NAD+

Not a peptide. NAD+ is a dinucleotide coenzyme — two nucleotides (one containing nicotinamide, one adenine) joined through their phosphate groups. It is included because it is constantly discussed alongside peptides, is sold as an injectable in the same channels, and people search for it here. The same evidence standards apply.

nicotinamide adenine dinucleotide (oxidised form); NADH is the reduced form; precursors NR (nicotinamide riboside), NMN (nicotinamide mononucleotide), niacin, nicotinamide

Longevity & cellular

Awaiting medical reviewEN ES DE FR PT ZH+ Follow for updates

Summary

Class: Naturally occurring dinucleotide coenzyme present in every living cell; the injectable or oral product is a synthetic or fermentation-derived copy. Precursors (NR, NMN) are vitamin-B3 derivatives
Mechanism: Shuttles electrons in energy metabolism (NAD+/NADH) and is consumed as a substrate by sirtuins, PARPs (DNA repair) and CD38; cellular levels fall with age, and raising them is the hypothesis behind all NAD+ products
Routes studied: Intravenous infusion (human: small studies, addiction clinics); oral NR and NMN (human RCTs); subcutaneous and intramuscular injection (community; almost no literature); intranasal and transdermal patches (community; no literature)
Dose range reported: IV NAD+: 250–1,000 mg per infusion over 2–8 hours in clinic practice; the one published pharmacokinetic study used 750 mg over 6 hours. Oral NR trials: 250–2,000 mg/day, most commonly 1,000 mg. Oral NMN trials: 250–1,250 mg/day. Community subcutaneous NAD+: 50–200 mg per injection, several times a week
Half-life: Extracellular NAD+ is degraded within minutes by CD38, CD73 and other enzymes; during a 6-hour infusion, plasma NAD+ did not rise above baseline until about 2 hours in, and most of the dose appeared as metabolites. Oral NAD+ is broken down in the gut; precursors are absorbed and converted inside cells
Storage: Lyophilised NAD+: refrigerate or freeze, protect from light and moisture; it is hygroscopic and degrades in solution, especially warm or at non-neutral pH. Oral NR/NMN capsules: cool, dry; NMN in particular degrades with heat and humidity
Regulatory status: NAD+ itself is not an approved medicine anywhere. NR is a permitted supplement ingredient in several regions; NMN's status has shifted repeatedly. See region table

Doses are as reported in studies or by the community — never recommendations.

1What it is

NAD+ is one of the oldest molecules in biology, used by every cell to move electrons around in the reactions that turn food into usable energy. It is also "spent" — consumed rather than recycled — by three families of enzymes that matter for ageing research: sirtuins (which regulate gene expression and stress responses), PARPs (which repair DNA) and CD38 (an immune enzyme whose activity rises with age). Tissue NAD+ levels fall with age in animals and, more patchily, in human data, and that decline is argued to contribute to metabolic and mitochondrial dysfunction.

Three distinct products get called "NAD+": the molecule itself, given intravenously in wellness and addiction clinics since the 1960s–2000s and more recently by injection in the peptide community; oral NR, the precursor with the most human trials; and oral NMN, the precursor made famous by David Sinclair's laboratory. Their evidence bases are different and this profile keeps them apart. The one thing they share is that the cell has to make its own NAD+ inside — the molecule does not simply enter cells from the blood.

2How it's thought to work

Redox. NAD+ accepts electrons (becoming NADH) in glycolysis, the TCA cycle and fatty-acid oxidation; NADH gives them to the mitochondrial electron transport chain. Low NAD+/NADH ratios impair mitochondrial function.

Sirtuins. SIRT1–7 need NAD+ to deacetylate proteins that control metabolism, inflammation, circadian rhythm and mitochondrial biogenesis. More NAD+ is argued to mean more sirtuin activity; this is the core "longevity" hypothesis and remains contested in humans.

DNA repair. PARPs consume large amounts of NAD+ when repairing DNA damage, which is one reason levels fall under chronic stress and with age.

CD38. This NADase increases with age and inflammation and is a major sink; CD38 inhibitors raise NAD+ in mice.

Why precursors. Cells import NR and (after conversion) NMN far more readily than NAD+; oral NR and NMN raise blood and tissue NAD+ metabolites reliably in humans. Intravenous NAD+ appears to be largely broken down outside cells into nicotinamide and other precursors, which cells then use — meaning an infusion may act mostly as a very expensive, slow-release precursor.

