Nicotinamide riboside

updated

What is Nicotinamide riboside?

Nicotinamide riboside (NR) is a small molecule sold as NR chloride, a food and supplement ingredient. FDA has no questions about a notifier's GRAS conclusion for conventional foods, EFSA found NR chloride safe at up to 300 mg/day in healthy adults, and no FDA-approved NR drug or label was found on 10 October 2026.

Nicotinamide riboside (NR) reliably raises blood NAD+ in people: whole-blood NAD+ rose 22%, 51% and 142% at 100, 300 and 1000 mg per day in an 8-week trial of 140 overweight adults. Regulators raised no safety objection for their defined uses, but the outcome trials are small and mostly null for healthy aging, and the 410-patient NOPARK trial in Parkinson disease favored placebo. NR is a food and supplement ingredient, not an approved drug, and its reduced form NRH has no human trial.

Vitamin B3 form sold to raise NAD+

  • PubChem lists the NR cation as CID 439924, C11H15N2O5+, 255.25 g/mol, CAS 1341-23-7. The chloride salt behind the commercial ingredient is CID 90480033, C11H15ClN2O5, 290.70 g/mol, CAS 23111-00-4.
  • The FDA letter for GRAS Notice GRN 000635, dated 3 August 2016, says FDA has no questions about the notifier's conclusion for NR chloride as a source of vitamin B3 in conventional foods. It is not a drug approval, and FDA made no GRAS determination of its own.
  • EFSA concluded in 2019 that NR chloride is safe at up to 300 mg/day for healthy adults excluding pregnant and lactating women, and Commission Implementing Regulation (EU) 2020/16 of 10 January 2020 authorized it as a novel food. This is a safety finding, not evidence of benefit.
  • In an 8-week randomized trial of 140 overweight adults, NR chloride at 100, 300 and 1000 mg per day raised whole-blood NAD+ by 22%, 51% and 142%. The trial was funded by ChromaDex and measured NAD+ chemistry and safety, not health outcomes.
  • In NOPARK (410 randomized, 393 analyzed), 500 mg NR twice daily for 52 weeks in early Parkinson disease gave an adjusted total MDS-UPDRS difference of 2.72 points favoring placebo (95% CI 0.47 to 4.98, P = .02).
  • A meta-analysis of randomized NR and NMN trials in participants with mean ages of 60.9 to 83 years concluded that current evidence does not support either for preserving muscle mass and function in adults over 60.

What is nicotinamide riboside, and is it approved?

Nicotinamide riboside (NR) is a small molecule sold as NR chloride, a food and supplement ingredient. FDA has no questions about a notifier's GRAS conclusion for conventional foods, EFSA found NR chloride safe at up to 300 mg/day in healthy adults, and no FDA-approved NR drug or label was found on 10 October 2026.

The NR cation is PubChem CID 439924, C11H15N2O5+, 255.25 g/mol, CAS 1341-23-7, with Niagen and TruNiagen among the listed synonyms. Nicotinamide riboside chloride, the salt behind the commercial ingredient, is CID 90480033, C11H15ClN2O5, 290.70 g/mol, CAS 23111-00-4. EFSA states its 300 mg/day figure as NR chloride, and a 2018 crossover trial gives its 500 mg dose as NR chloride (NIAGEN). Several trial abstracts write NR without naming the salt, so this page says NR chloride only where the source does. Some trials tested NR together with pterostilbene, which is a different product.

The FDA letter for GRAS Notice GRN 000635, dated 3 August 2016, concerns nicotinamide riboside chloride as a source of vitamin B3 in vitamin waters, protein shakes, nutrition bars, gum, chews and powdered beverages at a maximum of 0.0057% by weight as consumed. FDA says it has no questions at this time about the notifier's (ChromaDex's) GRAS conclusion and that it has not made its own GRAS determination. This is a conventional-food ingredient notice, not a drug approval and not an efficacy finding. On 10 October 2026, an openFDA Drugs@FDA query for nicotinamide riboside returned no match, and DailyMed drug-name searches for nicotinamide riboside, nicotinamide riboside chloride and niagen returned no labels, so no FDA-approved NR drug or drug label was found.

The EFSA NDA Panel opinion (EFSA Journal 2019) evaluated NR chloride for food supplements for healthy adults at up to 300 mg/day. It found that the production process, composition and specifications raised no safety concerns, found no genotoxicity concern, and concluded the novel food is safe at up to 300 mg/day for healthy adults excluding pregnant and lactating women, and that up to 230 mg/day is safe for pregnant and lactating women. It derived a NOAEL of 300 mg/kg body weight per day from rat and dog studies, and judged human studies of 100 mg for 1 day up to 2,000 mg/day for up to 12 weeks to raise no safety concerns. Commission Implementing Regulation (EU) 2020/16 of 10 January 2020 then authorized NR chloride as a novel food. Its recitals name ChromaDex Inc. as the applicant (request of 10 May 2018) and restrict placing on the market to the applicant for five years. This is a safety finding for a defined salt, dose and population, not evidence of benefit.

PubChem: NR cation and NR chloride identity

Chemical identity record

National Library of Medicine. PubChem compound records CID 439924 (nicotinamide riboside) and CID 90480033 (nicotinamide riboside chloride).

The nicotinamide riboside (NR) cation is PubChem CID 439924, C11H15N2O5+, 255.25 g/mol, CAS 1341-23-7, with Niagen and TruNiagen among the listed synonyms. Nicotinamide riboside chloride, the salt behind the commercial ingredient, is CID 90480033, C11H15ClN2O5, 290.70 g/mol, CAS 23111-00-4. EFSA states its 300 mg/day figure as NR chloride, and the 2018 crossover trial gives its 500 mg dose as NR chloride (NIAGEN).

Participants / model
Chemical identity, not a clinical population
Treatment
Defined cation and chloride salt
Follow-up
Not applicable
Study design
NLM chemical record
Funding
not stated in the source

Several trial abstracts write NR without naming the salt, so the page says NR chloride only where the source does. Some trials tested NR together with pterostilbene, which is a different product.

Read the original source
FDA GRAS letter GRN 000635, 3 August 2016: no questions, conventional foods; no NR drug found

Regulatory record

U.S. Food and Drug Administration. Agency response letter, GRAS Notice No. GRN 000635, dated 3 August 2016. openFDA Drugs@FDA and DailyMed queries run 10 October 2026.

The FDA letter for GRAS Notice GRN 000635 is dated 3 August 2016 and concerns nicotinamide riboside chloride as a source of vitamin B3 in vitamin waters, protein shakes, nutrition bars, gum, chews and powdered beverages at a maximum of 0.0057% by weight as consumed. FDA says it has no questions at this time about the notifier's (ChromaDex's) GRAS conclusion and that it has not made its own GRAS determination. On 2026-10-10 an openFDA Drugs@FDA query for nicotinamide riboside returned no match, and DailyMed drug-name searches for nicotinamide riboside, nicotinamide riboside chloride and niagen returned no labels, so no FDA-approved NR drug or drug label was found.

Participants / model
Not a clinical population
Treatment
Food ingredient notice; no drug application
Follow-up
Letter dated 2016-08-03; searches run on 2026-10-10
Study design
Official FDA record plus dated US approval-record search
Funding
not stated in the source

This is a conventional-food ingredient notice, not a drug approval and not an efficacy finding.

Read the original source
EFSA 2019 opinion and EU 2020/16: NR chloride safe at up to 300 mg/day in healthy adults

Regulatory record

Turck D et al. EFSA J. 2019;17(8):e05775. PMID 32626405.

The EFSA opinion evaluated NR chloride for food supplements for healthy adults at up to 300 mg/day. It found the production process, composition and specifications raised no safety concerns, found no genotoxicity concern, and concluded the novel food is safe at up to 300 mg/day for healthy adults excluding pregnant and lactating women, and that up to 230 mg/day is safe for pregnant and lactating women. It derived a NOAEL of 300 mg/kg body weight per day from rat and dog studies, and judged human studies of 100 mg for 1 day up to 2,000 mg/day for up to 12 weeks to raise no safety concerns. Commission Implementing Regulation (EU) 2020/16 of 10 January 2020 then authorized NR chloride as a novel food. Its recitals name ChromaDex Inc. as the applicant (request of 10 May 2018) and restrict placing on the market to the applicant for five years.

Participants / model
Healthy adults, with a separate limit for pregnant and lactating women; rats and dogs for the toxicology
Treatment
NR chloride in food supplements, up to 300 mg/day
Follow-up
Human studies judged ran up to 12 weeks
Study design
Regulator opinion and legal act
Funding
not stated in the source

This is a safety finding for a defined salt, dose and population, not evidence of benefit. The regulation text was read at the legislation.gov.uk copy.

Read the original source

Is NRH, the reduced form, a stronger version of NR?

