Nicotinamide mononucleotide

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]

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
CAS Number	1094-61-7 Y
3D model (JSmol)	Interactive image
Beilstein Reference	3570187
ChEBI	CHEBI:16171
ChEMBL	ChEMBL610238
ChemSpider	13553
ECHA InfoCard	100.012.851
EC Number	214-136-5
KEGG	C00455
PubChem CID	16219737
UNII	2KG6QX4W0V Y
CompTox Dashboard (EPA)	DTXSID50911152
InChI 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
SMILES c1cc(c[n+](c1)[C@H]2[C@@H]([C@@H]([C@H](O2)COP(=O)(O)[O-])O)O)C(=O)N
Properties
Chemical formula	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

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 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.^[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.^[20]

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.^[23] The similar molecule nicotinic acid mononucleotide (NaMN) opposes the activating effect of NMN on SARM1, and is a neuroprotector.^[27]