NAD+ shuttles electrons in the mitochondria (NAD+ ⇄ NADH) and is used up by sirtuins, by PARPs during DNA repair, and by CD38 on the cell surface.Schematic — not to scale

3What the research shows

Oral NR raises blood NAD+

Multiple show oral NR (250–2,000 mg/day) raises whole-blood NAD+ by roughly 40–100% within days to weeks and is well tolerated (Trammell 2016, Nat Commun — first-in-human; Martens 2018, Nat Commun — 1,000 mg/day for 6 weeks in older adults, with a signal of lower blood pressure in those with elevated ). Downstream clinical benefits in healthy or obese adults have been small or absent (e.g. Dollerup 2018, Am J Clin Nutr: no change in insulin sensitivity or body composition in obese men). [1][2][3]

Graded A (small)

Oral NMN raises blood NAD+ and some metabolic endpoints

A 10-week RCT in prediabetic postmenopausal women (250 mg/day) improved skeletal-muscle insulin sensitivity without changing other metabolic measures (Yoshino 2021, Science). Other small RCTs report improved walking distance or subjective vitality in middle-aged adults (Yi 2023, GeroScience), modest and heterogeneous. [4][7]

Graded A (mixed)

Neurodegeneration

NADPARK, a 30-day RCT of NR 1,000 mg/day in early Parkinson's, raised brain NAD+ on MR spectroscopy and shifted metabolic and inflammatory markers (Brakedal 2022, Cell Metab). The follow-on Phase 3 (NO-PARK) did not show slowing of disease progression at its 2025 readout †. Ataxia-telangiectasia and other rare-disease studies are ongoing or small. [6]

Intravenous NAD+ itself

The only pharmacokinetic study (n=11, 750 mg over 6 hours) found plasma NAD+ did not rise during the first two hours while metabolites did, implying rapid breakdown; the authors concluded most of the dose was being processed rather than taken up intact (Grant 2019, Front Aging Neurosci). Claims for IV NAD+ in addiction withdrawal, chronic fatigue and "anti-ageing" rest on clinic case series and uncontrolled reports. No RCT. [5]

Subcutaneous or intramuscular NAD+

No published human studies. Community reports describe improved energy and mental clarity; a large placebo and expectation component is likely for those outcomes.

Lifespan and healthspan in animals

NMN and NR improve metabolic health, mitochondrial function and some ageing phenotypes in mice; robust lifespan extension has been inconsistent (the NIA Interventions Testing Program found no lifespan benefit from NR †). Mouse data drive most of the enthusiasm.

4Reported side effects and interactions

Literature-reported

Literature (oral precursors). well tolerated in up to 2,000 mg/day NR and 1,250 mg/day NMN for weeks to months; mild nausea, flushing, leg cramps, headache occasionally reported. Long-term (years) safety data do not exist.

Literature and clinic reports (IV NAD+). infusion-rate-dependent chest pressure or tightness, nausea, abdominal cramping, flushing, headache, anxiety and a sense of "air hunger"; these are why infusions are run slowly over hours. Serious events are not reported in the limited literature.

Community-reported

Community-reported (subcutaneous). injection-site pain and redness (the solution can be acidic), nausea, flushing, fatigue or jitteriness on the day of injection, insomnia if taken late.

Theoretical. tumour cells need NAD+ for rapid growth, and a mouse study reported NR increased brain metastasis in a triple-negative breast cancer model (Maric 2023); human relevance is unknown but anyone with active cancer is advised to discuss this with their oncologist. Excess nicotinamide is methylated for excretion, which in theory can draw down methyl donors (raising homocysteine); some trials show increased methylated metabolites. High-dose nicotinamide has rarely caused liver enzyme rises. Sirtuin activation also affects circadian biology, which may explain sleep complaints.

Interactions. none well established. Additive flushing with niacin. Methyl-donor status (folate, B12, TMG) is a common community concern; evidence is indirect.

Markers researchers commonly monitor

Marker	Why it's watched
Whole-blood or intracellular NAD+	now available through some specialist labs and dried-blood-spot kits; the only direct read-out of whether a protocol raises levels. Assay variability is high; use the same lab each time.
Homocysteine	tracks methyl-donor consumption from nicotinamide clearance; the most physiologically grounded safety marker for sustained high-dose precursors.
Liver enzymes (ALT/AST)	rare hepatic effects of high-dose nicotinamide; relevant to the precursor pathway.
Fasting glucose, insulin, HbA1c and lipid panel	the metabolic outcomes trials have tested; also the ones most likely to show a real change if there is one.
Uric acid	purine-containing molecules (NAD+ contains adenine) are metabolised toward uric acid; a baseline is cheap for anyone with gout history.
Blood pressure	the Martens 2018 signal; easy to track.
Sleep log	community insomnia reports; sirtuins interact with circadian biology.
CBC and CMP	general baseline, especially for injected forms.

