NAD+ and Longevity: What the Research Actually Says

What NAD+ is and why it declines

Nicotinamide adenine dinucleotide (NAD+) is a coenzyme found in every living cell. It plays a central role in cellular energy metabolism — specifically in the mitochondrial processes that convert nutrients into ATP, the cell's primary energy currency.

NAD+ also serves as a substrate for sirtuins, a family of proteins involved in DNA repair, gene expression regulation, and cellular stress response. Research from David Sinclair's laboratory at Harvard Medical School has highlighted the relationship between NAD+ levels, sirtuin activity, and biological aging processes.

NAD+ levels decline with age — by some estimates, by approximately 50% between the ages of 40 and 60. This decline correlates with reduced mitochondrial function, impaired DNA repair capacity, and increased vulnerability to cellular stress.

NMN as a precursor

NAD+ cannot be directly supplemented — the molecule is too large to cross cell membranes efficiently when taken orally. Supplements instead provide NAD+ precursors: compounds that cells can use to synthesize NAD+ endogenously.

Nicotinamide mononucleotide (NMN) is one such precursor. Animal studies have demonstrated that NMN supplementation increases tissue NAD+ levels, with associated improvements in metabolic markers, mitochondrial function, and physical endurance in aged mice.

Human clinical data is more limited but growing. A randomized, placebo-controlled study published in Science (Yoshino et al., 2021) found that oral NMN supplementation increased skeletal muscle NAD+ metabolite levels in postmenopausal women with prediabetes, with improvements in insulin sensitivity. A study in the Journal of the International Society of Sports Nutrition (Liao et al., 2021) reported improvements in aerobic capacity in amateur runners taking NMN over 6 weeks.

What remains uncertain

The longevity effects demonstrated in mice have not been replicated in human trials at the scale or duration needed to draw firm conclusions. We can say that NMN appears to increase NAD+ levels in humans and that preliminary evidence suggests metabolic benefit. We cannot say it extends human lifespan.

At Stryō, we apply the same standard to our NAD+ formula as to all others: we use ingredients with a credible mechanistic rationale and emerging human evidence, at doses consistent with the studies showing the most promising outcomes. We do not extrapolate animal data into human longevity claims.

Sublingual delivery and NAD+ precursors

NMN delivered sublingually bypasses the gut and liver, where some degradation to nicotinamide may occur during oral transit. While the comparative bioavailability data for sublingual vs oral NMN in humans is still being established, the theoretical advantage of bypassing first-pass metabolism is consistent with the broader pharmacokinetic rationale for sublingual delivery.

*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.