NAD+
Nicotinamide Adenine Dinucleotide
Cellular energy coenzyme for longevity protocols
About
A coenzyme present in every cell that shuttles electrons during ATP production, powers DNA repair via PARP enzymes, and activates the sirtuin family of longevity regulators. Tissue NAD+ levels decline progressively with age, motivating restoration protocols via direct injection or precursor supplementation (NR, NMN). Technically a small-molecule coenzyme rather than a peptide. Injectable NAD+ is not FDA-approved and is available only through compounding pharmacies.
Mechanism
Acts as an electron carrier in mitochondrial oxidative phosphorylation. Substrate for sirtuins (SIRT1-7) that regulate metabolism, inflammation, and DNA repair. Cofactor for PARP enzymes during DNA damage response. CD38 hydrolyzes NAD+ at increasing rates with age, contributing to decline.
Dosage
Draw to 50 units on a U-100 insulin syringe
750 mg lyophilized · 7.5 mL bacteriostatic water BAC
When to take: Morning or early afternoon — energy-pathway activation can disrupt sleep if dosed late. Inject slowly to minimize site stinging. IV must be slow-drip; rapid infusion triggers chest tightness and flushing.
Reconstitution
Vial size (mg): 750 mg lyophilized · BAC water (mL): 7.5 mL bacteriostatic water · Concentration: 100 mg/mL
Some compounding pharmacies ship as pre-mixed solution — no reconstitution needed in that case. Inject water down vial wall, swirl gently. Discard if yellow or cloudy.
Benefits
- Sustained energy and reduced fatigue (subjective)
- Supports mitochondrial function and ATP synthesis
- Activates sirtuin-mediated longevity pathways
- Aids DNA damage repair via PARP cofactor role
- Reported improvement in recovery and mental clarity
Side effects
- Injection-site stinging, burning, or redness (SubQ)
- Flushing, warmth, chest tightness (IV, especially fast infusion)
- Nausea and headache during titration
- Transient anxiety or jitteriness
- Mild GI discomfort
Gender notes
Cautions
- Pregnancy and breastfeeding
- Active malignancy (sirtuin and PARP activity uncertain in cancer biology)
- Severe liver or kidney disease
- Concurrent high-dose niacin
- Glucose-lowering medications without monitoring
Research
- A pilot study investigating changes in the human plasma and urine NAD+ metabolome during a 6 hour intravenous infusion of NAD+
Frontiers in Aging Neuroscience · 2019
First human pharmacokinetic study of IV NAD+ — established that infused NAD+ is rapidly metabolized with measurable changes in metabolite pool.
- NAD+ precursor supplementation in human ageing: clinical evidence and challenges
Nature Reviews Endocrinology · 2025
Review of clinical trials using NR and NMN — confirms tissue NAD+ elevation, with mixed evidence for downstream aging biomarkers.
- Intravenous infusion of NAD+ versus nicotinamide riboside: a retrospective tolerability pilot study
Frontiers in Aging · 2026
Real-world tolerability comparison; both well-tolerated at studied doses, with IV NAD+ showing higher rate of infusion-reaction symptoms.