NRH is a different molecule, not a stronger NR, and no human trial of it was found. In cells and mice it raised NAD+ more than NR or NMN at equal concentrations, but cell papers report cytotoxicity in liver cancer cells and pro-inflammatory activation of macrophages.

NRH (dihydronicotinamide riboside, reduced nicotinamide riboside) is PubChem CID 11507134, C11H16N2O5, 256.25 g/mol, CAS 19132-12-8. It is a different molecule from NR, with two more hydrogens, and no NR dose or trial result transfers to it.

The NRH literature is cell and mouse work. NRH raised NAD+ more than NR or NMN at equal concentrations in cultured mammalian cells and raised NAD+ in tissues of mice given it by intraperitoneal injection (PMID 30948509). It was orally bioavailable in mice and prevented cisplatin-induced acute kidney injury in mice (PMID 31767171). Two cell papers report downsides: dose-dependent cytotoxicity in HepG3 liver cancer cells at 100 to 1000 uM with none in HEK293T cells (PMID 33166357), and pro-inflammatory activation of macrophages (PMID 35281060).

A PubMed search on 10 October 2026 for dihydronicotinamide riboside, reduced nicotinamide riboside or 1,4-dihydronicotinamide riboside in titles and abstracts returned 50 records. The first 40 by relevance were reviewed by title, and none was a human trial of NRH; most were about the NQO2 enzyme or cell and mouse NAD+ work. The same query limited to randomized controlled trial or clinical trial publication types returned 0 records, and a ClinicalTrials.gov search for dihydronicotinamide riboside returned 0 studies.

NRH: different molecule, cell and mouse work only, no human trial found

Chemical identity record

National Library of Medicine. PubChem compound record CID 11507134 (NRH). Related papers: PMIDs 30948509, 31767171, 33166357 and 35281060. PubMed and ClinicalTrials.gov searches run 10 October 2026.

NRH (dihydronicotinamide riboside, reduced nicotinamide riboside) is PubChem CID 11507134, C11H16N2O5, 256.25 g/mol, CAS 19132-12-8. It is a different molecule from NR (two more hydrogens), and no NR dose or trial result transfers to it. NRH raised NAD+ more than NR or NMN at equal concentrations in cultured mammalian cells and raised NAD+ in tissues of mice given it by intraperitoneal injection (PMID 30948509). It was orally bioavailable in mice and prevented cisplatin-induced acute kidney injury in mice (PMID 31767171). Two cell papers report dose-dependent cytotoxicity in HepG3 liver cancer cells at 100 to 1000 uM with none in HEK293T cells (PMID 33166357), and pro-inflammatory activation of macrophages (PMID 35281060). A PubMed search on 2026-10-10 for dihydronicotinamide riboside, reduced nicotinamide riboside or 1,4-dihydronicotinamide riboside in titles and abstracts returned 50 records; the first 40 by relevance were reviewed by title and none was a human trial of NRH. The same query limited to randomized controlled trial or clinical trial publication types returned 0 records, and a ClinicalTrials.gov search for dihydronicotinamide riboside returned 0 studies.

Participants / model
NRH: cultured mammalian cells and mice. Humans: no trial found
Treatment
Cell exposure and mouse injection or oral dosing
Follow-up
not stated in the source
Study design
Original preclinical studies plus a dated literature and registry search
Funding
not stated in the source

The cell and mouse papers are described from the same source record and are not separate page sources. No human trial of NRH was found.

Read the original source

What did the human trials find?

NR reliably raised blood NAD+ in healthy adults: whole-blood NAD+ rose 22%, 51% and 142% at 100, 300 and 1000 mg per day in an 8-week trial of 140 overweight adults. Outcome trials were small and mostly null: no metabolic benefit in obese men, inconsistent muscle NAD+ results, and a meta-analysis that does not support a muscle benefit over age 60.

In an 8-week randomized, double-blind, placebo-controlled trial of overweight but otherwise healthy men and women (140 enrolled, 35 per group), NR chloride at 100, 300 and 1000 mg per day raised whole-blood NAD+ by 22%, 51% and 142%, with increases seen within 2 weeks and kept through the study. Adverse events did not differ significantly from placebo, there were no reports of flushing, and LDL cholesterol was not raised. ChromaDex funded the study, two authors are ChromaDex employees, and Charles Brenner is the inventor of intellectual property licensed by ChromaDex and its chief scientific adviser. The trial measured NAD+ chemistry and safety, not health outcomes. The paper prints its registry number as NCT0271593, one digit short; the apparent match is NCT02712593 (KGK Science, 140 enrolled), which has no posted results.

In a 2 x 6-week randomized, double-blind, placebo-controlled crossover trial of healthy middle-aged and older adults, 500 mg NR chloride twice daily was well tolerated and raised PBMC NAD+ by about 60% over placebo. Of 60 people consented, 30 were randomized and 24 completed. Reductions in systolic blood pressure and aortic pulse wave velocity were exploratory and did not remain statistically significant after correction for multiple comparisons, and carotid compliance and brachial flow-mediated dilation did not change. The authors call for larger trials. ChromaDex supplied the pills and NR standards and gave partial funding, with NIH grants also listed (NCT02921659).

Muscle NAD+ results are not consistent. In a randomized, double-blind, placebo-controlled crossover trial, 12 aged men took 1 g NR per day for 21 days. The muscle NAD+ metabolome rose (nicotinic acid adenine dinucleotide and nicotinamide clearance products), circulating inflammatory cytokines fell, and muscle energy-metabolism and mitochondrial gene pathways were downregulated without any change in mitochondrial bioenergetics. In a 12-week trial of 40 obese, insulin-resistant men given 1000 mg NR or placebo twice daily, steady-state muscle NAD+ was unchanged, NAMPT protein fell 14%, and muscle mitochondrial respiration and content did not change (PMID 31710095). The metabolic report of a 40-man trial with the same regimen found no improvement in insulin sensitivity, glucose disposal, energy expenditure, lipolysis or body composition (PMID 29992272, NCT02303483). The abstracts do not confirm that the last two papers use the same cohort.

A systematic review and meta-analysis of randomized trials of NR or NMN versus placebo, in participants with mean ages of 60.9 to 83 years, concluded that current evidence does not support NMN or NR for preserving muscle mass and function in adults over 60. NMN showed no significant effect on skeletal muscle index, handgrip strength, gait speed or the 5-time chair stand test. For NR, the abstract reports a longer 6-minute walk distance in people with peripheral artery disease, but lower Short Physical Performance Battery scores and slower chair stands in people with mild cognitive impairment. The pooled estimates mostly concern NMN, so the NR-specific base is small.

8-week trial, 140 overweight adults: whole-blood NAD+ up 22%, 51%, 142%

Randomized controlled trial

Conze D et al. Sci Rep. 2019;9(1):9772. PMID 31278280.

In an 8-week randomized double-blind placebo-controlled trial of overweight but otherwise healthy men and women (140 enrolled, 35 per group), NR chloride at 100, 300 and 1000 mg per day raised whole-blood NAD+ by 22%, 51% and 142%, with increases seen within 2 weeks and kept through the study. Adverse events did not differ significantly from placebo, there were no reports of flushing, and LDL cholesterol was not raised.

Participants / model
Overweight, otherwise healthy men and women
Treatment
Oral NIAGEN (NR chloride) 100, 300 or 1000 mg per day
Follow-up
8 weeks
Study design
Randomized, double-blind, placebo-controlled trial, company-funded
Funding
ChromaDex funded the study; two authors are ChromaDex employees; Charles Brenner is the inventor of intellectual property licensed by ChromaDex and its chief scientific adviser

The trial measured NAD+ chemistry and safety, not health outcomes. The paper prints its registry number as NCT0271593, one digit short; the apparent match is NCT02712593 (KGK Science, 140 enrolled, first posted 2016-03-18), which has no posted results.

Read the original source
Crossover trial, 24 completers: PBMC NAD+ up about 60%, blood pressure result not significant after correction

Randomized controlled trial

Martens CR et al. Nat Commun. 2018;9(1):1286. PMID 29599478.

In a 2 x 6-week randomized double-blind placebo-controlled crossover trial of healthy middle-aged and older adults, 500 mg NR chloride twice daily was well tolerated and raised PBMC NAD+ by about 60% over placebo. Of 60 people consented, 30 were randomized and 24 completed. Reductions in systolic blood pressure and aortic pulse wave velocity were exploratory and did not remain statistically significant after correction for multiple comparisons; carotid compliance and brachial flow-mediated dilation did not change. The authors call for larger trials.

Participants / model
24 completers, healthy adults aged 55 to 79
Treatment
Oral NR chloride (NIAGEN) 500 mg twice daily
Follow-up
2 x 6 weeks
Study design
Randomized, double-blind, placebo-controlled crossover trial, partly company-supported
Funding
ChromaDex supplied the pills and NR standards and gave partial funding; NIH grants are also listed

The figures here come from the full text (Europe PMC); the abstract carries none of them. Registry number NCT02921659.

