NAD+ (nicotinamide adenine dinucleotide) is a coenzyme, not a peptide. It is essential to normal cellular metabolism and is sold as IV, injectable, and oral products. It is not an FDA-approved drug for the anti-aging or wellness uses described here. This page summarizes established biochemistry and areas of active interest.
The short answer
Two claims about NAD+ get treated as one. The first — that NAD+ is essential to metabolism and declines with age — is well supported. The second — that raising it produces a felt or measurable benefit — is where the human evidence thins out sharply, and the evidence that does exist concerns oral precursors rather than the intravenous NAD+ sold in clinics.
The most useful summary of the human record: supplementation reliably moves the biomarker and has repeatedly failed to move the outcome.
The part that is not in dispute
NAD+ is a redox cofactor required for glycolysis, the citric acid cycle, and oxidative phosphorylation, cycling between oxidized (NAD+) and reduced (NADH) forms. It is also a consumed substrate — not merely a catalyst — for sirtuins, PARPs, and CD38. The 2021 Nature Reviews Molecular Cell Biology review by Covarrubias and colleagues, NAD+ metabolism and its roles in cellular processes during ageing, maps the three biosynthetic routes — kynurenine, Preiss-Handler, and salvage — and the evidence that tissue NAD+ falls with age in animals and humans, with links to metabolic dysfunction, inflammation, neurodegeneration, and senescence.
None of that is controversial, and none of it is a clinical result.
Why aging researchers care
The interest is structural. Because sirtuins and PARPs consume NAD+ rather than recycling it, and because PARP activity rises with DNA damage, a decline in NAD+ availability plausibly links several hallmarks of aging to a single measurable pool. That makes NAD+ an attractive intervention point in a way most supplements are not.
The Covarrubias review is candid about the limits of that reasoning: it states that much remains unknown about how NAD+ influences human health and whether NAD+ repletion is safe and beneficial in ageing humans. A compelling framework and a demonstrated benefit are different things.
What the human trials found
The most-cited human trial is a 2×6-week randomized, double-blind, placebo-controlled crossover study in healthy middle-aged and older adults — 30 randomized, 24 completing — using 500 mg nicotinamide riboside twice daily (1,000 mg/day), published in Nature Communications in 2018 (Martens et al.; PMID 29599478). Its findings:
- NAD+ rose. Levels in peripheral blood mononuclear cells increased roughly 60% versus placebo.
- It was well tolerated. No serious adverse events occurred at the dose tested.
- The physiological readouts were exploratory. Systolic blood pressure trended down about 3.9 mmHg, not statistically significant after correction for multiple comparisons; a subgroup with elevated baseline pressure showed a larger reduction, and carotid-femoral pulse wave velocity trended down without reaching significance. The authors framed these as hypotheses for future trials.
The Covarrubias review summarizes the pattern across other NR studies in overweight and obese adults bluntly: while NR effectively increased NAD+ levels, participants "showed no signs of weight loss, increased insulin sensitivity or enhanced mitochondrial function." Raising the biomarker is not the same as changing the outcome — and this is the specific place where NAD+ marketing outruns its own literature.
The IV question, kept separate
Almost all controlled human data concern oral precursors: nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), which cells convert into NAD+. Intravenous NAD+ — the form most heavily marketed for energy, recovery, and "cellular repair" — is a different molecule delivered by a different route, and the precursor results cannot be transferred to it.
What direct IV data exist are small and mostly pharmacokinetic. A pilot study in Frontiers in Aging Neuroscience (PMID 31572171) ran a 6-hour intravenous NAD+ infusion at 3 µmol/min and tracked plasma and urine metabolites, reporting no change in plasma NAD+ or its metabolites until after 2 hours, with increased urinary excretion of NAD+ and methylnicotinamide by 6 hours. Its stated motivation was that no data existed on the fate of directly infused NAD+ in humans. That is a study establishing where the molecule goes, not a study showing it does anything.
What a benefit claim needs to clear
- Was the endpoint a biomarker (blood NAD+) or an outcome (strength, insulin sensitivity, walking distance)? Most positive headlines describe the former.
- Which molecule was tested? Results for oral NR do not automatically apply to NMN, and neither applies to IV NAD+.
- Which species? Much of the striking longevity data comes from mice and worms.
- How long? Six-to-twelve-week trials cannot address aging trajectories measured in decades.
NAD+ and NMN are not FDA-approved drugs for any indication, and NMN's status as a dietary-supplement ingredient has been contested in the United States because it has been investigated as a drug.