NMN
Also known as Nicotinamide mononucleotide, beta-nicotinamide mononucleotide, beta-NMN
Not a peptide but a nucleotide: an oral NAD+ precursor that reliably raises NAD+ and reliably little else.
At a glance
- Category
- Immune & longevity
- Status
- supplement
- Route
- oral (capsules, tablets, sublingual powders)
- Half-life
- Not well characterised in humans. NMN is dephosphorylated to nicotinamide riboside before cellular uptake in most tissues, so plasma NMN itself is a poor guide to what reaches the cell.
- Onset
- Blood NAD+ rises within days to weeks of daily dosing 3; no clinical endpoint has a reliable time course, because no clinical endpoint has reliably moved
- Molecular weight
- 334.22 g/mol (C11H15N2O8P) 9
NMN is not a peptide. It is a nucleotide - the direct biosynthetic precursor of the coenzyme NAD+ - included here because it is sold beside peptides and searched for alongside them. It is sold as a food supplement in most markets. Its US status has changed twice. On 11 October 2022 the FDA responded to a new dietary ingredient notification by concluding that NMN was excluded from the definition of a dietary supplement under the drug-preclusion clause, section 201(ff)(3)(B) of the Federal Food, Drug, and Cosmetic Act, because it had been authorised for investigation as a new drug; a letter of 4 November 2022 set aside an earlier acknowledgement given to a different notifier in May of the same year. The Natural Products Association and the Alliance for Natural Health petitioned against that reading. On 29 September 2025 the FDA granted the petition in part: having revised its interpretation of the race-to-market clause, it concluded that NMN is not excluded from the dietary supplement definition, on the ground that NMN was marketed as a dietary supplement in the United States before the drug authorisation - and that, contrary to its earlier position, that marketing need not have been lawful to count 5. Both the SyncoZymes and Kingdomway notifications appear in the FDA's public NDI notification list 6. NMN is not approved as a medicine for any indication in any jurisdiction.
Doping status: Not listed by WADA. An intravenous infusion of more than 100 ml per 12 hours would fall under the ban on intravenous infusions (M2.2), but oral NMN is not prohibited
Checked against the WADA 2026 Prohibited List. For a specific product and country, Global DRO is the lookup athletes are expected to use — the List names substances, not brand names.
Mechanism of action
NAD+ is the cell's central redox coenzyme and also the substrate consumed by sirtuins, PARPs and CD38. Tissue NAD+ falls with age in animals, and the hypothesis behind every product in this class is that restoring it restores something else worth having. NMN sits one step from NAD+ in the salvage pathway: nicotinamide phosphoribosyltransferase (NAMPT) converts nicotinamide to NMN, and NMN adenylyltransferases convert NMN to NAD+. Supplying NMN therefore bypasses the NAMPT step, which is the rate-limiting one.
The complication is transport. NMN is a phosphorylated, negatively charged molecule and does not cross most cell membranes intact. In the gut and in most tissues it is dephosphorylated to nicotinamide riboside, taken up, and re-phosphorylated inside the cell. A transporter that carries NMN directly, Slc12a8, has been described in mouse small intestine, but its role in humans is not settled. For practical purposes, oral NMN and oral nicotinamide riboside deliver much the same thing to the cell by slightly different routes - which is one reason the two entries in this reference read so similarly.
Raising blood NAD+ is the easy part, and it works. What has not been demonstrated is that raising it in a healthy adult changes anything downstream that a person would notice. Increased NAD+ in blood is a surrogate marker; the trials that measured real endpoints are the subject of the evidence section below. Readers comparing options should also see the NAD+ entry in this reference, which covers the coenzyme itself and the intravenous infusions sold on the same rationale, and the nicotinamide riboside entry, which covers NMN's commercial rival and the closest thing it has to a like-for-like comparison.
