NMN
Oral NMN repeatedly raises circulating NAD-related measures, but the assay and analyte differ across trials. A few small studies report narrow metabolic or physical-function effects; pooled glucose, lipid, muscle and most performance outcomes are null or inconsistent. No randomized human evidence establishes cognition, hormone restoration or longer life.
Beta-nicotinamide mononucleotide
- Blood NAD target engagement is replicated, but blood NAD is not a validated surrogate for brain benefit, disease prevention or lifespan.
- A 25-woman prediabetes trial improved muscle insulin sensitivity while liver, fat, weight, strength and mitochondrial-respiration outcomes were null.
- A four-week 30-person MIB-626 trial reported weight, diastolic-pressure and lipid signals among many outcomes; strength, aerobic capacity and insulin sensitivity were null.
- Exercise studies report selected ventilatory-threshold, gait or walking signals, while pooled strength and muscle outcomes are null.
- A controlled hormone panel found testosterone, estradiol, progesterone, DHEA-S and cortisol unchanged.
- The cited randomized human evidence reports no cognitive benefit or lifespan outcome.
What does an NMN biomarker increase actually establish?
NMN is a phosphorylated NAD-biosynthesis intermediate. Oral studies often raise whole-blood or circulating NAD-related measures, but intact NMN, nicotinamide, terminal metabolites, total NAD plus NADH and tissue NAD are different measurements. A blood change confirms target engagement; it does not by itself show better cognition, energy, healthspan or survival.
| Measurement | What it can show | What it cannot show |
|---|---|---|
| Intact parent NMN | A parent concentration-time curve if directly measured | Not provided by the first-in-human downstream-metabolite study |
| MNA, 2PY and 4PY | Nicotinamide metabolism after exposure | Parent NMN half-life or tissue delivery |
| Whole-blood NAD or serum total NAD plus NADH | Circulating target engagement | Brain NAD, muscle NAD or clinical benefit |
| Function or disease endpoints | Patient-relevant effect in the tested population | Lifespan unless lifespan was actually measured |
FDA GSRS · beta-NMN identity
Government substance database
U.S. Food and Drug Administration. Global Substance Registration System, beta-nicotinamide mononucleotide, UNII 2KG6QX4W0V.
The record identifies beta-NMN as C11H15N2O8P, molecular weight 334.22 g/mol, CAS 1094-61-7.
- Participants / model
- Not applicable
- Treatment
- Not applicable
- Follow-up
- Not applicable
- Study design
- Primary source record
Beta-NMN is distinct from reduced NMNH and from generic niacinamide; identity does not prove supplement legality or efficacy.
Read the original sourceFirst-in-human full paper · 10 men, three visits
Open-label nonrandomized human study
Irie J, Inagaki E, Fujita M, Nakaya H, Mitsuishi M, Yamaguchi S, Yamashita K, Shigaki S, Ono T, Yukioka H, Okano H, Mori S, Yamaguchi M, Itoh H. Effect of oral administration of nicotinamide mononucleotide on clinical parameters and nicotinamide metabolite levels in healthy Japanese men. Endocrine Journal. 2020;67(2):153-160. doi:10.1507/endocrj.EJ19-0313. PMID 31685720.
No severe symptoms or clinically meaningful changes in examinations, ophthalmology, or sleep were reported over five hours. Downstream MNA, 2Py, and 4Py rose and peaked at 300 minutes; parent NMN was not measured. Bilirubin rose 51.3%, while glucose, creatinine, and chloride fell 11.7%, 5.1%, and 2.3% at 300 minutes, remaining within reference ranges.
- Participants / model
- 10 healthy Japanese men aged 40-60; each received all three exposures on separate visits
- Treatment
- Single oral beta-NMN exposures of 100, 250, and 500 mg
- Follow-up
- Five-hour observation after each visit; mean interval 63±23 days
- Study design
- Open-label nonrandomized within-person ascending-exposure study
- Funding
- Keio University research support; industry relationships disclosed in the paper
No placebo, ten men, single exposures, and only five hours of follow-up. The assay measured downstream nicotinamide metabolites, not a parent NMN curve, so no parent half-life or Tmax follows.
Read the original source30-person RCT · blood NAD rose, broad outcomes null
Randomized double-blind placebo-controlled trial
PMCID PMC9036060.
Whole-blood NAD and NAMN rose while parent NMN did not; broad metabolic and body-composition outcomes were null.
- Participants / model
- 30 healthy adults; one placebo dropout
- Treatment
- Oral NMN 250 mg/day versus placebo
- Follow-up
- Twelve weeks
- Study design
- Randomized double-blind placebo-controlled trial
- Funding
- Mitsubishi product support
Four authors were Mitsubishi employees. Blood target engagement did not establish clinical benefit.
Read the original sourceHealthy adults full paper · 80 completed
Randomized double-blind placebo-controlled trial
Yi L, Maier AB, Tao R, Lin Z, Vaidya A, Pendse S, Thasma S, Andhalkar N, Avhad G, Kumbhar V. The efficacy and safety of beta-nicotinamide mononucleotide supplementation in healthy middle-aged adults: a randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial. GeroScience. 2023;45(1):29-43. doi:10.1007/s11357-022-00705-1. PMID 36482258.
Blood total NAD plus NADH and six-minute walk distance favored NMN groups over 60 days. HOMA-IR did not differ between groups; within-group HOMA-IR increased in the 600 and 900 mg arms. The proprietary Aging.Ai score also changed.
- Participants / model
- 80 healthy adults aged 40-65, 20 per placebo, 300 mg, 600 mg, and 900 mg arm; all completed
- Treatment
- Oral beta-NMN once daily or placebo
- Follow-up
- Sixty days
- Study design
- Multicenter randomized double-blind placebo-controlled four-arm parallel trial
- Funding
- NMN product supplied by EffePharm/AbinoNutra; company-linked authors and commercial support disclosed
Nine adverse events occurred in seven participants: six events in five placebo participants and three in two 300 mg participants, none in the 600/900 mg groups; all were mild or moderate and judged unrelated, with no serious event or dropout. The study used multiple outcomes and a proprietary aging score.
Read the original source65-person study · NMN and NR raised circulating NAD
Randomized open-label four-arm trial
PMID 41540253.
NMN and NR, but not chronic NAM, increased circulating NAD over 14 days; ex vivo work supported a proposed microbial route.
- Participants / model
- 65 modified-intention-to-treat healthy adults
- Treatment
- Placebo, NAM, NR or NMN
- Follow-up
- Fourteen days
- Study design
- Randomized open-label four-arm trial
- Funding
- Nestle and Cryptobiotix affiliations
No clinical-benefit endpoint; ex vivo mechanism did not directly prove the microbial route in vivo.
Read the original sourceWhat did FDA change, and what did it not approve?
FDA changed its prior interpretation that NMN was excluded from the dietary-supplement definition solely because of drug-investigation timing. That decision does not approve NMN as an anti-aging drug, verify a product, establish efficacy or settle every ingredient-status question. NDIN 1444 is a notification record, not a drug label.
| Record | Meaning |
|---|---|
| September 2025 petition response | Changed the prior drug-exclusion interpretation |
| NDIN 1444 listing | Records a new dietary ingredient notification |
| No FDA drug label | No approved anti-aging, cognition, metabolic or longevity indication |
FDA 2025 NMN supplement-definition decision
FDA regulatory response
Prater DA, Principal Deputy Director for Human Foods. Response to Citizen Petition FDA-2023-P-0872-2754. U.S. Food and Drug Administration. Digitally signed September 29, 2025.
FDA revised its interpretation of the drug-exclusion sequence for NMN and concluded that NMN was not excluded from the dietary-supplement definition on that basis because US supplement marketing preceded authorization of new-drug investigations. FDA did not declare every NMN product lawful, safe, or effective.
- Participants / model
- US dietary-supplement regulatory category
- Treatment
- NMN ingredient status under section 201(ff)(3)(B)
- Follow-up
- Current response issued 2025
- Study design
- FDA citizen-petition response
The digital signature is dated September 29, 2025, although the first-page printed year differs. The decision is not drug approval and does not waive NDI, safety, adulteration, or labeling law.
Read the original sourceFDA NDI list · notification is not approval
FDA regulatory listing
U.S. Food and Drug Administration. Submitted 75-Day Premarket Notifications for New Dietary Ingredients. Entry 1444, beta-Nicotinamide Mononucleotide, submitted November 17, 2025; response dated January 28, 2026.
FDA's current list includes an NMN new-dietary-ingredient notification and response date.
