A reference work, not a recommendation to use: this profile describes mechanism and evidence and does not replace medical advice. The claims come from marketing and forums and are tested here, not endorsed.

Claims checked

  • Slows aging and extends life

    Mixed results

    Longevity · healthy · Animal study

    Lifespan studied only in mice: extended in one study [3], no effect in the Interventions Testing Program [4]. In humans, there is no study with aging or lifespan endpoints; only the rise of NAD+ in blood is documented [5].

  • Better insulin sensitivity and more energy in metabolism

    No benefit

    Energy & metabolism · healthy (overweight or obesity) · Human, randomised small studiesEvery study behind this level and result had fewer than 100 participants. Small studies report larger effects on average than large ones, so the result is less certain.

    Two RCTs with a clamp test (40 and 13 participants) found no better insulin sensitivity and no change in energy expenditure or mitochondrial function [8][9][10].[8][9][10]

  • More muscle strength and physical performance

    No benefit

    Muscle & performance · healthy (mainly over 60 years) · Human, randomised

    Meta-analysis of RCTs without benefit for muscle mass and function in older adults [11]; no change in mitochondrial respiration in muscle [9]. A benefit appeared only in peripheral artery disease [12].

  • Better walking distance in circulatory disorders of the legs

    Single unconfirmed finding

    Heart & blood vessels · Patients: peripheral artery disease · Human, randomised small studiesEvery study behind this level and result had fewer than 100 participants. Small studies report larger effects on average than large ones, so the result is less certain.

    One RCT with 90 affected people found a six-minute walking distance 17.6 m longer than with placebo after six months; the authors call for a larger confirmatory study [12].

  • Protects the brain in Parkinson’s disease

    Worse performance

    Nervous system · Patients: early Parkinson’s disease · Human, randomised

    In the phase 3 RCT NOPARK, the Parkinson’s scale (MDS-UPDRS I–III) worsened by 2.72 points more with NR than with placebo after 52 weeks (95% CI 0.47–4.98; p = 0.02), as did non-motor symptoms; the difference is below the clinically relevant worsening of 5.2 points named by the authors [13].

small studies: Every study behind this level and result had fewer than 100 participants. Small studies report larger effects on average than large ones, so the result is less certain.

Mechanism of action

Evidence map: Nicotinamide riboside (NR)

Each line stands for a published finding; line style and color show where it comes from. The filter hides weaker evidence levels. Sources: see references.

Nicotinamide riboside (NR) is phosphorylated to NMN by nicotinamide riboside kinases and then converted to NAD+. In the first pharmacokinetic study in humans, the NAD+ metabolome in blood rose dose-dependently after single doses; nicotinic acid adenine dinucleotide (NAAD) proved to be a sensitive marker; several authors held shares in the NR manufacturer [1]. Isotope-labeled flux analyses in mice, however, showed that orally administered NR is largely broken down to nicotinamide in the liver, whereas intravenously administered NR reaches the tissues intact [2]. In old mice, NR rejuvenated muscle stem cells via the mitochondrial stress response and extended lifespan [3]; in the Interventions Testing Program, a program for testing possible life-extending substances in mice, NR, by contrast, did not extend the lifespan of genetically heterogeneous mice in either sex [4].

In humans, NR reliably raises NAD+ in blood. In a randomized crossover study with 30 healthy middle-aged and older adults, NAD+ in mononuclear blood cells rose by about 60%; blood pressure and arterial stiffness were evaluated only exploratorily [5]. A manufacturer-funded RCT in overweight adults found a dose-dependent rise in whole-blood NAD+ without an increase in adverse events [6]. In 12 older men, NR raised the NAD+ metabolome in muscle (mainly NAAD and breakdown products) and lowered inflammatory cytokines in blood but did not change mitochondrial bioenergetics [7].

