What Is NAD+?
Nicotinamide Adenine Dinucleotide · Last reviewed by the OPTML clinical team on April 20, 2026
NAD+ (nicotinamide adenine dinucleotide) is a coenzyme found in every living cell. It is essential for converting food into cellular energy (via the electron transport chain), for DNA repair, and for the activity of longevity-associated enzymes called sirtuins. Tissue NAD+ levels decline approximately 50% between ages 20 and 50 (Massudi H et al., PLOS One 2012). NAD+ therapy aims to restore cellular NAD+ pools through direct infusion/injection or oral precursors (NMN, NR).
Biological Role
NAD+ is a cofactor for enzymes in three major cellular processes:
- Energy metabolism, glycolysis, the citric acid cycle, and oxidative phosphorylation depend on NAD+/NADH redox cycling.
- DNA repair, PARP (poly-ADP-ribose polymerase) enzymes use NAD+ to repair DNA damage.
- Sirtuin activity, sirtuins (SIRT1-7) are NAD+-dependent deacetylases that regulate gene expression related to cellular stress, metabolism, and aging.
Age-Related Decline
NAD+ declines with age across human and animal tissues. Contributing factors include:
- Increased NAD+ consumption by CD38, a cell-surface enzyme that rises with inflammation.
- Reduced activity of NAD+ biosynthesis enzymes (NAMPT).
- Chronic low-grade inflammation ("inflammaging").
NAD+ Therapy: Formats
- Intravenous (IV) NAD+, traditionally administered in clinics. Infusion times range from 1-4 hours. High bioavailability but resource-intensive.
- Subcutaneous (SubQ) NAD+ injection, compounded by licensed pharmacies. Self-administered at home. High bioavailability, lower cost than IV.
- Oral NAD+ precursors (NMN, NR, NR acetate), increase plasma NAD+ via conversion in the liver and peripheral tissues.
Oral Precursors
NMN (nicotinamide mononucleotide) and NR (nicotinamide riboside) are the most studied precursors. Multiple RCTs show they raise blood NAD+ concentrations. Whether this translates to the broader longevity effects seen in animal models is still being evaluated in human trials.
What the Research Shows
Small human trials of NR and NMN have shown:
- Elevated blood NAD+ levels with oral supplementation.
- Improvements in insulin sensitivity in some cohorts.
- Modest improvements in cardiovascular fitness (VO₂ max) in some protocols.
- Improvements in sleep quality reported in subsets of patients.
Large outcomes-based RCTs linking NAD+ therapy to reduced mortality or extended lifespan in humans do not yet exist.
Safety
NAD+ and its precursors have been well-tolerated in human trials to date. The most common side effects are mild:
- Flushing sensation during injection.
- Brief chest tightness during rapid IV infusion.
- Mild headache or nausea, especially at higher doses.
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Start your consultation →References
- Massudi H, Grant R, Braidy N, et al. Age-associated changes in oxidative stress and NAD+ metabolism in human tissue. PLOS One. 2012;7(7):e42357.
- Verdin E. NAD+ in aging, metabolism, and neurodegeneration. Science. 2015;350(6265):1208-1213.
- Covarrubias AJ, Perrone R, Grozio A, Verdin E. NAD+ metabolism and its roles in cellular processes during ageing. Nat Rev Mol Cell Biol. 2021;22(2):119-141.
- Martens CR, Denman BA, Mazzo MR, 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.
- Yoshino J, Baur JA, Imai SI. NAD+ Intermediates: The Biology and Therapeutic Potential of NMN and NR. Cell Metab. 2018;27(3):513-528.