- Participants / model
- US dietary-supplement regulatory process
- Treatment
- Beta-NMN NDI notification
- Follow-up
- Submission and response dates in 2025-2026
- Study design
- FDA notification list
Appearance on the NDI list is not product approval, a universal safety finding, or permission for disease/anti-aging claims; the specific response letter governs the notifier's record.
Read the original sourceDoes NMN improve insulin sensitivity, weight, lipids or blood pressure?
One rigorous 25-woman prediabetes trial found a tissue-specific muscle-insulin-sensitivity signal. A separate 30-person MIB-626 study reported short-term weight, diastolic-pressure and lipid differences. Those positives did not generalize across each study or the pooled literature: liver and fat insulin sensitivity, broad glucose control, body composition and most lipid outcomes were null.
| Study | Positive result | Null result or limit |
|---|---|---|
| Prediabetes: 25 postmenopausal women | Muscle insulin-stimulated glucose disposal improved about 25% within the active arm; muscle signaling/remodeling changed | Hepatic/adipose insulin sensitivity, fasting measures, weight, liver/visceral fat, lipids, mitochondrial respiration, strength and fatigability null |
| MIB-626: 30 adults, 28 days | Between-group weight -1.9 kg, diastolic pressure -7.01 mmHg, total cholesterol -26.89 mg/dL, LDL -18.73 mg/dL | Insulin sensitivity, hepatic/intra-abdominal fat, strength, fatigability, aerobic capacity and stair power null; many endpoints and Metro conflicts |
| 2024 metabolic meta-analysis: 8 trials, 342 participants | No pooled benefit | Fasting glucose, insulin, HbA1c, HOMA-IR and lipids null overall |
| 2026 blood-pressure meta-analysis: 10 trials, 349 participants | Diastolic estimate -2.15 mmHg and older-adult systolic subgroup | Overall systolic pressure null; short heterogeneous trials |
Prediabetes RCT · 25 women, 10 weeks
Randomized controlled trial
Yoshino M, Yoshino J, Kayser BD, Patti GJ, Franczyk MP, Mills KF, Sindelar M, Pietka T, Patterson BW, Imai SI, Klein S. Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science. 2021;372(6547):1224-1229. doi:10.1126/science.abe9985. PMID 33888596.
Twenty-five postmenopausal women with prediabetes and overweight/obesity received oral NMN or placebo for ten weeks. Hyperinsulinemic-euglycemic clamp testing found improved muscle insulin sensitivity and signaling/remodeling markers with NMN.
- Participants / model
- 25 postmenopausal women with prediabetes and overweight/obesity
- Treatment
- Oral NMN 250 mg/day or placebo
- Follow-up
- Ten weeks
- Study design
- Randomized double-blind placebo-controlled trial
- Funding
- Academic and grant support with NMN supplied for study
Small, selected female metabolic population; no weight-loss, cognition, lifespan, or hard clinical outcome.
Read the original source30-person, 28-day trial · selected signals amid nulls
Randomized placebo-controlled trial
PMID 36740954; PMCID PMC11491622.
Weight, diastolic pressure, total cholesterol, LDL and non-HDL cholesterol favored MIB-626.
- Participants / model
- 30 adults aged at least 45 with overweight or obesity
- Treatment
- MIB-626 1000 mg twice daily versus placebo
- Follow-up
- Twenty-eight days
- Study design
- Randomized 2:1 placebo-controlled trial
- Funding
- Metro International Biotech
Insulin sensitivity, liver/intra-abdominal fat, strength, fatigability, aerobic capacity and stair power were null; many endpoints and company-employed authors.
Read the original sourceEight-trial meta-analysis · glucose and lipids null
Systematic review and meta-analysis
PMID 39531138.
Across eight randomized trials and 342 participants, fasting glucose, insulin, HbA1c, HOMA-IR and lipids were not materially improved.
- Participants / model
- 342 participants across eight randomized trials
- Treatment
- Oral NMN versus control
- Follow-up
- Short heterogeneous trials
- Study design
- Systematic review and meta-analysis
Pooled studies were small, short and heterogeneous.
Read the original sourceTen-trial meta-analysis · small diastolic estimate
Systematic review and meta-analysis
PMID 41901064.
Pooled diastolic pressure was estimated 2.15 mmHg lower; an older-adult systolic subgroup was positive.
- Participants / model
- 349 participants across ten trials
- Treatment
- Oral NMN versus control
- Follow-up
- Short heterogeneous trials
- Study design
- Systematic review and meta-analysis
Overall systolic pressure was null; subgroup and small pooled estimates are not cardiovascular-outcome evidence.
Read the original sourceDoes NMN improve strength, exercise, sleep, cognition or hormones?
The healthy-human record contains selected gait, walking, ventilatory-threshold and secondary sleep results, but no coherent enhancement effect. The runner trial did not improve VO2max, peak power or strength; the older-adult sleep trial missed its prespecified PSQI interaction; pooled muscle outcomes are null. No published randomized NMN study shows a cognitive benefit, and a controlled hormone panel was null.
| Study | Signal | Nulls and limits |
|---|---|---|
| Runners: 48, six weeks | Selected ventilatory-threshold measures, mainly higher doses | VO2max, peak power, body composition, grip, push-ups and flexibility null; single-leg stance only at 600 mg |
| Older men: 42 randomized | Selected gait-speed and left-grip comparisons | Only 20 completed week 12 after deviations; body composition, fat, glucose, lipids, right grip and most function null |
| Dose-ranging: 80 completed | Six-minute walk and NAD-related assay favored NMN | HOMA-IR between groups null; many outcomes, proprietary age score and product-company roles |
| Timing/sleep: 108 | Drowsiness and chair-stand interactions | Prespecified PSQI interaction null; afternoon NMN and afternoon placebo both improved within arm |
| Older adults: 60 | Four-meter walk and selected PSQI secondary results | Primary stepping test null; manufacturer funded |
| Hormones: 36 randomized | Nicotinamide metabolite increased | Testosterone, estradiol, progesterone, DHEA-S, cortisol, arterial stiffness, body composition and cardiometabolic measures null |
| 2025 muscle meta-analysis | No pooled benefit | Skeletal-muscle index, grip, gait and chair stand null |
48-runner trial · threshold signals, VO2max and strength null
Randomized double-blind placebo-controlled trial
DOI 10.1186/s12970-021-00442-4.
Selected ventilatory-threshold measures improved, mainly at higher doses.
- Participants / model
- 48 recreational runners
- Treatment
- NMN 300, 600 or 1200 mg/day versus placebo during training
- Follow-up
- Six weeks
- Study design
- Randomized double-blind placebo-controlled trial
VO2max, peak power, body composition, grip strength, push-ups and sit-and-reach were null; stance improved only at 600 mg.
Read the original sourceHealthy older-men RCT · 42 randomized
Randomized controlled trial
Igarashi M, Nakagawa-Nagahama Y, Miura M, Kashiwabara K, Yaku K, Sawada M, Sekine R, Fukamizu Y, Sato T, Sakurai T, Sato J, Ino K, Kubota N, Nakagawa T, Kadowaki T, Yamauchi T. Chronic nicotinamide mononucleotide supplementation elevates blood nicotinamide adenine dinucleotide levels and alters muscle function in healthy older men. npj Aging. 2022;8:5. doi:10.1038/s41514-022-00084-z. PMID 35927255.
Forty-two healthy older men were randomized 1:1 for 12 weeks. Blood NAD-related metabolites increased; gait speed and left-hand grip had nominal improvements, while body composition did not change. Protocol deviations affected later follow-up and 20 completed week 12.
- Participants / model
- 42 healthy older men randomized; 20 completed week 12 under the reported protocol deviations
- Treatment
- Oral NMN 250 mg/day or placebo
- Follow-up
- Six or twelve weeks
- Study design
- Randomized double-blind placebo-controlled parallel trial
- Funding
- Industry involvement and product support
Small, male-only, incomplete week-12 denominator, nominal unilateral/function findings, and multiple endpoints; no cognition or longevity result.
Read the original sourceHealthy adults full paper · 80 completed
Randomized double-blind placebo-controlled trial
Yi L, Maier AB, Tao R, Lin Z, Vaidya A, Pendse S, Thasma S, Andhalkar N, Avhad G, Kumbhar V. The efficacy and safety of beta-nicotinamide mononucleotide supplementation in healthy middle-aged adults: a randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial. GeroScience. 2023;45(1):29-43. doi:10.1007/s11357-022-00705-1. PMID 36482258.
Blood total NAD plus NADH and six-minute walk distance favored NMN groups over 60 days. HOMA-IR did not differ between groups; within-group HOMA-IR increased in the 600 and 900 mg arms. The proprietary Aging.Ai score also changed.