Read the original source
Muscle NAD+ trials: 12 aged men for 21 days; 40 obese men for 12 weeks

Randomized controlled trial

Elhassan YS et al. Cell Rep. 2019;28(7):1717-1728.e6. PMID 31412242.

In a randomized double-blind placebo-controlled crossover trial, 12 aged men took 1 g NR per day for 21 days. The muscle NAD+ metabolome rose (nicotinic acid adenine dinucleotide and nicotinamide clearance products), circulating inflammatory cytokines fell, and muscle energy-metabolism and mitochondrial gene pathways were downregulated without any change in mitochondrial bioenergetics. In a 12-week trial of 40 obese, insulin-resistant men given 1000 mg NR or placebo twice daily, steady-state muscle NAD+ was unchanged, NAMPT protein fell 14%, and muscle mitochondrial respiration and content did not change (PMID 31710095). The metabolic report of a 40-man trial with the same regimen found no improvement in insulin sensitivity, glucose disposal, energy expenditure, lipolysis or body composition (PMID 29992272, NCT02303483).

Participants / model
12 aged men; 40 obese insulin-resistant men aged 40 to 70
Treatment
Oral NR 1 g per day for 21 days; oral NR 1000 mg twice daily for 12 weeks
Follow-up
21 days; 12 weeks
Study design
Randomized, double-blind, placebo-controlled trials
Funding
not stated in the source

Muscle NAD+ results are not consistent. The abstracts do not confirm that the last two papers use the same cohort, and the two 12-week papers are described from the same source record and are not separate page sources.

Read the original source
Meta-analysis of NMN and NR trials: evidence does not support a muscle benefit over age 60

Systematic review and meta-analysis

Prokopidis K et al. J Cachexia Sarcopenia Muscle. 2025;16(3):e13799. PMID 40275690.

A systematic review and meta-analysis of randomized trials of NR or NMN versus placebo, in participants with mean ages of 60.9 to 83 years, concluded that current evidence does not support NMN or NR for preserving muscle mass and function in adults over 60. NMN showed no significant effect on skeletal muscle index, handgrip strength, gait speed or the 5-time chair stand test. For NR, the abstract reports a longer 6-minute walk distance in people with peripheral artery disease, but lower Short Physical Performance Battery scores and slower chair stands in people with mild cognitive impairment.

Participants / model
Adults with a mean age over 60, pooled across randomized trials, including people with peripheral artery disease or mild cognitive impairment
Treatment
Oral NMN or NR
Follow-up
not stated in the source
Study design
Systematic review and meta-analysis
Funding
not stated in the source

The pooled estimates mostly concern NMN, so the NR-specific base is small.

Read the original source

What did the phase 3 Parkinson disease trial find?

In NOPARK, 500 mg NR twice daily for 52 weeks in 410 patients with early Parkinson disease did not improve outcomes and was associated with worse ones: total MDS-UPDRS rose 2.45 points on NR and fell 0.27 on placebo, an adjusted difference of 2.72 points (P = .02) favoring placebo.

NOPARK, a randomized double-blind placebo-controlled phase 3 trial at 11 centers in Norway, gave 500 mg NR twice daily or placebo for 52 weeks to patients with Parkinson disease diagnosed within 2 years (410 randomized, 393 analyzed). Total MDS-UPDRS rose 2.45 points on NR and fell 0.27 on placebo, an adjusted mean difference of 2.72 points (95% CI 0.47 to 4.98, P = .02) favoring placebo. Nonmotor symptom burden worsened more on NR (adjusted difference 4.22 points, P = .009). Serious adverse events were 17 of 205 (8.3%) on NR and 29 of 205 (14.1%) on placebo. The authors conclude NR did not improve outcomes and was associated with worse outcomes than placebo.

This is a disease population, not healthy aging, but it is the largest NR trial found and a negative one. The record was published online on 8 October 2026 (NCT03568968).

NOPARK: 410 randomized, 52 weeks, total MDS-UPDRS worse on NR by 2.72 points

Randomized controlled trial

Brakedal B et al. JAMA. 2026. PMID 42848371.

NOPARK, a randomized double-blind placebo-controlled phase 3 trial at 11 centers in Norway, gave 500 mg NR twice daily or placebo for 52 weeks to patients with Parkinson disease diagnosed within 2 years (410 randomized, 393 analyzed). Total MDS-UPDRS rose 2.45 points on NR and fell 0.27 on placebo, an adjusted mean difference of 2.72 points (95% CI 0.47 to 4.98, P = .02) favoring placebo. Nonmotor symptom burden worsened more on NR (adjusted difference 4.22 points, P = .009). Serious adverse events were 17 of 205 (8.3%) on NR and 29 of 205 (14.1%) on placebo. The authors conclude NR did not improve outcomes and was associated with worse outcomes than placebo.

Participants / model
393 analyzed adults with early Parkinson disease
Treatment
Oral NR 500 mg twice daily or placebo
Follow-up
52 weeks
Study design
Randomized, double-blind, placebo-controlled phase 3 trial
Funding
not stated in the source

A disease population, not healthy aging, but the largest NR trial found and a negative one. Registry number NCT03568968.

Read the original source

Does nicotinamide riboside raise NAD+ and support healthy aging?

It raises NAD+ in humans. Healthy aging has no hard-outcome evidence and several null results in older adults: no mortality, lifespan or disease-incidence outcome was found for NR in healthy people, and NADage, the registered trial closest to the claim, has no results.

Sellers say nicotinamide riboside raises NAD+ and supports healthy aging, and sometimes present NRH, the reduced form, as a stronger version. The claim that it raises NAD+ is supported in humans. Healthy aging has no hard-outcome evidence and several null results in older adults, described above, and the stronger-version claim for NRH has no human trial behind it.

A PubMed search on 10 October 2026 for nicotinamide riboside with mortality, lifespan, longevity, biological age, epigenetic age or healthspan terms in titles and abstracts, limited to human studies, returned 42 records. The first 40 by relevance were reviewed by title; they were reviews, mechanism papers, and disease-population or short NAD+ trials, and none reported mortality, lifespan or disease-incidence outcomes for NR in healthy people. One reported an epigenetic-clock result in muscle (PMID 42481916, 5-month NR supplementation across three studies, lower muscle epigenetic age acceleration on some clocks); that is a biomarker, not an aging outcome.

The registered trial closest to the claim is NADage (NCT06208527), a 1-year randomized placebo-controlled study of 2000 mg NR per day in 100 adults aged 75 or older with frailty, with gait speed as the primary outcome. It is listed as recruiting, with completion listed as December 2030 and no results.

Searches, 10 October 2026: no hard-outcome evidence; NADage recruiting, no results

PubMed search record

PubMed search run on 10 October 2026: nicotinamide riboside[tiab] AND (mortality OR lifespan OR longevity OR biological age OR epigenetic age OR healthspan)[tiab] AND humans[mh], 42 records. ClinicalTrials.gov record NCT06208527 (NADage), no posted results.

The PubMed search returned 42 records. The first 40 by relevance were reviewed by title; they were reviews, mechanism papers, and disease-population or short NAD+ trials, and none reported mortality, lifespan or disease-incidence outcomes for NR in healthy people. One reported an epigenetic-clock result in muscle (PMID 42481916, 5-month NR supplementation across three studies, lower muscle epigenetic age acceleration on some clocks); that is a biomarker, not an aging outcome. The registered trial closest to the claim is NADage (NCT06208527), a 1-year randomized placebo-controlled study of 2000 mg NR per day in 100 adults aged 75 or older with frailty, primary outcome gait speed, status recruiting, completion listed as 2030-12, with no posted results.

Participants / model
Records reviewed and one registered trial, not a population
Treatment
Not applicable
Follow-up
Searches run on 2026-10-10; NADage planned at 1 year
Study design
Dated literature search and trial registry record
Funding
not stated in the source

A search result shows what the databases returned on that date. It is not proof that no unindexed study exists. NADage has no posted results.

Read the original source
NRH: different molecule, cell and mouse work only, no human trial found

Chemical identity record

National Library of Medicine. PubChem compound record CID 11507134 (NRH). Related papers: PMIDs 30948509, 31767171, 33166357 and 35281060. PubMed and ClinicalTrials.gov searches run 10 October 2026.