What the research shows
This is a well-studied supplement with a mostly negative result, which is an unusual and useful combination. Forty-nine studies are registered on ClinicalTrials.gov 7. Multiple randomised placebo-controlled trials show that oral NMN raises blood NAD+ - that finding is consistent and not in dispute 3. Meta-analyses of the same trials find no significant effect on fasting glucose, insulin, HbA1c, HOMA-IR or the lipid profile 23, and no benefit for skeletal muscle mass or function in older adults 4. Where signals do appear they are small, inconsistent between analyses, and drawn from trials whose risk-of-bias assessments are poor. The honest summary is that NMN does what it says biochemically and has not been shown to do what it is sold for.
Research in humans
There are dozens of randomised trials, most of them small, short and in relatively healthy adults. Yoshino and colleagues (2021) ran a ten-week randomised, placebo-controlled, double-blind trial of 250 mg NMN daily in 25 postmenopausal women with prediabetes who were overweight or obese, and reported increased insulin-stimulated glucose disposal by hyperinsulinaemic-euglycaemic clamp together with increased skeletal muscle insulin signalling 18. It is the most-cited positive human result and it is a 25-person study in one specific population; it drew several published commentaries. Set against it, the pooled analyses are consistently null. Chen and colleagues (2024) pooled eight RCTs, 342 middle-aged and older adults, doses of 250-2000 mg daily for 14 days to 12 weeks, and found no significant benefit on fasting glucose, fasting insulin, HbA1c, HOMA-IR or the lipid profile 2. Zhang and colleagues (2025) pooled 12 studies and 513 participants, found a significant overall effect on blood NAD+ but no significant difference from control on most clinically relevant outcomes, and rated seven studies as raising some concerns and five as high risk of bias, concluding in as many words that an exaggeration of the benefits of NMN supplementation may exist in the field 3. Prokopidis and colleagues (2025) pooled NMN and nicotinamide riboside trials in adults with a mean age over 60 and found no significant effect of NMN on skeletal muscle index, handgrip strength, gait speed or the five-time chair stand test, and no improvement in knee extension strength, SPPB or thigh muscle mass 4. A blood-pressure meta-analysis of 10 RCTs and 349 participants found a small significant reduction in diastolic pressure of about 2 mmHg, no significant effect on systolic pressure overall, and a systolic reduction only in the subgroup aged 60 and over; the authors describe their own findings as preliminary and suggestive 10. One meta-analysis of nine studies in middle-aged and elderly participants reports positive effects on gait speed and ALT 11, which sits directly against the muscle meta-analysis 4 - a disagreement that reflects how thin and heterogeneous the underlying trial base is.
Animal and lab research
In mice, NMN improves insulin sensitivity, mitochondrial function and physical capacity, and has been reported to mitigate age-related decline across several tissues. These results are the reason for the human trials. They have not translated into consistent clinical effects, which is the ordinary fate of ageing interventions that work in mice.
Caveats. Trial sizes are small - the pooled totals across entire meta-analyses are in the hundreds, not thousands. Durations are short, usually 6 to 12 weeks, against a claimed benefit measured in decades. Populations are mostly healthy or mildly impaired, where there is little room to improve. Risk of bias is poor: a formal RoB2 assessment rated seven of twelve studies as raising some concerns and five as high risk 3. Many trials are funded by, or conducted in collaboration with, companies selling the ingredient, and several prominent investigators in the NAD+ field hold related patents - the Science trial declares patent-licensing interests among its authors 1. Most importantly, the primary outcome in almost every trial is blood NAD+, which is a surrogate. Nothing about a higher NAD+ reading in plasma establishes that the intended intracellular effect occurred, and the endpoints that would matter have mostly not moved.
What it is used for
- Sold as an oral anti-ageing supplement, on the strength of a mechanism rather than clinical outcomes 3
- Raising blood NAD+ concentration - the one effect that is reliably reproduced 3
- Studied for insulin sensitivity and glucose control, where pooled analyses of randomised trials find no significant benefit 23
- Studied for muscle mass and physical function in older adults, where pooled analyses find no benefit 4
- Investigated as a drug in its own right, which is what triggered the FDA drug-preclusion question in the first place 5
Dosing
- The 250-2000 mg per day range and the 14-day to 12-week durations are those pooled by the 2024 meta-analysis of eight randomised trials 2. The 250 mg daily dose used in the most-cited positive trial 18 is at the low end of what is sold. There is no established dose-response: higher doses in trials have not produced better clinical outcomes, and pooled analyses across the full 250-2000 mg range find no significant metabolic benefit 2.
