Nicotinamide mononucleotide (NMN) is a bioactive nucleotide and a direct intermediate in nicotinamide adenine dinucleotide (NAD+) biosynthesis. Trace amounts occur in foods, while clinical research focuses on targeted supplementation that alters human NAD metabolism. Aging-related NAD biology is tissue- and context-dependent: human muscle and other tissues can show age-associated changes, but a 2026 seven-cohort study found whole-blood NAD+ remarkably stable with age. This corpus evaluates NMN target engagement, clinical outcomes, safety, pharmacology, product quality, and the limits of translating NAD biology into health claims.
Randomized placebo-controlled trial in hospitalized adults with COVID-19 and acute kidney injury; the sample was small and the trial was primarily pharmacodynamic/safety rather than powered for clinical efficacy.
Exploratory human component within a mixed mouse/human paper: only eight middle-aged men received NMN without a placebo or concurrent control, so the reported telomere change cannot establish causality.
Randomised, double-blind, placebo-controlled multiple-ascending-dose PK/PD trial in humans with validated LC–MS/MS analytics and pharmaceutical-grade study product; small sample (n=32), narrow age band (55–80), and 14-day duration constrain generalisability.
Randomized, open-label, placebo-controlled human trial with a pre-registered primary endpoint (NCT05517122): 67 participants were randomized and 65 were included in the modified intention-to-treat analysis. Validated metabolomics plus complementary ex vivo microbiome and whole-blood experiments strengthen mechanistic interpretation, but the open-label design, healthy population and indirect nature of the proposed gut mechanism limit inference.
Sourcedoi:10.1038/s42255-025-01421-8PMID 41540253PMC12855009
Randomized two-period crossover pharmacokinetic study providing direct within-person oral-versus-sublingual comparison; small male-only sample and 60-minute acute sampling limit generalizability and clinical interpretation.
Sourcedoi:10.1038/s41598-026-57552-9PMID 42304075PMC13534420
Randomized, double-blind, placebo-controlled 12-week human trial with direct whole-blood NAD+ measurement; modest sample size (n=30) and a biomarker/safety focus limit inference about clinical benefit.
Mechanistic preclinical tumor-immunology study with human immune-cell experiments and a murine mesothelioma model. Useful counterpoint demonstrating context-dependent cancer biology, but not human anticancer efficacy.
Sourcedoi:10.1016/j.omton.2026.201221PMID 42179971PMC13195322
Rigorous preclinical cancer study using multiple pancreatic-cancer cell lines and immunocompetent and immunodeficient mouse models. Highly relevant safety signal for active cancer/chemotherapy, but not evidence from cancer patients.
Randomized placebo-controlled 28-day human physiologic study with detailed NAD metabolomics and imaging/physiology endpoints; small sample, short duration, and substantial industry involvement limit certainty about clinical efficacy.
Systematic review and meta-analysis of randomized controlled trials focused on blood pressure; high-level evidence, but based on a small, short-term and heterogeneous NMN trial literature.
Controlled mouse pharmacokinetic/tissue-distribution study showing tissue-specific NAD+ differences when NMN was combined with resveratrol or ginsenosides. Relevant to stacking claims but not human clinical evidence.
Multicenter randomized, double-blind, placebo-controlled dose-ranging trial with 80 participants; industry sponsorship and multiple secondary/exploratory endpoints require cautious interpretation.
Randomized, double-blind, placebo-controlled four-arm human trial with an NMN-only arm, although it tested one acute 300 mg dose in a young male athletic population and was designed primarily around interoception rather than long-term performance.
Sourcedoi:10.1038/s41598-025-34191-0PMID 41651893PMC12886864
Large randomized, placebo-controlled, double-blind four-arm human trial with a dedicated NMN-only group and prespecified endurance endpoints; interpretation requires strong commercial-conflict context.
Randomized, double-blind, placebo-controlled four-arm human exercise trial with three NMN doses, but only 12 participants per arm, predominantly men, six-week duration, and exercise training in every group; outcomes support ventilatory-threshold effects rather than a clear VO2max improvement.
Peer-reviewed PRISMA-guided systematic review and network meta-analysis of 27 studies (25 RCTs, 2 quasi-experimental; 1,599 participants), including 7 NMN studies with 370 participants. High synthesis value for functional domains, but treatment rankings rely heavily on indirect placebo-centered networks and heterogeneous precursor studies.