NRH (dihydronicotinamide riboside, reduced nicotinamide riboside) is PubChem CID 11507134, C11H16N2O5, 256.25 g/mol, CAS 19132-12-8. It is a different molecule from NR (two more hydrogens), and no NR dose or trial result transfers to it. NRH raised NAD+ more than NR or NMN at equal concentrations in cultured mammalian cells and raised NAD+ in tissues of mice given it by intraperitoneal injection (PMID 30948509). It was orally bioavailable in mice and prevented cisplatin-induced acute kidney injury in mice (PMID 31767171). Two cell papers report dose-dependent cytotoxicity in HepG3 liver cancer cells at 100 to 1000 uM with none in HEK293T cells (PMID 33166357), and pro-inflammatory activation of macrophages (PMID 35281060). A PubMed search on 2026-10-10 for dihydronicotinamide riboside, reduced nicotinamide riboside or 1,4-dihydronicotinamide riboside in titles and abstracts returned 50 records; the first 40 by relevance were reviewed by title and none was a human trial of NRH. The same query limited to randomized controlled trial or clinical trial publication types returned 0 records, and a ClinicalTrials.gov search for dihydronicotinamide riboside returned 0 studies.

Participants / model
NRH: cultured mammalian cells and mice. Humans: no trial found
Treatment
Cell exposure and mouse injection or oral dosing
Follow-up
not stated in the source
Study design
Original preclinical studies plus a dated literature and registry search
Funding
not stated in the source

The cell and mouse papers are described from the same source record and are not separate page sources. No human trial of NRH was found.

Read the original source
8-week trial, 140 overweight adults: whole-blood NAD+ up 22%, 51%, 142%

Randomized controlled trial

Conze D et al. Sci Rep. 2019;9(1):9772. PMID 31278280.

In an 8-week randomized double-blind placebo-controlled trial of overweight but otherwise healthy men and women (140 enrolled, 35 per group), NR chloride at 100, 300 and 1000 mg per day raised whole-blood NAD+ by 22%, 51% and 142%, with increases seen within 2 weeks and kept through the study. Adverse events did not differ significantly from placebo, there were no reports of flushing, and LDL cholesterol was not raised.

Participants / model
Overweight, otherwise healthy men and women
Treatment
Oral NIAGEN (NR chloride) 100, 300 or 1000 mg per day
Follow-up
8 weeks
Study design
Randomized, double-blind, placebo-controlled trial, company-funded
Funding
ChromaDex funded the study; two authors are ChromaDex employees; Charles Brenner is the inventor of intellectual property licensed by ChromaDex and its chief scientific adviser

The trial measured NAD+ chemistry and safety, not health outcomes. The paper prints its registry number as NCT0271593, one digit short; the apparent match is NCT02712593 (KGK Science, 140 enrolled, first posted 2016-03-18), which has no posted results.

Read the original source
NOPARK: 410 randomized, 52 weeks, total MDS-UPDRS worse on NR by 2.72 points

Randomized controlled trial

Brakedal B et al. JAMA. 2026. PMID 42848371.

NOPARK, a randomized double-blind placebo-controlled phase 3 trial at 11 centers in Norway, gave 500 mg NR twice daily or placebo for 52 weeks to patients with Parkinson disease diagnosed within 2 years (410 randomized, 393 analyzed). Total MDS-UPDRS rose 2.45 points on NR and fell 0.27 on placebo, an adjusted mean difference of 2.72 points (95% CI 0.47 to 4.98, P = .02) favoring placebo. Nonmotor symptom burden worsened more on NR (adjusted difference 4.22 points, P = .009). Serious adverse events were 17 of 205 (8.3%) on NR and 29 of 205 (14.1%) on placebo. The authors conclude NR did not improve outcomes and was associated with worse outcomes than placebo.

Participants / model
393 analyzed adults with early Parkinson disease
Treatment
Oral NR 500 mg twice daily or placebo
Follow-up
52 weeks
Study design
Randomized, double-blind, placebo-controlled phase 3 trial
Funding
not stated in the source

A disease population, not healthy aging, but the largest NR trial found and a negative one. Registry number NCT03568968.

Read the original source

How does nicotinamide riboside work?

The trials show it raises NAD+ and related metabolites in human blood, and in muscle in one 21-day trial but not in a 12-week trial. The sources reviewed do not describe the route by which NR becomes NAD+, and the outcome trials described here show no clear functional benefit.

NR is notified in the US as a source of vitamin B3 in conventional foods. In people it raised whole-blood NAD+ by 22% to 142% across 100 to 1000 mg per day in 8 weeks, and PBMC NAD+ by about 60% over placebo at 500 mg twice daily in a crossover trial. The sources reviewed do not describe the route by which NR becomes NAD+.

Muscle results differ between trials. In 12 aged men given 1 g per day for 21 days, the muscle NAD+ metabolome rose and circulating inflammatory cytokines fell, while muscle energy-metabolism and mitochondrial gene pathways were downregulated without any change in mitochondrial bioenergetics. In 40 obese, insulin-resistant men given 1000 mg twice daily for 12 weeks, muscle NAD+ was unchanged, NAMPT protein fell 14%, and mitochondrial respiration and content did not change.

NR reliably raises NAD+, but the outcome trials on this page show no clear functional benefit: no improvement in insulin sensitivity in obese men, no muscle benefit in the meta-analysis, and a worse total MDS-UPDRS than placebo in NOPARK.

FDA GRAS letter GRN 000635, 3 August 2016: no questions, conventional foods; no NR drug found

Regulatory record

U.S. Food and Drug Administration. Agency response letter, GRAS Notice No. GRN 000635, dated 3 August 2016. openFDA Drugs@FDA and DailyMed queries run 10 October 2026.

The FDA letter for GRAS Notice GRN 000635 is dated 3 August 2016 and concerns nicotinamide riboside chloride as a source of vitamin B3 in vitamin waters, protein shakes, nutrition bars, gum, chews and powdered beverages at a maximum of 0.0057% by weight as consumed. FDA says it has no questions at this time about the notifier's (ChromaDex's) GRAS conclusion and that it has not made its own GRAS determination. On 2026-10-10 an openFDA Drugs@FDA query for nicotinamide riboside returned no match, and DailyMed drug-name searches for nicotinamide riboside, nicotinamide riboside chloride and niagen returned no labels, so no FDA-approved NR drug or drug label was found.

Participants / model
Not a clinical population
Treatment
Food ingredient notice; no drug application
Follow-up
Letter dated 2016-08-03; searches run on 2026-10-10
Study design
Official FDA record plus dated US approval-record search
Funding
not stated in the source

This is a conventional-food ingredient notice, not a drug approval and not an efficacy finding.

Read the original source
8-week trial, 140 overweight adults: whole-blood NAD+ up 22%, 51%, 142%

Randomized controlled trial

Conze D et al. Sci Rep. 2019;9(1):9772. PMID 31278280.

In an 8-week randomized double-blind placebo-controlled trial of overweight but otherwise healthy men and women (140 enrolled, 35 per group), NR chloride at 100, 300 and 1000 mg per day raised whole-blood NAD+ by 22%, 51% and 142%, with increases seen within 2 weeks and kept through the study. Adverse events did not differ significantly from placebo, there were no reports of flushing, and LDL cholesterol was not raised.

Participants / model
Overweight, otherwise healthy men and women
Treatment
Oral NIAGEN (NR chloride) 100, 300 or 1000 mg per day
Follow-up
8 weeks
Study design
Randomized, double-blind, placebo-controlled trial, company-funded
Funding
ChromaDex funded the study; two authors are ChromaDex employees; Charles Brenner is the inventor of intellectual property licensed by ChromaDex and its chief scientific adviser

The trial measured NAD+ chemistry and safety, not health outcomes. The paper prints its registry number as NCT0271593, one digit short; the apparent match is NCT02712593 (KGK Science, 140 enrolled, first posted 2016-03-18), which has no posted results.

Read the original source
Crossover trial, 24 completers: PBMC NAD+ up about 60%, blood pressure result not significant after correction

Randomized controlled trial

Martens CR et al. Nat Commun. 2018;9(1):1286. PMID 29599478.

In a 2 x 6-week randomized double-blind placebo-controlled crossover trial of healthy middle-aged and older adults, 500 mg NR chloride twice daily was well tolerated and raised PBMC NAD+ by about 60% over placebo. Of 60 people consented, 30 were randomized and 24 completed. Reductions in systolic blood pressure and aortic pulse wave velocity were exploratory and did not remain statistically significant after correction for multiple comparisons; carotid compliance and brachial flow-mediated dilation did not change. The authors call for larger trials.

Participants / model
24 completers, healthy adults aged 55 to 79
Treatment
Oral NR chloride (NIAGEN) 500 mg twice daily
Follow-up
2 x 6 weeks
Study design
Randomized, double-blind, placebo-controlled crossover trial, partly company-supported
Funding
ChromaDex supplied the pills and NR standards and gave partial funding; NIH grants are also listed

The figures here come from the full text (Europe PMC); the abstract carries none of them. Registry number NCT02921659.

Read the original source
Muscle NAD+ trials: 12 aged men for 21 days; 40 obese men for 12 weeks

Randomized controlled trial

Elhassan YS et al. Cell Rep. 2019;28(7):1717-1728.e6. PMID 31412242.