- These figures describe what has been administered in published studies. They are not a recommendation, and no dose has been shown to produce a clinical benefit in a healthy adult.
- Sublingual formulations are widely sold on the argument that they bypass gut dephosphorylation. PeptideX has found no published human pharmacokinetic comparison of sublingual against oral NMN that would support the claim.
- Product quality is a real variable rather than a theoretical one. NMN is chemically unstable in moisture and heat, and independent testing of NAD+ precursor products has repeatedly found label quantities to be inaccurate. Nothing on a supplement label allows a buyer to verify content.
- A consumer self-dosing pattern circulates alongside the trial doses and is set out as a circulating protocol below. The trials ran 14 days to 12 weeks 2; consumers take similar or larger amounts indefinitely, often sublingually and stacked, on claims the trials did not test. It is recorded because readers encounter it, not because it is validated.
These figures describe what the literature and published protocols report. They are not advice and not a dosing instruction.
Protocols
NMN for muscle insulin sensitivity in prediabetic postmenopausal women
published trial| 10 weeks | 250 mg NMN daily by mouth (two capsules), against placebo |
|---|
A 25-person trial in one narrow population - postmenopausal women with prediabetes who were overweight or obese - with insulin-stimulated glucose disposal by clamp as the endpoint. It is the strongest positive human result for NMN and it has not been replicated at scale; the larger pooled analyses of the wider trial base, cited in the evidence section above, find no significant effect on glucose control.
Consumer anti-ageing self-dosing (circulating)
user protocol — not validatedSource: Supplement retailer labelling, sublingual-powder sellers and longevity forums
This is not a validated schedule. It is a pattern that circulates among users and sellers, reproduced because it is what people actually follow — not because it has been tested. No trial established these doses, this interval or this duration, and nobody is checking what is in the vial. Treat every number below as an assertion, not a finding.
| Common consumer use | roughly 250-1000 mg per day, taken daily and indefinitely for anti-ageing — the amounts overlap the trials, the open-ended duration does not |
|---|---|
| At the higher end | 1-2 g per day, and stacking with trimethylglycine, resveratrol or pterostilbene on mechanistic reasoning |
| Sublingual | sublingual powders sold on the claim they bypass gut dephosphorylation — a claim with no published human pharmacokinetic comparison behind it |
The trial above was a 25-person, 10-week study in one narrow population 1; the wider randomised base runs 14 days to 12 weeks and is mostly null on clinical endpoints while consistently raising blood NAD+ 23. The circulating use takes similar or larger daily amounts for years against a claimed benefit measured in decades, so the divergence is duration and expectation more than dose. Megadosing raises the NAD+ metabolome further without evidence it changes anything downstream, and increases nicotinamide flux through nicotinamide N-methyltransferase, a methylation burden of unknown long-term consequence. The sublingual formulations widely sold rest on an absorption argument with no published human pharmacokinetic comparison against oral NMN. Product quality is a real variable rather than a theoretical one: NMN is unstable in moisture and heat, and independent testing has repeatedly found label amounts inaccurate, so nothing on a label lets a buyer verify content. These patterns are recorded because they circulate, not because any of them has been shown to produce a clinical benefit.
Schedules are reproduced as their source states them. Units, IU and milligrams explains why the figures are not interchangeable between products.
Reconstitution
- Storage
- Powder is hygroscopic and degrades with moisture and heat; supplement products are usually stored cool, dry and sealed, and some manufacturers recommend refrigeration
Sold as capsules, tablets or loose powder. Nothing to reconstitute.
