{"id":"nad-plus","name":"NAD+ and precursors","aliases":["NAD+","NMN","nicotinamide mononucleotide","NR","nicotinamide riboside","NAD injection"],"url":"https://lyoresearch.com/compounds/nad-plus","class":{"id":"longevity-compounds","name":"Mitochondrial, antioxidant and longevity compounds","url":"https://lyoresearch.com/classes/longevity-compounds"},"summary":"NAD+ is a coenzyme every cell uses for energy metabolism; it is not a peptide, but its precursors (NMN and NR) and intravenous NAD+ itself are sold across the same anti-ageing market. Randomised trials show the oral precursors reliably raise NAD+ levels and are well tolerated. What they have not yet shown is a clear clinical benefit — trials of metabolism, muscle and ageing are small, mixed and contested. Intravenous NAD+ has essentially no controlled evidence.","overall_grade":"C","overall_grade_meaning":"weak human evidence","human_trials":"Several RCTs of precursors","regulatory_status":"Sold as supplement (NR/NMN); IV NAD+ unlicensed","molecule":{"formula":"C21H27N7O14P2","molecular_weight":"663.4","cas":"53-84-9","pubchem_cid":5892,"note":"Recorded as nadide, the oxidised coenzyme"},"pharmacokinetics":{"basis":"human","route":"Intravenous infusion (healthy men, 750 mg over 6 hours)","half_life":"No half-life reported; plasma NAD+ did not rise for the first 2 hours of infusion, then rose about four-fold by 6 hours","licensed_regimen":null,"product":null,"source":{"title":"Grant R, et al. A pilot study investigating changes in the human plasma and urine NAD+ metabolome during a 6 hour intravenous infusion of NAD+. Front Aging Neurosci 2019;11:257","url":"https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2019.00257/full"}},"outcomes":[{"outcome":"Raising NAD+ levels","grade":"B","grade_meaning":"probable, not settled","effect_size":"moderate","adverse":false,"human_studies":"Multiple RCTs (NR, NMN)","evidence":"Oral nicotinamide riboside and NMN reliably and safely increase blood NAD+ in randomised trials — the one thing that is well established.","references":[{"citation":"Martens CR, et al. Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults.","where":"Nat Commun, 2018;9:1286","url":"https://pubmed.ncbi.nlm.nih.gov/29599478/"}],"verbatim":{"text":"chronic supplementation with the NAD+ precursor vitamin, nicotinamide riboside (NR), is well tolerated and effectively stimulates NAD+ metabolism in healthy middle-aged and older adults.","citation":"Martens CR, et al. Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults.","url":"https://pubmed.ncbi.nlm.nih.gov/29599478/"}},{"outcome":"Insulin sensitivity / metabolic health","grade":"C","grade_meaning":"weak human evidence","effect_size":"small","adverse":false,"human_studies":"1 small RCT (n=25), contested","evidence":"A 10-week NMN trial in prediabetic postmenopausal women improved muscle insulin sensitivity — a single small study whose interpretation was publicly disputed and which has not been replicated.","references":[{"citation":"Yoshino M, et al. Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women.","where":"Science, 2021;372:1224–1229","url":"https://pubmed.ncbi.nlm.nih.gov/33888596/"}],"verbatim":{"text":"These results demonstrate that NMN increases muscle insulin sensitivity, insulin signaling, and remodeling in women with prediabetes who are overweight or obese.","citation":"Yoshino M, et al. Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women.","url":"https://pubmed.ncbi.nlm.nih.gov/33888596/"}},{"outcome":"Anti-ageing / physical function","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"No outcome trials","evidence":"Despite the marketing, no trial has shown NAD+ or its precursors slow ageing or improve hard clinical outcomes in people. Some trials found no effect on muscle mitochondrial function.","references":[{"citation":"Dollerup OL, et al. Nicotinamide riboside does not alter mitochondrial respiration, content or morphology in skeletal muscle from obese and insulin-resistant men.","where":"J Physiol, 2020;598:731–754","url":"https://pubmed.ncbi.nlm.nih.gov/31710095/"}]},{"outcome":"Safety (oral precursors)","grade":"B","grade_meaning":"probable, not settled","effect_size":"small","adverse":true,"human_studies":"Multiple RCTs","evidence":"Oral NR and NMN are well tolerated in trials up to several months. Intravenous NAD+ is a different matter — unstudied in controlled trials and associated with infusion reactions.","references":[{"citation":"Martens CR, et al. Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults.","where":"Nat Commun, 2018;9:1286","url":"https://pubmed.ncbi.nlm.nih.gov/29599478/"}]}],"regions":[{"region":"European Union","status":"Mixed; NMN restricted","note":"NR is an authorised novel food; NMN's food status is unsettled in the EU. Intravenous NAD+ for 'wellness' is an unlicensed medical use."},{"region":"United States","status":"Supplement status contested","note":"NR is sold as a dietary supplement. The FDA has taken the position that NMN is excluded from the supplement definition because it was investigated as a drug; enforcement is unsettled. IV NAD+ is offered by clinics without FDA approval."},{"region":"United Kingdom","status":"Supplement / unlicensed","note":"Oral precursors are sold as supplements; IV NAD+ is an unlicensed medical service."},{"region":"Australia","status":"Supplement / clinic use","note":"Oral products sold as complementary medicines; IV NAD+ offered by some clinics outside standard registration."},{"region":"Canada","status":"Natural health product / clinic use","note":"Some oral products carry NPN numbers; IV NAD+ is a clinic service, not an approved therapy."},{"region":"Sport (WADA)","status":"Not prohibited","note":"NAD+ and its precursors are not on the 2026 Prohibited List."}],"faq":[{"q":"Do NAD+ supplements work?","a":"They reliably raise NAD+ levels and are well tolerated. Whether that produces any health benefit is unproven — the outcome trials so far are small, mixed and, in the most-cited case, contested."},{"q":"Is NMN or NR better?","a":"No head-to-head trial answers that. Both raise NAD+; neither has shown a clear clinical benefit in a large trial."},{"q":"What about NAD+ IV drips?","a":"Intravenous NAD+ has essentially no controlled-trial evidence. The randomised data are for the oral precursors, not the drips."}],"references":[{"cite":"Martens CR, et al. Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults.","where":"Nat Commun, 2018;9:1286","url":"https://pubmed.ncbi.nlm.nih.gov/29599478/","note":"24 adults, crossover; NR raises NAD+, well tolerated."},{"cite":"Yoshino M, et al. Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women.","where":"Science, 2021;372:1224–1229","url":"https://pubmed.ncbi.nlm.nih.gov/33888596/","note":"25 women, 10 weeks; single, contested trial."},{"cite":"Dollerup OL, et al. Nicotinamide riboside does not alter mitochondrial respiration, content or morphology in skeletal muscle from obese and insulin-resistant men.","where":"J Physiol, 2020;598:731–754","url":"https://pubmed.ncbi.nlm.nih.gov/31710095/","note":"A representative null metabolic result."}],"last_reviewed":"2026-09-03","literature_searched_to":"2026-09-03","changelog":[{"date":"2026-09-03","note":"Initial publication. Grade B for raising NAD+, C/D for clinical outcomes."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"}