NAD+ synergists — what stacks with NMN and why.
NMN raises NAD+. But NAD+ is only part of the longevity equation. These compounds amplify the effect — through sirtuins, methylation support, and mitochondrial synergy.
- Raising NAD+ is only part of the longevity equation — synergists amplify the downstream effect.
- Sirtuin activators, methylation support and mitochondrial cofactors are the main synergist categories.
- Methyl donors (TMG/betaine) matter because NAD+ metabolism consumes methyl groups.
- Stacking is about complementary mechanisms, not simply taking more of the same.
Resveratrol activates SIRT1 directly and works synergistically with NAD+ — NAD+ provides the fuel, resveratrol pushes the accelerator. Pterostilbene is the more bioavailable analogue with longer half-life. David Sinclair's core protocol includes 1g NMN + 1g resveratrol daily.
✓ Strong sirtuin synergy · Take with fat for absorptionNMN metabolism consumes methyl groups. Without replenishment, you can deplete SAM (S-adenosylmethionine) — the body's primary methyl donor. TMG (500mg–1g/day) donates methyl groups to keep this pathway running and avoid potential side effects of NMN supplementation at higher doses.
✓ Essential methylation support · Often overlookedA flavonoid that inhibits CD38 — the enzyme that degrades NAD+. CD38 increases significantly with age and is a major driver of NAD+ decline. Blocking it preserves more of the NAD+ you produce. Found in parsley, chamomile. Supplement dose: 50–100mg/day.
✓ CD38 inhibitor · Preserves NAD+ · Low costBoth a CD38 inhibitor and a senolytic compound. Works synergistically with fisetin and dasatinib in senolytic protocols. Also has anti-inflammatory and antioxidant properties. Typical dose: 500–1000mg with EGCG or fisetin for senolytic effect.
✓ Dual role: CD38 inhibitor + senolyticWorks alongside NAD+ in the mitochondrial electron transport chain. CoQ10 declines with age and with statin use. Ubiquinol (the reduced form) has better bioavailability than ubiquinone. If you're doing a serious mitochondrial protocol, CoQ10 200–400mg/day complements NMN well.
✓ Mitochondrial synergy · Take with fatA mitochondria-derived peptide that activates AMPK and improves insulin sensitivity. Works in parallel with NAD+/sirtuin pathways to improve metabolic function. Available from several EU vendors — COA verified options tracked on PeptideCompare.
✓ Mitochondrial peptide · AMPK activation