Functionally, the results in metabolically healthy people remained disappointing. In 40 obese, insulin-resistant men, NR over twelve weeks improved neither insulin sensitivity in the clamp test nor energy expenditure or body composition [8]; NAD+ in muscle, mitochondrial respiration and mitochondrial content were likewise unchanged [9]. In a crossover study with 13 overweight adults, NAD+ markers in muscle and fat-free mass rose slightly, while insulin sensitivity, mitochondrial function and blood pressure did not change [10]. A meta-analysis found no benefit of NR or NMN for muscle mass and function in people over 60; in peripheral artery disease, NR increased walking distance [11], by 17.6 m compared with placebo in an RCT with 90 affected people [12]. In the phase 3 trial NOPARK with 410 people with early Parkinson’s disease, the total score on the Parkinson’s scale worsened more with NR than with placebo, as did the non-motor symptoms [13]. In a mouse model of triple-negative breast cancer, NR increased cancer incidence and brain metastases [14]. In 2019, EFSA assessed NR chloride as safe for healthy adults and as a bioavailable source of nicotinamide [15].

Targets

TargetTypeActionKey dataEvidence
Nicotinamide riboside kinases (NRK)EnzymeBinding Animal study[1][2]
NAD+ pool (via NMN)OtherActivatorNAD+ in mononuclear blood cells ≈ +60% (human, vs. placebo) Human, randomised[5]

Effect profile

Which signaling systems the compound affects according to current data. ↑ enhanced, ↓ dampened, ≈ modulated, ○ no effect; dots = evidence level.

  • Dopamineno data
  • Noradrenalineno data
  • Serotoninno data
  • Acetylcholineno data
  • Glutamate · AMPAno data
  • Glutamate · NMDAno data
  • GABAno data
  • Histamineno data
  • Orexinno data
  • Adenosineno data
  • Opioidsno data
  • Melatoninno data
  • Neurotrophinsno data
  • Blood flowno data
  • Nitric oxideno data
  • Energy metabolism↑ · NAD+ in blood rises in RCTs; in muscle only NAD+ side metabolites, no change in mitochondrial function[5][7][9]
  • Insulin · glucoseno effect · no better insulin sensitivity in the clamp test in overweight and obesity[8][10]
  • Inflammation · oxidative↓ · inflammatory cytokines in blood of older men lowered (small crossover study); no change in inflammatory markers in another RCT[7][10]
  • Stress axisno data
  • Testosterone axisno data
  • Endocannabinoidsno data
  • Autophagy · senescenceno data
  • Immune systemno data
  • Lipid metabolismno data
  • Coagulation · fibrinolysisno data
  • Methylationno data

Routes of administration and bioavailability

How much of a compound reaches the blood or target tissue depends on the route into the body and on the dosage form. All routes of administration explained

  • Oral (swallowed) · NR chloride (capsules)

    absolute bioavailability not determined; NAD+ metabolome in blood rises dose-dependently (human)

    Single doses and intake over several weeks raise NAD+ and NAAD in blood [1][5][6]. In mice, orally administered NR is mostly broken down to nicotinamide in the liver [2]. EFSA regards NR chloride as a bioavailable source of nicotinamide [15].[1][5][6]

    Human, randomised

  • Intravenous · Infusion (animal experiment)

    In mice, intravenously administered NR reached the tissues intact [2]. Controlled human studies on intravenous administration were not found.

    Animal study

Human studies

  • NAD+ in healthy older adults

    RCT, double-blind, placebo-controlled, crossover · healthy (55 to 79 years) · n = 30 · 2 × 6 weeks

    Measured: NAD+ in mononuclear blood cells, tolerability; blood pressure exploratory

    Result: NAD+ ≈ +60% vs. placebo; well tolerated.[5]

    Human, randomised

  • Muscle NAD+ metabolome in older men

    RCT, double-blind, placebo-controlled, crossover · healthy (older men) · n = 12 · 21 days

    Measured: NAD+ metabolome and transcriptome in muscle, mitochondrial function, cytokines

    Result: NAD+ metabolome in muscle increased, cytokines lowered, mitochondrial bioenergetics unchanged.[7]

    Human, randomised

  • Obese insulin-resistant men

    RCT, double-blind, placebo-controlled · healthy (obesity, insulin resistance) · n = 40 · 12 weeks

    Measured: Insulin sensitivity (clamp), energy expenditure, body composition; mitochondria in muscle

    Result: No effect on insulin sensitivity, energy expenditure, muscle NAD+ or mitochondria.[8]

    Human, randomised

  • Overweight adults

    RCT, double-blind, placebo-controlled, crossover · healthy (overweight, obesity) · n = 13 · 2 × 6 weeks

