Research index

Neutral one-line summaries with a link to each primary source. Null and negative findings are listed alongside positive ones.

Nicotinamide riboside is uniquely and orally bioavailable in mice and humans — The paper that opened the human precursor literature, and a study of NR rather than of NAD+. The authors report that single oral doses of 100, 300 and 1,000 mg of NR produced dose-dependent increases in the blood NAD+ metabolome in what they describe as the first clinical trial of NR pharmacokinetics in humans, and that nicotinic acid adenine dinucleotide (NAAD) is formed from NR and is a sensitive biomarker of NAD+ repletion. The pilot human observation of a 2.7-fold rise was in one individual. ChromaDex supplied the NR and sponsored the clinical study. source
Quantitative Analysis of NAD Synthesis-Breakdown Fluxes — The mechanism paper that matters most for reading everything else here, and it is isotope-tracer work in cells and mice rather than a clinical study. The authors report that in cell lines NAD was made from nicotinamide and consumed largely by PARPs and sirtuins; that in vivo NAD was made from tryptophan selectively in the liver, which then excreted nicotinamide; that NAD fluxes varied widely across tissues; and — the finding this file leans on — that intravenous NR or NMN delivered intact molecules to multiple tissues while the same agents given orally were metabolised to nicotinamide in the liver. source
A Pilot Study Investigating Changes in the Human Plasma and Urine NAD+ Metabolome During a 6 Hour Intravenous Infusion of NAD — The only located human study of NAD+ administered directly rather than as a precursor. During and after a 6 h 3 micromol/min intravenous infusion, the authors report that no change in plasma NAD+ or its metabolites was observed until after 2 h, that NAD+ was rapidly and completely removed from plasma over that period, that the metabolite profile was consistent with NAD+ glycohydrolase and pyrophosphatase activity, and that urinary excretion products included NAD+ and methylnicotinamide but not nicotinamide. Two of the authors are affiliated with an NAD+ research company and a wellness centre. It measures metabolite fate, nothing else. source
Intravenous infusion of nicotinamide adenine dinucleotide (NAD+) versus nicotinamide riboside (NR): a retrospective tolerability pilot study in a real-world setting — A retrospective electronic-record review from a commercial wellness provider, comparing four consecutive days of 500 mg NAD+ or NR intravenously with 30 days of follow-up. The authors report that participants receiving NAD+ described moderate to severe gastrointestinal symptoms, increased heart rate and chest pressure during infusions while the NR group described minor tingling and mild cramping, that all symptoms resolved on completion, and that infusion times averaged 97 min for NAD+ against 37 min for NR. No significant changes were seen in ALT, AST, hsCRP, BUN/creatinine or TSH. Seven authors were employed by the company whose clients were reviewed. source
A randomized placebo-controlled clinical trial of nicotinamide riboside in obese men: safety, insulin-sensitivity, and lipid-mobilizing effects — A null result, recorded because this literature seldom foregrounds them. Forty sedentary men with a BMI above 30 were randomised to NR or placebo for 12 weeks. The authors report that insulin sensitivity, endogenous glucose production, glucose disposal and oxidation were not improved, that there was no effect on resting energy expenditure, lipolysis, lipid oxidation or body composition, and that the supplementation appeared safe with normal safety blood tests. A study of NR, not of NAD+. source
Nicotinamide riboside supplementation alters body composition and skeletal muscle acetylcarnitine concentrations in healthy obese humans — A crossover trial in 13 healthy overweight or obese men and women over 6 weeks. The authors report that markers of NAD+ synthesis rose in skeletal muscle and that acetylcarnitine concentrations and fat-free mass changed, but that "no effects of NR were found on insulin sensitivity, mitochondrial function, hepatic and intramyocellular lipid accumulation, cardiac energy status, cardiac ejection fraction, ambulatory blood pressure, plasma markers of inflammation, or energy metabolism". A study of NR, not of NAD+. source
Safety and Metabolism of Long-term Administration of NIAGEN (Nicotinamide Riboside Chloride) in a Randomized, Double-Blind, Placebo-controlled Clinical Trial of Healthy Overweight Adults — An 8-week dose-ranging safety and kinetics study of NR in overweight but otherwise healthy adults. The authors report that 100, 300 and 1000 mg NR dose-dependently increased whole blood NAD+ by 22%, 51% and 142% within 2 weeks and that the increases were maintained, with no reports of flushing and no significant difference in adverse events against placebo. Two authors are ChromaDex employees, a third is the inventor of intellectual property licensed by ChromaDex, and ChromaDex funded the study. source
Nicotinamide Riboside Augments the Aged Human Skeletal Muscle NAD+ Metabolome and Induces Transcriptomic and Anti-inflammatory Signatures — A placebo-controlled crossover trial in 12 aged men given 1 gram of NR for 21 days. The authors report that targeted metabolomics showed NR elevated the muscle NAD+ metabolome, that muscle RNA sequencing showed downregulation of energy metabolism and mitochondria pathways "without altering mitochondrial bioenergetics", and that circulating inflammatory cytokines were depressed. Twelve participants, one site, and a study of NR. source
Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults — A crossover trial in healthy middle-aged and older adults across two 6-week periods. The authors report that chronic NR supplementation was well tolerated and stimulated NAD+ metabolism, and frame their physiological findings prospectively — that "future clinical trials should further assess" the possibilities they raise, which is a statement about what has not been shown yet. A study of NR. source
Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women — The most-cited NMN trial: a 10-week randomised placebo-controlled double-blind study in postmenopausal women with prediabetes who were overweight or obese (NCT03151239). The authors report that insulin-stimulated glucose disposal measured by hyperinsulinaemic-euglycaemic clamp and skeletal muscle insulin signalling increased after NMN and did not change after placebo. PubMed records four published comments on this paper, including one in Science itself, which is a signal that the result was contested. A study of NMN, not of NAD+. source
Effect of oral administration of nicotinamide mononucleotide on clinical parameters and nicotinamide metabolite levels in healthy Japanese men — A single-arm, non-randomised safety study of single oral NMN doses of 100, 250 and 500 mg in 10 healthy men, followed for 5 h after each administration. The authors report no significant clinical symptoms or changes in heart rate, blood pressure, oxygen saturation or body temperature, no significant laboratory changes outside normal ranges, and dose-dependent increases in two nicotinamide metabolites. Ten men, one dose each, five hours of observation — the safety claim it supports is correspondingly narrow. source
NAD+ metabolism and its roles in cellular processes during ageing — A narrative review, used here only for its descriptive biochemistry: NAD+ as a coenzyme for redox reactions and an essential cofactor for sirtuins, CD38 and poly(ADP-ribose) polymerases, influencing metabolic pathways, DNA repair, chromatin remodelling, cellular senescence and immune cell function. The review's own closing position is that "much remains to be learnt about how NAD+ influences human health and ageing biology", including "how to effectively restore NAD+ levels during ageing, whether doing so is safe and whether NAD+ repletion will have beneficial effects in ageing humans". Its forward-looking claims are not carried onto this site. source

What the research does not show

The central limitation is not that the evidence is weak. It is that most of the evidence is about a different molecule. Of the human trials routinely cited for "NAD+" — Trammell 2016, Dollerup 2018, Martens 2018, Conze 2019, Elhassan 2019, Remie 2020, Yoshino 2021 — every one administered nicotinamide riboside or nicotinamide mononucleotide, not NAD+. PubChem records NAD+, NR and NMN as three separate compounds with three different molecular formulas. A finding about a precursor is not a finding about the coenzyme, and this page does not conflate them. source
The naming problem is not hypothetical; it reaches into the trial registry. NCT02942888 is registered under the title "The Effects of NAD on Brain Function and Cognition" with the condition "NAD", and its registered interventions are oral nicotinamide riboside (Niagen) and a placebo compounded by ChromaDex. Anyone citing that study as evidence about NAD+ is citing a study of an oral precursor. Read the intervention field, not the title. source
Route is not a detail here; it changes what reaches tissue. Liu 2018 reports that nicotinamide riboside and nicotinamide mononucleotide given intravenously delivered intact molecules to multiple tissues, while the same agents given orally were metabolised to nicotinamide in the liver. Oral precursor, intravenous precursor and intravenous coenzyme are three different experiments, and results from one do not transfer to another. source
What is actually known about NAD+ given directly to a person is one pilot study. Grant 2019 states that before its own work "no data are currently available on the fate of directly infused NAD+ in a human cohort", and reports that during a 6 h infusion NAD+ was rapidly and completely removed from plasma for at least the first 2 h, with a metabolite profile the authors read as consistent with glycohydrolase and pyrophosphatase activity. That is a bioavailability question raised, not answered — and it is the entire human dataset on the coenzyme's fate by that route. source
The comparative tolerability data that exists is retrospective, small, and produced by the company selling the service. Reyna 2026 reviewed electronic medical records from a commercial wellness setting in which clients received four consecutive days of 500 mg NAD+ or NR intravenously. Participants receiving NAD+ reported moderate to severe gastrointestinal symptoms, increased heart rate and chest pressure during infusions, with infusion times averaging 97 min against 37 min for NR. The authors' own conflict-of-interest statement records that seven of them were employed by the company whose clients were reviewed. A record review is not a controlled trial. source
