What is NAD+?
NAD+ (nicotinamide adenine dinucleotide) is not a peptide but a coenzyme present in all living cells. It is the most abundant cofactor of cellular metabolism, participating in more than 500 enzymatic reactions. Its inclusion in the context of longevity peptides is due to its frequent administration in similar ways (injectable vials, dosing protocols) and because its decline with aging is one of the central topics in anti-aging biology.
NAD+ levels decline steadily with age:
- At age 20: ~100% of reference level.
- At age 40: ~50%.
- At age 60: ~25–30%.
This decline correlates with reductions in mitochondrial energy, DNA repair capacity, and cognitive function.
Mechanism: sirtuins, PARP, and energy metabolism
Sirtuins (SIRT1–SIRT7):
- Sirtuins are NAD+-dependent enzymes that regulate gene expression, DNA repair, inflammation, and metabolism.
- David Sinclair (Harvard) popularized the idea that NAD+ decline is a cause of aging because it leaves sirtuins “without fuel.”
- SIRT1 and SIRT3 in particular are associated with longevity in multiple organisms.
PARP (Poly-ADP ribose polymerase):
- PARP enzymes “consume” NAD+ to repair DNA damage.
- With age, accumulated DNA damage increases, depleting NAD+ more rapidly — creating a vicious cycle.
Energy metabolism (Krebs cycle, respiratory chain):
- NAD+ is the electron acceptor in glycolysis and the Krebs cycle.
- Without sufficient NAD+, mitochondrial ATP production is compromised, producing the fatigue and low energy associated with aging.
Replenishment routes
| Route | Form | Bioavailability | Advantages |
|---|---|---|---|
| Oral | NMN (nicotinamide mononucleotide) | Moderate-high | Convenient, cost-effective |
| Oral | NR (nicotinamide riboside) | Moderate | Well studied in humans |
| IV | Direct NAD+ | High and rapid | Fast effect, useful in addiction |
| SC/IM | NAD+ | Moderate | Between oral and IV |
Clinical evidence
NAD+ precursors (NMN, NR) have shown positive results in Phase 1 and Phase 2 human trials:
- Increased NAD+ levels in blood and muscle.
- Improvements in metabolic parameters in older adults with diabetes or prediabetes.
- Reduction in inflammatory markers.
NAD+ IV infusions are used in longevity clinics and for addiction treatment (alcoholism, opioids), although controlled evidence is limited.
IV NAD+ is not FDA approved as a treatment. For research use only. Oral precursors (NMN, NR) are supplements without drug approval. Consult a functional or longevity medicine physician for individualized protocols.
Reported protocol (research reference)
| Vial sizes | 500 mg, 1000 mg |
|---|---|
| Reported dose | IV infusion: 500–1,500 mg over 4–8 hours. Oral (as NMN or NR): 250–500 mg/day. No approved standard protocol for IV infusion. |
| Half-life | Very short in plasma (~1 hour). Rapidly converted to active metabolites inside cells. |
| FDA status | Not FDA approved |