In a randomized double-blind placebo-controlled crossover trial, 12 aged men took 1 g NR per day for 21 days. The muscle NAD+ metabolome rose (nicotinic acid adenine dinucleotide and nicotinamide clearance products), circulating inflammatory cytokines fell, and muscle energy-metabolism and mitochondrial gene pathways were downregulated without any change in mitochondrial bioenergetics. In a 12-week trial of 40 obese, insulin-resistant men given 1000 mg NR or placebo twice daily, steady-state muscle NAD+ was unchanged, NAMPT protein fell 14%, and muscle mitochondrial respiration and content did not change (PMID 31710095). The metabolic report of a 40-man trial with the same regimen found no improvement in insulin sensitivity, glucose disposal, energy expenditure, lipolysis or body composition (PMID 29992272, NCT02303483).

Participants / model
12 aged men; 40 obese insulin-resistant men aged 40 to 70
Treatment
Oral NR 1 g per day for 21 days; oral NR 1000 mg twice daily for 12 weeks
Follow-up
21 days; 12 weeks
Study design
Randomized, double-blind, placebo-controlled trials
Funding
not stated in the source

Muscle NAD+ results are not consistent. The abstracts do not confirm that the last two papers use the same cohort, and the two 12-week papers are described from the same source record and are not separate page sources.

Read the original source
Meta-analysis of NMN and NR trials: evidence does not support a muscle benefit over age 60

Systematic review and meta-analysis

Prokopidis K et al. J Cachexia Sarcopenia Muscle. 2025;16(3):e13799. PMID 40275690.

A systematic review and meta-analysis of randomized trials of NR or NMN versus placebo, in participants with mean ages of 60.9 to 83 years, concluded that current evidence does not support NMN or NR for preserving muscle mass and function in adults over 60. NMN showed no significant effect on skeletal muscle index, handgrip strength, gait speed or the 5-time chair stand test. For NR, the abstract reports a longer 6-minute walk distance in people with peripheral artery disease, but lower Short Physical Performance Battery scores and slower chair stands in people with mild cognitive impairment.

Participants / model
Adults with a mean age over 60, pooled across randomized trials, including people with peripheral artery disease or mild cognitive impairment
Treatment
Oral NMN or NR
Follow-up
not stated in the source
Study design
Systematic review and meta-analysis
Funding
not stated in the source

The pooled estimates mostly concern NMN, so the NR-specific base is small.

Read the original source
NOPARK: 410 randomized, 52 weeks, total MDS-UPDRS worse on NR by 2.72 points

Randomized controlled trial

Brakedal B et al. JAMA. 2026. PMID 42848371.

NOPARK, a randomized double-blind placebo-controlled phase 3 trial at 11 centers in Norway, gave 500 mg NR twice daily or placebo for 52 weeks to patients with Parkinson disease diagnosed within 2 years (410 randomized, 393 analyzed). Total MDS-UPDRS rose 2.45 points on NR and fell 0.27 on placebo, an adjusted mean difference of 2.72 points (95% CI 0.47 to 4.98, P = .02) favoring placebo. Nonmotor symptom burden worsened more on NR (adjusted difference 4.22 points, P = .009). Serious adverse events were 17 of 205 (8.3%) on NR and 29 of 205 (14.1%) on placebo. The authors conclude NR did not improve outcomes and was associated with worse outcomes than placebo.

Participants / model
393 analyzed adults with early Parkinson disease
Treatment
Oral NR 500 mg twice daily or placebo
Follow-up
52 weeks
Study design
Randomized, double-blind, placebo-controlled phase 3 trial
Funding
not stated in the source

A disease population, not healthy aging, but the largest NR trial found and a negative one. Registry number NCT03568968.

Read the original source

What is known about the safety of nicotinamide riboside?

Short trials in healthy adults found NR well tolerated, and EFSA found no safety concern for NR chloride at up to 300 mg/day in healthy adults who are not pregnant or lactating. In NOPARK, outcomes were worse than placebo in early Parkinson disease, although serious adverse events were fewer on NR (8.3% versus 14.1%). The human studies EFSA judged ran up to 12 weeks.

EFSA concluded NR chloride is safe at up to 300 mg/day for healthy adults excluding pregnant and lactating women, and up to 230 mg/day for pregnant and lactating women. It found no genotoxicity concern, derived a NOAEL of 300 mg/kg body weight per day from rat and dog studies, and judged human studies from 100 mg for 1 day up to 2,000 mg/day for up to 12 weeks to raise no safety concerns. This is a safety finding for a defined salt, dose and population, not evidence of benefit.

In the 8-week trial of 140 overweight adults, adverse events did not differ significantly from placebo, no flushing was reported and LDL cholesterol was not raised. In the crossover trial of 500 mg NR chloride twice daily, the dose was well tolerated. In NOPARK, serious adverse events were 17 of 205 (8.3%) on NR and 29 of 205 (14.1%) on placebo, but total MDS-UPDRS and nonmotor symptom burden were worse on NR, and the authors conclude NR was associated with worse outcomes than placebo in early Parkinson disease.

Two cell papers on NRH report dose-dependent cytotoxicity in HepG3 liver cancer cells at 100 to 1000 uM and pro-inflammatory activation of macrophages. No NR safety result transfers to NRH.

Trial and regulator findings apply to the NR chloride salts, doses and populations studied. Several abstracts do not name the salt, and some trials combined NR with pterostilbene, a different product. Whether retail NR products match the salts and doses used in trials was not tested.

EFSA 2019 opinion and EU 2020/16: NR chloride safe at up to 300 mg/day in healthy adults

Regulatory record

Turck D et al. EFSA J. 2019;17(8):e05775. PMID 32626405.

The EFSA opinion evaluated NR chloride for food supplements for healthy adults at up to 300 mg/day. It found the production process, composition and specifications raised no safety concerns, found no genotoxicity concern, and concluded the novel food is safe at up to 300 mg/day for healthy adults excluding pregnant and lactating women, and that up to 230 mg/day is safe for pregnant and lactating women. It derived a NOAEL of 300 mg/kg body weight per day from rat and dog studies, and judged human studies of 100 mg for 1 day up to 2,000 mg/day for up to 12 weeks to raise no safety concerns. Commission Implementing Regulation (EU) 2020/16 of 10 January 2020 then authorized NR chloride as a novel food. Its recitals name ChromaDex Inc. as the applicant (request of 10 May 2018) and restrict placing on the market to the applicant for five years.

Participants / model
Healthy adults, with a separate limit for pregnant and lactating women; rats and dogs for the toxicology
Treatment
NR chloride in food supplements, up to 300 mg/day
Follow-up
Human studies judged ran up to 12 weeks
Study design
Regulator opinion and legal act
Funding
not stated in the source

This is a safety finding for a defined salt, dose and population, not evidence of benefit. The regulation text was read at the legislation.gov.uk copy.

Read the original source
8-week trial, 140 overweight adults: whole-blood NAD+ up 22%, 51%, 142%

Randomized controlled trial

Conze D et al. Sci Rep. 2019;9(1):9772. PMID 31278280.

In an 8-week randomized double-blind placebo-controlled trial of overweight but otherwise healthy men and women (140 enrolled, 35 per group), NR chloride at 100, 300 and 1000 mg per day raised whole-blood NAD+ by 22%, 51% and 142%, with increases seen within 2 weeks and kept through the study. Adverse events did not differ significantly from placebo, there were no reports of flushing, and LDL cholesterol was not raised.

Participants / model
Overweight, otherwise healthy men and women
Treatment
Oral NIAGEN (NR chloride) 100, 300 or 1000 mg per day
Follow-up
8 weeks
Study design
Randomized, double-blind, placebo-controlled trial, company-funded
Funding
ChromaDex funded the study; two authors are ChromaDex employees; Charles Brenner is the inventor of intellectual property licensed by ChromaDex and its chief scientific adviser

The trial measured NAD+ chemistry and safety, not health outcomes. The paper prints its registry number as NCT0271593, one digit short; the apparent match is NCT02712593 (KGK Science, 140 enrolled, first posted 2016-03-18), which has no posted results.

Read the original source
Crossover trial, 24 completers: PBMC NAD+ up about 60%, blood pressure result not significant after correction

Randomized controlled trial

Martens CR et al. Nat Commun. 2018;9(1):1286. PMID 29599478.

In a 2 x 6-week randomized double-blind placebo-controlled crossover trial of healthy middle-aged and older adults, 500 mg NR chloride twice daily was well tolerated and raised PBMC NAD+ by about 60% over placebo. Of 60 people consented, 30 were randomized and 24 completed. Reductions in systolic blood pressure and aortic pulse wave velocity were exploratory and did not remain statistically significant after correction for multiple comparisons; carotid compliance and brachial flow-mediated dilation did not change. The authors call for larger trials.