PRISMA systematic review of seven preclinical NMN fertility studies plus transcriptomic analysis of 46 human oocytes. Strong synthesis of translational biology, but no human NMN supplementation fertility trial.
Sourcedoi:10.1007/s10815-025-03720-1PMID 41160202PMC12831783
Detailed mechanistic and reproductive-aging study demonstrating improved oocyte quality and fertility in aged mice. Important preclinical fertility evidence, but there is no corresponding human fertility RCT.
Sourcedoi:10.1016/j.celrep.2020.01.058PMID 32049001PMC7063679
Prospective human intervention with objective hair imaging and metabolomics, but it was an open-label single-arm pre/post study in only 15 women with no placebo control and substantial sponsor/author industry involvement.
Preclinical study combining a DHT-induced mouse hair-loss model with mechanistic experiments in human dermal papilla cells. Relevant to hair biology but not a human supplementation trial.
Peer-reviewed phase 1/2 human intervention in a clinically important disease, but single-arm and open-label with only 25 participants; efficacy signals require randomized confirmation.
Randomized, double-blind, placebo-controlled high-dose safety trial in humans; small sample and four-week duration limit detection of rare or long-term harms.
Randomized, double-blind, placebo-controlled high-dose human safety study with complete follow-up, but only 30 participants and four weeks of exposure.
Sourcedoi:10.2131/fts.12.67
Peer-reviewed human-trial-focused narrative review that maps published and registered NMN studies and evidence gaps; valuable context, but not a systematic review or meta-analysis.
Sourcedoi:10.1016/j.advnut.2023.08.008PMID 37619764PMC10721522
Randomized, double-blind, placebo-controlled human trial using the hyperinsulinemic-euglycemic clamp and muscle biopsies, but only 25 postmenopausal women completed the study, so the strong mechanistic endpoints have limited population generalizability.
Post-hoc association analysis of an existing randomized trial; it does not represent an independent randomized experiment and the reported laboratory associations are exploratory.
Sourcedoi:10.1007/s11357-025-01968-0PMID 41162813PMC13355995
Systematic review and random-effects meta-analysis restricted to human RCTs; high-level evidence for glucose/lipid outcomes, though only eight short-term trials were available.
Sourcedoi:10.1007/s11892-024-01557-zPMID 39531138PMC11557618
Systematic review with random-effects meta-analysis of 12 adult NMN studies and formal RoB 2 assessment; high-level synthesis, tempered by substantial risk-of-bias concerns in the underlying trials.
Placebo-controlled, randomized, double-blind human supplementation study with a focused molecular endpoint; the cohort was small and the outcome is an exploratory epitranscriptomic biomarker rather than a clinical endpoint.
Peer-reviewed systematic review and meta-analysis of randomized placebo-controlled nicotinamide-precursor trials in adults with mean ages above 60 years, with NMN-specific pooled analyses for key sarcopenia outcomes.
Systematic review and meta-analysis of randomized trials in middle-aged and older adults; high-level synthesis, but the small evidence base and limited accessible reporting warrant cautious interpretation.
Randomised placebo-controlled counterbalanced crossover trial in humans with muscle-biopsy endpoints, but the sample is small (n=11 young men) and the intervention is short (7 days), which limits generalisability.
Sourcedoi:10.1080/15502783.2026.2632284PMID 41705654PMC12918316
Multicentre randomized, double-blind, placebo-controlled human study, but the post-unblinding analytic handling is a material limitation: 66 were randomized, allocation was 31 active/35 placebo, and four placebo participants were removed by random subsampling after unblinding so that 31 per group were analyzed.
PRISMA-guided systematic review of 113 eligible intervention studies, including 33 human studies (28 randomized) and 80 rodent studies. Broad synthesis of NAD-related interventions; strong for evidence mapping, though it is primarily narrative rather than a pooled NMN-only meta-analysis.
Large multi-cohort human observational/metabolomics analysis using a rigorously validated whole-blood NAD+ assay across seven independent cohorts. High-quality evidence for the specific question of whole-blood NAD+ and aging, but it does not establish that NAD+ is age-stable in every tissue.
Phase I, open-label pharmacokinetic study with a randomized crossover stage directly comparing NR and NMN in six healthy adults, followed by longer NR exposure in healthy adults and people with Parkinson’s disease. Valuable direct comparative human PK evidence, but extremely small and not an efficacy trial.
Sourcedoi:10.1016/j.isci.2026.114764PMID 41858901PMC12996706
Secondary ophthalmic analysis of the very small Akasaka randomized trial: controlled and double-blind, but only seven patients per group and multiple retinal subfields make the positive regional finding exploratory.
