NMN at 500mg, after two years.

Renue’s sublingual NMN has been in my morning stack for eighteen months. This is a working log — what shifted, what didn’t, and the questions I’d ask before adding it to yours.

NMN — nicotinamide mononucleotide — is a direct precursor to NAD+, a cofactor central to mitochondrial energy production and DNA repair. NAD+ declines roughly 50% by midlife. Supplementing a precursor is one of the more researched longevity bets currently available, though “researched” still means “early human trials, mostly small.”

NMN converts to NAD+ via the salvage pathway, raising intracellular NAD+ levels. The downstream effects of interest: sirtuin activation (linked to cellular repair), improved mitochondrial function, and — in animal models — measurable extension of healthspan. The sublingual form is meant to bypass first pass metabolism in the liver; whether that materially changes bioavailability is still debated.

The most cited human trials so far: Yoshino et al. 2021 (postmenopausal women, 250mg daily, improved muscle insulin sensitivity); Yamaguchi et al. 2022 (older men, 250mg, gait speed and grip strength signal); Liao et al. 2021 (runners, performance markers). Sample sizes are small (n=10–80), durations are short (8–12 weeks), and effects are modest. Longevity claims are extrapolations from rodent data, which is not the same evidence base.

Adults over 35–40 with a longevity orientation and the budget to absorb a $80–$120/month line item. People already optimizing the cheaper, higher evidence interventions first — sleep, training, omega 3, vitamin D, social fitness — for whom NMN is the next 5% rather than the first move.

Anyone who hasn’t first dialed in sleep, training, and the basic deficiencies. Anyone with active cancer or on chemotherapy — sirtuin activation in that context is poorly understood and a conversation for an oncologist. Anyone for whom $100/month is a stretch — the cheaper, higher evidence interventions are still where the leverage is.

500mg sublingual, dissolved under the tongue, taken with the morning stack at roughly 7am. Held for 60 seconds before swallowing. Paired with TMG (trimethylglycine) 1g to support methylation, which NAD+ pathways draw down. Cycled — 12 weeks on, 4 weeks off.

Sleep efficiency on Oura ring up roughly 4% on average over 18 months. HRV trended up by ~8ms. Perceived recovery from training improved markedly in months 6–12. Nothing dramatic in months 1–3. Nothing measurable in my standard blood panel beyond what training alone explains. No subjective “younger” feeling. No noticeable difference in cognitive performance, despite the popular claims.

— Alvin