COMPOUND

Compounds / Supplements

NR

Nicotinamide Riboside (Niagen / Tru Niagen)

Supplements Oral OTC supplement

NAD+ precursor: two enzymatic steps from NAD+ (NR → NMN → NAD+). Most-studied NAD+ precursor with multiple human RCTs showing dose-dependent elevation of blood NAD+ (22% at 100 mg, 51% at 300 mg, 142% at 1000 mg in Conze 2019). Marketed primarily as Niagen (ChromaDex) and Tru Niagen. Clear regulatory status as a dietary supplement (GRAS notification accepted by FDA, multiple NDIs accepted). Generally regarded as the safer/cleaner option vs NMN due to longer history of human dosing.

At a glance

Half-life
~2.7 h Plasma NR Tmax ~2.7h; rapidly metabolized. NAD+ pool elevation persists for hours-to-days post-dose; chronic dosing produces sustained NAD+ elevation over 2 weeks.
Routes
Oral
Evidence base
5 studies 5 human

Mechanism

Oral NR enters cells via equilibrative nucleoside transporters (ENTs). Phosphorylated to NMN by NRK1/NRK2 kinases, then converted to NAD+ by NMNAT. Bypasses some salvage pathway steps, resulting in direct NAD+ pool elevation. Like NMN, raises NAD+ for downstream sirtuin and PARP activity. Some NR is also de-glycosylated to nicotinamide before re-entering salvage.

Dosing

Any amounts shown here are reported from published studies only. 5 of 5 catalogued studies involved human subjects. COMPOUND does not publish its own dosing guidance.

Where a study reports an amount, it appears in that study's entry below, attributed to the source.

Published evidence

  1. Human RCT 2023

    NR-SAFE: a randomized, double-blind safety trial of high dose NR in Parkinson's disease

    Brakedal B, Dölle C, Riemer F, et al. Nature Communications

    n=20 PD patients, 4 weeks of 1500 mg BID (3000 mg/day). Safe, no moderate or severe AEs. Pronounced augmentation of NAD metabolome. NO methyl donor depletion (SAM and homocysteine unchanged). Supports dose escalation to 3 g/day.

    PMID 38016950

  2. Human RCT 2019

    Safety and Metabolism of Long-term NIAGEN (NR Chloride) Administration in Healthy Overweight Adults

    Conze D, Brenner C, Kruger CL Scientific Reports

    n=140, 8-week dose-ranging trial (100/300/1000 mg). Dose-dependent NAD+ elevation: +22%, +51%, +142%. No adverse events differentially attributable to NR. Foundational dose-response and safety demonstration.

    PMID 31278280

  3. Human RCT 2019

    NR Augments the Aged Human Skeletal Muscle NAD+ Metabolome and Induces Anti-inflammatory Signatures

    Elhassan YS, Kluckova K, Fletcher RS, et al. Cell Reports

    n=12 aged men (70-80 y/o), 21 days at 1000 mg/day NR vs placebo crossover. Skeletal muscle NAD+ metabolome elevated. Reduced circulating inflammatory cytokines.

    PMID 31412242

  4. Human RCT 2018

    Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults

    Martens CR, Denman BA, Mazzo MR, et al. Nature Communications

    n=24, 6-week crossover RCT, 1000 mg/day NR. Elevated whole-blood NAD+ ~60%. Trend toward reduced systolic BP and arterial stiffness in subgroup with stage 1 hypertension. Foundational human trial demonstrating PD effect of chronic NR.

    PMID 29599478

  5. Human RCT 2018

    A randomized placebo-controlled clinical trial of NR in obese men: safety, insulin-sensitivity, and lipid-mobilizing effects

    Dollerup OL, Christensen B, Svart M, et al. Am J Clin Nutr

    n=40 obese sedentary men, 12 weeks of 1000 mg BID (2g/day). NO improvement in insulin sensitivity (clamp). No change in fasting glucose, HbA1c, lipids, or ALT. Plasma TG increased modestly. NEGATIVE result for insulin sensitivity in obese men.

    PMID 29992272

Reported side effects

Generally well-tolerated
Very common Mild · Across multiple RCTs (Martens 2018, Dollerup 2018, Conze 2019, Elhassan 2019, NR-SAFE 2023), AE rates similar to placebo. NR-SAFE confirmed safety up to 3000 mg/day x 4 weeks. No reports of flushing (unlike high-dose niacin).
Mild GI symptoms
Occasional Mild · Pruritus, excessive sweating, bloating, mild stool changes, acid reflux, loose stools reported in Dollerup 2018 (4 NR vs 2 placebo participants). All mild, transient.
Modest TG elevation at high dose
Occasional Mild · Plasma TG increased modestly in Dollerup 2018 at 2g/day. Reasonable to monitor lipids if dosing chronically at >1g/day.

Interactions

  • NMN Redundant

    Same NAD+ pool target. No proven additive benefit from stacking.

Storage

Capsules room temp, dry, dark. Niagen crystal form is more stable than amorphous NR. Third-party tested products preferred; generic NR products show variable purity.