NAD+ precursors (nicotinamide riboside and nicotinamide mononucleotide)

Most trials are small and short, and several were funded by NR or NMN makers. Our grades are proposals per outcome; the evidence grading method explains what each grade requires.

Do NAD+ precursors improve endurance?

The three trials below tested NMN; for NR, the only endurance signal was in a clinical population [5]. Two small trials found gains on some measures and one found none; all three had industry funding or donated product [2][3][4]. In a 6-week double-blind trial, 48 recreationally trained runners took 300, 600 or 1200 mg/day of NMN or placebo while training 5-6 times a week [2]. Power at the first and second ventilatory thresholds rose more in the 600 and 1200 mg groups than with placebo, but VO2max and peak power did not differ [2]. GeneHarbor (Hong Kong) Biotechnologies provided the NMN and placebo [2].

In 80 healthy middle-aged adults, 300, 600 or 900 mg of NMN daily for 60 days raised six-minute walking distance more than placebo at days 30 and 60 [3]. That trial was fully funded by two NMN manufacturers, Aba Chemicals and Abinopharm, which employed some of its authors [3]. In 30 overweight or obese adults aged 45 and older given 1000 mg of MIB-626 twice daily for 28 days, aerobic capacity and muscle fatigability did not differ significantly from placebo, in a trial funded in part by MIB-626's developer, Metro International Biotech [4].

A 2026 network meta-analysis pooled 27 studies with 1,599 participants [1]. It found dose-dependent gains in endurance with NMN (medium dose SMD 0.66, 95% CI 0.09-1.23; high dose SMD 1.02, 95% CI 0.43-1.60) [1]. Its cohorts included clinical groups [1]. In people with peripheral artery disease, a clinical population, NR was associated with a longer six-minute walk; results may not apply to healthy adults [5].

Do NAD+ precursors improve strength?

Not in the pooled evidence so far [5][1]. A 2025 meta-analysis of randomized trials in adults with a mean age of 60.9 to 83, including some clinical groups, found no significant effect of NMN on handgrip strength (left grip MD 0.61, 95% CI -0.89 to 2.10) or gait speed (MD -0.01, 95% CI -0.08 to 0.06) [5]. NMN also did not improve knee extension strength or thigh muscle mass, and the authors concluded the evidence does not support NR or NMN for preserving muscle mass and function in adults with a mean age over 60 [5]. The 2026 network meta-analysis likewise found neuromuscular strength unchanged [1]. In people with mild cognitive impairment, a clinical population, the review reported lower SPPB scores and a slower chair-stand test with NR [5].

Most single trials were null or weak. The 28-day MIB-626 trial, funded in part by its developer, found no significant difference in muscle strength or stair-climbing power [4]. In 108 older Japanese adults, the authors reported that afternoon NMN improved a sit-to-stand test (d = 0.72), although sit-to-stand times improved in all groups, including placebo [7]. In healthy older men given 250 mg/day of NMN for 6 or 12 weeks, improvements in gait speed and left grip were only nominally significant, and the authors said they need validating in larger studies [6]. That trial was funded by Mitsubishi Corporation Life Sciences [6]. One 2025 meta-analysis of 9 trials with 412 middle-aged and older adults did report faster gait speed with NMN (SMD 0.34, 95% CI 0.03 to 0.66) [25]. Gait speed measures walking, not strength.

Do NAD+ precursors lower blood pressure?

For NMN, two meta-analyses found a small drop in diastolic pressure and no clear change in systolic pressure [9][10]. A 2026 meta-analysis pooled 10 trials with 349 adults who had no cardiovascular disease or diabetes, most with above-normal blood pressure [9]. Compared with placebo, NMN was associated with a modest 2.15 mmHg reduction in resting diastolic pressure (95% CI -3.68 to -0.61), and the drop in systolic pressure was not statistically significant [9]. In a subgroup aged 60 and older, systolic pressure fell by 3.94 mmHg (95% CI -7.06 to -0.82), and the authors called the evidence preliminary and suggestive [9].

In the 28-day MIB-626 trial, diastolic pressure fell by 7.01 mmHg more than with placebo, in a trial funded in part by the drug's developer [4].

For NR, results have not reached significance [11][12][13]. In a 6-week crossover trial in 24 healthy middle-aged and older adults, 500 mg of NR twice daily lowered systolic pressure by a mean 3.9 mmHg, a trend that was not significant after correction for multiple comparisons [11]. In 54 sedentary adults aged 55 and older with raised daytime systolic pressure, NR at 1000 mg/day with walking exercise was not superior to placebo with exercise [12]. A 6-week crossover in 13 overweight or obese adults found no effect of NR on ambulatory blood pressure [13]. A 2024 meta-analysis of 19 trials of NAD+ precursors, including nicotinic acid and other vitamin B3 forms, found lower total cholesterol and triglycerides and no significant effect on its other metabolic outcomes; the authors rated the evidence very low to low quality [26]. A 2026 NMN-only meta-analysis found no significant effect on lipids [10].

