NAD+
Nicotinamide Adenine Dinucleotide (NAD+) is a critical coenzyme found in every cell of the body, essential for energy metabolism, DNA repair, cellular signaling, and the regulation of sirtuins. NAD+ levels decline significantly with age, contributing to cellular dysfunction and age-related diseases. Supplementation with NAD+ or its precursors (NMN, NR) has emerged as a promising anti-aging and metabolic intervention.
Chemical Information
Sequence:
Molecular Weight:
663.43 g/mol
Source:
NAD+ is synthesized endogenously through the de novo pathway from tryptophan and the salvage pathway from nicotinamide. Therapeutic NAD+ is produced through chemical synthesis or enzymatic conversion, provided as a lyophilized powder or liquid formulation for parenteral administration.
Clinical Information
Purposes:
Dosing:
IV: 250-1000mg per session. IM/SubQ: 50-100mg per injection. Oral precursors (NMN/NR): 250-1000mg daily.
Related Peptides:
Safety Information
Side Effects:
- Flushing and warmth during IV infusion (common, transient)
- Nausea (especially with rapid IV infusion)
- Headache (usually mild)
- Muscle cramping (particularly with higher doses)
- Chest tightness during infusion (resolve with slower rate)
- Fatigue (paradoxical, usually temporary)
- Abdominal discomfort
- Anxiety or restlessness during infusion
- Injection site reactions (IM/SubQ)
Contraindications:
- Known hypersensitivity to NAD+ or nicotinamide
- Active cancer (theoretical concern - consult oncologist)
- Pregnancy and breastfeeding (insufficient safety data)
- Severe liver or kidney impairment
- Uncontrolled hypertension
Research & References
- Rajman L, et al. Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence. Cell Metab. 2018;27(3):529-547.
- https://pubmed.ncbi.nlm.nih.gov/29514064/
- Yoshino J, et al. NAD+ Intermediates: The Biology and Therapeutic Potential of NMN and NR. Cell Metab. 2018;27(3):513-528.
- https://pubmed.ncbi.nlm.nih.gov/29249689/
- Martens CR, et al. Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Nat Commun. 2018;9(1):1286.
- https://pubmed.ncbi.nlm.nih.gov/29599478/
Detailed Information
Also Known As
Nicotinamide Adenine Dinucleotide, Coenzyme I, DPN (Diphosphopyridine nucleotide), NAD
Primary Uses
Mechanism of Action
NAD+ serves as a crucial coenzyme in cellular metabolism and signaling through multiple mechanisms:
1. Energy Metabolism
NAD+ acts as an electron carrier in the mitochondrial electron transport chain, facilitating the conversion of nutrients to ATP. It alternates between oxidized (NAD+) and reduced (NADH) forms during glycolysis, the citric acid cycle, and oxidative phosphorylation.
2. Sirtuin Activation
NAD+ is an essential substrate for sirtuin enzymes (SIRT1-7), which regulate cellular processes including:
- Gene expression and DNA repair (SIRT1, SIRT6)
- Mitochondrial biogenesis and function (SIRT3)
- Inflammation and immune response
- Circadian rhythm regulation
- Cellular stress resistance
3. DNA Repair
PARP enzymes (Poly ADP-ribose polymerases) consume NAD+ during DNA repair processes. NAD+ depletion impairs DNA repair capacity, contributing to genomic instability.
4. CD38 and NAD+ Consumption
CD38, a NAD+-consuming enzyme, increases with age and chronic inflammation. This contributes to age-related NAD+ decline and metabolic dysfunction.
Pharmacokinetics
NAD+ pharmacokinetics vary significantly by route of administration:
Intravenous Administration
IV NAD+ provides 100% bioavailability with rapid distribution to tissues. Plasma levels peak during infusion and decline over several hours post-infusion. NAD+ is metabolized to nicotinamide and other metabolites.
Oral Precursors (NMN/NR)
Oral NAD+ precursors are absorbed in the small intestine and converted to NAD+ through the salvage pathway. NMN may be directly transported via the SLC12A8 transporter, while NR enters cells via nucleoside transporters.
Plasma: 30-60 minutes (IV); Tissue: 8-12 hours
IV: 100%; Oral precursors: 30-50% (variable)
Research Areas
Related Peptides
Source Information
NAD+ is synthesized endogenously through the de novo pathway from tryptophan and the salvage pathway from nicotinamide. Therapeutic NAD+ is produced through chemical synthesis or enzymatic conversion, provided as a lyophilized powder or liquid formulation for parenteral administration.