    Measured: Insulin sensitivity (clamp), mitochondrial function, body composition

    Result: Fat-free mass slightly increased; insulin sensitivity, mitochondrial function and blood pressure unchanged.[10]

    Human, randomised

  • Peripheral artery disease (NICE)

    RCT, double-blind, placebo-controlled · Patients: peripheral artery disease · n = 90 · 6 months

    Measured: Six-minute walking distance

    Result: +17.6 m vs. placebo (90% CI from +1.8 m).[12]

    Human, randomised

  • Early Parkinson’s disease (NOPARK)

    RCT, phase 3, double-blind, placebo-controlled, 11 centers · Patients: early Parkinson’s disease · n = 410 · 52 weeks

    Measured: MDS-UPDRS parts I to III

    Result: 2.72 points worse with NR than with placebo (p = 0.02); non-motor symptoms also worse.[13]

    Human, randomised

Risks and warnings

  • Worsening in Parkinson’s disease

    In the phase 3 trial NOPARK, the total scale and non-motor symptoms were worse with NR than with placebo; serious adverse events were less frequent with NR (8.3% vs. 14.1%) [13].

    Human, randomised

  • Theoretical: cancer

    In a mouse model of triple-negative breast cancer, NR increased cancer incidence and brain metastases [14]; not studied in humans.

    Animal study

  • Pregnancy and lactation

    EFSA considered the margin of safety from a developmental toxicity study in rats insufficient for the full proposed amount in pregnant and lactating women and concluded that a lower intake level is safe for them [15]. The authorization rests on this: the Union list (version of August 10, 2026) permits NR chloride in food supplements for pregnant and lactating women with its own, lower maximum level [17][18].

    Animal study

  • Manufacturer involvement

    Pharmacokinetic and safety studies were funded by the NR manufacturer or written by people with shares, consulting contracts or patents [1][6].

    No data

Fact check: common claims

  • supported

    “NR raises the NAD+ level”

    Shown in blood in several RCTs [5][6]; in muscle, NAD+ side metabolites rise rather than NAD+ itself [7][9].

  • not supported

    “NR extends life”

    Mouse data only, and these contradict each other: life extension in one study [3], no effect in the Interventions Testing Program [4].

  • refuted

    “NR improves mitochondrial function in muscle”

    In RCTs, mitochondrial respiration, mitochondrial content and function remained unchanged [7][9][10].

  • refuted

    “NR makes you leaner and more insulin-sensitive”

    Two clamp RCTs in overweight and obesity without effect on insulin sensitivity and energy expenditure [8][10].

  • refuted

    “NR protects the nerves in Parkinson’s disease”

    The phase 3 trial NOPARK found no benefit, but worse courses than with placebo [13].

Pharmacokinetics

Absorption
Oral; dose-dependent rise of the NAD+ metabolome in blood [1][6]. In mice, oral NR is largely broken down to nicotinamide in the liver [2].
Half-life
Not verified.
Metabolism
Phosphorylation by NRK to NMN, then NAD+; NAAD as a sensitive marker [1]; degradation to nicotinamide [2].
Entry into the brain
Not measured directly in humans.

Legal status

Germany
Novel food: in 2019, EFSA assessed NR chloride as safe for dietary supplements in healthy adults excluding pregnant and lactating women, and for pregnant and lactating women only up to a lower intake level [15]. NR chloride has been in the Union list of novel foods since February 20, 2020 (see EU) [17].
EU
Permitted niacin form in food supplements: “nicotinamide riboside chloride” is listed in Annex II, Part A, point 7(d) of Directive 2002/46/EC, inserted by Regulation (EU) 2021/418 [16]. Novel food: entry “nicotinamide riboside chloride” in the consolidated Union list, authorized on February 20, 2020 (Implementing Regulation (EU) 2020/16), conditions of use and specification in the version of Implementing Regulation (EU) 2022/1160; applicant ChromaDex Inc.; according to the Union list, data protection under Article 26 of Regulation (EU) 2015/2283 expired on February 20, 2025. For food supplements, the Union list names separate conditions for adults excluding pregnant and lactating women and for pregnant and lactating women. The labelling statement that the foods should be consumed only by persons over 18 years, excluding pregnant and lactating women, applies only to foods for special medical purposes, total diet replacement for weight control and meal replacements [17]. The basis was the positive EFSA opinion of 2019 [15]. Maximum amounts are not reproduced.
USA
According to a manufacturer-funded study, a crystalline NR chloride form is considered GRAS and was the subject of two notifications as a new dietary ingredient [6]; not verified in FDA documents.
Other countries
Not verified.