- Participants / model
- 80 healthy adults aged 40-65, 20 per placebo, 300 mg, 600 mg, and 900 mg arm; all completed
- Treatment
- Oral beta-NMN once daily or placebo
- Follow-up
- Sixty days
- Study design
- Multicenter randomized double-blind placebo-controlled four-arm parallel trial
- Funding
- NMN product supplied by EffePharm/AbinoNutra; company-linked authors and commercial support disclosed
Nine adverse events occurred in seven participants: six events in five placebo participants and three in two 300 mg participants, none in the 600/900 mg groups; all were mild or moderate and judged unrelated, with no serious event or dropout. The study used multiple outcomes and a proprietary aging score.
Read the original source108-person timing trial · primary sleep interaction null
Randomized double-blind placebo-controlled trial
PMID 35215405; PMCID PMC8877443.
Drowsiness and chair-stand interactions were reported, with several within-arm improvements.
- Participants / model
- 108 older Japanese adults; 105 completed
- Treatment
- NMN 250 mg/day morning or afternoon versus matched placebo
- Follow-up
- Twelve weeks
- Study design
- Randomized double-blind four-arm timing trial
- Funding
- Mitsubishi product support
Prespecified PSQI group-by-time interaction was null; afternoon NMN and afternoon placebo both improved drowsiness. Many comparisons and commercial ties.
Read the original source60-person study · primary stepping test null
Randomized double-blind placebo-controlled trial
PMID 38789831.
Four-meter walking time and selected PSQI global/daytime-dysfunction outcomes favored NMN.
- Participants / model
- 60 sedentary adults aged 65-75
- Treatment
- NMN 250 mg/day versus placebo
- Follow-up
- Twelve weeks
- Study design
- Randomized double-blind placebo-controlled trial
- Funding
- Meiji
The primary stepping-test endpoint was null at four and 12 weeks. The abstract does not report complete multiplicity or event tables.
Read the original source36-person RCT · testosterone and hormone panel null
Randomized double-blind placebo-controlled trial
PMID 36797393; PMCID PMC9935856.
A nicotinamide metabolite increased; pulse-wave velocity only trended.
- Participants / model
- 36 healthy adults aged 40-59; 34 completed
- Treatment
- NMN 250 mg/day versus placebo
- Follow-up
- Twelve weeks
- Study design
- Randomized double-blind placebo-controlled trial
- Funding
- DHC grant
Testosterone, estradiol, progesterone, DHEA-S, cortisol, blood pressure, glucose, lipids and body composition were null.
Read the original source2025 meta-analysis · pooled muscle outcomes null
Systematic review and meta-analysis
PMID 40275690.
No pooled benefit was found for skeletal-muscle index, grip strength, gait speed or five-chair-stand performance.
- Participants / model
- Human NMN trials with muscle or function outcomes
- Treatment
- Oral NMN versus control
- Follow-up
- Short heterogeneous studies
- Study design
- Systematic review and meta-analysis
Narrative evidence also did not show convincing knee-extension, SPPB, thigh-mass or resistance-training benefit.
Read the original sourceCompleted 24-person record · no posted results
Clinical trial registry
ClinicalTrials.gov. NCT04910061.
The completed record planned McNair cognition, SF-36, sleep and fatigue measures but posts no results.
- Participants / model
- 24 healthy adults in Canada
- Treatment
- NMN 400 mg/day
- Follow-up
- Twenty-nine days
- Study design
- Randomized trial registry
A results-silent record is neither positive nor null.
Read the original sourceWhat do Chinese trials and registries add?
China-linked evidence spans different questions. A 48-runner training study reported selected ventilatory-threshold results; the 60-man Beijing acute PQQ/NMN trial found no NMN-specific overall advantage; a 25-person immune-thrombocytopenia study was open-label; and a 36-person Shanghai study measured NAD and RNA chemistry rather than clinical benefit. The 80-person dose-ranging cohort was conducted in Pune, India, despite Chinese ingredient and sponsor links.
| Record | Result | Boundary |
|---|---|---|
| 48 recreational runners | Selected ventilatory-threshold signal | Strength, VO2max, peak power and body composition null |
| 60 Beijing physical-education students | No overall supplement or NMN-specific interoception advantage | One acute session; PQQ signal cannot be assigned to NMN |
| 25 adults with immune thrombocytopenia | Five met platelet-response endpoint after two weeks | Single arm, disease treatment, no wellness inference |
| 36 healthy adults in Shanghai | Blood/PBMC NAD turnover and NAD-capped RNA changed | Paywalled full article; no patient-centered endpoint |
48-runner trial · threshold signals, VO2max and strength null
Randomized double-blind placebo-controlled trial
DOI 10.1186/s12970-021-00442-4.
Selected ventilatory-threshold measures improved, mainly at higher doses.
- Participants / model
- 48 recreational runners
- Treatment
- NMN 300, 600 or 1200 mg/day versus placebo during training
- Follow-up
- Six weeks
- Study design
- Randomized double-blind placebo-controlled trial
VO2max, peak power, body composition, grip strength, push-ups and sit-and-reach were null; stance improved only at 600 mg.
Read the original sourceBeijing RCT · 60 students, single exposure
Randomized double-blind placebo-controlled trial
Zhao C, Wu B, Sui H, Kuan G, Wei G, Yan Y. The effects of pyrroloquinoline quinone and nicotinamide mononucleotide supplementation on interoception following acute exhaustive exercise: a randomised, double-blind, placebo-controlled study. Scientific Reports. 2026;16:5408. doi:10.1038/s41598-025-34191-0. PMID 41651893.
There was no overall between-group advantage for interoception after exhaustive exercise. One MAIA Body Listening interaction was significant (p=0.016), driven by a within-PQQ change rather than an NMN-specific effect.
- Participants / model
- 60 male physical-education students in Beijing, mean age about 19; 15 per arm
- Treatment
- Single pre-exercise exposure: placebo, PQQ 20 mg, NMN 300 mg, or both
- Follow-up
- One acute exhaustive-exercise session
- Study design
- Randomized double-blind placebo-controlled four-arm trial; retrospectively registered
- Funding
- Fundamental Research Funds for the Central Universities
This was an acute exercise/interoception study in young men, not a cognition or aging trial. Adverse events were not reported.
Read the original sourceChina phase 1/2 ITP · 25, single arm
Phase 1/2 human trial
Li H, Xu Y, Chen Y, Ji L, Xu Y, Zheng W, Sun T, Fu R, Pei X, Liu X, Xue F, Liu W, Wang W, Chi Y, Yang R, Wei J, Zhang L. Low-dose oral nicotinamide mononucleotide for immune thrombocytopenia: a phase 1/2 trial. Nature Medicine. 2026;32(6):2026-2036. doi:10.1038/s41591-026-04366-x. PMID 42056497.
In China, 25 adults with steroid-refractory or steroid-dependent immune thrombocytopenia received open-label oral NMN for two weeks. No dose-limiting toxicities or treatment-related serious adverse events occurred; five participants (20%) met the prespecified platelet-response endpoint.
- Participants / model
- 25 adults with steroid-refractory or steroid-dependent immune thrombocytopenia
- Treatment
- Open-label oral NMN 450 mg twice daily
- Follow-up
- Two weeks, with exploratory follow-up through week 8
- Study design
- Single-arm phase 1/2 clinical trial with supporting mouse experiments
- Funding
- Chinese academic program
No control arm, tiny disease-specific cohort, short exposure, and an immune/platelet endpoint. This is not longevity, cognition, or healthy-user evidence.
Read the original source36-person Shanghai study · molecular endpoints only
Controlled human biomarker study
PMID 41072840.
Blood and PBMC NAD turnover and NAD-capped RNA measures changed.
- Participants / model
- 36 healthy adults in Shanghai; 20 NMN and 16 placebo
- Treatment
- NMN 300 mg/day versus placebo
- Follow-up
- Two months
- Study design
- Controlled human biomarker study
The abstract reports no patient-centered endpoint.
Read the original sourceChina insomnia protocol · planned n=400
Clinical trial protocol
Gao X, Li J, Xu S, Li X, Wang X, Li Y, Huang Y, Liu S, Zeng Q. Oral nicotinamide mononucleotide (NMN) as a treatment for chronic insomnia: protocol for the multicenter, randomized, double-blind, placebo-controlled trial. Trials. 2023. Chinese Clinical Trial Registry ChiCTR2200058001.
The protocol plans 400 adults with chronic insomnia randomized 1:1 to oral NMN or placebo in multiple Chinese centers. It does not provide completed outcome results.
