |last3=Orsomando |first3=G |last4=Mori |first4=V |last5=Gilley |first5=J |last6=Brown |first6=R |last7=Janeckova |first7=L |last8=Vargas |first8=M E |last9=Worrell |first9=L A |last10=Loreto |first10=A |last11=Tickle |first11=J |last12=Patrick |first12=J |last13=Webster |first13=J R M |last14=Marangoni |first14=M |last15=Carpi |first15=F M |last16=Pucciarelli |first16=S |last17=Rossi |first17=F |last18=Meng |first18=W |last19=Sagasti |first19=A |last20=Ribchester |first20=R R |last21=Magni |first21=G |last22=Coleman |first22=M P |last23=Conforti |first23=L |title=A rise in NAD precursor nicotinamide mononucleotide (NMN) after injury promotes axon degeneration |journal=Cell Death and Differentiation |date=April 2015 |volume=22 |issue=5 |pages=731–742 |doi=10.1038/cdd.2014.164 |pmid=25323584 |pmc=4392071 |hdl=11581/387761 |hdl-access=free }}{{cite journal |last1=Zhao |first1=Zhi Ying |last2=Xie |first2=Xu Jie |last3=Li |first3=Wan Hua |last4=Liu |first4=Jun |last5=Chen |first5=Zhe |last6=Zhang |first6=Ben |last7=Li |first7=Ting |last8=Li |first8=Song Lu |last9=Lu |first9=Jun Gang |last10=Zhang |first10=Liangren |last11=Zhang |first11=Li-he |last12=Xu |first12=Zhengshuang |last13=Lee |first13=Hon Cheung |last14=Zhao |first14=Yong Juan |title=A Cell-Permeant Mimetic of NMN Activates SARM1 to Produce Cyclic ADP-Ribose and Induce Non-apoptotic Cell Death |journal=iScience |date=4 May 2019 |volume=15 |pages=452–466 |doi=10.1016/j.isci.2019.05.001 |pmid=31128467 |pmc=6531917 }} NMNAT is an enzyme with neurorescuing properties that functions to deplete NMN and produce NAD+, attenuating SARM1 activity and aiding neuronal survival in vitro,{{cite journal |last1=Brazill |first1=Jennifer M. |last2=Li |first2=Chong |last3=Zhu |first3=Yi |last4=Zhai |first4=R. Grace |title=NMNAT: It's an NAD+ Synthase... It's a Chaperone... It's a Neuroprotector |journal=Current Opinion in Genetics & Development |date=26 April 2017 |volume=44 |pages=156–162 |doi=10.1016/j.gde.2017.03.014 |pmid=28445802 |pmc=5515290 }}{{cite journal |last1=Gerdts |first1=Josiah |last2=Summers |first2=Daniel W. |last3=Milbrandt |first3=Jeffrey |last4=DiAntonio |first4=Aaron |title=Axon self destruction: new links among SARM1, MAPKs, and NAD+ metabolism |journal=Neuron |date=3 February 2016 |volume=89 |issue=3 |pages=449–460 |doi=10.1016/j.neuron.2015.12.023 |pmid=26844829 |pmc=4742785 }} 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.{{cite journal |last1=Sasaki |first1=Yo |last2=Zhu |first2=Jian |last3=Shi |first3=Yun |last4=Gu |first4=Weixi |last5=Kobe |first5=Bostjan |last6=Ve |first6=Thomas |last7=DiAntonio |first7=Aaron |last8=Milbrandt |first8=Jeffrey |title=Nicotinic acid mononucleotide is an allosteric SARM1 inhibitor promoting axonal protection |journal=Experimental Neurology |date=November 2021 |volume=345 |pages=113842 |doi=10.1016/j.expneurol.2021.113842 |pmid=34403688 |pmc=8571713 |hdl=10072/407468 |hdl-access=free }}