A systematic review A review that searches for every study on a question in a set way and weighs them together, rather than picking a few. of 113 human and rodent studies found no outcome trials of intravenous or intramuscular NAD+ for anti-aging or wellness. It judged the clinical benefit of raising NAD+ for these goals inconclusive1Systematic review · 2026NAD⁺ supplementation for anti-aging and wellness: A PRISMA-guided systematic review of preclinical and clinical evidence.Overall, NAD⁺ augmentation shows clear biological activity, but clinical effectiveness for anti-aging or wellness outcomes remains inconclusive. Larger, well-designed randomized trials with longer follow-up and prespecified clinically meaningful endpoints are needed, particularly for parenteral approaches.Ageing Res Rev.
The review found one small non-randomized trial People are assigned by chance to the treatment or a comparison, so a difference in results is likely caused by the treatment itself. of intravenous NMN (a precursor, not NAD+ itself). It gave only short-term safety and blood-marker information. An IV NAD+ pilot study with no usable clinical outcomes was treated as background only1Systematic review · 2026NAD⁺ supplementation for anti-aging and wellness: A PRISMA-guided systematic review of preclinical and clinical evidence.Overall, NAD⁺ augmentation shows clear biological activity, but clinical effectiveness for anti-aging or wellness outcomes remains inconclusive. Larger, well-designed randomized trials with longer follow-up and prespecified clinically meaningful endpoints are needed, particularly for parenteral approaches.Ageing Res Rev.
Oral precursors reliably raised blood NAD levels in people, but effects on function, metabolism and blood vessels were mixed and often null1Systematic review · 2026NAD⁺ supplementation for anti-aging and wellness: A PRISMA-guided systematic review of preclinical and clinical evidence.Overall, NAD⁺ augmentation shows clear biological activity, but clinical effectiveness for anti-aging or wellness outcomes remains inconclusive. Larger, well-designed randomized trials with longer follow-up and prespecified clinically meaningful endpoints are needed, particularly for parenteral approaches.Ageing Res Rev. In a trial of 65 healthy adults, NR and NMN roughly doubled blood NAD+ after 14 days, and nicotinamide did not8Randomized trial · 2026 · 65 peopleThe differential impact of three different NAD+ boosters on circulatory NAD and microbial metabolism in humans.ClinicalTrials. gov identifier: NCT05517122 .Nat Metab.
Several randomized trials found no muscle benefit. In 40 obese men, 12 weeks of nicotinamide riboside (NR) did not change muscle mitochondria, the cell's energy units3Randomized trial · 2020 · 40 peopleNicotinamide riboside does not alter mitochondrial respiration, content or morphology in skeletal muscle from obese and insulin-resistant men.Our data do not support the hypothesis that dietary NR supplementation has significant impact on skeletal muscle mitochondria in obese and insulin-resistant men. Future studies on the effects of NR on human skeletal muscle may include both sexes and potentially provide comparisons between young and older people.J Physiol. In 14 older adults with impaired physical function, 32 days of niacin-type precursors did not improve muscle energy use7Randomized trial · 2021NAD+-Precursor Supplementation With L-Tryptophan, Nicotinic Acid, and Nicotinamide Does Not Affect Mitochondrial Function or Skeletal Muscle Function in Physically Compromised Older Adults.Our findings are consistent with previous findings on NAD+ efficacy in humans, and we show in community-dwelling, older adults with impaired physical function that NAD+-precursor supplementation through L-tryptophan, nicotinic acid, and nicotinamide does not improve mitochondrial or skeletal muscle function. This…J Nutr.
Some small trials were positive. In 60 older adults, 250 mg a day of NMN for 12 weeks shortened a 4-metre walk and improved sleep scores. The main test, a stepping test, showed no difference, so these may be chance findings6Randomized trial · 2024 · 60 peopleIngestion 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.Together, these results indicate that NMN intake could increase blood NAD + levels, maintain walking speed, and improve sleep quality in older adults. Interventions involving NMN aimed at maintaining walking speed could contribute to extended healthy life expectancy.Geroscience.
In Werner syndrome, a rare premature-aging disease, NR at 1,000 mg a day improved artery stiffness and skin ulcers in a crossover trial. This doesn't apply to healthy people9Randomized trial · 2025Nicotinamide Riboside Supplementation Benefits in Patients With Werner Syndrome: A Double-Blind Randomized Crossover Placebo-Controlled Trial.NR treatment significantly improved arterial stiffness, as indicated by CAVI, and likely suppressed renal functional decline in patients with WS. Therefore, NR may be beneficial for preventing atherosclerosis, skin ulcers, and kidney dysfunction in patients with WS.Aging Cell.
