NAD+
Published research and evidence base
Nicotinamide adenine dinucleotide (NAD+) is a redox cofactor and enzyme substrate for sirtuins, PARPs and CD38, and tissue NAD+ concentrations decline with age in preclinical models. Because NAD+ itself is poorly absorbed orally, most human work has used precursors, principally nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN); randomised trials consistently show these raise circulating NAD+ two- to threefold and are well tolerated over weeks to months. Functional and clinical endpoints are far less consistent: individual trials have reported improvements in walking distance, insulin sensitivity and sleep quality, while meta-analyses of muscle, glucose and lipid outcomes have been null. Lifespan extension and stem-cell rejuvenation findings are from rodent studies and have not been demonstrated in humans.
- Studies cited
- 15
- Published 2023+
- 11
- Newest paper
- 2026
- Last reviewed
- Aug 2026
Recurring themes in the literature
- Age-associated decline in tissue NAD+ and sirtuin/PARP/CD38 substrate availability
- Oral NAD+ precursor pharmacokinetics: NR and NMN reliably raise blood NAD+, NAD+ itself is not orally bioavailable
- Mitochondrial respiration, oxidative stress and skeletal-muscle function
- Dissociation between NAD+ elevation and clinical endpoint improvement
- Neurodegeneration and cerebral NAD+ (Parkinson's disease, mild cognitive impairment)
- Immunometabolism and the CD38-NAD+ axis
- Safety and tolerability across doses from 250 mg to 3000 mg per day
Compound identifiers
- CAS
- 53-84-9
- PubChem
- 5892
What NAD+ is, chemically.
- Molecular formula
- C21H27N7O14P2
- Molecular weight
- 663.4 g/mol
- CAS number
- 53-84-9
- PubChem CID
- 5892
nadide, coenzyme I, beta-NAD
These figures come from the PubChem record for this compound and describe the free base. Lyophilised peptide is normally supplied as an acetate or trifluoroacetate salt and carries residual water, so the mass of powder in a vial is not the same quantity as the molecular weight above would suggest. Chromatographic purity on a certificate of analysis does not resolve that difference either — how to read a certificate of analysis explains why.
15 published studies.
Ordered by strength of study design, then by recency. Every entry links to its source record so the finding can be checked against the paper rather than taken on our word.
- 01Systematic review2026
Safety and Metabolism-Related Outcomes of Oral Nicotinamide Mononucleotide Supplementation in Adults: A Systematic Review and Meta-Analysis
Yang W, et al. · Nutrients · systematic review and random-effects meta-analysis of 15 parallel randomised controlled trials of oral NMN, doses 250-2000 mg/day, durations 14 days to 24 weeks, GRADE assessment
NMN did not increase overall, serious or system-specific adverse events and did not elevate ALT or AST. No significant effects were found on body weight, BMI, fasting glucose, HbA1c, lipids or systolic blood pressure; diastolic blood pressure decreased slightly and HOMA-IR showed a non-significant downward trend.
- 02Systematic review2025
The Effect of Nicotinamide Mononucleotide and Riboside on Skeletal Muscle Mass and Function: A Systematic Review and Meta-Analysis
Prokopidis K, et al. · Journal of Cachexia, Sarcopenia and Muscle · systematic review and random-effects meta-analysis of randomised controlled trials of NMN or NR versus placebo, participant mean ages 60.9 to 83 years
NMN showed no significant effect on skeletal muscle index, handgrip strength, gait speed or the five-time chair stand test. NR was associated with longer 6-minute walk distance in peripheral artery disease but with poorer SPPB and chair-stand scores in mild cognitive impairment; the authors concluded current evidence does not support these precursors for preserving muscle mass or function.
- 03Human clinical2026
The differential impact of three different NAD+ boosters on circulatory NAD and microbial metabolism in humans
Christen S, et al. · Nature Metabolism · randomised open-label placebo-controlled study, 65 healthy participants, 14 days of nicotinamide, nicotinamide riboside or nicotinamide mononucleotide, with ex vivo human microbiota fermentation and whole-blood assays
Nicotinamide riboside and nicotinamide mononucleotide comparably increased circulatory NAD+ over 14 days whereas nicotinamide did not, and only nicotinamide acutely altered the whole-blood NAD+ metabolome. Ex vivo work indicated NR and NMN are converted by gut microbiota to nicotinic acid, which was the potent direct NAD+ booster in whole blood.
