NAD+: what the research literature shows

What it is

A coenzyme, not a peptide

NAD+ is a dinucleotide: two nucleotides joined together. One carries the base nicotinamide and the other carries adenine, and they are linked through their phosphate groups.¹ PubChem lists it as nadide, with the formula C21H27N7O14P2 and a molecular weight of 663.4 g/mol, and records the synonyms coenzyme I and diphosphopyridine nucleotide.¹

A peptide is a chain of amino acids joined by peptide bonds, as the guide to peptides, proteins and amino acids explains. NAD+ has neither.

Oxidized and reduced forms

The coenzyme is an electron carrier: it is alternately oxidized, as NAD+, and reduced, as NADH.¹ PubChem’s formula for NADH, C21H29N7O14P2, has two more hydrogen atoms.¹³

The enzymes that consume it

Review A 2021 review by Covarrubias and colleagues describes the redox role as what makes NAD+ central to energy metabolism, and names three groups of enzymes that depend on it outside redox chemistry: sirtuins, PARPs and CD38.² It lists DNA repair, chromatin remodelling, cellular senescence and immune-cell function among the processes NAD+ influences.²

Cell study In isotope-tracer experiments on cell lines, NAD+ was consumed largely by PARPs and sirtuins.¹⁴

How cells make and recycle it

Animal study A tracer study in mice found that NAD+ was made from the amino acid tryptophan selectively in the liver, which then excreted nicotinamide.¹⁴ Flux differed widely between tissues: high in the small intestine and spleen, low in skeletal muscle.¹⁴

Cell study A second route is recycling, or salvage: in the same work, cell lines made NAD+ from nicotinamide.¹⁴ In cultured human cells, nicotinamide, nicotinic acid and their nucleosides (the base joined to a ribose sugar) entered readily, while the nucleotides NAD+ and nicotinamide mononucleotide (NMN) were first degraded outside the cell into permeable precursors.¹⁵ Inside the cell, precursors were converted to NMN, the substrate for forming NAD+ in mitochondria, described as the largest pool in the cell.¹⁵

How it is studied

Concentrations in blood have been measured by a cycling assay and by liquid chromatography with mass spectrometry, a technique covered in the guide to analytical methods.⁸ Isotope tracers add flux, the rate at which NAD+ is made and broken down, which a concentration alone does not show.⁴¹⁴ A magnetic resonance method on a high-field scanner has estimated NAD+ and NADH in the living human brain.⁶

The guide to evidence levels explains the badges used below.

What the literature reports

Tissue levels and age in animals

Animal study Using isotope tracing across the tissues of aged mice, McReynolds and colleagues found tissue NAD+ modestly depleted, with a median decrease of about 30 per cent, while circulating precursors were not significantly changed and synthesis of nicotinamide from tryptophan was unimpaired.⁴ In most tissues the smaller pool turned over somewhat faster, so absolute synthesis was maintained, which the authors read as more active consumption and not failed production.⁴

Animal study In a second mouse study, the expression and activity of CD38, an enzyme that degrades NAD+, increased with age, and the authors reported that CD38 was required for the age-related fall in NAD+ and the mitochondrial dysfunction that came with it.¹⁶

Review The Covarrubias review states that NAD+ declines gradually with age in model organisms, including rodents and humans, and lists as unknown whether restoring it is safe or has favourable effects in aging humans.²

What human measurements show

Human study In pelvic skin samples from 49 people, from newborns to adults of 77, NAD+ content correlated negatively with age in both sexes.⁵ In males, PARP activity rose with age and correlated inversely with tissue NAD+; these associations were less evident in females.⁵

Human study In the brain, the magnetic resonance assay found NADH higher in older healthy volunteers, and NAD+, total NAD and the NAD+/NADH redox potential lower.⁶

Human study In muscle, a cross-sectional study compared young adults with older adults who were exercise-trained, normally active or physically impaired.⁷ NAD+ was among the metabolites most clearly lower in the older groups; the gap was widest in the impaired group, and trained older adults had levels closer to those of the young.⁷ NAD+ abundance also correlated positively with average daily steps.⁷

Human study In blood, a study of 1,518 adults from one community in China found a decline with age only in men, significant only in the group aged 60 and over; in women, whole-blood NAD+ did not differ significantly across five age groups.⁸

Review A 2021 review by Peluso and colleagues covered NAD+ measurements from yeast to humans and concluded that the evidence for an overall decline with age is very limited and often confined to a single tissue or cell type, particularly in humans, and called for larger, preferably longitudinal studies.⁹

Precursor trials: NR and NMN

Review A 2026 systematic review of NAD-related compounds, covering January 2010 to October 2025, found 33 human intervention studies, 28 of them randomized.³ For NMN and nicotinamide riboside (NR), the nucleoside of nicotinamide, taken by mouth, it reported consistent rises in NAD-related metabolites in blood or blood cells and described both as generally well tolerated over weeks to months, while effects on functional, metabolic and vascular outcomes were heterogeneous and often null.³

Human study Two randomized, double-blind, placebo-controlled trials show the spread. In 40 sedentary men with obesity, NR did not change insulin sensitivity, glucose production, resting energy expenditure or body composition, and no serious adverse events were attributed to it.¹⁷ In postmenopausal women with prediabetes who were overweight or obese, insulin-stimulated glucose disposal and muscle insulin signalling increased after NMN and did not change after placebo.¹⁸

Human evidence

Human evidence for NAD+ itself is thin. Three kinds of human study appear on this page: measurements of the body’s own NAD+, trials of precursors, and studies in which NAD+ itself was given. The third is the smallest.