Key studies
Study
Who
What it found
Review of 113 studies, 20261Systematic review · 2026NAD⁺ supplementation for anti-aging and wellness: A PRISMA-guided systematic review of preclinical and clinical evidence.Overall, NAD⁺ augmentation shows clear biological activity, but clinical effectiveness for anti-aging or wellness outcomes remains inconclusive. Larger, well-designed randomized trials with longer follow-up and prespecified clinically meaningful endpoints are needed, particularly for parenteral approaches.Ageing Res Rev
Humans and rodents
No IV NAD+ outcome trials; benefit inconclusive
Trial, 20268Randomized trial · 2026 · 65 peopleThe differential impact of three different NAD+ boosters on circulatory NAD and microbial metabolism in humans.ClinicalTrials. gov identifier: NCT05517122 .Nat Metab
65 healthy adults
NR and NMN doubled blood NAD+ in 14 days
Trial, 20246Randomized trial · 2024 · 60 peopleIngestion 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.Together, these results indicate that NMN intake could increase blood NAD + levels, maintain walking speed, and improve sleep quality in older adults. Interventions involving NMN aimed at maintaining walking speed could contribute to extended healthy life expectancy.Geroscience
60 older adults
Faster walk and better sleep; main test unchanged
Trial, 20203Randomized trial · 2020 · 40 peopleNicotinamide riboside does not alter mitochondrial respiration, content or morphology in skeletal muscle from obese and insulin-resistant men.Our data do not support the hypothesis that dietary NR supplementation has significant impact on skeletal muscle mitochondria in obese and insulin-resistant men. Future studies on the effects of NR on human skeletal muscle may include both sexes and potentially provide comparisons between young and older people.J Physiol
40 obese, insulin-resistant men
NR did not change muscle mitochondria
Trial, 20217Randomized trial · 2021NAD+-Precursor Supplementation With L-Tryptophan, Nicotinic Acid, and Nicotinamide Does Not Affect Mitochondrial Function or Skeletal Muscle Function in Physically Compromised Older Adults.Our findings are consistent with previous findings on NAD+ efficacy in humans, and we show in community-dwelling, older adults with impaired physical function that NAD+-precursor supplementation through L-tryptophan, nicotinic acid, and nicotinamide does not improve mitochondrial or skeletal muscle function. This…J Nutr
14 older adults
No muscle function gain
Safety
Oral NAD-related supplements were generally well tolerated over weeks to months1Systematic review · 2026NAD⁺ supplementation for anti-aging and wellness: A PRISMA-guided systematic review of preclinical and clinical evidence.Overall, NAD⁺ augmentation shows clear biological activity, but clinical effectiveness for anti-aging or wellness outcomes remains inconclusive. Larger, well-designed randomized trials with longer follow-up and prespecified clinically meaningful endpoints are needed, particularly for parenteral approaches.Ageing Res Rev. A review of 10 trials found side effects in every study, most often muscle pain, nervous system complaints, fatigue, sleep disturbance and headache, none serious2Systematic review · 2024 · 489 peopleEvaluation of safety and effectiveness of NAD in different clinical conditions: a systematic review.NADH supplementation is safe and has a low incidence of side effects. Future investigations are needed to evidence the clinical benefits regarding specific diseases and doses administered.Am J Physiol Endocrinol Metab. Those were mostly oral products, so they don't establish IV safety. A review of the wider research raised theoretical concerns about toxic breakdown products, tumor growth and cellular aging with long-term NAD+ raising4Systematic review · 2020NAD+ therapy in age-related degenerative disorders: A benefit/risk analysis.Potential risks in raising NAD+ levels in various clinical disorders using NAD+ precursors include the accumulation of putative toxic metabolites, tumorigenesis and promotion of cellular senescence. Therefore, NAD+ metabolism represents a promising target and further studies are needed to recapitulate the preclinical…Exp Gerontol.
What we don't know
Whether IV NAD+ gives any benefit, or how safe repeated infusions are.
Whether raising blood NAD levels improves how people feel, function or age.
Written by AI from the studies listed, without review by a clinician, and graded with the GRADE method. It can be wrong, so check the studies it cites. Education, not medical advice.