NMN

Nicotinamide mononucleotide (NMN) is a nucleotide derived from nicotinamide (vitamin B3) and ribose. It serves as a direct precursor to nicotinamide adenine dinucleotide (NAD+), an essential coenzyme found in all living cells. NAD+ is critical for hundreds of enzymatic reactions, particularly those involved in energy metabolism, mitochondrial function, and DNA repair.

NAD+ levels decline significantly with age - by approximately 50% between ages 40-60. This decline is associated with reduced mitochondrial function, impaired DNA repair, and various age-related metabolic changes. The discovery that NAD+ precursors could extend lifespan in yeast and improve health markers in mice sparked intense interest in NMN supplementation.

Unlike nicotinamide riboside (NR), another NAD+ precursor, NMN is one step closer to NAD+ in the biosynthetic pathway. The enzyme NMNAT converts NMN directly to NAD+. For years, it was debated whether NMN could be absorbed intact from the gut or had to convert to NR first. Recent evidence suggests specific transporters exist that allow direct NMN uptake into cells.

Current human studies show NMN is safe and increases NAD+ levels. Some trials demonstrate improvements in muscle function, insulin sensitivity, and walking speed in middle-aged and older adults. However, the field is young, and long-term human data on longevity outcomes remains unavailable. Most evidence comes from animal studies showing remarkable improvements in metabolism, physical function, and lifespan.

NMN's primary mechanism is increasing cellular NAD+ levels. NAD+ is a cofactor for three major classes of enzymes:

1. Sirtuins (SIRT1-7): NAD+-dependent deacetylases that regulate cellular stress responses, DNA repair, mitochondrial biogenesis, and inflammation. Sirtuins are often called "longevity genes" due to their role in calorie restriction benefits.

2. PARPs (Poly ADP-ribose polymerases): Enzymes critical for DNA repair. Excessive PARP activation can deplete NAD+, creating competition with sirtuins. Restoring NAD+ supports both DNA repair and sirtuin function.

3. CD38: An NAD+-consuming enzyme that increases with age, contributing to NAD+ decline. Higher NAD+ levels may help counteract CD38-mediated depletion.

NMN is transported into cells via specific transporters (recently identified as Slc12a8 in mice). Once inside, the enzyme nicotinamide mononucleotide adenylyltransferase (NMNAT) converts NMN to NAD+ in a single step. This is more direct than nicotinamide riboside (NR), which must first be phosphorylated to NMN.

Elevated NAD+ levels enhance mitochondrial function by activating sirtuins that promote mitochondrial biogenesis (particularly SIRT1 and PGC-1α pathway). This improves cellular energy production and may counteract age-related mitochondrial dysfunction.

For vascular health, NAD+ supports endothelial nitric oxide production and reduces oxidative stress. In muscle tissue, improved NAD+ status enhances oxidative metabolism and may improve insulin signaling through sirtuin-mediated pathways.

NMN occurs naturally in small amounts in various foods. However, dietary intake is insufficient to significantly raise NAD+ levels compared to supplementation.

No established RDA. Human studies have used 250-900 mg/day. Common supplemental doses range from 250-500 mg daily, with some using up to 1000 mg.

NMN extends lifespan in yeast, worms, and mice. Human longevity data not yet available but biomarker improvements suggest potential. Primary mechanism through NAD+ restoration and sirtuin activation.

NMN is available in capsules, sublingual tablets, and powder forms. Recent discoveries of NMN-specific transporters suggest good bioavailability, though sublingual delivery may bypass first-pass metabolism.