Participants / model
24 completers, healthy adults aged 55 to 79
Treatment
Oral NR chloride (NIAGEN) 500 mg twice daily
Follow-up
2 x 6 weeks
Study design
Randomized, double-blind, placebo-controlled crossover trial, partly company-supported
Funding
ChromaDex supplied the pills and NR standards and gave partial funding; NIH grants are also listed

The figures here come from the full text (Europe PMC); the abstract carries none of them. Registry number NCT02921659.

Read the original source
NOPARK: 410 randomized, 52 weeks, total MDS-UPDRS worse on NR by 2.72 points

Randomized controlled trial

Brakedal B et al. JAMA. 2026. PMID 42848371.

NOPARK, a randomized double-blind placebo-controlled phase 3 trial at 11 centers in Norway, gave 500 mg NR twice daily or placebo for 52 weeks to patients with Parkinson disease diagnosed within 2 years (410 randomized, 393 analyzed). Total MDS-UPDRS rose 2.45 points on NR and fell 0.27 on placebo, an adjusted mean difference of 2.72 points (95% CI 0.47 to 4.98, P = .02) favoring placebo. Nonmotor symptom burden worsened more on NR (adjusted difference 4.22 points, P = .009). Serious adverse events were 17 of 205 (8.3%) on NR and 29 of 205 (14.1%) on placebo. The authors conclude NR did not improve outcomes and was associated with worse outcomes than placebo.

Participants / model
393 analyzed adults with early Parkinson disease
Treatment
Oral NR 500 mg twice daily or placebo
Follow-up
52 weeks
Study design
Randomized, double-blind, placebo-controlled phase 3 trial
Funding
not stated in the source

A disease population, not healthy aging, but the largest NR trial found and a negative one. Registry number NCT03568968.

Read the original source
NRH: different molecule, cell and mouse work only, no human trial found

Chemical identity record

National Library of Medicine. PubChem compound record CID 11507134 (NRH). Related papers: PMIDs 30948509, 31767171, 33166357 and 35281060. PubMed and ClinicalTrials.gov searches run 10 October 2026.

NRH (dihydronicotinamide riboside, reduced nicotinamide riboside) is PubChem CID 11507134, C11H16N2O5, 256.25 g/mol, CAS 19132-12-8. It is a different molecule from NR (two more hydrogens), and no NR dose or trial result transfers to it. NRH raised NAD+ more than NR or NMN at equal concentrations in cultured mammalian cells and raised NAD+ in tissues of mice given it by intraperitoneal injection (PMID 30948509). It was orally bioavailable in mice and prevented cisplatin-induced acute kidney injury in mice (PMID 31767171). Two cell papers report dose-dependent cytotoxicity in HepG3 liver cancer cells at 100 to 1000 uM with none in HEK293T cells (PMID 33166357), and pro-inflammatory activation of macrophages (PMID 35281060). A PubMed search on 2026-10-10 for dihydronicotinamide riboside, reduced nicotinamide riboside or 1,4-dihydronicotinamide riboside in titles and abstracts returned 50 records; the first 40 by relevance were reviewed by title and none was a human trial of NRH. The same query limited to randomized controlled trial or clinical trial publication types returned 0 records, and a ClinicalTrials.gov search for dihydronicotinamide riboside returned 0 studies.

Participants / model
NRH: cultured mammalian cells and mice. Humans: no trial found
Treatment
Cell exposure and mouse injection or oral dosing
Follow-up
not stated in the source
Study design
Original preclinical studies plus a dated literature and registry search
Funding
not stated in the source

The cell and mouse papers are described from the same source record and are not separate page sources. No human trial of NRH was found.

Read the original source
PubChem: NR cation and NR chloride identity

Chemical identity record

National Library of Medicine. PubChem compound records CID 439924 (nicotinamide riboside) and CID 90480033 (nicotinamide riboside chloride).

The nicotinamide riboside (NR) cation is PubChem CID 439924, C11H15N2O5+, 255.25 g/mol, CAS 1341-23-7, with Niagen and TruNiagen among the listed synonyms. Nicotinamide riboside chloride, the salt behind the commercial ingredient, is CID 90480033, C11H15ClN2O5, 290.70 g/mol, CAS 23111-00-4. EFSA states its 300 mg/day figure as NR chloride, and the 2018 crossover trial gives its 500 mg dose as NR chloride (NIAGEN).

Participants / model
Chemical identity, not a clinical population
Treatment
Defined cation and chloride salt
Follow-up
Not applicable
Study design
NLM chemical record
Funding
not stated in the source

Several trial abstracts write NR without naming the salt, so the page says NR chloride only where the source does. Some trials tested NR together with pterostilbene, which is a different product.

Read the original source

Why does nicotinamide riboside sit in C tier?

NR reliably raises blood NAD+, regulators found no safety objection for their defined uses, and short trials show it is well tolerated. The outcome trials are small and mostly null for healthy aging, and a phase 3 Parkinson disease trial favored placebo, which puts NR level with NMN.

No trial found a metabolic benefit in obese men, a muscle benefit in the older-adult populations pooled, or any hard outcome in healthy people. NOPARK, the largest NR trial, was negative. The grade does not extend to NRH, which has no human trial.

8-week trial, 140 overweight adults: whole-blood NAD+ up 22%, 51%, 142%

Randomized controlled trial

Conze D et al. Sci Rep. 2019;9(1):9772. PMID 31278280.

In an 8-week randomized double-blind placebo-controlled trial of overweight but otherwise healthy men and women (140 enrolled, 35 per group), NR chloride at 100, 300 and 1000 mg per day raised whole-blood NAD+ by 22%, 51% and 142%, with increases seen within 2 weeks and kept through the study. Adverse events did not differ significantly from placebo, there were no reports of flushing, and LDL cholesterol was not raised.

Participants / model
Overweight, otherwise healthy men and women
Treatment
Oral NIAGEN (NR chloride) 100, 300 or 1000 mg per day
Follow-up
8 weeks
Study design
Randomized, double-blind, placebo-controlled trial, company-funded
Funding
ChromaDex funded the study; two authors are ChromaDex employees; Charles Brenner is the inventor of intellectual property licensed by ChromaDex and its chief scientific adviser

The trial measured NAD+ chemistry and safety, not health outcomes. The paper prints its registry number as NCT0271593, one digit short; the apparent match is NCT02712593 (KGK Science, 140 enrolled, first posted 2016-03-18), which has no posted results.

Read the original source
Muscle NAD+ trials: 12 aged men for 21 days; 40 obese men for 12 weeks

Randomized controlled trial

Elhassan YS et al. Cell Rep. 2019;28(7):1717-1728.e6. PMID 31412242.

In a randomized double-blind placebo-controlled crossover trial, 12 aged men took 1 g NR per day for 21 days. The muscle NAD+ metabolome rose (nicotinic acid adenine dinucleotide and nicotinamide clearance products), circulating inflammatory cytokines fell, and muscle energy-metabolism and mitochondrial gene pathways were downregulated without any change in mitochondrial bioenergetics. In a 12-week trial of 40 obese, insulin-resistant men given 1000 mg NR or placebo twice daily, steady-state muscle NAD+ was unchanged, NAMPT protein fell 14%, and muscle mitochondrial respiration and content did not change (PMID 31710095). The metabolic report of a 40-man trial with the same regimen found no improvement in insulin sensitivity, glucose disposal, energy expenditure, lipolysis or body composition (PMID 29992272, NCT02303483).

Participants / model
12 aged men; 40 obese insulin-resistant men aged 40 to 70
Treatment
Oral NR 1 g per day for 21 days; oral NR 1000 mg twice daily for 12 weeks
Follow-up
21 days; 12 weeks
Study design
Randomized, double-blind, placebo-controlled trials
Funding
not stated in the source

Muscle NAD+ results are not consistent. The abstracts do not confirm that the last two papers use the same cohort, and the two 12-week papers are described from the same source record and are not separate page sources.

Read the original source
Meta-analysis of NMN and NR trials: evidence does not support a muscle benefit over age 60

Systematic review and meta-analysis

Prokopidis K et al. J Cachexia Sarcopenia Muscle. 2025;16(3):e13799. PMID 40275690.

A systematic review and meta-analysis of randomized trials of NR or NMN versus placebo, in participants with mean ages of 60.9 to 83 years, concluded that current evidence does not support NMN or NR for preserving muscle mass and function in adults over 60. NMN showed no significant effect on skeletal muscle index, handgrip strength, gait speed or the 5-time chair stand test. For NR, the abstract reports a longer 6-minute walk distance in people with peripheral artery disease, but lower Short Physical Performance Battery scores and slower chair stands in people with mild cognitive impairment.

Participants / model
Adults with a mean age over 60, pooled across randomized trials, including people with peripheral artery disease or mild cognitive impairment
Treatment
Oral NMN or NR
Follow-up
not stated in the source
Study design
Systematic review and meta-analysis
Funding
not stated in the source

The pooled estimates mostly concern NMN, so the NR-specific base is small.

