NAD Precursor Supplementation (NR, NMN, IV NAD)

NAD (nicotinamide adenine dinucleotide) is a coenzyme/electron shuttle active in 500–600 cellular pathways; 99% of its role is shuttling electrons as the NAD/NADH pair. The total NAD pool is tightly regulated regardless of age — what actually declines with age is 'redox potential' (electron-shuttling capacity), reflecting declining mitochondrial function rather than NAD depletion itself. NAD is also consumed as a substrate by sirtuins during DNA repair, which fed the (later falsified — see Caloric Restriction & the Sirtuin Hypothesis) idea that boosting NAD would boost sirtuin activity and thereby longevity.

Because NAD itself is not orally bioavailable, precursors are used instead:

NR (nicotinamide riboside) crosses cell membranes directly. Typically dosed 300–600 mg.
NMN (nicotinamide mononucleotide) carries an extra phosphate group that must be cleaved before uptake, giving it weaker bioavailability evidence than NR (though no head-to-head blood-NAD trial has ever directly compared them). Typically dosed ~1500 mg.
IV NAD infusion bypasses oral bioavailability entirely via direct infusion (30 min–3 hr, 500–1000 mg, ~$300–1000/session), but evidence of meaningful benefit relative to cost is lacking.

The evidence base is weak: NR failed ITP testing entirely — no lifespan extension, no healthspan improvement, no change in blood NAD — while rapamycin, acarbose, SGLT2 inhibitors, and 17-alpha estradiol all extended lifespan in the same program. The NMN vs. NR debate is largely commercial posturing rather than a scientific one; the FDA reclassified NMN as an investigational drug (blocking supplement sales) after a company began drug trials with it, paralleling what happened with NAC — GRAS status (which NR retains) confers legal sale ability, not proof of efficacy.

The one plausible positive human signal: NAD precursors showed a 60–80% reduction in basal and squamous cell (not melanoma) skin carcinomas, which aligns with skin showing the largest age-related NAD decline of any tissue.

Contrast with Rapamycin as a Geroprotective Molecule and Caloric Restriction & the Sirtuin Hypothesis, the two interventions with robust cross-species lifespan evidence — NAD precursors currently lack comparable support. See Longevity Intervention Classification Frameworks for where NAD-pathway supplementation sits in the broader taxonomy of longevity approaches.

Из тем: Longevity Interventions