- Participants / model
- Planned 400 adults with chronic insomnia in China
- Treatment
- Oral NMN or placebo
- Follow-up
- Protocol-defined trial period
- Study design
- National multicenter randomized double-blind placebo-controlled protocol
- Funding
- China Health Promotion Foundation
A protocol proves a planned test, not efficacy or safety. The registry posts no results, and the cited sources include no outcome paper.
Read the original sourceCompleted China-linked crossover · no posted outcomes
Clinical trial registry
ClinicalTrials.gov. NCT05882214.
The 22-person crossover completed in April 2025. The registry posts no results, and the cited sources include no matched publication.
- Participants / model
- 22 participants in China
- Treatment
- NMN and acute alcohol exposure conditions
- Follow-up
- Crossover
- Study design
- Completed clinical trial registry
No outcome should be inferred from a results-silent record.
Read the original sourceDoes NMN reach the human brain or extend life?
In a six-person randomized-order experiment, NMN raised whole-blood NAD about 69%, but the cerebral NAD comparison was not significant. The longer four-week brain-NAD stage used nicotinamide riboside, not NMN. No human NMN trial has shown longer life, fewer major diseases, or slower validated biological aging.
| Evidence | Finding | What it cannot establish |
|---|---|---|
| Six-person NMN/NR study | NMN raised blood NAD; NMN brain comparison not significant | Human brain target engagement or cognition |
| Classic 12-month mouse study | Selected age-associated physiology and NAD metabolism improved | Human healthspan or lifespan |
| 2024 mouse preprint | Median lifespan reportedly +8.5% in females, not males | Peer-reviewed or human longevity |
| Retinal same-cohort reanalysis | One temporal outer-grid thickness difference, +1.14 vs -2.77 micrometers; acuity null | Independent replication or global ocular rejuvenation |
Six-person NMN stage · blood positive, brain not established
Randomized-order exploratory crossover
PMID 41858901; PMCID PMC12996706.
NMN raised whole-blood NAD about 69% after eight days.
- Participants / model
- Six healthy adults in the NMN/NR crossover stage
- Treatment
- NMN and NR, each 1200 mg/day for eight days
- Follow-up
- Eight-day periods with washout
- Study design
- Randomized-order exploratory crossover
The NMN cerebral-NAD comparison did not reach significance. The longer four-week brain result used NR only. No cognition endpoint.
Read the original sourceWild-type mice · 12 months
Mouse preclinical study
Mills KF, Yoshida S, Stein LR, Grozio A, Kubota S, Sasaki Y, Redpath P, Migaud ME, Apte RS, Uchida K, Yoshino J, Imai SI. Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice. Cell Metabolism. 2016;24(6):795-806. doi:10.1016/j.cmet.2016.09.013. PMID 28068222.
Wild-type mice received oral NMN in drinking water for 12 months. The study reported tissue NAD-related changes and mitigation of several age-associated physiological measures.
- Participants / model
- Wild-type mice
- Treatment
- NMN in drinking water
- Follow-up
- Twelve months
- Study design
- Long-term controlled mouse experiment
The study did not establish human lifespan extension; species, exposure, endpoints, and metabolism differ.
Read the original source2024 mouse preprint · female-only lifespan signal
Animal preprint
PMCID PMC11230277.
Median lifespan reportedly increased 8.5% in female mice, not males; frailty and activity measures changed.
- Participants / model
- Laboratory mice
- Treatment
- Chronic NMN exposure
- Follow-up
- Long term
- Study design
- Animal preprint experiment
Preprint, animal, and sex-specific result cannot establish human longevity.
Read the original sourceSame 14-person cohort · one grid signal, acuity null
Exploratory same-cohort analysis
PMID 42082179.
One temporal outer-grid thickness comparison was +1.14 versus -2.77 micrometers, p=.006.
- Participants / model
- Same older diabetes/frailty cohort; seven people and 14 eyes per arm
- Treatment
- NMN 250 mg/day versus placebo
- Follow-up
- Twenty-four weeks
- Study design
- Same-cohort exploratory retinal analysis
Visual acuity was unchanged; nine grid regions and correlated eyes complicate inference. Not an independent cohort.
Read the original sourceWhat is known about absorption, routes and safety?
The first-in-human ten-man study followed downstream metabolites, not intact NMN, so it does not provide a parent half-life or Tmax. A 14-man crossover found more early 2PY and 4PY after sublingual exposure, but NMN, nicotinamide and NAD did not differ by route. Trials generally report short-term tolerability over two to 24 weeks; multi-year, pregnancy, interaction and rare-event safety remain open.
| Study | Result | Boundary |
|---|---|---|
| First human study: 10 men | MNA, 2PY and 4PY rose over five hours | Parent NMN not measured; unblinded visits |
| Oral vs sublingual: 14 men | Early terminal catabolites higher sublingually | NMN, NAM and NAD did not differ; no clinical endpoint; Meiji employees |
| High-dose studies: 31 and 30 adults | No clinically concerning four-week signal at 1250 or 1500 mg/day | Small, short and company-linked; no chronic inference |
| COVID-AKI: 42 hospitalized adults | Blood NAD engagement | Kidney, inflammatory and clinical-status endpoints null; 5 vs 1 cardiovascular events, causality unresolved |
| EFSA 2026 | Specified ingredient considered safe at 300 mg/day for adults | Pregnancy/lactation excluded; efficacy, arbitrary products, higher doses and indefinite use not covered |
First-in-human full paper · 10 men, three visits
Open-label nonrandomized human study
Irie J, Inagaki E, Fujita M, Nakaya H, Mitsuishi M, Yamaguchi S, Yamashita K, Shigaki S, Ono T, Yukioka H, Okano H, Mori S, Yamaguchi M, Itoh H. Effect of oral administration of nicotinamide mononucleotide on clinical parameters and nicotinamide metabolite levels in healthy Japanese men. Endocrine Journal. 2020;67(2):153-160. doi:10.1507/endocrj.EJ19-0313. PMID 31685720.
No severe symptoms or clinically meaningful changes in examinations, ophthalmology, or sleep were reported over five hours. Downstream MNA, 2Py, and 4Py rose and peaked at 300 minutes; parent NMN was not measured. Bilirubin rose 51.3%, while glucose, creatinine, and chloride fell 11.7%, 5.1%, and 2.3% at 300 minutes, remaining within reference ranges.
- Participants / model
- 10 healthy Japanese men aged 40-60; each received all three exposures on separate visits
- Treatment
- Single oral beta-NMN exposures of 100, 250, and 500 mg
- Follow-up
- Five-hour observation after each visit; mean interval 63±23 days
- Study design
- Open-label nonrandomized within-person ascending-exposure study
- Funding
- Keio University research support; industry relationships disclosed in the paper
No placebo, ten men, single exposures, and only five hours of follow-up. The assay measured downstream nicotinamide metabolites, not a parent NMN curve, so no parent half-life or Tmax follows.
Read the original source14-man crossover · no NMN, NAM or NAD route difference
Randomized crossover pharmacology study
PMID 42304075.
Sublingual exposure increased early 2PY and 4PY area under the curve.
- Participants / model
- 14 healthy men
- Treatment
- One oral and one sublingual NMN exposure
- Follow-up
- Blood sampled through 60 minutes with eight-day washout
- Study design
- Randomized crossover
- Funding
- Meiji
NMN, NAM and NAD did not differ by route; metabolite source unresolved and no clinical endpoint. All authors were Meiji employees.
Read the original source31-person four-week trial · short-term safety only
Randomized double-blind placebo-controlled trial
PMID 36002548.
No severe event or clinically concerning laboratory or physiological change was reported.
- Participants / model
- 31 healthy adults aged 20-65
- Treatment
- NMN 1250 mg/day versus placebo
- Follow-up
- Four weeks
- Study design
- Randomized double-blind placebo-controlled trial
- Funding
- Mitsubishi
Small, short, manufacturer-funded study; five authors were employees. It cannot establish rare or chronic safety.
Read the original source30-person 2025 trial · telomere null, short safety
Randomized placebo-controlled trial
Functional Foods in Health and Disease. 2025.
Blood NAD rose and no clinically problematic four-week examination or laboratory signal was reported.
- Participants / model
- 30 healthy Japanese adults; all completed
- Treatment
- Placebo, NMN 750 mg/day or 1500 mg/day
- Follow-up
- Four weeks
- Study design
- Randomized placebo-controlled trial
- Funding
- Company-linked program
Telomere length did not change; short commercial study cannot establish anti-aging or chronic safety.
Read the original source42-person RCT · target engagement without clinical rescue
Randomized placebo-controlled clinical trial
PMID 40746868; PMCID PMC12312518.
Blood NAD metabolites rose.