Null and contradictory results exist in the precursor literature and are rarely cited alongside the positive ones. Dollerup 2018, a randomised placebo-controlled trial in 40 obese, insulin-resistant men over 12 weeks, concluded that NR "does not improve insulin sensitivity and whole-body glucose metabolism in obese, insulin-resistant men", with no effect on resting energy expenditure, lipolysis, lipid oxidation or body composition. Remie 2020, a crossover trial in 13 overweight or obese volunteers, found no effect of NR on insulin sensitivity, mitochondrial function, hepatic or intramyocellular lipid, cardiac energy status, ejection fraction, ambulatory blood pressure, inflammation markers or energy metabolism. Both raised the muscle or blood NAD+ metabolome and neither produced the downstream effect the rodent work predicted. source
Raising a biomarker is not the same as changing an outcome, and the precursor literature separates the two cleanly. Conze 2019 reported that NR dose-dependently raised whole blood NAD+ by 22%, 51% and 142% across its three doses within 2 weeks. Elhassan 2019 reported that oral NR elevated the muscle NAD+ metabolome in 12 aged men without altering muscle mitochondrial bioenergetics. The biomarker moved in both; that is what those papers establish. source
A large part of this literature is funded by, or authored by people with an interest in, the products it studies. Trammell 2016 discloses that three authors own stock in ChromaDex, the supplier of the NR and the sponsor of the clinical study, and that one author is chief scientific adviser to a company selling NR supplements. Conze 2019 discloses that two authors are ChromaDex employees, that a third is the inventor of intellectual property licensed by ChromaDex, and that ChromaDex funded the study. This is normal for a commercial ingredient and is not an accusation; it does mean the most-cited results are not independent replications. source
There is no established storage condition, in-use period or shelf life, and FDA identified stability as the specific problem. FDA's 2019 evaluation states that NAD "degrades substantially when exposed to light, moisture, alkaline pH, or standard room temperatures and would not be stable under ordinary storage conditions absent multiple compensatory measures". No pharmacopoeial monograph and no approved product label exists for this substance, so nobody with the standing to determine handling conditions has done so. source
FDA's own assessment of the evidence, on the record, was that there was not enough of it to judge. Evaluating NAD as a bulk drug substance, FDA wrote that nonclinical data in the literature "are inadequate to characterize the potential toxicity profile for NAD" and that it "did not find sufficient clinical data about NAD to evaluate whether it is safe for use in compounded drug products". Its advisory committee voted not to add the substance to the 503A Bulks List on May 8, 2017. That assessment is about the coenzyme itself, not about any precursor. source
Product quality, not pharmacology, is where the documented harm in this category sits. FDA states it is aware of compounders using food-grade NAD+ to make intravenous products and that food-grade ingredients are not suitable for compounding sterile drugs, and reports adverse event reports following use of NAD+ injectable drugs including severe chills, shaking, vomiting and fatigue, some requiring medical attention, which it describes as consistent with excessive endotoxin levels. A 2026 warning letter records a compounded NAD+ product testing at 3,360 EU/mL of bacterial endotoxins and three patients developing symptoms after administration from the same vial. source
The trial registry overstates how much of this work is about the coenzyme. A ClinicalTrials.gov intervention query for "nicotinamide adenine dinucleotide" returns 264 studies, of which only 14 name NAD or nicotinamide adenine dinucleotide in an intervention at all — and one of those 14 is a resuscitation study using NAD as an unrelated acronym. Counting registry hits by compound name measures naming conventions, not evidence. source
The regulatory position of the precursors is not the regulatory position of the coenzyme, and the precursors do not share one with each other. Nicotinamide riboside chloride has a closed GRAS notice with a no-questions response for specified food uses. NMN's status as a dietary ingredient was determined, reversed on a citizen petition, and rests on a race-to-market argument about pre-2017 marketing rather than on any safety finding. NAD+ itself has neither; FDA has considered it only as a bulk drug substance for compounding and proposed not to list it. Three molecules, three unrelated regulatory tracks. source
Long-term safety is not established for NAD+ administered by any route. No controlled long-term study of the coenzyme given directly to people was located during data entry, in the published literature or in the trial registry, and the two registered studies comparing intravenous NAD+ with intravenous nicotinamide riboside have posted no results.
The anti-doping position is unresolved rather than permissive. No statement from a national or international anti-doping authority naming NAD+, nicotinamide riboside or nicotinamide mononucleotide was retrievable during data entry, and this file does not infer one in either direction.
The published research does not establish a dose, a route, a schedule, a duration or a formulation for any use of this compound in a person, and no source consulted here does either. Nothing on this page should be read as describing how anything is used.
An assigned nonproprietary name is not an approval. This molecule carries an INN, a USAN and a JAN, which places it among a small minority of the compounds in this category, and none of that constitutes a finding by any authority that it is safe or effective for anything.