Read the original source
NOPARK: 410 randomized, 52 weeks, total MDS-UPDRS worse on NR by 2.72 points

Randomized controlled trial

Brakedal B et al. JAMA. 2026. PMID 42848371.

NOPARK, a randomized double-blind placebo-controlled phase 3 trial at 11 centers in Norway, gave 500 mg NR twice daily or placebo for 52 weeks to patients with Parkinson disease diagnosed within 2 years (410 randomized, 393 analyzed). Total MDS-UPDRS rose 2.45 points on NR and fell 0.27 on placebo, an adjusted mean difference of 2.72 points (95% CI 0.47 to 4.98, P = .02) favoring placebo. Nonmotor symptom burden worsened more on NR (adjusted difference 4.22 points, P = .009). Serious adverse events were 17 of 205 (8.3%) on NR and 29 of 205 (14.1%) on placebo. The authors conclude NR did not improve outcomes and was associated with worse outcomes than placebo.

Participants / model
393 analyzed adults with early Parkinson disease
Treatment
Oral NR 500 mg twice daily or placebo
Follow-up
52 weeks
Study design
Randomized, double-blind, placebo-controlled phase 3 trial
Funding
not stated in the source

A disease population, not healthy aging, but the largest NR trial found and a negative one. Registry number NCT03568968.

Read the original source
EFSA 2019 opinion and EU 2020/16: NR chloride safe at up to 300 mg/day in healthy adults

Regulatory record

Turck D et al. EFSA J. 2019;17(8):e05775. PMID 32626405.

The EFSA opinion evaluated NR chloride for food supplements for healthy adults at up to 300 mg/day. It found the production process, composition and specifications raised no safety concerns, found no genotoxicity concern, and concluded the novel food is safe at up to 300 mg/day for healthy adults excluding pregnant and lactating women, and that up to 230 mg/day is safe for pregnant and lactating women. It derived a NOAEL of 300 mg/kg body weight per day from rat and dog studies, and judged human studies of 100 mg for 1 day up to 2,000 mg/day for up to 12 weeks to raise no safety concerns. Commission Implementing Regulation (EU) 2020/16 of 10 January 2020 then authorized NR chloride as a novel food. Its recitals name ChromaDex Inc. as the applicant (request of 10 May 2018) and restrict placing on the market to the applicant for five years.

Participants / model
Healthy adults, with a separate limit for pregnant and lactating women; rats and dogs for the toxicology
Treatment
NR chloride in food supplements, up to 300 mg/day
Follow-up
Human studies judged ran up to 12 weeks
Study design
Regulator opinion and legal act
Funding
not stated in the source

This is a safety finding for a defined salt, dose and population, not evidence of benefit. The regulation text was read at the legislation.gov.uk copy.

Read the original source
FDA GRAS letter GRN 000635, 3 August 2016: no questions, conventional foods; no NR drug found

Regulatory record

U.S. Food and Drug Administration. Agency response letter, GRAS Notice No. GRN 000635, dated 3 August 2016. openFDA Drugs@FDA and DailyMed queries run 10 October 2026.

The FDA letter for GRAS Notice GRN 000635 is dated 3 August 2016 and concerns nicotinamide riboside chloride as a source of vitamin B3 in vitamin waters, protein shakes, nutrition bars, gum, chews and powdered beverages at a maximum of 0.0057% by weight as consumed. FDA says it has no questions at this time about the notifier's (ChromaDex's) GRAS conclusion and that it has not made its own GRAS determination. On 2026-10-10 an openFDA Drugs@FDA query for nicotinamide riboside returned no match, and DailyMed drug-name searches for nicotinamide riboside, nicotinamide riboside chloride and niagen returned no labels, so no FDA-approved NR drug or drug label was found.

Participants / model
Not a clinical population
Treatment
Food ingredient notice; no drug application
Follow-up
Letter dated 2016-08-03; searches run on 2026-10-10
Study design
Official FDA record plus dated US approval-record search
Funding
not stated in the source

This is a conventional-food ingredient notice, not a drug approval and not an efficacy finding.

Read the original source
Searches, 10 October 2026: no hard-outcome evidence; NADage recruiting, no results

PubMed search record

PubMed search run on 10 October 2026: nicotinamide riboside[tiab] AND (mortality OR lifespan OR longevity OR biological age OR epigenetic age OR healthspan)[tiab] AND humans[mh], 42 records. ClinicalTrials.gov record NCT06208527 (NADage), no posted results.

The PubMed search returned 42 records. The first 40 by relevance were reviewed by title; they were reviews, mechanism papers, and disease-population or short NAD+ trials, and none reported mortality, lifespan or disease-incidence outcomes for NR in healthy people. One reported an epigenetic-clock result in muscle (PMID 42481916, 5-month NR supplementation across three studies, lower muscle epigenetic age acceleration on some clocks); that is a biomarker, not an aging outcome. The registered trial closest to the claim is NADage (NCT06208527), a 1-year randomized placebo-controlled study of 2000 mg NR per day in 100 adults aged 75 or older with frailty, primary outcome gait speed, status recruiting, completion listed as 2030-12, with no posted results.

Participants / model
Records reviewed and one registered trial, not a population
Treatment
Not applicable
Follow-up
Searches run on 2026-10-10; NADage planned at 1 year
Study design
Dated literature search and trial registry record
Funding
not stated in the source

A search result shows what the databases returned on that date. It is not proof that no unindexed study exists. NADage has no posted results.

Read the original source

Studies and sources

PubChem: NR cation and NR chloride identity

Chemical identity record

National Library of Medicine. PubChem compound records CID 439924 (nicotinamide riboside) and CID 90480033 (nicotinamide riboside chloride).

The nicotinamide riboside (NR) cation is PubChem CID 439924, C11H15N2O5+, 255.25 g/mol, CAS 1341-23-7, with Niagen and TruNiagen among the listed synonyms. Nicotinamide riboside chloride, the salt behind the commercial ingredient, is CID 90480033, C11H15ClN2O5, 290.70 g/mol, CAS 23111-00-4. EFSA states its 300 mg/day figure as NR chloride, and the 2018 crossover trial gives its 500 mg dose as NR chloride (NIAGEN).

Participants / model
Chemical identity, not a clinical population
Treatment
Defined cation and chloride salt
Follow-up
Not applicable
Study design
NLM chemical record
Funding
not stated in the source

Several trial abstracts write NR without naming the salt, so the page says NR chloride only where the source does. Some trials tested NR together with pterostilbene, which is a different product.

Read the original source
NRH: different molecule, cell and mouse work only, no human trial found

Chemical identity record

National Library of Medicine. PubChem compound record CID 11507134 (NRH). Related papers: PMIDs 30948509, 31767171, 33166357 and 35281060. PubMed and ClinicalTrials.gov searches run 10 October 2026.

NRH (dihydronicotinamide riboside, reduced nicotinamide riboside) is PubChem CID 11507134, C11H16N2O5, 256.25 g/mol, CAS 19132-12-8. It is a different molecule from NR (two more hydrogens), and no NR dose or trial result transfers to it. NRH raised NAD+ more than NR or NMN at equal concentrations in cultured mammalian cells and raised NAD+ in tissues of mice given it by intraperitoneal injection (PMID 30948509). It was orally bioavailable in mice and prevented cisplatin-induced acute kidney injury in mice (PMID 31767171). Two cell papers report dose-dependent cytotoxicity in HepG3 liver cancer cells at 100 to 1000 uM with none in HEK293T cells (PMID 33166357), and pro-inflammatory activation of macrophages (PMID 35281060). A PubMed search on 2026-10-10 for dihydronicotinamide riboside, reduced nicotinamide riboside or 1,4-dihydronicotinamide riboside in titles and abstracts returned 50 records; the first 40 by relevance were reviewed by title and none was a human trial of NRH. The same query limited to randomized controlled trial or clinical trial publication types returned 0 records, and a ClinicalTrials.gov search for dihydronicotinamide riboside returned 0 studies.

Participants / model
NRH: cultured mammalian cells and mice. Humans: no trial found
Treatment
Cell exposure and mouse injection or oral dosing
Follow-up
not stated in the source
Study design
Original preclinical studies plus a dated literature and registry search
Funding
not stated in the source

The cell and mouse papers are described from the same source record and are not separate page sources. No human trial of NRH was found.

Read the original source
FDA GRAS letter GRN 000635, 3 August 2016: no questions, conventional foods; no NR drug found

Regulatory record

U.S. Food and Drug Administration. Agency response letter, GRAS Notice No. GRN 000635, dated 3 August 2016. openFDA Drugs@FDA and DailyMed queries run 10 October 2026.

