NR (Nicotinamide Riboside): The Human Trial Record
Of all NAD+ boosters, nicotinamide riboside has the longest human track record — roughly 44 registered trials. Oral NR reliably raises blood NAD+. The harder question: does it improve mitochondrial function? Here is every major human finding, graded.
What NR is
Nicotinamide riboside is an NAD+ precursor vitamin. Note for the NMN-curious: extracellular NMN is converted to NR before cellular uptake — the two converge on the same salvage pathway, so they are not as different as marketing suggests.
Dose–response: oral NR raises blood NAD+ in humans
Trammell et al. 2016, the first human pharmacokinetic study, found that 100, 300 and 1,000 mg produced dose-dependent rises in the blood NAD+ metabolome. Conze et al. 2019, an eight-week RCT in overweight adults, found whole-blood NAD+ rose 22%, 51% and 142% at 100, 300 and 1,000 mg within two weeks and stayed elevated — with no flushing, adverse-event differences versus placebo, LDL effect or one-carbon effect. The trial was ChromaDex-funded, and authors included ChromaDex employees and its chief scientific adviser.
Dellinger et al. 2017 studied Elysium’s NR plus pterostilbene in 120 adults aged 60–80 and reported roughly 40–90% rises; it was Elysium-funded. Martens et al. 2018 found NAD+ rose in PBMCs. NR-SAFE 2023 found 3,000 mg/day produced up to a five-fold blood NAD+ rise. The critical caveat is blood ≠ tissue. Dollerup et al. 2020 found skeletal-muscle NAD+ unchanged after 12 weeks of 2,000 mg/day despite the blood effect; Stocks et al. 2021 found the same. Blood NAD+ rise is at best Preliminary evidence of tissue repletion.
Muscle mitochondria — the direct measurements
Four muscle-biopsy trials measured mitochondrial function directly, and all came back null. Dollerup 2020 (40 men, 2,000 mg/day, 12 weeks, high-resolution respirometry) found no change in respiratory capacity, mitochondrial protein abundance, fractional area, morphology, muscle NAD+ metabolites or PGC-1α mRNA; the authors wrote that the data “do not support the hypothesis that dietary NR supplementation has significant impact on skeletal muscle mitochondria.”
Remie 2020 found no change in mitochondrial function; only breakdown products rose in muscle. Elhassan 2019 found that 1 g/day for 21 days augmented the muscle NAD+ metabolome but left mitochondrial bioenergetics unchanged, with energy-metabolism pathways downregulated on RNA-seq. Stocks 2021 found no effect on respiration or signaling. Exercise performance did not improve in Martens 2018 or Remie 2020. Established · null
Metabolic outcomes — insulin sensitivity, glucose, body composition
Dollerup 2018 (40 obese insulin-resistant men, 2,000 mg/day, 12 weeks, gold-standard clamp) found no effect on insulin sensitivity, body composition, fasting glucose, HbA1c or cholesterol; a follow-up found no effect on glucose tolerance, insulin, GLP-1 or beta-cell indices. Remie 2020 likewise found no effect on whole-body or tissue-specific insulin sensitivity. In mice, NR improves glycemic control — but that is Preliminary · animal evidence, and human translation has failed so far.
Cardiovascular signals
Martens 2018 (24 adults, 1,000 mg/day, six weeks) found lower systolic blood pressure and aortic stiffness, with the largest changes in participants starting above normal. A 2023 Science Advances critical review notes these findings “have not been supported by other reports”; Remie 2020 and Wang 2022 in heart-failure patients found no cardiovascular changes. General claims that NR “lowers blood pressure” or “reverses arterial aging” are Marketing ahead of evidence.
Brain and neurological signals
NADPARK 2022 (30 newly diagnosed Parkinson’s patients, 1,000 mg/day, 30 days, phase I) was the first demonstration that oral NR raises brain NAD+ in humans, measured by 31P-MRS; 10 of 13 recipients responded. It also found altered cerebral metabolism on FDG-PET and upregulation of mitochondrial, lysosomal and proteasomal gene sets — transcriptomic evidence, not measured respiration or ATP. The study was small and short, and needs phase II. Two authors filed a patent application on NR use in Parkinson’s.
Small studies in ALS and ataxia telangiectasia reported functional signals, but they remain preliminary. No human data support general “cognitive enhancement” in healthy people. Marketing ahead of evidence
Safety
NR has been well tolerated at tested doses up to 2,000–3,000 mg/day over weeks to months, with no serious-adverse-event signal, no flushing unlike niacin, no LDL elevation and no one-carbon dysregulation at 1,000 mg/day or less. But no published trial exceeds about six months, so long-term safety data do not exist.
The cancer question is animal-only, mixed and unresolved: NR increased triple-negative breast cancer prevalence and brain metastasis in immunocompromised mice; NMN raised UV-induced skin-cancer burden in mice; NAD+ precursors reduced chemotherapy efficacy in pancreatic-cancer models; while one mouse study found NR suppressed liver-cancer progression. There are no human data. Anyone with active cancer or high risk should know this is unstudied in humans.
NMN in brief
Meta-analyses from 2024–2026 find NMN is well tolerated and raises NAD+ biomarkers, with no consistent effects on fasting glucose, HbA1c, insulin, lipids, weight or BMI. One distinctive signal: Yoshino 2021 reported about 25% higher muscle insulin sensitivity in 25 postmenopausal women with prediabetes after 250 mg/day for 10 weeks — small, sex-specific and unreplicated Preliminary — while muscle NAD+ itself was unchanged. In September 2025, FDA reversed its 2022 position: NMN may lawfully be marketed as a dietary supplement again. That reversal is not an efficacy endorsement.
The mitochondrial bottom line
NR reliably raises blood NAD+ Established. Four muscle-biopsy trials found no improvement in measured mitochondrial respiration, content or bioenergetics Established · null. Claims that NR “improves mitochondrial function” in humans are Marketing ahead of evidence; the animal evidence has not translated.