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Nicotinamide riboside

Also known as NR, Niagen, nicotinamide riboside chloride, NR chloride

Not a peptide but a vitamin B3 form: an oral NAD+ precursor, well studied, with modest clinical results.

early-clinical Immune & longevity supplement

At a glance

Category
Immune & longevity
Status
supplement
Route
oral (capsules and tablets)
Half-life
Short in plasma. NR is cleared rapidly and largely converted to nicotinamide, so plasma NR is a poor proxy for the effect; trials measure the NAD+ metabolome in whole blood or in muscle biopsies instead 3
Onset
Blood NAD+ rises within days of daily dosing and stays elevated for the duration of supplementation 2
Molecular weight
255.25 g/mol for the cation (C11H15N2O5+); the material sold is the chloride salt, which is heavier 9

Nicotinamide riboside is not a peptide. It is a pyridinium nucleoside, a form of vitamin B3, included here because it is sold alongside peptides and searched for beside them. It is sold as a food supplement, most prominently as Niagen, and its regulatory position in the United States is more settled than NMN's. In August 2016 the FDA responded to GRAS Notice 635, filed by ChromaDex, stating that it had no questions regarding the company's conclusion that nicotinamide riboside chloride is generally recognised as safe as a source of vitamin B3 in specified foods at a maximum level of 0.0057 per cent by weight - while noting explicitly that the agency had not made its own determination of GRAS status 7. Nicotinamide riboside chloride is also the subject of accepted new dietary ingredient notifications 8. It is not approved as a medicine for any indication anywhere.

Doping status: Not listed by WADA. An intravenous infusion of more than 100 ml per 12 hours would fall under the ban on intravenous infusions (M2.2), but oral NR is not prohibited

Checked against the WADA 2026 Prohibited List. For a specific product and country, Global DRO is the lookup athletes are expected to use — the List names substances, not brand names.

Mechanism of action

NAD+ is the cell's central redox coenzyme and the substrate consumed by sirtuins, PARPs and CD38. Nicotinamide riboside is a salvage-pathway precursor: nicotinamide riboside kinases phosphorylate it to nicotinamide mononucleotide inside the cell, and NMN adenylyltransferases convert that to NAD+. Unlike NMN, NR is uncharged and crosses membranes without needing to be dephosphorylated first, which is the pharmacological argument usually made in its favour.

In practice the distinction is smaller than the marketing suggests. Oral NMN is dephosphorylated to NR in the gut before absorption in most accounts, so 'NMN versus NR' is to a large extent a question about what happens in the intestinal lumen rather than about two different mechanisms. Both raise blood NAD+; a substantial part of an oral dose of either is degraded to plain nicotinamide by gut microbes and liver before it reaches peripheral tissue. There is no head-to-head randomised trial in humans that establishes one as superior on a clinical endpoint, and readers looking for one should be aware that the comparison is usually made with reference to mechanism rather than outcome. See also the NMN and NAD+ entries in this reference.

One consequence of the salvage route deserves stating. A large NAD+ precursor dose ultimately increases the flux of nicotinamide through nicotinamide N-methyltransferase, which consumes methyl groups from S-adenosylmethionine. Whether that methylation burden matters at supplement doses over years has not been established either way.

What the research shows

NR is one of the better-studied supplements in this reference: over a hundred registered studies and a substantial randomised literature 10. The result is consistent and modest. NR reliably and dose-dependently raises the NAD+ metabolome in blood and in skeletal muscle, and it is well tolerated at doses up to 2 g per day for 12 weeks 123. Clinical endpoints have largely not moved. The most rigorous metabolic trial - a hyperinsulinaemic-euglycaemic clamp study in obese insulin-resistant men - was flatly negative 1, and pooled analysis finds no benefit for muscle mass or function in older adults 5. Where NR looks most interesting is in specific disease settings such as Parkinson's disease, where it has reached the brain and altered cerebral metabolism in a phase I trial 4 - which is a mechanistic result, not a clinical one.

