Nicotinamide mononucleotide

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). 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. However, this observation has been challenged, and the matter remains unsettled.

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. 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. Dietary supplement companies have aggressively marketed NMN products, claiming those benefits. 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. Single-dose administration of up to 500 mg was shown safe in men in a study at Keio University. One 2021 clinical trial found that NMN improved muscular insulin sensitivity in prediabetic women, while another found that it improved aerobic capacity in amateur runners. A 2023 clinical trial showed that NMN improves performance on a six-minute walking test and a subjective general health assessment.

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

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, 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.

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. 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, a protein responsible for initiating cellular degeneration pathways such as MAP kinase and inducing axonal loss and neuronal death. NMNAT is an enzyme with neurorescuing properties that functions to deplete NMN and produce NAD+, attenuating SARM1 activity and aiding neuronal survival in-vitro, 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.