- Participants / model
- 42 hospitalized adults with COVID-19 and acute kidney injury; 25 active, 17 placebo
- Treatment
- MIB-626 1000 mg twice daily versus placebo
- Follow-up
- Fourteen days
- Study design
- Randomized placebo-controlled trial
- Funding
- Metro International Biotech
Creatinine, cystatin C, kidney-injury markers, inflammation, WHO status and SOFA endpoints were null. Cardiovascular events were 5 versus 1; small trial cannot establish causality.
Read the original sourceEFSA 2026 · specified 300 mg/day boundary
Regulatory food-safety opinion
PMID 42125559; PMCID PMC13158811.
EFSA judged a specified synthetic beta-NMN ingredient safe at 300 mg/day for adults.
- Participants / model
- Proposed adult novel-food users; pregnancy and lactation excluded
- Treatment
- Specified synthetic beta-NMN ingredient
- Follow-up
- Regulatory assessment
- Study design
- EFSA novel-food safety opinion
The opinion is not efficacy approval and does not cover arbitrary products, higher doses, pregnancy/lactation or indefinite use.
Read the original sourceWhich published and unpublished gaps matter?
Food or supplement status does not answer efficacy. Several completed trials remain results-silent, including a 131-man exercise-recovery study, a 24-person healthy cognition and sleep study, and a 22-person Chinese alcohol-exposure crossover. The cited public records include no primary Russian randomized human NMN efficacy trial. Marketplace and review pages are not clinical evidence.
| Record | Planned question | Status |
|---|---|---|
| NCT04664361: 131 healthy active men | Wingate recovery after 250 or 500 mg/day | Completed; no posted table or matched publication |
| NCT04910061: 24 healthy adults | Cognition, fatigue, mood, sleep and quality of life | Completed; no posted results |
| NCT05882214: 22-person Chinese crossover | Acute alcohol-exposure outcomes | Completed; no posted results or matched paper |
FDA 2025 NMN supplement-definition decision
FDA regulatory response
Prater DA, Principal Deputy Director for Human Foods. Response to Citizen Petition FDA-2023-P-0872-2754. U.S. Food and Drug Administration. Digitally signed September 29, 2025.
FDA revised its interpretation of the drug-exclusion sequence for NMN and concluded that NMN was not excluded from the dietary-supplement definition on that basis because US supplement marketing preceded authorization of new-drug investigations. FDA did not declare every NMN product lawful, safe, or effective.
- Participants / model
- US dietary-supplement regulatory category
- Treatment
- NMN ingredient status under section 201(ff)(3)(B)
- Follow-up
- Current response issued 2025
- Study design
- FDA citizen-petition response
The digital signature is dated September 29, 2025, although the first-page printed year differs. The decision is not drug approval and does not waive NDI, safety, adulteration, or labeling law.
Read the original sourceChina SAMR · NMN food/health-food policy response
Chinese government regulatory response
State Administration for Market Regulation of the People's Republic of China. Response to Recommendation No. 1067 of the Fourth Session of the 13th National People's Congress. December 30, 2021.
SAMR described NMN anti-aging products as an emerging area and explained that applicants would need to submit NMN through the new-food-raw-material and health-food ingredient/function processes; the response did not authorize NMN anti-aging claims.
- Participants / model
- Chinese food/health-food regulatory framework
- Treatment
- NMN ingredient proposals
- Follow-up
- Government policy response
- Study design
- Government response
A 2023 NHC receipt for an NMN food-additive application and a 2025/2026 export-test standard do not establish domestic food authorization. The cited NHC records include no later authorization.
Read the original sourceCompleted 131-man trial · no posted results
Clinical trial registry
ClinicalTrials.gov. NCT04664361.
The study completed with actual enrollment of 131. The registry posts no tabular results, and the cited sources include no matched publication.
- Participants / model
- 131 healthy active men in France
- Treatment
- Placebo, NMN 250 mg/day or 500 mg/day
- Follow-up
- Completed 2023
- Study design
- Randomized clinical trial registry
Planned Wingate recovery outcomes cannot be inferred from a results-silent record.
Read the original sourceCompleted 24-person record · no posted results
Clinical trial registry
ClinicalTrials.gov. NCT04910061.
The completed record planned McNair cognition, SF-36, sleep and fatigue measures but posts no results.
- Participants / model
- 24 healthy adults in Canada
- Treatment
- NMN 400 mg/day
- Follow-up
- Twenty-nine days
- Study design
- Randomized trial registry
A results-silent record is neither positive nor null.
Read the original sourceCompleted China-linked crossover · no posted outcomes
Clinical trial registry
ClinicalTrials.gov. NCT05882214.
The 22-person crossover completed in April 2025. The registry posts no results, and the cited sources include no matched publication.
- Participants / model
- 22 participants in China
- Treatment
- NMN and acute alcohol exposure conditions
- Follow-up
- Crossover
- Study design
- Completed clinical trial registry
No outcome should be inferred from a results-silent record.
Read the original sourceWhat does C tier mean for each NMN claim?
C tier reflects replicated biochemical target engagement plus a few narrow physiological signals. Confidence is strongest for short-term blood NAD changes, lower for the selected prediabetes muscle-insulin result, and low or absent for sleep, performance, cognition, hormone optimization, disease prevention and longevity. Positive biomarkers and null clinical endpoints can both be true.
| Claim | Judgment |
|---|---|
| Raises circulating NAD-related measures | Supported short-term; assay and analyte caveats apply |
| Improves metabolic health | One tissue-specific prediabetes signal; broader pooled results mostly null |
| Improves strength, exercise or sleep | Selected inconsistent findings; pooled muscle outcomes null |
| Improves cognition or mood | No demonstrated randomized human benefit |
| Raises testosterone or restores hormones | Controlled hormone panel null |
| Extends human life | No human evidence |
| Safe indefinitely | Only short-term defined-product tolerability supported |
30-person RCT · blood NAD rose, broad outcomes null
Randomized double-blind placebo-controlled trial
PMCID PMC9036060.
Whole-blood NAD and NAMN rose while parent NMN did not; broad metabolic and body-composition outcomes were null.
- Participants / model
- 30 healthy adults; one placebo dropout
- Treatment
- Oral NMN 250 mg/day versus placebo
- Follow-up
- Twelve weeks
- Study design
- Randomized double-blind placebo-controlled trial
- Funding
- Mitsubishi product support
Four authors were Mitsubishi employees. Blood target engagement did not establish clinical benefit.
Read the original sourcePrediabetes RCT · 25 women, 10 weeks
Randomized controlled trial
Yoshino M, Yoshino J, Kayser BD, Patti GJ, Franczyk MP, Mills KF, Sindelar M, Pietka T, Patterson BW, Imai SI, Klein S. Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science. 2021;372(6547):1224-1229. doi:10.1126/science.abe9985. PMID 33888596.
Twenty-five postmenopausal women with prediabetes and overweight/obesity received oral NMN or placebo for ten weeks. Hyperinsulinemic-euglycemic clamp testing found improved muscle insulin sensitivity and signaling/remodeling markers with NMN.
- Participants / model
- 25 postmenopausal women with prediabetes and overweight/obesity
- Treatment
- Oral NMN 250 mg/day or placebo
- Follow-up
- Ten weeks
- Study design
- Randomized double-blind placebo-controlled trial
- Funding
- Academic and grant support with NMN supplied for study
Small, selected female metabolic population; no weight-loss, cognition, lifespan, or hard clinical outcome.
Read the original sourceEight-trial meta-analysis · glucose and lipids null
Systematic review and meta-analysis
PMID 39531138.
Across eight randomized trials and 342 participants, fasting glucose, insulin, HbA1c, HOMA-IR and lipids were not materially improved.
- Participants / model
- 342 participants across eight randomized trials
- Treatment
- Oral NMN versus control
- Follow-up
- Short heterogeneous trials
- Study design
- Systematic review and meta-analysis
Pooled studies were small, short and heterogeneous.
Read the original source2025 meta-analysis · pooled muscle outcomes null
Systematic review and meta-analysis
PMID 40275690.
No pooled benefit was found for skeletal-muscle index, grip strength, gait speed or five-chair-stand performance.
- Participants / model
- Human NMN trials with muscle or function outcomes
- Treatment
- Oral NMN versus control
- Follow-up
- Short heterogeneous studies
- Study design
- Systematic review and meta-analysis
Narrative evidence also did not show convincing knee-extension, SPPB, thigh-mass or resistance-training benefit.
Read the original source36-person RCT · testosterone and hormone panel null
Randomized double-blind placebo-controlled trial
PMID 36797393; PMCID PMC9935856.