Research in humans

Martens and colleagues (2018) ran a 2 x 6-week randomised, double-blind, placebo-controlled crossover trial in healthy middle-aged and older adults and reported that chronic NR was well tolerated and effectively stimulated NAD+ metabolism; the authors framed effects on blood pressure and arterial stiffness as a signal warranting future trials rather than as a demonstrated benefit 2. Dollerup and colleagues (2018) is the most important negative result: forty obese, insulin-resistant men randomised to 1000 mg NR twice daily or placebo for 12 weeks, with insulin sensitivity measured by hyperinsulinaemic-euglycaemic clamp and body composition by DXA and MRI. Insulin sensitivity, endogenous glucose production, glucose disposal and oxidation were not improved; resting energy expenditure, lipolysis, lipid oxidation and body composition were unchanged; and no serious adverse events occurred 1. Elhassan and colleagues (2019) gave 12 aged men 1 g NR daily for 21 days in a placebo-controlled crossover trial with muscle biopsies, and found the muscle NAD+ metabolome elevated and circulating inflammatory cytokines depressed - but muscle mitochondrial bioenergetics unaltered, and the muscle transcriptome showing downregulation rather than upregulation of energy metabolism and mitochondrial pathways 3. The NADPARK study (2022) gave 30 newly diagnosed, treatment-naive Parkinson's patients 1000 mg NR or placebo for 30 days: NR was well tolerated and produced a significant but variable increase in cerebral NAD levels measured by 31P magnetic resonance spectroscopy, with altered cerebral metabolism in those whose brain NAD rose 4. Prokopidis and colleagues (2025) pooled NR and NMN trials in adults with a mean age over 60: NR was associated with a longer six-minute walking distance in peripheral artery disease, but with lower SPPB scores and slower chair-stand times in people with mild cognitive impairment, and the review concluded that current evidence does not support either precursor for preserving muscle mass and function 5.

Animal and lab research

In rodents, NR improves metabolic parameters, muscle regeneration and mitochondrial function in models of obesity, ageing and mitochondrial disease. These findings are consistent and are the reason for the human programme. The pattern by which they have not carried across to humans - biochemistry replicates, physiology does not - is the same one seen with NMN.

Caveats. Trials are small and short: the largest cited here has forty participants and the longest runs twelve weeks. Most are in healthy or mildly impaired adults, where there is limited room to improve. A great deal of the literature involves the commercial sponsor of Niagen, either through funding or through co-authorship by investigators associated with the ingredient, and this should be weighed when reading positive secondary outcomes. The primary endpoint in most trials is the NAD+ metabolome, which is a surrogate marker; Elhassan's biopsy study is instructive precisely because it showed the surrogate moving while the mitochondrial function it was supposed to predict did not 3. Finally, the Prokopidis pooled analysis found NR associated with worse physical performance in one subgroup 5, which is a reminder that a null literature is not the same as a uniformly reassuring one.

What it is used for

  • Sold as an oral anti-ageing and 'cellular energy' supplement, on the strength of the NAD+ mechanism rather than clinical outcomes 5
  • Raising the NAD+ metabolome in blood and skeletal muscle - the effect that is reliably reproduced 23
  • As a source of vitamin B3, which is the use for which its GRAS notification was filed 7
  • Studied for insulin sensitivity in obesity, where a clamp-based randomised trial found no benefit 1
  • Studied in Parkinson's disease, where a phase I trial showed it reaches the brain and raises cerebral NAD 4
  • Marketed in direct competition with NMN; there is no randomised head-to-head trial establishing either as clinically superior

Dosing

Dose
250-1000 mg per day in most trials; 2000 mg per day has been used and found safe over 12 weeks
Frequency
once or twice daily
Route
oral
Duration
Published trials run 21 days to 12 weeks; nothing longer has been reported
  • 1000 mg daily is the dose used in the muscle-biopsy trial, which ran 21 days 3, and in the Parkinson's phase I trial, which ran 30 days 4. 2000 mg daily for 12 weeks was safe but produced no metabolic benefit in obese insulin-resistant men 1; 12 weeks is the longest published randomised exposure.
  • There is no established dose-response for a clinical outcome, because no clinical outcome has consistently responded. Higher doses raise the NAD+ metabolome further; they have not been shown to raise anything a person would notice.
  • These figures describe what has been administered in published trials. They are not a recommendation.
  • Labels usually state nicotinamide riboside chloride. The chloride salt is heavier than the NR cation 9, so a milligram figure on a label is not directly comparable with a milligram figure for NMN.
  • For anyone weighing NR against NMN, the honest position is that the two have never been compared head to head on a clinical endpoint in a randomised trial. NR has the clearer regulatory position in the US 7 and the more complete published safety record; that is not the same as being more effective.
  • A consumer and IV-clinic pattern circulates alongside the trial doses and is set out as a circulating protocol below. The trials ran 21 days to 12 weeks 13; consumers take similar or larger amounts indefinitely, and some clinics give NR intravenously outside the oral evidence base 6. It is recorded because readers encounter it, not because it is validated.

These figures describe what the literature and published protocols report. They are not advice and not a dosing instruction.

