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NR

/ Nicotinamide riboside; NAD+ precursor (small molecule)

TIER 2 · TranslationalN = 0 · TESTING PENDINGMW 255.20 g·mol⁻¹

ALIAS · NR · Nicotinamide riboside chloride · Niagen

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Research use onlyAny dose figures below describe what specific cited studies used, reported factually. Nothing on this page is guidance for human use.READ FIRST →

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§ A · Identity

Primary sequence— sequence not captured —

MW · 255.20CLASS · Nicotinamide riboside; NAD+ precursor (small molecule)CATEGORY · Longevity

Tier 2. Nicotinamide riboside is the most extensively studied NAD+ precursor in human pharmacology, with multiple Phase 1 and small Phase 2 trials. Niagen (ChromaDex's NR formulation) has GRAS notification in the US and is sold as a dietary supplement; NR has also been studied at the prescription-investigational level in Parkinson disease (NADPARK / Brakedal 2022) and ataxia-telangiectasia. The geroscience research from the Charles Brenner laboratory (NR's original discoverer) and collaborators is substantial.

§ B · Mechanism of action

Nicotinamide riboside is converted to NAD+ via the salvage pathway through NRK1/NRK2 (nicotinamide riboside kinases), bypassing the rate-limiting Preiss-Handler steps from nicotinic acid. This kinetic feature is the proposed pharmacological advantage over niacin and nicotinamide. Oral NR raises whole-blood and tissue NAD+ levels in human pharmacokinetic studies (Trammell 2016) and in chronic dosing regimens (Martens 2018, Brakedal 2022), with downstream effects on sirtuin substrate availability inferred from preclinical work but not directly measured in tissue under typical dosing schedules.

§ C · Human clinical evidence

Tier 2. Trammell 2016 established human pharmacokinetics — single oral doses of NR 100–1000 mg raised whole-blood NAD+ in a dose-dependent manner. Martens 2018 reported a randomised crossover trial of NR 500 mg twice daily for six weeks in healthy older adults, with elevation of whole-blood NAD+ and modest reductions in systolic blood pressure and aortic stiffness in a subgroup. Brakedal 2022 used NR in Parkinson disease as the cerebral-NAD+-elevation arm. No Phase 3 RCT in any indication.

§ D · Primary literature

PubMed27721479Trammell SA et al. — Nicotinamide riboside is uniquely and orally bioavailable in mice and humans · Nature Communications · human-phase-1Single oral doses of NR raised whole-blood NAD+ in humans in a dose-dependent fashion; established human oral bioavailability and the metabolome signature of NR dosing.Limitations: Phase 1 PK; small n; healthy volunteers; single-dose pharmacokinetics rather than chronic dosing.2016

PubMed29599478Martens CR et al. — Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults · Nature Communications · human-phase-2Six-week NR 500 mg twice daily was well tolerated and elevated whole-blood NAD+ in healthy middle-aged and older adults; secondary endpoints suggested modest effects on systolic blood pressure and aortic stiffness in a subgroup.Limitations: Small randomised crossover; secondary cardiovascular endpoints exploratory; healthy population.2018

§ F · Safety signal

Well tolerated in published Phase 1 and Phase 2 work at doses up to 2 g daily over weeks-to-months. Common adverse events include nausea and flushing at higher doses; the flushing pattern is milder than niacin's. No identified major chronic-administration safety signal, but the long-term safety database is limited.

§ H · Regulatory status

Regulatory status

FDA status:: Not FDA-approved

§ I · Notable gaps and controversies

As with NMN, the geroscience research is real but the human disease-modifying-outcome database is small. Sold widely in the US as Niagen and other supplement formulations; product specifications vary by manufacturer and the supplement-channel pathway does not import the methodological control of the published academic trials.