A nicotinamide metabolite increased; pulse-wave velocity only trended.
- Participants / model
- 36 healthy adults aged 40-59; 34 completed
- Treatment
- NMN 250 mg/day versus placebo
- Follow-up
- Twelve weeks
- Study design
- Randomized double-blind placebo-controlled trial
- Funding
- DHC grant
Testosterone, estradiol, progesterone, DHEA-S, cortisol, blood pressure, glucose, lipids and body composition were null.
Read the original sourceEFSA 2026 · specified 300 mg/day boundary
Regulatory food-safety opinion
PMID 42125559; PMCID PMC13158811.
EFSA judged a specified synthetic beta-NMN ingredient safe at 300 mg/day for adults.
- Participants / model
- Proposed adult novel-food users; pregnancy and lactation excluded
- Treatment
- Specified synthetic beta-NMN ingredient
- Follow-up
- Regulatory assessment
- Study design
- EFSA novel-food safety opinion
The opinion is not efficacy approval and does not cover arbitrary products, higher doses, pregnancy/lactation or indefinite use.
Read the original sourceStudies and sources
FDA GSRS · beta-NMN identity
Government substance database
U.S. Food and Drug Administration. Global Substance Registration System, beta-nicotinamide mononucleotide, UNII 2KG6QX4W0V.
The record identifies beta-NMN as C11H15N2O8P, molecular weight 334.22 g/mol, CAS 1094-61-7.
- Participants / model
- Not applicable
- Treatment
- Not applicable
- Follow-up
- Not applicable
- Study design
- Primary source record
Beta-NMN is distinct from reduced NMNH and from generic niacinamide; identity does not prove supplement legality or efficacy.
Read the original sourceFDA 2025 NMN supplement-definition decision
FDA regulatory response
Prater DA, Principal Deputy Director for Human Foods. Response to Citizen Petition FDA-2023-P-0872-2754. U.S. Food and Drug Administration. Digitally signed September 29, 2025.
FDA revised its interpretation of the drug-exclusion sequence for NMN and concluded that NMN was not excluded from the dietary-supplement definition on that basis because US supplement marketing preceded authorization of new-drug investigations. FDA did not declare every NMN product lawful, safe, or effective.
- Participants / model
- US dietary-supplement regulatory category
- Treatment
- NMN ingredient status under section 201(ff)(3)(B)
- Follow-up
- Current response issued 2025
- Study design
- FDA citizen-petition response
The digital signature is dated September 29, 2025, although the first-page printed year differs. The decision is not drug approval and does not waive NDI, safety, adulteration, or labeling law.
Read the original sourceFDA NDI list · notification is not approval
FDA regulatory listing
U.S. Food and Drug Administration. Submitted 75-Day Premarket Notifications for New Dietary Ingredients. Entry 1444, beta-Nicotinamide Mononucleotide, submitted November 17, 2025; response dated January 28, 2026.
FDA's current list includes an NMN new-dietary-ingredient notification and response date.
- Participants / model
- US dietary-supplement regulatory process
- Treatment
- Beta-NMN NDI notification
- Follow-up
- Submission and response dates in 2025-2026
- Study design
- FDA notification list
Appearance on the NDI list is not product approval, a universal safety finding, or permission for disease/anti-aging claims; the specific response letter governs the notifier's record.
Read the original sourcePrediabetes RCT · 25 women, 10 weeks
Randomized controlled trial
Yoshino M, Yoshino J, Kayser BD, Patti GJ, Franczyk MP, Mills KF, Sindelar M, Pietka T, Patterson BW, Imai SI, Klein S. Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science. 2021;372(6547):1224-1229. doi:10.1126/science.abe9985. PMID 33888596.
Twenty-five postmenopausal women with prediabetes and overweight/obesity received oral NMN or placebo for ten weeks. Hyperinsulinemic-euglycemic clamp testing found improved muscle insulin sensitivity and signaling/remodeling markers with NMN.
- Participants / model
- 25 postmenopausal women with prediabetes and overweight/obesity
- Treatment
- Oral NMN 250 mg/day or placebo
- Follow-up
- Ten weeks
- Study design
- Randomized double-blind placebo-controlled trial
- Funding
- Academic and grant support with NMN supplied for study
Small, selected female metabolic population; no weight-loss, cognition, lifespan, or hard clinical outcome.
Read the original sourceHealthy older-men RCT · 42 randomized
Randomized controlled trial
Igarashi M, Nakagawa-Nagahama Y, Miura M, Kashiwabara K, Yaku K, Sawada M, Sekine R, Fukamizu Y, Sato T, Sakurai T, Sato J, Ino K, Kubota N, Nakagawa T, Kadowaki T, Yamauchi T. Chronic nicotinamide mononucleotide supplementation elevates blood nicotinamide adenine dinucleotide levels and alters muscle function in healthy older men. npj Aging. 2022;8:5. doi:10.1038/s41514-022-00084-z. PMID 35927255.
Forty-two healthy older men were randomized 1:1 for 12 weeks. Blood NAD-related metabolites increased; gait speed and left-hand grip had nominal improvements, while body composition did not change. Protocol deviations affected later follow-up and 20 completed week 12.
- Participants / model
- 42 healthy older men randomized; 20 completed week 12 under the reported protocol deviations
- Treatment
- Oral NMN 250 mg/day or placebo
- Follow-up
- Six or twelve weeks
- Study design
- Randomized double-blind placebo-controlled parallel trial
- Funding
- Industry involvement and product support
Small, male-only, incomplete week-12 denominator, nominal unilateral/function findings, and multiple endpoints; no cognition or longevity result.
Read the original sourceHealthy adults full paper · 80 completed
Randomized double-blind placebo-controlled trial
Yi L, Maier AB, Tao R, Lin Z, Vaidya A, Pendse S, Thasma S, Andhalkar N, Avhad G, Kumbhar V. The efficacy and safety of beta-nicotinamide mononucleotide supplementation in healthy middle-aged adults: a randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial. GeroScience. 2023;45(1):29-43. doi:10.1007/s11357-022-00705-1. PMID 36482258.
Blood total NAD plus NADH and six-minute walk distance favored NMN groups over 60 days. HOMA-IR did not differ between groups; within-group HOMA-IR increased in the 600 and 900 mg arms. The proprietary Aging.Ai score also changed.
- Participants / model
- 80 healthy adults aged 40-65, 20 per placebo, 300 mg, 600 mg, and 900 mg arm; all completed
- Treatment
- Oral beta-NMN once daily or placebo
- Follow-up
- Sixty days
- Study design
- Multicenter randomized double-blind placebo-controlled four-arm parallel trial
- Funding
- NMN product supplied by EffePharm/AbinoNutra; company-linked authors and commercial support disclosed
Nine adverse events occurred in seven participants: six events in five placebo participants and three in two 300 mg participants, none in the 600/900 mg groups; all were mild or moderate and judged unrelated, with no serious event or dropout. The study used multiple outcomes and a proprietary aging score.
Read the original sourceChina phase 1/2 ITP · 25, single arm
Phase 1/2 human trial
Li H, Xu Y, Chen Y, Ji L, Xu Y, Zheng W, Sun T, Fu R, Pei X, Liu X, Xue F, Liu W, Wang W, Chi Y, Yang R, Wei J, Zhang L. Low-dose oral nicotinamide mononucleotide for immune thrombocytopenia: a phase 1/2 trial. Nature Medicine. 2026;32(6):2026-2036. doi:10.1038/s41591-026-04366-x. PMID 42056497.
In China, 25 adults with steroid-refractory or steroid-dependent immune thrombocytopenia received open-label oral NMN for two weeks. No dose-limiting toxicities or treatment-related serious adverse events occurred; five participants (20%) met the prespecified platelet-response endpoint.
- Participants / model
- 25 adults with steroid-refractory or steroid-dependent immune thrombocytopenia
- Treatment
- Open-label oral NMN 450 mg twice daily
- Follow-up
- Two weeks, with exploratory follow-up through week 8
- Study design
- Single-arm phase 1/2 clinical trial with supporting mouse experiments
- Funding
- Chinese academic program
No control arm, tiny disease-specific cohort, short exposure, and an immune/platelet endpoint. This is not longevity, cognition, or healthy-user evidence.
Read the original sourceChina insomnia protocol · planned n=400
Clinical trial protocol
Gao X, Li J, Xu S, Li X, Wang X, Li Y, Huang Y, Liu S, Zeng Q. Oral nicotinamide mononucleotide (NMN) as a treatment for chronic insomnia: protocol for the multicenter, randomized, double-blind, placebo-controlled trial. Trials. 2023. Chinese Clinical Trial Registry ChiCTR2200058001.
