NMN (Nicotinamide Mononucleotide) — NAD+ precursor / nutraceutical
NMN and NR are precursors to NAD+ (nicotinamide adenine dinucleotide), a coenzyme essential for >400 cellular processes including mitochondrial oxidative phosphorylation, DNA repair (via PARP), gene expression regulation (via sirtuins SIRT1-7), circadian rhythm maintenance, and calcium signaling. NAD+ levels decline ~50% between ages 20–60 in human muscle tissue. NMN → NMN is converted to NAD+ via NMNAT enzymes. NR → NMN → NAD+. Key differences: NMN requires CD73 cell surface transport or may enter cells directly as NMN (controversy). NR crosses cell membranes directly. Phase 2 RCT data (Yoshino 2021, n=25 postmenopausal women): 250 mg NMN/day increased skeletal muscle NAD+ levels 15.7% vs. control.
Overview
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Compound Class
NAD+ precursor / nutraceutical
Mechanism of Action
NMN and NR are precursors to NAD+ (nicotinamide adenine dinucleotide), a coenzyme essential for >400 cellular processes including mitochondrial oxidative phosphorylation, DNA repair (via PARP), gene expression regulation (via sirtuins SIRT1-7), circadian rhythm maintenance, and calcium signaling. NAD+ levels decline ~50% between ages 20–60 in human muscle tissue. NMN → NMN is converted to NAD+ via NMNAT enzymes. NR → NMN → NAD+. Key differences: NMN requires CD73 cell surface transport or may enter cells directly as NMN (controversy). NR crosses cell membranes directly. Phase 2 RCT data (Yoshino 2021, n=25 postmenopausal women): 250 mg NMN/day increased skeletal muscle NAD+ levels 15.7% vs. control.
Regulatory Status
Complex. NMN: FDA issued 2022 guidance it cannot be sold as dietary supplement (pre-IND exclusion). NR: Sold as supplement, GRAS self-affirmed by ChromaDex. Market products widely available despite regulatory ambiguity.
Evidence Level
Emerging — Phase 1/2 RCT data in humans (2021–2024). Robust animal evidence. No long-term RCT data on longevity endpoints. Regulatory status uncertain in US.