GradedHealth

NMN and NR raise NAD+ levels — but a new review finds mixed health benefits

A 2026 review of 33 human studies finds NMN and NR reliably raise blood NAD+ and look safe short-term — but the health payoff is still mixed.

Published October 2026

Short answer

NAD+ rises — about two-fold at 1 g a day — and short-term use looks safe. But trials haven't shown consistent gains in strength, energy or metabolism, and aging benefits are untested in humans. Evidence grade C (Limited). A 2026 systematic review of 33 human studies (28 randomised) plus newer meta-analyses: NAD+ rises consistently, but health benefits are mixed and often null; trials are small, short and sometimes industry-funded.

Key takeaways

  • In an 8-week trial of 140 adults with overweight, 100, 300 and 1,000 mg a day of NR raised whole-blood NAD+ by 22%, 51% and 142% [1].
  • A 2026 head-to-head trial found 1 g a day of NR or NMN raised blood NAD+ about two-fold in 14 days, while nicotinamide did not [2].
  • A 2025 meta-analysis of 10 trials in adults over 60 found no clear effect of NMN on muscle mass, grip strength, walking speed or chair-stand time [3].
  • A 2026 network meta-analysis of 27 studies (1,599 people) found NMN improved endurance performance dose-dependently, but no NAD+ supplement reduced perceived fatigue [4].
  • Short-term use looks safe: NMN did not increase side effects versus placebo across 10 trials [5], and 33 human studies found NR and NMN generally well tolerated [6].

What the study did

Researchers reviewed 113 studies of NAD+ supplements published between 2010 and 2025: 33 human trials (28 of them randomised), plus 80 studies in animals [6]. The review asked two questions: do NR and NMN raise NAD+, and does that translate into health benefits [6].

What it found

In humans, oral NR and NMN consistently raised NAD-related metabolites in blood and cells, and were generally well tolerated over weeks to months [6]. Their effects on physical function, metabolism, blood vessels and other healthspan measures were mixed — many trials found no difference from placebo [6]. In animals, NAD+ supplementation was often linked to better metabolic and physical outcomes, but results varied [6]. The reviewers concluded that NAD+ supplements clearly do something in the body, but their clinical value for anti-aging or wellness is not yet established [6].

How it fits

The NAD+ half of the story is solid. In an 8-week trial of 140 adults with overweight, 100, 300 and 1,000 mg a day of NR raised whole-blood NAD+ by 22%, 51% and 142% [1]. In the first head-to-head comparison, 1 g a day of NR or NMN raised whole-blood NAD+ about two-fold over 14 days, while nicotinamide did not — and much of the effect appears to run through gut bacteria [2].

Whether that matters is where the evidence splits. A 2025 meta-analysis of 10 randomised trials in adults over 60 found no clear effect of NMN on muscle mass, grip strength, gait speed or chair-stand time, concluding the evidence does not support either supplement for preserving muscle [3]. Another 2025 meta-analysis reported small gait-speed gains (standardised mean difference 0.34) and lower liver enzymes with NMN [7]. In a 2026 network meta-analysis of 27 studies (1,599 people), medium and high doses of NMN improved endurance-type performance (standardised mean difference 0.66 and 1.02), while no precursor improved muscle strength [4].

Individual trials show real signals. NMN improved muscle insulin sensitivity in postmenopausal women with prediabetes [8]. Twelve weeks of NMN was linked to a slightly faster 4-metre walk and better sleep-quality scores in older adults, while the main stepping test was unchanged [9]. In a small 28-day trial, NMN reduced weight, LDL cholesterol and diastolic blood pressure in 30 adults with overweight [10]. NR improved six-minute walking distance in people with peripheral artery disease — by 17.6 m overall, and 31 m in those who took at least three-quarters of their pills [11].

Other results are flat. Pooled data from 8 randomised trials found no meaningful change in blood sugar, insulin resistance or cholesterol with NMN [12]. Two small trials in mild cognitive impairment found NR raised NAD+ but did not improve cognition [13][14]. On blood pressure, a 2026 meta-analysis of 10 small trials found diastolic pressure about 2 mmHg lower and systolic pressure about 4 mmHg lower in people over 60, which the authors called preliminary [15].