Safety
Side effects
- Generally well tolerated in trials up to 12 weeks, with adverse event rates similar to placebo 23
- Mild gastrointestinal upset, nausea and loose stools at higher doses
- Headache and flushing have been reported, though flushing is more characteristic of nicotinic acid than of NMN
- Long-term safety beyond a few months has not been studied in humans - the entire randomised evidence base runs from 14 days to 12 weeks 2
- High-dose NAD+ precursor intake increases the methylation burden through nicotinamide N-methyltransferase, which consumes methyl groups; whether this matters clinically has not been established
Do not use if
- Pregnancy and breastfeeding: no data
- Active malignancy: NAD+ supports DNA repair and cell proliferation, and the effect on tumour growth has not been studied in humans - this is a theoretical concern rather than a demonstrated harm, but it is the one that is repeatedly raised and never resolved
- Children and adolescents: no data
- Not a substitute for treatment of diagnosed diabetes or dyslipidaemia - the pooled evidence shows no significant effect on either 23
Interactions
Not systematically studied. Interaction with chemotherapy that relies on DNA damage is theoretically relevant, since NAD+ is a substrate for PARP-mediated repair, and has not been investigated in people. Nicotinamide at high doses inhibits sirtuins, so the metabolic fate of a large NAD+ precursor dose is not straightforwardly beneficial. No clinically significant drug interaction has been documented, which reflects the absence of studies rather than the absence of interactions.
Sources
- Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic womenScience, 2021 - Yoshino, Yoshino, Kayser et al.; randomised placebo-controlled trial, 25 participants. Authors declare patent-licensing interests related to NMN
- Effects of Nicotinamide Mononucleotide on Glucose and Lipid Metabolism in Adults: A Systematic Review and Meta-analysis of Randomised Controlled TrialsCurrent Diabetes Reports, 2024 - Chen et al.; 8 RCTs, 342 participants; no significant benefit on any glycaemic or lipid outcome
- Efficacy of oral nicotinamide mononucleotide supplementation on glucose and lipid metabolism for adults: a systematic review with meta-analysis on randomized controlled trialsCritical Reviews in Food Science and Nutrition, 2025 - Zhang, Poon and Wong; 12 studies, 513 participants; NAD+ rises, clinical outcomes do not; 5 of 12 studies at high risk of bias
- The Effect of Nicotinamide Mononucleotide and Riboside on Skeletal Muscle Mass and Function: A Systematic Review and Meta-AnalysisJournal of Cachexia, Sarcopenia and Muscle, 2025 - Prokopidis et al.; no significant effect of NMN on muscle index, grip strength, gait speed or chair stand
- FDA response to citizen petition on the regulatory status of beta-nicotinamide mononucleotide, docket FDA-2023-P-0872US Food and Drug Administration, Human Foods Program, 29 September 2025 - petition granted in part; FDA concludes NMN is not excluded from the dietary supplement definition under section 201(ff)(3)(B), setting aside its October and November 2022 letters
- New Dietary Ingredient Notifications received by FDA (complete list)US Food and Drug Administration - lists the NMN notifications from SyncoZymes (submitted 21 March 2022) and others
- ClinicalTrials.gov registry search for nicotinamide mononucleotideUS National Library of Medicine - 49 registered studies as of July 2026
- Effect of Nicotinamide Mononucleotide (NMN) on Cardiometabolic Function (NCT03151239)ClinicalTrials.gov - registry record for the Science 2021 trial; 250 mg daily, 25 participants
- PubChem compound summary: nicotinamide mononucleotide (CID 14180)NCBI PubChem
- Effects of Nicotinamide Mononucleotide Supplementation on Blood Pressure: A Systematic Review and Meta-Analysis of Randomized Controlled TrialsNutrients, 2026 - Zhang et al.; 10 RCTs, 349 participants; diastolic reduction about 2 mmHg, systolic not significant overall
- Effects of Nicotinamide Mononucleotide Supplementation on Muscle and Liver Functions Among the Middle-aged and Elderly: A Systematic Review and Meta-analysis of Randomized Controlled TrialsCurrent Pharmaceutical Biotechnology, 2025 - Wang et al.; 9 studies, 412 participants; reports positive effects on gait speed and ALT, in disagreement with the larger muscle meta-analysis