NMN (Nicotinamide Mononucleotide)
A direct precursor to NAD+, the coenzyme that powers DNA repair, sirtuin signalling, and mitochondrial energy. NAD+ falls ~50% by age 60 — NMN attempts to restore it.
Mouse studies are extensive and positive (Sinclair, Imai labs). Human trials so far: confirms safety, raises NAD+ levels measurably, shows improvements in physical performance, walking endurance, and some metabolic markers. Hard clinical outcome data (longevity, disease prevention) is years away. Biomarker effects: 4–12 weeks.
NMN is a molecule the body uses to make NAD+, the essential coenzyme involved in over 500 enzymatic reactions including DNA repair (PARP), gene-silencing longevity signals (sirtuins), and energy production (oxidative phosphorylation). NAD+ levels decline steadily with age — by 50–60% from your 30s to your 60s — paralleling many aspects of aging. The hypothesis: replenish NAD+ via precursor supplementation and slow some of those declines. Mouse studies are striking. Human studies are accumulating, showing safety and biomarker improvements but still building the case for clinical benefits. NMN sits alongside NR (nicotinamide riboside) as the two leading precursors.
- Form
- Sublingual NMN — bypasses first-pass metabolism, debated whether it adds much. Liposomal NMN — better absorption. Plain NMN capsules — work but at higher doses. Quality matters hugely here — third-party testing essential (counterfeit / under-dosed product is a real problem in this category).
- Dose
- 250–1,000 mg/day. Sinclair lab uses 1 g/day in their human work. Most users in the 500 mg range.
- Timing
- AM on empty stomach. NAD+ can be mildly energising — avoid PM dosing. The Sinclair protocol pairs with resveratrol (in yogurt or fat for absorption).
- Schedule
- Daily.
- Side effects
- Generally well-tolerated. Mild flushing (less than niacin), nausea, indigestion. Long-term safety beyond a few years is unknown.
- Interactions
- Theoretical interaction with chemotherapy (NAD+ may support cancer cell metabolism — discuss with oncology). Generally clean.
- Contraindications
- Active cancer (theoretical — NAD+ supports proliferating cells). Discuss with oncologist if relevant. Pregnancy / lactation — no data.
- Lab markers
- Whole-blood NAD+ (specialty labs offer this — Jinfiniti, ChromaDex). Less common: NAD+:NADH ratio. Worth a baseline + 12-week follow-up if you're committing to the cost.
- Food sources
- Trace amounts in broccoli, edamame, cucumber, cabbage, avocado, tomato — far below supplemental doses. Cannot reach therapeutic NAD+ elevation through food.
Pairs with
TMG (betaine) — NMN metabolism consumes methyl groups; TMG replaces them. Almost mandatory pairing if running NMN long-term. Resveratrol / pterostilbene (sirtuin activators that need NAD+). CoQ10 + PQQ (mitochondrial synergy). Apigenin (slows NAD+ degradation).
within Coenzymes & mitochondrial cofactors