NMN

NMN (nicotinamide mononucleotide, or beta-NMN in its natural form) is a nucleotide built from nicotinamide, ribose and one phosphate group (PubChem CID 14180). It is the direct precursor of NAD+. In the salvage pathway, the enzyme NAMPT turns nicotinamide into NMN (Yoshino et al., 2011), and NMN adenylyltransferases (NMNATs) combine NMN with ATP to form NAD+ (Nikiforov et al., 2011). It is studied in cells, mice and small human trials.

PubChem CID 14180 lists the same CAS number, formula and weight and is the source of the synonyms, INN and structure.

NMN research falls into five areas. Each summary below states the model used. Mechanism data come from cells and mice; the human trials are small and short.

Place in the NAD+ salvage pathway

In mouse fibroblasts, NAMPT was the rate-limiting step of NAD synthesis from nicotinamide: raising NAMPT, but not NMNAT, increased cellular NAD (Revollo et al., 2004). The three human NMNAT isoforms sit in the nucleus (NMNAT1), the Golgi complex (NMNAT2) and mitochondria (NMNAT3) (Berger et al., 2005).

In human cell lines, precursors were converted to NMN in the cytosol, and NMNAT3 used NMN inside mitochondria to make NAD (Nikiforov et al., 2011). Nicotinamide riboside (NR) joins the route when NR kinases phosphorylate it to NMN (Ratajczak et al., 2016). Models: cultured mouse and human cells, and human enzymes.

How NMN reaches the inside of cells

Whether cells import NMN intact is debated. In human cell lines, extracellular NMN was broken down outside the cell into permeable precursors (Nikiforov et al., 2011), and in liver cells isotope-labeled NMN became NR before uptake, with NRK1 required for its use (Ratajczak et al., 2016).

In 2019, another group reported that Slc12a8, abundant in mouse small intestine, is a sodium-dependent NMN transporter: knocking it down blocked NMN uptake in cells and mice, and its loss lowered NAD+ in the jejunum and ileum (Grozio et al., 2019). Schmidt and Brenner argued that the methods, transport data and interpretation did not support NMN transport (Schmidt and Brenner, 2019). The original authors answered with proteoliposome and isotope-tracing data (Grozio et al., 2019). Models: cell lines, hepatocytes, proteoliposomes and mice.

Mouse studies

In C57BL/6 mice made diabetic by a high-fat diet, intraperitoneal NMN at 500 mg/kg/day for 7 to 10 days restored NAD+ in liver and white adipose tissue, normalized glucose tolerance in females, with a milder effect in males, and enhanced hepatic insulin sensitivity. In naturally diabetic aged males, a single bolus normalized glucose tolerance (Yoshino et al., 2011).

In the longest study, male C57BL/6N mice drank NMN-containing water at 100 or 300 mg/kg/day from 5 to 17 months of age, with no obvious toxicity and no difference in survival. Compared with controls, they showed higher energy expenditure, greater insulin sensitivity, better plasma lipid profiles, more tear production and larger rod responses on electroretinography. After a 300 mg/kg gavage, plasma NMN rose within 2.5 minutes (Mills et al., 2016). Models: mice.

Human clinical studies

The first human study, single-arm and non-randomized, gave 10 healthy men single amounts at three levels. No significant clinical symptoms or vital-sign changes occurred, and plasma NMN metabolites rose with the amount (Irie et al., 2020). In a 10-week randomized, double-blind, placebo-controlled trial in 25 postmenopausal women with prediabetes and overweight or obesity, clamp-measured muscle insulin sensitivity rose 25 percent with NMN and not with placebo, while muscle NAD+ content, liver insulin sensitivity, body composition and plasma lipids did not change (Yoshino et al., 2021).

In a manufacturer-funded randomized, double-blind trial, 80 healthy middle-aged adults received placebo or one of three daily amounts for 60 days; blood NAD, the primary endpoint, rose in all NMN groups, and HOMA-IR did not differ (Yi et al., 2023).

In a 14-day placebo-controlled study in 32 adults aged 55 to 80, MIB-626, a crystalline beta-NMN formulation, raised blood NAD in step with the amount (Pencina et al., 2023). In a randomized trial in 42 adults hospitalized with COVID-19 and acute kidney injury, it raised blood NAD+, but kidney injury, inflammation and severity markers did not differ from placebo (Pencina et al., 2025). Model: human clinical studies.