Free for everyone. Safety information is never behind a paywall.

5Formulation and handling

Oral NR and NMN come as capsules or powders; NMN is sensitive to heat and moisture and some products have tested below label claim, so storage in a cool, dry place matters. Sublingual and liposomal NMN forms exist without comparative human data. Injectable NAD+ is sold as powder (commonly 100–1,000 mg vials) or pre-mixed solution; it is with , refrigerated, protected from light and used within a few weeks because it degrades in solution. The solution is often acidic, which accounts for injection pain; some dilute further. Intravenous use belongs in a clinical setting with a slow controlled infusion rate. Doses are in milligrams, often hundreds, so unit confusion is less of a problem here than with peptides, but volume per injection can be large.

6Commonly studied alongside

In trials: pterostilbene (with NR, the "Basis" combination), resveratrol and other sirtuin activators (community), TMG/betaine as a methyl donor (community). In peptide-community protocols it sits alongside MOTS-c, SS-31 (elamipretide), Epitalon and Humanin in "mitochondrial and longevity" stacks, and alongside Semaglutide (#3) in weight-loss contexts, without combined data. Spermidine (#100) is the other non-peptide longevity compound in the same conversations.

Informational cross-links. Not stack recommendations.

7Regulatory status by region

Region	Status (checked —)
United States	NAD+ itself is not FDA-approved. It has been nominated for the 503A compounding bulk-substances list; its category status should be checked †. NR is GRAS and a notified dietary ingredient. NMN: FDA stated in 2022 that it was excluded from the supplement definition because it had been authorised for drug investigation; in 2025 FDA indicated it would reconsider and NMN has returned to the market †
European Union	NAD+ not authorised as a medicine. NR chloride is an authorised novel food (2021) for food supplements. NMN is not an authorised novel food
United Kingdom	NAD+ not licensed. NR follows the EU novel-food position (retained); NMN not authorised as a novel food
Australia	NAD+ injectables are unapproved; TGA has acted against advertising and compounding of injectable NAD+ †. NR and NMN supplements are available but NMN's listing status has been contested †
South Africa	NAD+ not registered; NR/NMN supplements available with no specific status
Sport (WADA)	Not prohibited. (Note: intravenous infusions over 100 ml in a 12-hour period are themselves prohibited under M2 unless medically justified, regardless of substance)

8Open questions

Does intravenous or NAD+ do anything that oral precursors do not, given it appears to be broken down into precursors before cells use it?
Do higher NAD+ levels translate into any hard health outcome in humans? Twenty years of mouse data; the human trials so far are small and metabolic.
Long-term safety of chronically elevated NAD+ pools, including cancer and methylation questions.
Which tissues actually see higher NAD+ after oral precursors, and at what dose.

9References

1Trammell SAJ et al. (2016). Nicotinamide riboside is uniquely and orally bioavailable in mice and humans. Nat Commun. PubMed · DOI
2Martens CR et al. (2018). Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Nat Commun. PubMed · DOI
3Dollerup OL et al. (2018). A randomized placebo-controlled clinical trial of nicotinamide riboside in obese men: safety, insulin-sensitivity, and lipid-mobilizing effects. Am J Clin Nutr. PubMed · DOI
4Yoshino M et al. (2021). Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science. PubMed · DOI
5Grant R et al. (2019). A pilot study investigating changes in the human plasma and urine NAD+ metabolome during a 6 hour intravenous infusion of NAD+. Front Aging Neurosci. PubMed · DOI
6Brakedal B et al. (2022). The NADPARK study: a randomized phase I trial of nicotinamide riboside supplementation in Parkinson's disease. Cell Metab. PubMed · DOI
7Yi L et al. (2023). The efficacy and safety of beta-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults: a randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial. GeroScience. PubMed · DOI
8Covarrubias AJ et al. (2021). NAD+ metabolism and its roles in cellular processes during ageing. Nat Rev Mol Cell Biol. PubMed · DOI
9Maric T et al. (2023). A bioluminescent-based probe for in vivo non-invasive monitoring of nicotinamide riboside uptake reveals a link between metastasis and NAD+ metabolism. Biosens Bioelectron. PubMed · DOI

† Being confirmed by our reviewers against current sources.

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11Page history

26 Oct 2026Profile published — awaiting medical review

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