Related compounds

Nicotinamide mononucleotide (NMN)same classNicotinamid (Niacinamid)other form (German only)Nicotinsäureother form (German only)

Open questions

  • Why does NAD+ rise markedly in blood but hardly in muscle, and what is the significance of the side metabolites?
  • Is the walking distance benefit in peripheral artery disease confirmed in larger studies?
  • What explains the worse course with NR in the Parkinson’s trial?
  • Are the findings on breast cancer metastases in mice relevant to humans?

References

  1. Trammell SA, Schmidt MS, Weidemann BJ, Redpath P, Jaksch F, Dellinger RW, et al. Nicotinamide riboside is uniquely and orally bioavailable in mice and humans. Nat Commun. 2016;7:12948. doi:10.1038/ncomms12948 · PubMed
  2. Liu L, Su X, Quinn WJ, Hui S, Krukenberg K, Frederick DW, et al. Quantitative analysis of NAD synthesis-breakdown fluxes. Cell Metab. 2018;27(5):1067–80.e5. doi:10.1016/j.cmet.2018.03.018 · PubMed
  3. Zhang H, Ryu D, Wu Y, Gariani K, Wang X, Luan P, et al. NAD+ repletion improves mitochondrial and stem cell function and enhances life span in mice. Science. 2016;352(6292):1436–43. doi:10.1126/science.aaf2693 · PubMed
  4. Harrison DE, Strong R, Reifsnyder P, Kumar N, Fernandez E, Flurkey K, et al. 17-a-estradiol late in life extends lifespan in aging UM-HET3 male mice; nicotinamide riboside and three other drugs do not affect lifespan in either sex. Aging Cell. 2021;20(5):e13328. doi:10.1111/acel.13328 · PubMed
  5. Martens CR, Denman BA, Mazzo MR, Armstrong ML, Reisdorph N, McQueen MB, et al. Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Nat Commun. 2018;9(1):1286. doi:10.1038/s41467-018-03421-7 · PubMed
  6. Conze D, Brenner C, Kruger CL. 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. Sci Rep. 2019;9(1):9772. doi:10.1038/s41598-019-46120-z · PubMed
  7. Elhassan YS, Kluckova K, Fletcher RS, Schmidt MS, Garten A, Doig CL, et al. Nicotinamide riboside augments the aged human skeletal muscle NAD+ metabolome and induces transcriptomic and anti-inflammatory signatures. Cell Rep. 2019;28(7):1717–28.e6. doi:10.1016/j.celrep.2019.07.043 · PubMed
  8. Dollerup OL, Christensen B, Svart M, Schmidt MS, Sulek K, Ringgaard S, et al. A randomized placebo-controlled clinical trial of nicotinamide riboside in obese men: safety, insulin-sensitivity, and lipid-mobilizing effects. Am J Clin Nutr. 2018;108(2):343–53. doi:10.1093/ajcn/nqy132 · PubMed
  9. Dollerup OL, Chubanava S, Agerholm M, Søndergård SD, Altıntaş A, Møller AB, et al. Nicotinamide riboside does not alter mitochondrial respiration, content or morphology in skeletal muscle from obese and insulin-resistant men. J Physiol. 2020;598(4):731–54. doi:10.1113/JP278752 · PubMed
