NAD+

Also known as: Nicotinamide Adenine Dinucleotide, Coenzyme I, DPN (diphosphopyridine nucleotide)

Evidence: Clinical

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Overview

Nicotinamide adenine dinucleotide, the central redox coenzyme; a 2026 randomized trial of intravenous NAD+ at 10 mg/day for 7 days raised ejection fraction in 180 ischemic cardiomyopathy patients.

NAD+ is a dinucleotide coenzyme, not a peptide (PubChem CID 5892). Direct administration is studied far less than its precursors. The one randomized controlled trial gave 10 mg/day intravenously for 7 days alongside guideline therapy to 180 patients with ischemic cardiomyopathy and an ejection fraction of 45% or less: ejection fraction at 1 month was higher than placebo (45.4% versus 42.4%), while NT-proBNP, event rates and NYHA class showed trends only (Yu 2026). A pilot infusion study found that at 3 micromol/min no rise in plasma NAD+ or its metabolites appeared for the first 2 hours, implying rapid and complete removal from plasma, with NAD+ and methylnicotinamide later appearing in urine (Grant 2019). A 2026 retrospective comparison of commercial infusions found NAD+ markedly less tolerable than nicotinamide riboside.

Benefits

Higher left ventricular ejection fraction after 7 days of intravenous dosing in ischemic cardiomyopathy (human RCT, n=180), raised urinary NAD+ and methylnicotinamide excretion during infusion (human pilot, n small), improved metabolic markers in aged animals (rodent only)

Dosing reference

Research dose: 50 to 100 mg subcutaneous or intramuscular: clinic and community range. The only randomized trial used 10 mg/day intravenously, and commercial infusion protocols use 500 mg per session
Range: 50000 to 100000 mcg, 1-3x weekly
Reconstitution: 5 mL bacteriostatic water
Common vial sizes: 100 mg, 250 mg, 500 mg

Published human doses, verbatim: 10 mg/day intravenously for 7 days in the randomized cardiomyopathy trial (Yu 2026); 500 mg intravenously on four consecutive days in a commercial setting, where moderate to severe gastrointestinal symptoms, higher heart rate and chest pressure stretched mean infusion time to 97 minutes against 37 minutes for nicotinamide riboside (Reyna 2026); 3 micromol/min for 6 hours, about 720 mg total, in a pilot pharmacokinetic study (Grant 2019). Infusion rate, not total dose, drives the symptoms. Subcutaneous and intramuscular dosing has no published study at all.

Mechanism

NAD+ is the electron carrier in the NAD+/NADH couple and the substrate for sirtuin deacetylases, PARP DNA-repair enzymes and CD38. Tissue NAD+ declines with age across species, which is the rationale for repletion (Verdin 2015; Covarrubias 2021). What direct administration does is less clear. In the one published human infusion study, plasma NAD+ did not rise for 2 hours at 3 micromol/min and the metabolite profile was consistent with extracellular NAD+ glycohydrolase and pyrophosphatase activity, meaning the molecule is largely degraded before any cell takes it up intact; urinary excretion of NAD+ itself and methylnicotinamide followed (Grant 2019). Any benefit from injected NAD+ may therefore run through its breakdown products rather than through intact uptake.

Evidence

Clinical: at least one published human trial or an approved drug

Intravenous NAD+ 10 mg/day for 7 days in 180 patients with ischemic cardiomyopathy raised 1-month ejection fraction over placebo (45.4% versus 42.4%); NT-proBNP, 6-month composite events and NYHA class improvement all trended in favor without reaching significance, and ventricular dimensions did not change (Yu et al., 2026)
In a 6-hour infusion at 3 micromol/min, plasma NAD+ and its metabolites did not rise for the first 2 hours, indicating rapid and complete plasma clearance; urinary NAD+ and methylnicotinamide rose by 6 hours (Grant et al., 2019)
A retrospective comparison of 500 mg intravenous NAD+ against intravenous nicotinamide riboside over four consecutive days found moderate to severe gastrointestinal symptoms, raised heart rate and chest pressure in the NAD+ group, with no changes in liver, renal, inflammatory or thyroid markers in either (Reyna et al., 2026)
Tissue NAD+ decline with age and the resulting effects on sirtuin and PARP activity are established in animal models and reviewed extensively; the clinical translation remains at the precursor stage (Verdin et al., 2015; Covarrubias et al., 2021)
Human-trial status: one randomized placebo-controlled trial of injected NAD+ exists, in cardiology, with a surrogate primary endpoint. No trial supports use for fatigue, addiction or aging, no regulator has approved NAD+ for any indication, and openFDA returns no approved US drug product containing it

References

Side effects

Infusion symptoms are the dominant finding. In a retrospective comparison of 500 mg intravenous NAD+ with intravenous nicotinamide riboside, the NAD+ group reported moderate to severe gastrointestinal symptoms, raised heart rate and chest pressure during infusion, all resolving when the infusion finished, and infusions took 97 minutes on average against 37 (Reyna 2026). Liver enzymes, renal markers, hsCRP and TSH did not change in either group over 30 days. In the randomized cardiology trial at 10 mg/day no safety signal was reported (Yu 2026). Injection-site pain with subcutaneous use is commonly reported (anecdotal). Long-term safety of direct NAD+ administration is unstudied.

Storage

Storage: Refrigerate 2-8°C (36-46°F)
Lyophilized: 2+ years at room temp, 3+ years refrigerated
Reconstituted: 28-30 days refrigerated

Pharmacology

Half-life: Not formally reported. During a 6-hour infusion at 3 micromol/min, plasma NAD+ did not rise for 2 hours, which the authors read as rapid and complete removal from plasma (Grant 2019)
Bioavailability: Intravenous: does not produce a measurable plasma rise at 3 micromol/min, with the metabolite pattern pointing to extracellular degradation (Grant 2019). Subcutaneous and intramuscular: no data. Oral: not studied for NAD+ itself; the oral literature is on precursors
Molecular weight: 663.43 Da