NAD+/NMN

In simple words

NMN is not a peptide but a precursor of NAD+, a key molecule for energy production in cells, whose supply declines with age. It is being studied as a way to improve insulin sensitivity and endurance and to slow aging.

What this molecule is

Not a peptide. NMN: C₁₁H₁₅N₂O₈P, a precursor of NAD+. NR (nicotinamide riboside): an alternative precursor. ~334 Da.

Why it is studied

↑cellular NAD+ → ↑activity of the sirtuins SIRT1/SIRT3/SIRT6 → anti-aging effects. RCT (n=48): ↑muscle insulin sensitivity in prediabetes. RCT: ↑aerobic endurance. ↑NAD+ in older men over 12 weeks.

How it works

NMN → NAD+ (enzyme NMNAT). NAD+ → ↑SIRT1/3 → ↑autophagy, ↑mitochondrial biogenesis, ↑DNA repair, ↑β-oxidation. SIRT1 activates AMPK and PGC1-α. SIRT3 protects mitochondrial proteins from oxidation.

Doses used in studies

Studies used NMN 250–500 mg/day orally (in the morning) and NR 300–600 mg/day; forms — capsules or sublingual. For IV NAD+ there are only pilot data, with no standard.

Combined with in studies

• 5-Amino-1MQ — ↓degradation + ↑synthesis of NAD+
• SS-31 — mitochondrial synergy
• Epitalon — Longevity stack
• Resveratrol/Quercetin — SIRT1 cofactors

Level of evidence

Level A Human clinical trials. There are randomized controlled trials (RCTs), or the compound has been approved by a regulatory agency. The most reliable level. 5 RCTs. FDA-approved as a dietary supplement.

Important to know

Honest caveat: A direct effect on weight loss has not been proven. Long-term safety is being studied. Theoretical risk of stimulating cell growth in cancer.

Studies in PubMed

1. Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. (Science, 2021)
2. The efficacy and safety of β-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults: a randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial. (Geroscience, 2023)
3. Nicotinamide mononucleotide supplementation enhances aerobic capacity in amateur runners: a randomized, double-blind study. (J Int Soc Sports Nutr, 2021)
4. The Safety and Antiaging Effects of Nicotinamide Mononucleotide in Human Clinical Trials: an Update. (Adv Nutr, 2023)
5. A Pilot Study Investigating Changes in the Human Plasma and Urine NAD+ Metabolome During a 6 Hour Intravenous Infusion of NAD. (Front Aging Neurosci, 2019)
6. Nicotinamide Adenine Dinucleotide (NAD+) and Enkephalinase Inhibition (IV1114589NAD) Infusions Significantly Attenuate Psychiatric Burden Sequalae in Substance Use Disorder (SUD) in Fifty Cases. (Curr Psychiatry Res Rev, 2022)