  10. Remie CME, Roumans KHM, Moonen MPB, Connell NJ, Havekes B, Mevenkamp J, et al. Nicotinamide riboside supplementation alters body composition and skeletal muscle acetylcarnitine concentrations in healthy obese humans. Am J Clin Nutr. 2020;112(2):413–26. doi:10.1093/ajcn/nqaa072 · PubMed
  11. Prokopidis K, Moriarty F, Bahat G, McLean J, Church DD, Patel HP. The effect of nicotinamide mononucleotide and riboside on skeletal muscle mass and function: a systematic review and meta-analysis. J Cachexia Sarcopenia Muscle. 2025;16(3):e13799. doi:10.1002/jcsm.13799 · PubMed
  12. McDermott MM, Martens CR, Domanchuk KJ, Zhang D, Peek CB, Criqui MH, et al. Nicotinamide riboside for peripheral artery disease: the NICE randomized clinical trial. Nat Commun. 2024;15(1):5046. doi:10.1038/s41467-024-49092-5 · PubMed
  13. Brakedal B, Skeie GO, Derad C, Alstadhaug KB, Anundskås I, Berven H, et al. Nicotinamide riboside for patients with early-stage Parkinson disease: the NOPARK randomized clinical trial. JAMA. 2026:e2618828. Epub ahead of print. doi:10.1001/jama.2026.18828 · PubMed
  14. Maric T, Bazhin A, Khodakivskyi P, Mikhaylov G, Solodnikova E, Yevtodiyenko A, et al. A bioluminescent-based probe for in vivo non-invasive monitoring of nicotinamide riboside uptake reveals a link between metastasis and NAD+ metabolism. Biosens Bioelectron. 2023;220:114826. doi:10.1016/j.bios.2022.114826 · PubMed
  15. EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA); Turck D, Castenmiller J, de Henauw S, Hirsch-Ernst KI, Kearney J, Maciuk A, et al. Safety of nicotinamide riboside chloride as a novel food pursuant to Regulation (EU) 2015/2283 and bioavailability of nicotinamide from this source, in the context of Directive 2002/46/EC. EFSA J. 2019;17(8):e05775. doi:10.2903/j.efsa.2019.5775 · PubMed
  16. Richtlinie 2002/46/EG des Europäischen Parlaments und des Rates vom 10. Juni 2002 zur Angleichung der Rechtsvorschriften der Mitgliedstaaten über Nahrungsergänzungsmittel. ABl. L 183 vom 12.7.2002, S. 51. Konsolidierte Fassung vom 26.11.2025 (CELEX 02002L0046-20251126).
  17. Durchführungsverordnung (EU) 2017/2470 der Kommission vom 20. Dezember 2017 zur Erstellung der Unionsliste der neuartigen Lebensmittel gemäß der Verordnung (EU) 2015/2283. ABl. L 351 vom 30.12.2017, S. 72. Konsolidierte Fassung vom 10.08.2026 (CELEX 02017R2470-20260810).
  18. Durchführungsverordnung (EU) 2020/16 der Kommission vom 10. Januar 2020 zur Genehmigung des Inverkehrbringens von Nicotinamid-Ribosidchlorid als neuartiges Lebensmittel gemäß der Verordnung (EU) 2015/2283 des Europäischen Parlaments und des Rates sowie zur Änderung der Durchführungsverordnung (EU) 2017/2470 der Kommission. ABl. L 7 vom 13.1.2020, S. 6 (CELEX 32020R0016).
How this profile was checked