Safety has looked reassuring. Across 10 NMN trials, side effects and liver enzymes were no different from placebo [5], and 3,000 mg a day of NR for four weeks caused no moderate or severe side effects in a Parkinson's trial [16].

Limits

The 2026 review is a synthesis, not a pooled calculation, and most of its human trials were small and short — weeks to a few months [6]. Several were run by supplement makers, including ChromaDex [1], Meiji [9] and Nestlé [2]. Quality problems show up in the pooled analyses too: in one review of NMN and metabolic markers, 5 of 12 studies were at high risk of bias [17], and a cholesterol review rated its evidence very low to low [18]. And the review found that no human study has yet tracked whether NAD+ supplements affect aging itself, rather than short-term markers [6].

Go deeper

  • NAD+ Supplements — NR and NMN supplements raise blood NAD+ levels — by about 50% at 300 mg a day and more than double at 1,000 mg — and short-term use has been well tolerated.

References

  1. Safety and Metabolism of Long-term Administration of NIAGEN (Nicotinamide Riboside Chloride) in a Randomized, Double-Blind, Placebo-controlled Clinical Trial of Healthy Overweight Adults.. Sci Rep, 2019.
  2. The differential impact of three different NAD+ boosters on circulatory NAD and microbial metabolism in humans.. Nat Metab, 2026.
  3. The Effect of Nicotinamide Mononucleotide and Riboside on Skeletal Muscle Mass and Function: A Systematic Review and Meta-Analysis.. J Cachexia Sarcopenia Muscle, 2025.
  4. Domain-specific effects of NAD+ precursors on fatigue and functional performance: a systematic review and network meta-analysis.. Front Nutr, 2026.
  5. Safety and Metabolism-Related Outcomes of Oral Nicotinamide Mononucleotide Supplementation in Adults: A Systematic Review and Meta-Analysis.. Nutrients, 2026.
  6. NAD⁺ supplementation for anti-aging and wellness: A PRISMA-guided systematic review of preclinical and clinical evidence.. Ageing Res Rev, 2026.
  7. Effects of Nicotinamide Mononucleotide Supplementation on Muscle and Liver Functions Among the Middle-aged and Elderly: A Systematic Review and Meta-analysis of Randomized Controlled Trials.. Curr Pharm Biotechnol, 2025.
  8. Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women.. Science, 2021.
  9. Ingestion of β-nicotinamide mononucleotide increased blood NAD levels, maintained walking speed, and improved sleep quality in older adults in a double-blind randomized, placebo-controlled study.. Geroscience, 2024.
  10. Nicotinamide Adenine Dinucleotide Augmentation in Overweight or Obese Middle-Aged and Older Adults: A Physiologic Study.. J Clin Endocrinol Metab, 2023.
  11. Nicotinamide riboside for peripheral artery disease: the NICE randomized clinical trial.. Nat Commun, 2024.
  12. Effects of Nicotinamide Mononucleotide on Glucose and Lipid Metabolism in Adults: A Systematic Review and Meta-analysis of Randomised Controlled Trials.. Curr Diab Rep, 2024.
  13. A randomized placebo-controlled trial of nicotinamide riboside in older adults with mild cognitive impairment.. Geroscience, 2024.
  14. A phase-II randomized controlled pilot study of nicotinamide riboside supplementation in older adults with amnestic mild cognitive impairment.. Alzheimers Dement, 2026.
  15. Effects of Nicotinamide Mononucleotide Supplementation on Blood Pressure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.. Nutrients, 2026.
  16. NR-SAFE: a randomized, double-blind safety trial of high dose nicotinamide riboside in Parkinson's disease.. Nat Commun, 2023.
  17. Efficacy of oral nicotinamide mononucleotide supplementation on glucose and lipid metabolism for adults: a systematic review with meta-analysis on randomized controlled trials.. Crit Rev Food Sci Nutr, 2025.
  18. Effects of Supplementation with NAD + Precursors on Metabolic Syndrome Parameters: A Systematic Review and Meta-Analysis.. Horm Metab Res, 2024.