Review The 2026 systematic review found no eligible outcomes trial of NAD+ itself, given by infusion or into muscle, for anti-aging or wellness indications, and called clinical effectiveness for those outcomes inconclusive.³

Human study Grant and colleagues ran a pilot in eleven healthy men, eight assigned to an NAD+ infusion and three to saline.¹⁰ Plasma NAD+ and its metabolites did not change until after two hours, which the authors read as rapid and complete removal from plasma over that time.¹⁰ Urinary methylnicotinamide and NAD+ had risen by the end of the infusion.¹⁰ The study measured metabolites, not clinical outcomes, and two of its authors were affiliated with a wellness centre, one also with a company, NAD+ Research Inc..¹⁰

Human study A 2026 retrospective review of records from a commercial wellness provider compared six clients given NAD+ infusions with eight given NR infusions.¹¹ Those given NAD+ reported moderate to severe gastrointestinal symptoms, a raised heart rate and chest pressure during infusions, which took longer to complete; those given NR reported minor tingling and mild cramping.¹¹ All symptoms resolved when the infusion ended.¹¹ Liver, kidney, inflammation and thyroid markers did not change significantly over 30 days, and HDL cholesterol fell in the NAD+ group.¹¹ This was not a randomized or placebo-controlled trial, and all its authors were employed by the provider.¹¹

Human study The one randomized, placebo-controlled trial of NAD+ itself in patients cited here, run at a single centre in China, enrolled 180 adults with heart failure caused by ischemic cardiomyopathy and added NAD+ infusions, or placebo, to guideline-directed therapy.¹² At one month, left ventricular ejection fraction, a measure of the heart’s pumping function, was 45.4 per cent in the NAD+ group and 42.4 per cent in the placebo group, a difference in the primary endpoint reported as statistically significant.¹² Differences in the blood marker NT-proBNP, in a six-month composite of major cardiac and cerebrovascular events and in functional class did not reach significance.¹² The abstract does not describe the trial as double-blind, and the authors called for larger multicentre trials built around clinical endpoints.¹²

ClinicalTrials.gov lists two randomized studies from one research institute that compare NAD+ with a branded NR product in healthy adults; neither had posted results on 8 October 2026.¹⁹²⁰

Regulatory status

On 8 October 2026 Health Canada’s Drug Product Database returned no product under the ingredient names nadide, nicotinamide adenine dinucleotide or NADH.²¹ Under the Latin name nadidum it listed four multi-ingredient homeopathic products from one manufacturer, all with the status “cancelled post market”.²¹ Health Canada’s natural health product databases were not searched.

On the same date the FDA’s Drugs@FDA data returned no approved application with nadide or nicotinamide adenine dinucleotide as an active ingredient.²² The agency’s National Drug Code directory data held 56 listings naming nadide and 22 naming nicotinamide adenine dinucleotide, all marked as unapproved homeopathic products, bulk ingredients, a drug for further processing or, in one case, an unapproved drug.²³ The directory states that assignment of a code does not denote FDA approval.²³

The FDA’s list of bulk drug substances nominated for compounding under section 503A, updated 14 May 2026, places nicotinamide adenine dinucleotide in category 1, headed “Bulk Drug Substances Under Evaluation”; the agency describes these as nominated substances that may be eligible for its compounding list.²⁴²⁵

Products on this site are sold for laboratory research use only, as set out in the research use only policy.

In the laboratory

Horizon lists NAD+ as a lyophilized (freeze-dried) powder in sealed vials. Three published observations bear on its behaviour in solution:

• Chemistry study Heat. At 85 °C, NAD+ broke down mostly into nicotinamide and ADP-ribose.²⁶
• Chemistry study pH. The introduction to a 2024 stability study states that NAD+ degrades by a base-catalyzed route at high pH and NADH by an acid-catalyzed route at low pH.²⁷
• Chemistry study Buffer. There, over 43 days at 19 °C and pH 8.5, NAD+ was most stable in Tris buffer and almost entirely degraded in HEPES, in a qualitative comparison by ultraviolet absorbance.²⁷

NAD+ has no peptide bonds, so these are not the routes covered in the guide to peptide stability and degradation. General conditions for keeping freeze-dried material are in the peptide storage guide. Batch documents, when they exist, are published on the Lab Results page.