The FDA letter for GRAS Notice GRN 000635 is dated 3 August 2016 and concerns nicotinamide riboside chloride as a source of vitamin B3 in vitamin waters, protein shakes, nutrition bars, gum, chews and powdered beverages at a maximum of 0.0057% by weight as consumed. FDA says it has no questions at this time about the notifier's (ChromaDex's) GRAS conclusion and that it has not made its own GRAS determination. On 2026-10-10 an openFDA Drugs@FDA query for nicotinamide riboside returned no match, and DailyMed drug-name searches for nicotinamide riboside, nicotinamide riboside chloride and niagen returned no labels, so no FDA-approved NR drug or drug label was found.

Participants / model
Not a clinical population
Treatment
Food ingredient notice; no drug application
Follow-up
Letter dated 2016-08-03; searches run on 2026-10-10
Study design
Official FDA record plus dated US approval-record search
Funding
not stated in the source

This is a conventional-food ingredient notice, not a drug approval and not an efficacy finding.

Read the original source
EFSA 2019 opinion and EU 2020/16: NR chloride safe at up to 300 mg/day in healthy adults

Regulatory record

Turck D et al. EFSA J. 2019;17(8):e05775. PMID 32626405.

The EFSA opinion evaluated NR chloride for food supplements for healthy adults at up to 300 mg/day. It found the production process, composition and specifications raised no safety concerns, found no genotoxicity concern, and concluded the novel food is safe at up to 300 mg/day for healthy adults excluding pregnant and lactating women, and that up to 230 mg/day is safe for pregnant and lactating women. It derived a NOAEL of 300 mg/kg body weight per day from rat and dog studies, and judged human studies of 100 mg for 1 day up to 2,000 mg/day for up to 12 weeks to raise no safety concerns. Commission Implementing Regulation (EU) 2020/16 of 10 January 2020 then authorized NR chloride as a novel food. Its recitals name ChromaDex Inc. as the applicant (request of 10 May 2018) and restrict placing on the market to the applicant for five years.

Participants / model
Healthy adults, with a separate limit for pregnant and lactating women; rats and dogs for the toxicology
Treatment
NR chloride in food supplements, up to 300 mg/day
Follow-up
Human studies judged ran up to 12 weeks
Study design
Regulator opinion and legal act
Funding
not stated in the source

This is a safety finding for a defined salt, dose and population, not evidence of benefit. The regulation text was read at the legislation.gov.uk copy.

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8-week trial, 140 overweight adults: whole-blood NAD+ up 22%, 51%, 142%

Randomized controlled trial

Conze D et al. Sci Rep. 2019;9(1):9772. PMID 31278280.

In an 8-week randomized double-blind placebo-controlled trial of overweight but otherwise healthy men and women (140 enrolled, 35 per group), NR chloride at 100, 300 and 1000 mg per day raised whole-blood NAD+ by 22%, 51% and 142%, with increases seen within 2 weeks and kept through the study. Adverse events did not differ significantly from placebo, there were no reports of flushing, and LDL cholesterol was not raised.

Participants / model
Overweight, otherwise healthy men and women
Treatment
Oral NIAGEN (NR chloride) 100, 300 or 1000 mg per day
Follow-up
8 weeks
Study design
Randomized, double-blind, placebo-controlled trial, company-funded
Funding
ChromaDex funded the study; two authors are ChromaDex employees; Charles Brenner is the inventor of intellectual property licensed by ChromaDex and its chief scientific adviser

The trial measured NAD+ chemistry and safety, not health outcomes. The paper prints its registry number as NCT0271593, one digit short; the apparent match is NCT02712593 (KGK Science, 140 enrolled, first posted 2016-03-18), which has no posted results.

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Crossover trial, 24 completers: PBMC NAD+ up about 60%, blood pressure result not significant after correction

Randomized controlled trial

Martens CR et al. Nat Commun. 2018;9(1):1286. PMID 29599478.

In a 2 x 6-week randomized double-blind placebo-controlled crossover trial of healthy middle-aged and older adults, 500 mg NR chloride twice daily was well tolerated and raised PBMC NAD+ by about 60% over placebo. Of 60 people consented, 30 were randomized and 24 completed. Reductions in systolic blood pressure and aortic pulse wave velocity were exploratory and did not remain statistically significant after correction for multiple comparisons; carotid compliance and brachial flow-mediated dilation did not change. The authors call for larger trials.

Participants / model
24 completers, healthy adults aged 55 to 79
Treatment
Oral NR chloride (NIAGEN) 500 mg twice daily
Follow-up
2 x 6 weeks
Study design
Randomized, double-blind, placebo-controlled crossover trial, partly company-supported
Funding
ChromaDex supplied the pills and NR standards and gave partial funding; NIH grants are also listed

The figures here come from the full text (Europe PMC); the abstract carries none of them. Registry number NCT02921659.

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Muscle NAD+ trials: 12 aged men for 21 days; 40 obese men for 12 weeks

Randomized controlled trial

Elhassan YS et al. Cell Rep. 2019;28(7):1717-1728.e6. PMID 31412242.

In a randomized double-blind placebo-controlled crossover trial, 12 aged men took 1 g NR per day for 21 days. The muscle NAD+ metabolome rose (nicotinic acid adenine dinucleotide and nicotinamide clearance products), circulating inflammatory cytokines fell, and muscle energy-metabolism and mitochondrial gene pathways were downregulated without any change in mitochondrial bioenergetics. In a 12-week trial of 40 obese, insulin-resistant men given 1000 mg NR or placebo twice daily, steady-state muscle NAD+ was unchanged, NAMPT protein fell 14%, and muscle mitochondrial respiration and content did not change (PMID 31710095). The metabolic report of a 40-man trial with the same regimen found no improvement in insulin sensitivity, glucose disposal, energy expenditure, lipolysis or body composition (PMID 29992272, NCT02303483).

Participants / model
12 aged men; 40 obese insulin-resistant men aged 40 to 70
Treatment
Oral NR 1 g per day for 21 days; oral NR 1000 mg twice daily for 12 weeks
Follow-up
21 days; 12 weeks
Study design
Randomized, double-blind, placebo-controlled trials
Funding
not stated in the source

Muscle NAD+ results are not consistent. The abstracts do not confirm that the last two papers use the same cohort, and the two 12-week papers are described from the same source record and are not separate page sources.

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Meta-analysis of NMN and NR trials: evidence does not support a muscle benefit over age 60

Systematic review and meta-analysis

Prokopidis K et al. J Cachexia Sarcopenia Muscle. 2025;16(3):e13799. PMID 40275690.

A systematic review and meta-analysis of randomized trials of NR or NMN versus placebo, in participants with mean ages of 60.9 to 83 years, concluded that current evidence does not support NMN or NR for preserving muscle mass and function in adults over 60. NMN showed no significant effect on skeletal muscle index, handgrip strength, gait speed or the 5-time chair stand test. For NR, the abstract reports a longer 6-minute walk distance in people with peripheral artery disease, but lower Short Physical Performance Battery scores and slower chair stands in people with mild cognitive impairment.

Participants / model
Adults with a mean age over 60, pooled across randomized trials, including people with peripheral artery disease or mild cognitive impairment
Treatment
Oral NMN or NR
Follow-up
not stated in the source
Study design
Systematic review and meta-analysis
Funding
not stated in the source

The pooled estimates mostly concern NMN, so the NR-specific base is small.

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NOPARK: 410 randomized, 52 weeks, total MDS-UPDRS worse on NR by 2.72 points

Randomized controlled trial

Brakedal B et al. JAMA. 2026. PMID 42848371.

NOPARK, a randomized double-blind placebo-controlled phase 3 trial at 11 centers in Norway, gave 500 mg NR twice daily or placebo for 52 weeks to patients with Parkinson disease diagnosed within 2 years (410 randomized, 393 analyzed). Total MDS-UPDRS rose 2.45 points on NR and fell 0.27 on placebo, an adjusted mean difference of 2.72 points (95% CI 0.47 to 4.98, P = .02) favoring placebo. Nonmotor symptom burden worsened more on NR (adjusted difference 4.22 points, P = .009). Serious adverse events were 17 of 205 (8.3%) on NR and 29 of 205 (14.1%) on placebo. The authors conclude NR did not improve outcomes and was associated with worse outcomes than placebo.

Participants / model
393 analyzed adults with early Parkinson disease
Treatment
Oral NR 500 mg twice daily or placebo
Follow-up
52 weeks
Study design
Randomized, double-blind, placebo-controlled phase 3 trial
Funding
not stated in the source

A disease population, not healthy aging, but the largest NR trial found and a negative one. Registry number NCT03568968.

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Why is Nicotinamide riboside in C tier?

C fits an ingredient whose NAD+ chemistry holds up but whose outcome trials do not. NR reliably raises blood NAD+ at the doses tested, EFSA and FDA reviews raised no safety objection for their defined uses, and short trials show it is well tolerated. The outcome trials are small and mostly null for healthy aging, and a phase 3 Parkinson disease trial favored placebo, which puts NR level with NMN.