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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 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.[27] The similar molecule nicotinic acid mononucleotide (NaMN) opposes the activating effect of NMN on SARM1, and is a neuroprotector.[28]
^ abSong 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