Last reviewed: 2026-10-25. All sources with a DOI or PMID were resolved automatically via Crossref or doi.org and PubMed.

Translated from the German profile (version of 2026-10-25); translation checked on 2026-10-26.

Checked

  • All references retrieved via PubMed; DOIs and PMIDs taken from the PubMed records.
  • Checked against the abstract: dose-dependent rise, NAAD as a marker, shares and employment at the manufacturer [1]; oral degradation to nicotinamide, intravenous intact (mouse) [2]; life extension (mouse) [3]; no lifespan effect in the ITP [4]; whole-blood NAD+ dose-dependent, manufacturer funding, GRAS statement [6]; 12 men, NAD+ metabolome, cytokines, mitochondria unchanged [7]; 40 men, clamp without effect [8]; NAMPT −14%, muscle NAD+ and mitochondria unchanged [9]; 13 participants, fat-free mass, otherwise no effect [10]; meta-analysis without benefit, PAD walking distance [11]; 90 patients, +17.6 m [12]; 410 randomized, +2.72 points in favor of placebo, NMSS worse, serious adverse events 8.3% vs. 14.1% [13]; breast cancer model [14]; EFSA: safe for healthy adults, margin of safety for pregnant women insufficient [15].
  • Checked in the full text: 30 participants, 55 to 79 years, NAD+ in PBMC ≈ +60% [5].
  • ClinicalTrials.gov: 128 entries for “nicotinamide riboside” (October 23, 2026).
  • Legal status (October 24, 2026, package kat-p1): Directive 2002/46/EC, consolidated version 02002L0046-20251126, Annex II, Part A, point 7(d) “nicotinamide riboside chloride” with amendment note M8 = Regulation (EU) 2021/418 according to the amendment list of the version [16]; Union list 02017R2470-20260810: entry “nicotinamide riboside chloride”, “Authorised on 20 February 2020”, applicant ChromaDex, data protection under Article 26, expired on February 20, 2025 (“Date on which the data protection expires: 20 February 2025”), entry with note M92 = Implementing Regulation (EU) 2022/1160, insertion originally M40 = Implementing Regulation (EU) 2020/16 [17]. Cellar SPARQL: 32020R0016, 32022R1160, 32021R0418, plus 32023R1065 (Annex II of Regulation 1925/2006) and 32023R0439 (Regulation 609/2013), the last two captured only via the title.
  • Cross-check on October 24, 2026, Union list 02017R2470-20260810 (German and English, XHTML via Cellar), table structure of the entry: row “food supplements as defined in Directive 2002/46/EC” with separate maximum levels for adults excluding pregnant and lactating women and for pregnant and lactating women; the labelling cell beginning “(2) … only by persons over 18 years and excluding pregnant and lactating women” starts only in the row “foods for special medical purposes” (rowspan=4: FSMP, total diet replacement, meal replacements). For food supplements, only the designation requirement applies (cell rowspan=2). Maximum levels deliberately not reproduced.
  • Related entries checked on October 24, 2026 according to K1/G1 and G12: family nad-vorstufen remains; nicotinamide “other form” (no prodrug construction from mouse data); reverse link to nicotinsaeure “other form” added because the nicotinic acid profile links NR (reverse links on both sides). Otherwise no changes in content in this task.
  • October 25, 2026: decision q056 rechecked (NR pregnancy, EFSA 2019 vs. Union list). Abstract [15] (PubMed efetch): safe for healthy adults excluding pregnant and lactating women; for pregnant and lactating women, margin of safety from the developmental toxicity study insufficient for the proposed amount, a lower intake safe. Implementing Regulation (EU) 2020/16 (CELEX 32020R0016, Cellar, XHTML) read: recital 8 adopts both conclusions of the opinion, the table inserts the separate conditions for adults and for pregnant and lactating women [18]. Finding: the condition in the Union list comes from the EFSA opinion 2019; risk text and status.deutschland specified accordingly, entry in “nicht_verifiziert” deleted. Maximum amounts not reproduced. Decision q010: area of the Parkinson’s claim “Regeneration & Heilung” → “Nervensystem” (neurological disease). Decision q114: status.eu and status.deutschland already correspond to the checked status (Annex II Part A point 7(d), Union list), no change. Abstract only checked (q012): all study findings except [5] (full text).
  • October 25, 2026, decision q097 (Tilman: family remains, health claims only if the form is marketed with them): family nad-vorstufen remains; no field health_claims, because there is no evidence that nicotinamide riboside chloride is marketed with an authorized niacin claim.
  • Precision flags (m004, implementation by Claude on October 26, 2026, pending confirmation by Tilman): “Better insulin sensitivity and more energy in metabolism” → “kleine_studien”: [8] n = 40, [9] same study with 40 participants, [10] n = 13 (each per abstract).
  • Precision flags (m004, implementation by Claude on October 26, 2026, pending confirmation by Tilman): “Better walking distance in circulatory disorders of the legs” → “kleine_studien”: [12] n = 90 (abstract).
  • Cross-check on October 26, 2026 (m004, implementation by Claude, pending confirmation by Tilman): evidence for the set precision flags (participant numbers and funding and conflict-of-interest information) transferred from the review notes into the rationale so that readers can verify it; participant numbers compared again against the PubMed abstracts.

Not verified

  • US status (GRAS, NDI) not checked in agency documents; the GRAS statement comes from a manufacturer study [6].
  • Half-life of NR in humans.
  • Controlled human studies on intravenous NR administration not found.

No dosages, no sources of supply. This information does not replace medical advice.

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