Protocols

NR in obese, insulin-resistant men (negative clamp trial)

published trial

Source: American Journal of Clinical Nutrition, 2018 - Dollerup et al.; randomised, double-blind, placebo-controlled, parallel group, 40 participants

12 weeks1000 mg nicotinamide riboside twice daily (2000 mg per day), against placebo

The schedule is reproduced because the trial is the strongest test of the metabolic claim and it failed it. Insulin sensitivity by clamp, endogenous glucose production, glucose disposal and oxidation, resting energy expenditure, lipolysis and body composition were all unchanged. Safety bloods were normal and no serious adverse events were attributed to NR.

NR in newly diagnosed Parkinson's disease (NADPARK phase I)

published trial

Source: Cell Metabolism, 2022 - Brakedal et al.; double-blinded phase I, 30 treatment-naive patients

30 days1000 mg nicotinamide riboside daily, against placebo

A phase I safety and target-engagement study, not an efficacy trial. It established that oral NR raises cerebral NAD as measured by 31P magnetic resonance spectroscopy, though the increase was variable between individuals. It does not show that NR changes the course of Parkinson's disease.

Consumer anti-ageing use and IV clinics (circulating)

user protocol — not validated

Source: Supplement retailer labelling, longevity forums and IV-clinic menus

This is not a validated schedule. It is a pattern that circulates among users and sellers, reproduced because it is what people actually follow — not because it has been tested. No trial established these doses, this interval or this duration, and nobody is checking what is in the vial. Treat every number below as an assertion, not a finding.

Common consumer useroughly 300-1000 mg per day taken daily and indefinitely for 'cellular energy' and anti-ageing — the amounts overlap the trials, but the open-ended duration does not
At the higher endmegadosing toward 1-2 g per day, and stacking with trimethylglycine, resveratrol or pterostilbene on mechanistic reasoning
Injected routeintravenous NR given by some private clinics, outside any approval and outside the oral evidence base

The trial schedules above ran 21 days to 12 weeks with the NAD+ metabolome as the endpoint 134; the circulating use takes similar or larger daily amounts for years, for anti-ageing benefits the trials did not demonstrate. The honest divergence is duration and expectation, not usually dose: consumer amounts often sit inside the studied range, but nothing longer than twelve weeks has been studied and the clinical endpoints that were measured largely did not move 15, so indefinite use rests on a rising surrogate marker rather than a shown benefit. Megadosing raises the NAD+ metabolome further without evidence it raises anything a person would notice, and increases nicotinamide flux through nicotinamide N-methyltransferase, a methylation burden of unknown long-term consequence. Intravenous NR sold by clinics has no oral-trial support behind it; a retrospective real-world series describes only its tolerability 6. Product content is a real variable, since independent testing of NAD+ precursor products has repeatedly found label amounts inaccurate. These patterns are recorded because they circulate, not because they are validated.

Schedules are reproduced as their source states them. Units, IU and milligrams explains why the figures are not interchangeable between products.

Reconstitution

Storage
Store cool, dry and sealed; nicotinamide riboside chloride degrades with moisture and heat

Sold as capsules or tablets. Nothing to reconstitute.

Safety

Side effects

  • Well tolerated in every randomised trial cited here, including at 2000 mg per day for 12 weeks, with safety blood tests normal and no serious adverse events attributed to the supplement 1
  • Mild gastrointestinal upset, nausea and loose stools, mostly at higher doses
  • Headache and fatigue have been reported at rates similar to placebo
  • Flushing is not characteristic of NR, unlike nicotinic acid
  • In one pooled analysis, NR was associated with lower SPPB scores and slower five-time chair stand times in participants with mild cognitive impairment 5 - a single subgroup finding in a small literature, but it belongs in this list rather than in a footnote
  • Nothing is known about safety beyond twelve weeks, which is the longest published randomised exposure
  • NR is also given intravenously by some private clinics, outside any approval and outside the oral evidence base described here; a retrospective real-world comparison of intravenous NAD+ against intravenous NR describes the tolerability of that practice 6

Do not use if

  • Pregnancy and breastfeeding: no data
  • Active malignancy: NAD+ supports DNA repair and cell proliferation, and the effect on tumour growth in humans has not been studied - a theoretical concern that recurs across this whole class and has not been resolved
  • Children and adolescents: no data
  • Not a treatment for insulin resistance or type 2 diabetes - the best-designed trial of exactly that question was negative 1

Interactions

Not systematically studied. Interaction with chemotherapy that depends on DNA damage is theoretically relevant because NAD+ is the substrate for PARP-mediated repair, and has not been investigated in people. Because NR ultimately increases nicotinamide flux through nicotinamide N-methyltransferase, an interaction with methyl-group availability is plausible and unquantified. No clinically significant drug interaction has been documented, which reflects the absence of studies rather than the absence of interactions.

Sources