- 04Human clinical2026
Safety and efficacy of individualised exercise and NAD+ precursor supplementation in patients with Friedreich's ataxia in the USA: a single-centre, 2 × 2 factorial, randomised controlled trial
Lin KY, et al. · The Lancet Neurology · phase 2 single-centre 2 × 2 factorial randomised controlled trial, 66 individuals aged 10-40 with Friedreich's ataxia, 12 weeks of weight-based nicotinamide riboside (300-900 mg) and/or individualised home exercise
Nicotinamide riboside combined with exercise significantly increased peak VO2 versus control (difference 0.21 L/min, adjusted p = 0.0299), while nicotinamide riboside alone and exercise alone did not reach significance. Combination therapy was not statistically different from exercise alone, and all adverse events were mild or moderate.
- 05Human clinical2026
A phase-II randomized controlled pilot study of nicotinamide riboside supplementation in older adults with amnestic mild cognitive impairment
Martens CR, et al. · Alzheimer's & Dementia · 12-week phase II double-blind randomised placebo-controlled pilot trial, 42 older adults with amnestic mild cognitive impairment (NR n = 22, placebo n = 20)
Blood NAD+ approximately doubled in the NR group with no serious adverse effects, but the primary cognitive outcome, total cerebral blood flow and blood pressure were unchanged. Exploratory analysis suggested possible regional cerebral blood flow increases, particularly in the hippocampus.
- 06Human clinical2026
Low-dose oral nicotinamide mononucleotide for immune thrombocytopenia: a phase 1/2 trial
Li H, et al. · Nature Medicine · single-arm open-label phase 1/2 trial, 25 adults with steroid-refractory or steroid-dependent immune thrombocytopenia, 450 mg NMN twice daily for 2 weeks, with supporting mouse macrophage experiments
NMN was well tolerated with no dose-limiting toxicities or treatment-related serious adverse events, and 5 of 25 patients (20.0%) met the primary platelet-response endpoint. The mechanistic work identified CD38-mediated NAD+ depletion driving M1-like macrophage polarisation and FcγRI-dependent platelet phagocytosis in mice.
- 07Human clinical2025
Nicotinamide riboside combined with exercise to treat hypertension in middle-aged and older adults: a pilot randomized clinical trial
Lin Y, et al. · GeroScience · double-blind pilot randomised trial, 54 sedentary adults aged 55+ with daytime systolic BP at or above 130 mmHg, 6 weeks of 1000 mg/day NR plus supervised walking, placebo plus walking, or NR alone
NR plus exercise was not superior to placebo plus exercise for the primary outcome of daytime systolic blood pressure. NAD+ catabolites were higher in the NR groups, and post hoc analysis showed a trend toward greater nighttime blood pressure reduction in unmedicated participants.
- 08Human clinical2025
Effects of nicotinamide riboside on NAD+ levels, cognition, and symptom recovery in long-COVID: a randomized controlled trial
Wu CY, et al. · EClinicalMedicine · 24-week double-blind placebo-controlled trial with placebo lead-in, 58 adults with long-COVID, 2000 mg/day nicotinamide riboside
NR raised blood NAD+ 2.6- to 3.1-fold within 5 to 10 weeks and elevation persisted to 20 weeks. There were no significant between-group differences in cognition, fatigue, sleep quality, anxiety or depression, and dropout was substantially higher in the NR arm.
- 09Human clinical2024
Nicotinamide riboside for peripheral artery disease: the NICE randomized clinical trial
McDermott MM, et al. · Nature Communications · randomised double-blind placebo-controlled trial, 90 adults with lower-extremity peripheral artery disease, 6 months of nicotinamide riboside with or without resveratrol
Nicotinamide riboside improved 6-minute walk distance compared with placebo (between-group difference +17.6 m), with a larger difference of 31.0 m among participants taking at least 75% of study pills. Adding resveratrol conferred no additional benefit.
- 10Human clinical2024
Ingestion of β-nicotinamide mononucleotide increased blood NAD levels, maintained walking speed, and improved sleep quality in older adults in a double-blind randomized, placebo-controlled study
Morifuji M, et al. · GeroScience · randomised double-blind placebo-controlled parallel-group trial, 60 older adults, 250 mg/day NMN for 12 weeks
The primary outcome, a stepping test, showed no significant difference between groups at 4 or 12 weeks. Secondary outcomes favoured NMN: blood NAD+ and its metabolites rose, 4-metre walking time was shorter and Pittsburgh Sleep Quality Index scores improved versus placebo.
