NR (Nicotinamide Riboside)

Blood NAD+. Trammell et al. (Nat Commun, 2016; PMID 27721479): first human pharmacokinetics, sponsored by the NR supplier; oral NR raises blood NAD+. Martens et al. (Nat Commun, 2018; PMID 29599478): NIH-funded 2 by 6-week crossover in healthy middle-aged and older adults; NAD+ raised, well tolerated, blood pressure and arterial stiffness signals exploratory. Conze et al. (Sci Rep, 2019; PMID 31278280): 8-week dose-ranging trial funded by the NR supplier, with its employees among the authors; 100, 300 and 1,000 mg/day raised whole-blood NAD+ by 22, 51 and 142 percent. Clinical outcomes. Dollerup et al. (Am J Clin Nutr, 2018; PMID 29992272): 40 obese insulin-resistant men, 2,000 mg/day for 12 weeks, investigator-initiated; clamp-measured insulin sensitivity, glucose metabolism, energy expenditure and body composition unchanged. Orr et al. (GeroScience, 2024; PMID 37994989): 20 older adults with mild cognitive impairment, 1 g/day for 10 weeks, NIH-funded with product from the supplier; NAD+ 2.6-fold higher, cognition unchanged. Martens et al. (Alzheimers Dement, 2026; PMID 42478598): phase-II randomized, double-blind, placebo-controlled pilot in amnestic mild cognitive impairment, 42 completers over 12 weeks; blood NAD+ doubled, cognition (the primary outcome), total cerebral blood flow and blood pressure unchanged. Wu et al. (EClinicalMedicine, 2025; PMID 41357333): 58 adults with long COVID, 2,000 mg/day, 24 weeks, with authors holding equity in the NR company; NAD+ up 2.6- to 3.1-fold, no difference in cognition, fatigue, sleep, anxiety or depression, and dropout of 51 percent on NR. McDermott et al. (Nat Commun, 2024; PMID 38871717), NICE: 90 people with peripheral artery disease, 6 months, American Heart Association funded; six-minute walk 17.6 m better than placebo at a one-sided 0.10 significance level, the one positive NR-alone clinical trial, unreplicated. Dolopikou et al. (Eur J Nutr, 2020; PMID 30725213): acute single-dose crossover in 12 young and 12 old men; VO2max and concentric torque unchanged, isometric torque 8 percent higher and fatigue index better in the old men only, so not an exercise-performance benefit. Dellinger et al. (NPJ Aging Mech Dis, 2017; PMID 29184669): NR combined with pterostilbene, funded by the company that sells the combination with its employees as authors; raises NAD+ but does not isolate nicotinamide riboside. Ratajczak et al. (Nat Commun, 2016; PMID 27725675): cell and mouse work on NRK1, mechanism only, no weight for a human grade. Brakedal et al. (JAMA, 2026; PMID 42848371), NOPARK: phase 3 randomized double-blind trial, 410 adults with early Parkinson disease, 1,000 mg/day for 52 weeks, publicly funded with product from the supplier; the primary rating score (MDS-UPDRS I to III) worsened 2.72 points more than on placebo and non-motor symptoms also worsened more, so this use carries the harm badge. Grade C: one unreplicated positive clinical trial, the rest null, and one trial with the treated arm worse than placebo.