Post-hoc analysis of the previously published 80-person randomized Yi 2023 trial; useful for response heterogeneity but not an independent randomized experiment.
Randomized, double-blind, placebo-controlled study in 42 older men with NAD+ metabolomics and physical-function endpoints. However, a supplier error after week 6 switched supplements for 22 participants, so their week-12 data were excluded and only 20 participants contributed valid week-12 data.
Placebo-controlled, double-blind 24-week human trial in an older, clinically relevant population, but only 14 participants were analyzed and the primary physical-performance outcomes were null.
Randomized, double-blind, placebo-controlled 12-week study in 60 older adults; the prespecified primary stepping-test outcome was null and positive walking/sleep findings were secondary.
Sourcedoi:10.1007/s11357-024-01204-1PMID 38789831PMC11336149
PRISMA-guided systematic review of randomized trials focused on physical performance and safety, but without a formal pooled meta-analysis and with a limited, heterogeneous evidence base.
Influential 12-month controlled mouse study with extensive physiological phenotyping and food-NMN measurements. Strong preclinical evidence but not direct human efficacy evidence.
Peer-reviewed analytical validation study applying an isomer-specific LC-MS/MS method to eight commercial NMN supplements. Strong evidence for product-authentication and label-quality claims, not evidence of clinical efficacy.
Formal EFSA regulatory scientific opinion integrating identity, manufacturing, toxicology, bioavailability and human evidence for a specified β-NMN novel food. High authority for safety under the evaluated conditions, not efficacy.
PRISMA-reported systematic review and random-effects meta-analysis of adult randomized controlled trials with RoB 2 and GRADE assessment. It is the highest-level evidence in this uploaded set, although the underlying trials are small, heterogeneous and generally short-term.
First-in-human, nonblinded, non-placebo-controlled safety/pharmacokinetic study in only 10 healthy men using single doses. Useful for acute tolerability and metabolite kinetics, but it cannot establish efficacy or long-term safety.
Eight-week single-center, single-arm open-label human study with detailed NAD+ measurements but only 11 participants and no placebo control.
Peer-reviewed mechanistic in-vitro study in human HaCaT keratinocytes. It provides current human-cell skin-inflammation biology but enrolled no human participants and cannot establish oral or topical clinical efficacy.
Sourcedoi:10.1007/s11033-026-11615-2PMID 41779073PMC12960338
Mechanistic study in young and aged human melanocytes with confirmation in a reconstructed human-skin model. Human-derived tissue evidence, but not an oral or topical clinical trial in living participants.
Controlled oral NMN preclinical study in UV-B-exposed hairless mice with skin-barrier, wrinkle, collagen and molecular outcomes; directly relevant to oral-skin claims but not human evidence.
Small peer-reviewed human split-face intervention with objective skin measurements, but side allocation was fixed rather than randomized, the test condition combined nano-NMN with cold plasma/electroporation/microjet delivery, and the control also received topical nano-NMN. It supports device-assisted topical delivery, not oral NMN supplementation or NMN-alone efficacy.
Peer-reviewed mechanistic mouse neurophysiology study identifying an NMN-responsive supramammillary circuit and REM-sleep effect. It strengthens biological plausibility for sleep effects but provides no human clinical efficacy evidence.
Sourcedoi:10.1016/j.isci.2026.115741PMID 42170103PMC13187527
Randomized, double-blind, placebo-controlled four-arm human trial with 108 older adults and 12 weeks of dosing; interpretation is limited by substantial time/placebo effects, subjective sleep/fatigue outcomes, and no physiological biomarker measurements.
Blinded analytical study using a purpose-developed and validated HPLC coupled to triple-quadrupole mass spectrometry method, with recovery, precision, accuracy and matrix-effect validation reported, and independent academic authorship with a declared absence of competing interests. Strong within its scope — label accuracy for a snapshot of products — and silent on efficacy.
Includes a randomized human intervention showing blood-pressure and vascular-function signals, but the human trial was very small and open-label, and the paper combines human, animal, cellular and mechanistic experiments.
Sourcedoi:10.1038/s41392-023-01577-3PMID 37718359PMC10505611
Randomized, double-blind, placebo-controlled 12-week human trial, but small sample size (36 randomized, 34 analyzed) and baseline imbalances in arterial-stiffness measurements limit certainty; subgroup vascular findings are exploratory.