- 11Human clinical2023
The efficacy and safety of β-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults: a randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial
Yi L, et al. · GeroScience · randomised multicentre double-blind placebo-controlled parallel-group trial, 80 healthy middle-aged adults, placebo or 300/600/900 mg/day NMN for 60 days
All NMN doses significantly raised blood NAD+ versus placebo and were well tolerated with no safety signals. Six-minute walk distance and SF-36 scores improved versus placebo, with the largest effects at 600 mg/day; HOMA-IR did not differ significantly.
- 12Human clinical2021
Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women
Yoshino M, et al. · Science · randomised double-blind placebo-controlled trial, 25 postmenopausal women with prediabetes and overweight/obesity, 250 mg/day NMN for 10 weeks, hyperinsulinaemic-euglycaemic clamp
NMN increased muscle insulin sensitivity and insulin-signalling gene expression relative to placebo. Body composition, hepatic and whole-body insulin sensitivity, blood pressure and lipids were not significantly changed.
- 13Human clinical2016
Nicotinamide riboside is uniquely and orally bioavailable in mice and humans
Trammell SA, et al. · Nature Communications · quantitative NAD+ metabolomics in mice plus first-in-human single oral doses of nicotinamide riboside in healthy adults
Oral nicotinamide riboside raised blood NAD+ in humans in a dose-dependent manner and did so more effectively than equivalent molar doses of nicotinamide or nicotinic acid. The work established the analytical basis for measuring the NAD+ metabolome.
- 14Animal in vivo2016
NAD⁺ repletion improves mitochondrial and stem cell function and enhances life span in mice
Zhang H, et al. · Science · aged mice supplemented with nicotinamide riboside; muscle, neural and melanocyte stem cell assays
Nicotinamide riboside supplementation restored mitochondrial function in muscle stem cells of aged mice and modestly extended murine lifespan. These outcomes were observed in mice only and have not been reproduced in humans.
- 15Review2021
NAD⁺ metabolism and its roles in cellular processes during ageing
Covarrubias AJ, et al. · Nature Reviews Molecular Cell Biology · narrative review of NAD+ biosynthesis, consumption and age-related decline
The review summarised evidence that NAD+ availability falls with age across tissues and that sirtuins, PARPs and CD38 compete for the same NAD+ pool. It framed NAD+ decline as a contributor to mitochondrial dysfunction and inflammation in ageing models.
What this evidence does not establish.
Human trials reliably show that oral NR and NMN raise circulating NAD+ and are well tolerated for up to about six months, but no trial has demonstrated that this translates into durable improvements in muscle mass, cognition, glycaemic control or blood pressure, and meta-analyses of these endpoints are null. Lifespan extension, stem-cell rejuvenation and tissue NAD+ restoration remain rodent findings; no human data address long-term safety beyond six months, optimal dosing, or whether individuals with low baseline NAD+ respond differently.
Common questions about the research.
- What is NAD+?
NAD+ (nicotinamide adenine dinucleotide) is a coenzyme found in all living cells. It carries electrons in central energy metabolism and acts as the consumed co-substrate for the sirtuin, PARP, and CD38 enzyme families studied in ageing and metabolic research.
- How does direct NAD+ differ from precursors such as NR or NMN?
Nicotinamide riboside and nicotinamide mononucleotide are precursors that enter the salvage pathway and are converted to NAD+ inside the cell, whereas NAD+ itself is the intact dinucleotide. The cited reviews discuss the bioavailability trade-offs between the two strategies, including evidence that circulating NAD+ is extensively metabolised before uptake.
- Why has most human research used NAD+ precursors rather than NAD+ itself?
NAD+ itself is poorly absorbed orally, so published human work has overwhelmingly used the precursors nicotinamide riboside and nicotinamide mononucleotide. Randomised trials consistently report that these raise circulating NAD+ two- to threefold and are well tolerated over weeks to months. Functional endpoints have been far less consistent: individual trials reported improvements in walking distance, insulin sensitivity and sleep quality, while meta-analyses of muscle, glucose and lipid outcomes were null.
Available from our catalog
For research purposes only. Not for human consumption, diagnosis, treatment, or prevention of any condition. Nothing on this page is medical advice, and no study summarised here should be read as a recommendation.