The protocol plans 400 adults with chronic insomnia randomized 1:1 to oral NMN or placebo in multiple Chinese centers. It does not provide completed outcome results.
- Participants / model
- Planned 400 adults with chronic insomnia in China
- Treatment
- Oral NMN or placebo
- Follow-up
- Protocol-defined trial period
- Study design
- National multicenter randomized double-blind placebo-controlled protocol
- Funding
- China Health Promotion Foundation
A protocol proves a planned test, not efficacy or safety. The registry posts no results, and the cited sources include no outcome paper.
Read the original sourceFirst-in-human full paper · 10 men, three visits
Open-label nonrandomized human study
Irie J, Inagaki E, Fujita M, Nakaya H, Mitsuishi M, Yamaguchi S, Yamashita K, Shigaki S, Ono T, Yukioka H, Okano H, Mori S, Yamaguchi M, Itoh H. Effect of oral administration of nicotinamide mononucleotide on clinical parameters and nicotinamide metabolite levels in healthy Japanese men. Endocrine Journal. 2020;67(2):153-160. doi:10.1507/endocrj.EJ19-0313. PMID 31685720.
No severe symptoms or clinically meaningful changes in examinations, ophthalmology, or sleep were reported over five hours. Downstream MNA, 2Py, and 4Py rose and peaked at 300 minutes; parent NMN was not measured. Bilirubin rose 51.3%, while glucose, creatinine, and chloride fell 11.7%, 5.1%, and 2.3% at 300 minutes, remaining within reference ranges.
- Participants / model
- 10 healthy Japanese men aged 40-60; each received all three exposures on separate visits
- Treatment
- Single oral beta-NMN exposures of 100, 250, and 500 mg
- Follow-up
- Five-hour observation after each visit; mean interval 63±23 days
- Study design
- Open-label nonrandomized within-person ascending-exposure study
- Funding
- Keio University research support; industry relationships disclosed in the paper
No placebo, ten men, single exposures, and only five hours of follow-up. The assay measured downstream nicotinamide metabolites, not a parent NMN curve, so no parent half-life or Tmax follows.
Read the original sourceWild-type mice · 12 months
Mouse preclinical study
Mills KF, Yoshida S, Stein LR, Grozio A, Kubota S, Sasaki Y, Redpath P, Migaud ME, Apte RS, Uchida K, Yoshino J, Imai SI. Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice. Cell Metabolism. 2016;24(6):795-806. doi:10.1016/j.cmet.2016.09.013. PMID 28068222.
Wild-type mice received oral NMN in drinking water for 12 months. The study reported tissue NAD-related changes and mitigation of several age-associated physiological measures.
- Participants / model
- Wild-type mice
- Treatment
- NMN in drinking water
- Follow-up
- Twelve months
- Study design
- Long-term controlled mouse experiment
The study did not establish human lifespan extension; species, exposure, endpoints, and metabolism differ.
Read the original sourceChina SAMR · NMN food/health-food policy response
Chinese government regulatory response
State Administration for Market Regulation of the People's Republic of China. Response to Recommendation No. 1067 of the Fourth Session of the 13th National People's Congress. December 30, 2021.
SAMR described NMN anti-aging products as an emerging area and explained that applicants would need to submit NMN through the new-food-raw-material and health-food ingredient/function processes; the response did not authorize NMN anti-aging claims.
- Participants / model
- Chinese food/health-food regulatory framework
- Treatment
- NMN ingredient proposals
- Follow-up
- Government policy response
- Study design
- Government response
A 2023 NHC receipt for an NMN food-additive application and a 2025/2026 export-test standard do not establish domestic food authorization. The cited NHC records include no later authorization.
Read the original sourceBeijing RCT · 60 students, single exposure
Randomized double-blind placebo-controlled trial
Zhao C, Wu B, Sui H, Kuan G, Wei G, Yan Y. The effects of pyrroloquinoline quinone and nicotinamide mononucleotide supplementation on interoception following acute exhaustive exercise: a randomised, double-blind, placebo-controlled study. Scientific Reports. 2026;16:5408. doi:10.1038/s41598-025-34191-0. PMID 41651893.
There was no overall between-group advantage for interoception after exhaustive exercise. One MAIA Body Listening interaction was significant (p=0.016), driven by a within-PQQ change rather than an NMN-specific effect.
- Participants / model
- 60 male physical-education students in Beijing, mean age about 19; 15 per arm
- Treatment
- Single pre-exercise exposure: placebo, PQQ 20 mg, NMN 300 mg, or both
- Follow-up
- One acute exhaustive-exercise session
- Study design
- Randomized double-blind placebo-controlled four-arm trial; retrospectively registered
- Funding
- Fundamental Research Funds for the Central Universities
This was an acute exercise/interoception study in young men, not a cognition or aging trial. Adverse events were not reported.
Read the original source30-person RCT · blood NAD rose, broad outcomes null
Randomized double-blind placebo-controlled trial
PMCID PMC9036060.
Whole-blood NAD and NAMN rose while parent NMN did not; broad metabolic and body-composition outcomes were null.
- Participants / model
- 30 healthy adults; one placebo dropout
- Treatment
- Oral NMN 250 mg/day versus placebo
- Follow-up
- Twelve weeks
- Study design
- Randomized double-blind placebo-controlled trial
- Funding
- Mitsubishi product support
Four authors were Mitsubishi employees. Blood target engagement did not establish clinical benefit.
Read the original source30-person, 28-day trial · selected signals amid nulls
Randomized placebo-controlled trial
PMID 36740954; PMCID PMC11491622.
Weight, diastolic pressure, total cholesterol, LDL and non-HDL cholesterol favored MIB-626.
- Participants / model
- 30 adults aged at least 45 with overweight or obesity
- Treatment
- MIB-626 1000 mg twice daily versus placebo
- Follow-up
- Twenty-eight days
- Study design
- Randomized 2:1 placebo-controlled trial
- Funding
- Metro International Biotech
Insulin sensitivity, liver/intra-abdominal fat, strength, fatigability, aerobic capacity and stair power were null; many endpoints and company-employed authors.
Read the original sourceEight-trial meta-analysis · glucose and lipids null
Systematic review and meta-analysis
PMID 39531138.
Across eight randomized trials and 342 participants, fasting glucose, insulin, HbA1c, HOMA-IR and lipids were not materially improved.
- Participants / model
- 342 participants across eight randomized trials
- Treatment
- Oral NMN versus control
- Follow-up
- Short heterogeneous trials
- Study design
- Systematic review and meta-analysis
Pooled studies were small, short and heterogeneous.
Read the original sourceTen-trial meta-analysis · small diastolic estimate
Systematic review and meta-analysis
PMID 41901064.
Pooled diastolic pressure was estimated 2.15 mmHg lower; an older-adult systolic subgroup was positive.
- Participants / model
- 349 participants across ten trials
- Treatment
- Oral NMN versus control
- Follow-up
- Short heterogeneous trials
- Study design
- Systematic review and meta-analysis
Overall systolic pressure was null; subgroup and small pooled estimates are not cardiovascular-outcome evidence.
Read the original source48-runner trial · threshold signals, VO2max and strength null
Randomized double-blind placebo-controlled trial
DOI 10.1186/s12970-021-00442-4.
Selected ventilatory-threshold measures improved, mainly at higher doses.
- Participants / model
- 48 recreational runners
- Treatment
- NMN 300, 600 or 1200 mg/day versus placebo during training
- Follow-up
- Six weeks
- Study design
- Randomized double-blind placebo-controlled trial
VO2max, peak power, body composition, grip strength, push-ups and sit-and-reach were null; stance improved only at 600 mg.
Read the original source108-person timing trial · primary sleep interaction null
Randomized double-blind placebo-controlled trial
PMID 35215405; PMCID PMC8877443.
Drowsiness and chair-stand interactions were reported, with several within-arm improvements.
- Participants / model
- 108 older Japanese adults; 105 completed
- Treatment
- NMN 250 mg/day morning or afternoon versus matched placebo
- Follow-up
- Twelve weeks
- Study design
- Randomized double-blind four-arm timing trial
- Funding
- Mitsubishi product support
Prespecified PSQI group-by-time interaction was null; afternoon NMN and afternoon placebo both improved drowsiness. Many comparisons and commercial ties.
Read the original source60-person study · primary stepping test null
Randomized double-blind placebo-controlled trial
PMID 38789831.
Four-meter walking time and selected PSQI global/daytime-dysfunction outcomes favored NMN.