Do NAD+ precursors improve sleep quality?

The evidence is limited and mixed [8][7][1]. In 60 older adults, 250 mg/day of NMN for 12 weeks lowered global Pittsburgh Sleep Quality Index (PSQI) scores compared with placebo, in a trial run by researchers employed by Meiji Holdings [8]. Its primary outcome, a stepping test, did not differ [8]. In 108 older Japanese adults given 250 mg of NMN or placebo in the morning or afternoon for 12 weeks, the abstract reports significant interactions only for a sit-to-stand test and drowsiness [7]. The 2026 network meta-analysis abstract reports that no precursor significantly improved sleep quality [1], but its full text says sleep quality was excluded from the network analysis because too few trials connected [1].

Do NAD+ precursors reduce fatigue?

Not in the pooled evidence [1]. The 2026 network meta-analysis found that no NAD+ precursor significantly improved perceived fatigue, but it mixed four precursors and included clinical cohorts [1]. In the 12-week trial in older Japanese adults, drowsiness improved within both afternoon groups, including placebo; the authors reported a significant interaction and concluded that afternoon NMN reduced drowsiness [7].

What the evidence does not show

The trials above do not establish that a rise in blood NAD+ translates into better function. In 20 older adults with mild cognitive impairment, a clinical population, NR at 1 g/day for 10 weeks, with NR and placebo provided by ChromaDex, raised blood NAD+ 2.6-fold while cognitive test scores stayed stable [22]. In postmenopausal women with prediabetes who were overweight or obese, a clinical population, a laboratory measure of muscle insulin sensitivity rose after 10 weeks of NMN but not after placebo [18]. That is a metabolic change, not a functional benefit, and may not apply to healthy adults [18].

Blood NAD+ rises within weeks of starting NR [23][11][17]. In 8 healthy volunteers, NR uptitrated to 1000 mg twice daily raised whole-blood NAD+ by 100% [23]. In an 8-week trial funded by ChromaDex, 100, 300 and 1000 mg of NR raised whole-blood NAD+ by 22%, 51% and 142% within 2 weeks, and the increases were maintained to the end of the study [14]. At 1500 mg twice daily in people with Parkinson's disease, NR gave up to a 5-fold increase in blood NAD+ [17].

In a 14-day open-label trial in 65 healthy adults, NR and NMN, but not nicotinamide, raised circulating NAD+ by comparable amounts; the trial was run by researchers employed by Nestlé Research [27].

On timing, one 12-week trial gave 250 mg of NMN in the morning or afternoon; the authors concluded that afternoon intake reduced drowsiness, but drowsiness also improved in the afternoon placebo group [7].

In short trials, NR and NMN were well tolerated [10][15]. A 2026 meta-analysis of 15 NMN trials, 10 with safety data, at 250-2000 mg/day for 14 days to 24 weeks found no increase in overall, serious or withdrawal-related adverse events and no rise in the liver enzymes ALT or AST [10]. The authors called for longer trials [10].

For NR, an 8-week trial funded by ChromaDex found no flushing, no difference in adverse events from placebo, and no rise in LDL cholesterol [14]. In 40 obese, insulin-resistant men, 2000 mg/day of NR for 12 weeks caused no serious adverse events and safety blood tests were normal [15]. In a 4-week safety trial in 20 people with Parkinson's disease, a clinical population, NR at 1500 mg twice daily caused no moderate or severe adverse events, though serum homocysteine rose slightly at first [17].

EFSA assessed the proposed use of NR chloride at up to 300 mg/day and found it safe for healthy adults; for pregnancy and lactation it judged only up to 230 mg/day safe, because the margin of exposure from a rat developmental toxicity study was insufficient at the higher intake [19]. In a later opinion, EFSA noted experimental pathways by which intakes of nicotinamide or its precursors well above need might cause adverse effects [20]. For NMN, EFSA found one product safe for adults, excluding pregnant and lactating women; a 90-day rat study showed effects on reproductive organs, but EFSA judged the margin of exposure sufficient [21].

As of November 11, 2026 we found no human study of NR or NMN interacting with a medicine (PubMed search, November 11, 2026). Health Canada's NMN monograph requires products to tell people with diabetes to ask a health care practitioner before use, citing a trial in which NMN changed muscle insulin sensitivity [36][18].

If you take medicines for diabetes or any other prescription medicine, talk to your doctor or pharmacist before combining them with NR or NMN.