NMN (Nicotinamide Mononucleotide)
A direct NAD+ precursor marketed heavily as an anti-aging supplement. It reliably raises NAD+ in animals and shows striking metabolic benefits in aged mice, but human trials are small, short, and mostly report modest biomarker changes rather than clinical outcomes. US regulatory status has been contested by the FDA.
01 Overview
Nicotinamide mononucleotide is a nucleotide formed from nicotinamide and ribose that sits one enzymatic step from NAD+, the coenzyme central to energy metabolism and to sirtuin and PARP activity, which declines with age. Popularised by David Sinclair's laboratory, NMN restored NAD+ and improved insulin sensitivity, mitochondrial function, and vascular health in aged rodents.
Human data are limited: several small randomised trials (typically 250-900 mg/day for 4-12 weeks) show NMN is well tolerated and can raise blood NAD+ metabolites, with inconsistent, generally modest effects on insulin sensitivity, walking endurance, or muscle. No trial has demonstrated an effect on human lifespan or age-related disease. In late 2022 the FDA took the position that NMN is excluded from the dietary-supplement definition because it was investigated as a drug, leaving its US retail status unsettled.
02 Mechanism
Converted by NMNAT enzymes to NAD+, replenishing the coenzyme pool that supports mitochondrial respiration, sirtuin deacylation, and DNA-repair enzymes.
03 Dosing
| Tier | Dose | Route | Notes |
|---|---|---|---|
| Common | 250–500 mg/day | Oral | Most human trials used 250-500 mg daily. |
| Higher trial dose | 600–900 mg/day | Oral | Upper end of doses studied for metabolic endpoints. |
04 Effects
| Effect | Magnitude | Evidence | |
|---|---|---|---|
| Raised blood NAD+ metabolitesOral NMN consistently increases circulating NAD+ and related metabolites in short human trials. | ~1.5-2x NAD+ metabolites | Clinical | |
| Improved insulin sensitivity (context-dependent)Improved skeletal-muscle insulin sensitivity in prediabetic postmenopausal women in one RCT; not replicated in all cohorts. | modest | Clinical | |
| Metabolic and vascular benefits (animal)Reverses age-related metabolic decline, improves mitochondrial function and vascular compliance in rodents. | large in aged mice | Preclinical |
05 Side effects
| Effect | Severity | Frequency | Evidence | Countermeasures |
|---|---|---|---|---|
| Mild GI upsetOccasional nausea, bloating, or loose stools reported in trials; overall tolerability is good. | Mild | Uncommon | Clinical | |
| Unknown long-term safetyNo long-term human safety data; theoretical concerns include NAD+ overload effects on inflammation and potential fuelling of existing malignancy remain unresolved. | Moderate | Uncharacterised | Unconfirmed |