- Participants / model
- 60 sedentary adults aged 65-75
- Treatment
- NMN 250 mg/day versus placebo
- Follow-up
- Twelve weeks
- Study design
- Randomized double-blind placebo-controlled trial
- Funding
- Meiji
The primary stepping-test endpoint was null at four and 12 weeks. The abstract does not report complete multiplicity or event tables.
Read the original source36-person RCT · testosterone and hormone panel null
Randomized double-blind placebo-controlled trial
PMID 36797393; PMCID PMC9935856.
A nicotinamide metabolite increased; pulse-wave velocity only trended.
- Participants / model
- 36 healthy adults aged 40-59; 34 completed
- Treatment
- NMN 250 mg/day versus placebo
- Follow-up
- Twelve weeks
- Study design
- Randomized double-blind placebo-controlled trial
- Funding
- DHC grant
Testosterone, estradiol, progesterone, DHEA-S, cortisol, blood pressure, glucose, lipids and body composition were null.
Read the original source2025 meta-analysis · pooled muscle outcomes null
Systematic review and meta-analysis
PMID 40275690.
No pooled benefit was found for skeletal-muscle index, grip strength, gait speed or five-chair-stand performance.
- Participants / model
- Human NMN trials with muscle or function outcomes
- Treatment
- Oral NMN versus control
- Follow-up
- Short heterogeneous studies
- Study design
- Systematic review and meta-analysis
Narrative evidence also did not show convincing knee-extension, SPPB, thigh-mass or resistance-training benefit.
Read the original sourceCompleted 24-person record · no posted results
Clinical trial registry
ClinicalTrials.gov. NCT04910061.
The completed record planned McNair cognition, SF-36, sleep and fatigue measures but posts no results.
- Participants / model
- 24 healthy adults in Canada
- Treatment
- NMN 400 mg/day
- Follow-up
- Twenty-nine days
- Study design
- Randomized trial registry
A results-silent record is neither positive nor null.
Read the original source36-person Shanghai study · molecular endpoints only
Controlled human biomarker study
PMID 41072840.
Blood and PBMC NAD turnover and NAD-capped RNA measures changed.
- Participants / model
- 36 healthy adults in Shanghai; 20 NMN and 16 placebo
- Treatment
- NMN 300 mg/day versus placebo
- Follow-up
- Two months
- Study design
- Controlled human biomarker study
The abstract reports no patient-centered endpoint.
Read the original sourceCompleted China-linked crossover · no posted outcomes
Clinical trial registry
ClinicalTrials.gov. NCT05882214.
The 22-person crossover completed in April 2025. The registry posts no results, and the cited sources include no matched publication.
- Participants / model
- 22 participants in China
- Treatment
- NMN and acute alcohol exposure conditions
- Follow-up
- Crossover
- Study design
- Completed clinical trial registry
No outcome should be inferred from a results-silent record.
Read the original sourceSix-person NMN stage · blood positive, brain not established
Randomized-order exploratory crossover
PMID 41858901; PMCID PMC12996706.
NMN raised whole-blood NAD about 69% after eight days.
- Participants / model
- Six healthy adults in the NMN/NR crossover stage
- Treatment
- NMN and NR, each 1200 mg/day for eight days
- Follow-up
- Eight-day periods with washout
- Study design
- Randomized-order exploratory crossover
The NMN cerebral-NAD comparison did not reach significance. The longer four-week brain result used NR only. No cognition endpoint.
Read the original source2024 mouse preprint · female-only lifespan signal
Animal preprint
PMCID PMC11230277.
Median lifespan reportedly increased 8.5% in female mice, not males; frailty and activity measures changed.
- Participants / model
- Laboratory mice
- Treatment
- Chronic NMN exposure
- Follow-up
- Long term
- Study design
- Animal preprint experiment
Preprint, animal, and sex-specific result cannot establish human longevity.
Read the original sourceSame 14-person cohort · one grid signal, acuity null
Exploratory same-cohort analysis
PMID 42082179.
One temporal outer-grid thickness comparison was +1.14 versus -2.77 micrometers, p=.006.
- Participants / model
- Same older diabetes/frailty cohort; seven people and 14 eyes per arm
- Treatment
- NMN 250 mg/day versus placebo
- Follow-up
- Twenty-four weeks
- Study design
- Same-cohort exploratory retinal analysis
Visual acuity was unchanged; nine grid regions and correlated eyes complicate inference. Not an independent cohort.
Read the original source14-man crossover · no NMN, NAM or NAD route difference
Randomized crossover pharmacology study
PMID 42304075.
Sublingual exposure increased early 2PY and 4PY area under the curve.
- Participants / model
- 14 healthy men
- Treatment
- One oral and one sublingual NMN exposure
- Follow-up
- Blood sampled through 60 minutes with eight-day washout
- Study design
- Randomized crossover
- Funding
- Meiji
NMN, NAM and NAD did not differ by route; metabolite source unresolved and no clinical endpoint. All authors were Meiji employees.
Read the original source31-person four-week trial · short-term safety only
Randomized double-blind placebo-controlled trial
PMID 36002548.
No severe event or clinically concerning laboratory or physiological change was reported.
- Participants / model
- 31 healthy adults aged 20-65
- Treatment
- NMN 1250 mg/day versus placebo
- Follow-up
- Four weeks
- Study design
- Randomized double-blind placebo-controlled trial
- Funding
- Mitsubishi
Small, short, manufacturer-funded study; five authors were employees. It cannot establish rare or chronic safety.
Read the original source30-person 2025 trial · telomere null, short safety
Randomized placebo-controlled trial
Functional Foods in Health and Disease. 2025.
Blood NAD rose and no clinically problematic four-week examination or laboratory signal was reported.
- Participants / model
- 30 healthy Japanese adults; all completed
- Treatment
- Placebo, NMN 750 mg/day or 1500 mg/day
- Follow-up
- Four weeks
- Study design
- Randomized placebo-controlled trial
- Funding
- Company-linked program
Telomere length did not change; short commercial study cannot establish anti-aging or chronic safety.
Read the original source42-person RCT · target engagement without clinical rescue
Randomized placebo-controlled clinical trial
PMID 40746868; PMCID PMC12312518.
Blood NAD metabolites rose.
- Participants / model
- 42 hospitalized adults with COVID-19 and acute kidney injury; 25 active, 17 placebo
- Treatment
- MIB-626 1000 mg twice daily versus placebo
- Follow-up
- Fourteen days
- Study design
- Randomized placebo-controlled trial
- Funding
- Metro International Biotech
Creatinine, cystatin C, kidney-injury markers, inflammation, WHO status and SOFA endpoints were null. Cardiovascular events were 5 versus 1; small trial cannot establish causality.
Read the original sourceEFSA 2026 · specified 300 mg/day boundary
Regulatory food-safety opinion
PMID 42125559; PMCID PMC13158811.
EFSA judged a specified synthetic beta-NMN ingredient safe at 300 mg/day for adults.
- Participants / model
- Proposed adult novel-food users; pregnancy and lactation excluded
- Treatment
- Specified synthetic beta-NMN ingredient
- Follow-up
- Regulatory assessment
- Study design
- EFSA novel-food safety opinion
The opinion is not efficacy approval and does not cover arbitrary products, higher doses, pregnancy/lactation or indefinite use.
Read the original sourceCompleted 131-man trial · no posted results
Clinical trial registry
ClinicalTrials.gov. NCT04664361.
The study completed with actual enrollment of 131. The registry posts no tabular results, and the cited sources include no matched publication.
- Participants / model
- 131 healthy active men in France
- Treatment
- Placebo, NMN 250 mg/day or 500 mg/day
- Follow-up
- Completed 2023
- Study design
- Randomized clinical trial registry
Planned Wingate recovery outcomes cannot be inferred from a results-silent record.
Read the original source65-person study · NMN and NR raised circulating NAD
Randomized open-label four-arm trial
PMID 41540253.
NMN and NR, but not chronic NAM, increased circulating NAD over 14 days; ex vivo work supported a proposed microbial route.
- Participants / model
- 65 modified-intention-to-treat healthy adults
- Treatment
- Placebo, NAM, NR or NMN
- Follow-up
- Fourteen days
- Study design
- Randomized open-label four-arm trial
- Funding
- Nestle and Cryptobiotix affiliations
No clinical-benefit endpoint; ex vivo mechanism did not directly prove the microbial route in vivo.
Read the original sourceWhy is NMN in C tier?
Tier C: short-term blood NAD target engagement is well supported and selected metabolic or physical signals justify continued clinical research. Clinical outcomes remain inconsistent, pooled metabolic and muscle findings are mostly null, and cognition, hormone optimization, disease prevention and human longevity have not been demonstrated. Short-term tolerability does not establish multi-year safety.