NAD+
The cellular energy currency and sirtuin activator — declines with age, supplementation supports mitochondrial function, DNA repair, and longevity pathways.
Research facts
| Half-life | Minutes (IV) / 1–4h SubQ equivalent |
|---|---|
| Route | IV / SubQ / Nasal / Oral (NMN/NR) |
| Typical dose | 100–500 mg (IV/SubQ) |
| Frequency | Weekly IV or daily SubQ nasal |
| Solvent | Sterile saline (IV) / BAC water (SubQ) |
| pH | 7.0–7.4 |
| Stability | Use IV within 24h; SubQ 7 days at +4°C |
Mechanism of action
NAD+ (Nicotinamide Adenine Dinucleotide) is a coenzyme present in every living cell, functioning as the central electron carrier in oxidative phosphorylation (accepting H⁺ as NADH in the citric acid cycle and ETC) and as a substrate for sirtuin deacylases (SIRT1–7) and PARP enzymes involved in DNA repair.
NAD+ levels decline 50% between age 40–60. This reduction impairs mitochondrial function (less NADH for ATP synthesis), reduces sirtuin activity (less DNA repair, less metabolic regulation), and compromises PARP-mediated genome maintenance. Restoring NAD+ via direct supplementation or precursors (NMN, NR) aims to reverse these age-associated deficits.
Multiple human RCTs with NMN and NR (oral precursors) demonstrate that NAD+ levels in blood can be meaningfully elevated. IV NAD+ bypasses conversion steps for rapid elevation. David Sinclair (Harvard) and Bryan Johnson both incorporate NAD+ supplementation in documented longevity protocols, though direct injectable NAD+ data is less robust than oral precursor data.
Documented effects (research-model)
- Mitochondrial function support via NADH provision for ETC
- Sirtuin (SIRT1, SIRT3) activation for DNA repair and metabolic regulation
- PARP enzyme substrate for genome integrity maintenance
- Circadian rhythm regulation via NAMPT pathway
- Muscle energy metabolism and exercise recovery
- Cognitive function and neuroprotection in animal models
Research protocols
| Protocol | Dose | Frequency | Cycle | Vial |
|---|---|---|---|---|
| SubQ/Nasal | 100 mg SubQ daily or nasal spray | Daily | Ongoing with quarterly breaks | 500mg / 5mL sterile water |
| IV Protocol | 250–500 mg IV | Weekly or monthly | Ongoing wellness protocol | IV preparation |
Research context only. Not medical advice. Consult a qualified healthcare professional before any protocol decision.
Synergies
- SS-31 HIGH
SS-31 optimises ETC function; NAD+ provides the substrate. Direct mitochondrial metabolic synergy. - GHK-Cu MODERATE
Dual anti-ageing pathway: GHK-Cu at tissue gene expression level + NAD+ at cellular energy/sirtuin level. - MOTS-c HIGH
MOTS-c encoded by mitochondrial genome; NAD+ supports mitochondrial function. Synergistic mitochondrial support.
Myths & misconceptions
Evidence gaps
- Direct injectable NAD+ (SubQ) lacks robust clinical trial data — most NAD+ trials use oral NMN/NR.
- Whether blood NAD+ elevation translates to meaningful tissue-level NAD+ increases in humans is debated.
- Long-term cancer risk of sustained NAD+ elevation is a theoretical concern needing longitudinal study.
Safety notes
IV NAD+ can cause flushing, chest tightness, nausea — must be administered slowly. SubQ generally well-tolerated. Oral precursors (NMN, NR) have superior safety data. Monitor LFTs, kidney function.
Biomarkers to monitor
Primary-source citations
- PMID 34728542 — Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women (Science. 2021)
- PMID 33186449 — Long-term NMN administration increases NAD+ levels and improves metabolic function in mice (Nat Metab. 2020)
Frequently asked
What is NAD+?
NAD+ (Nicotinamide Adenine Dinucleotide — IV / SubQ / Nasal Administration) is a research compound classified in our library as Tier B — Some human data + strong preclinical evidence.. The cellular energy currency and sirtuin activator — declines with age, supplementation supports mitochondrial function, DNA repair, and longevity pathways.
What is the evidence tier for NAD+?
We classify NAD+ as Tier B: Some human data + strong preclinical evidence. See our full peptide evidence tiers explainer for how we assign S/A/B/C/D.
What is the research dose of NAD+?
For NAD+, typical research dose is 100–500 mg (IV/SubQ), route is IV / SubQ / Nasal / Oral (NMN/NR), half-life is Minutes (IV) / 1–4h SubQ equivalent. Protocols vary by research goal — see the protocols section on this page for standard and advanced dosing schedules. Research use only, not medical advice.
What does NAD+ stack well with?
NAD+ stacks well with SS-31. SS-31 optimises ETC function; NAD+ provides the substrate. Direct mitochondrial metabolic synergy.
Is NAD+ safe?
IV NAD+ can cause flushing, chest tightness, nausea — must be administered slowly. SubQ generally well-tolerated. Research context only — no compound on this site is approved for human therapeutic use unless explicitly noted.