NMN and NR

Save the money. If you take them anyway, know that no trial has shown a health benefit in healthy adults, and that they share breakdown products with high-dose niacin that have been linked to heart events.

What they are

NAD+ (nicotinamide adenine dinucleotide) is a coenzyme central to energy metabolism and DNA repair. NMN and NR are two of its precursors (building blocks), related to vitamin B3 and sold as supplements; NR's best-known brand is Niagen. Both reliably raise blood NAD+ at 250–1,000 mg a day. Whether that translates into any clinical benefit in healthy adults is essentially unproven. The wider vitamin B3 picture is on B vitamins; the high-dose form used as a cholesterol drug is on Niacin.

Is there a decline to fix?

The sales pitch assumes NAD+ falls with age. It does in mice,^[1] but in people the picture depends on where you measure. A 2025 review found a consistent age-related decline in only a limited number of human studies.^[2] Muscle NAD+ is lower in older than in younger adults, most of all in the physically impaired, though that comparison is a single snapshot rather than a trial.^[3] Whole-blood NAD+, by contrast, looked remarkably stable with age in a study pooling seven independent human cohorts.^[4] So a supplement that raises blood NAD+ may be topping up a level that was not low to begin with. How NAD+ fits the cell's fuel-sensing machinery is covered on deregulated nutrient sensing.

Metabolism: one positive trial, then mostly nothing

• The positive result. In postmenopausal women with prediabetes, 250 mg of NMN a day improved muscle insulin sensitivity.^[5]
• The negative one. In men with obesity, 2,000 mg of NR a day did nothing for insulin sensitivity, mitochondrial function or body composition.^[6]
• Pooled. Across eight randomised trials in 342 adults, NMN moved neither fasting glucose, fasting insulin, HbA1c (a marker of longer-term blood sugar), HOMA-IR (the standard fasting index of insulin resistance) nor blood lipids.^[7] A larger 2026 pooling of 15 NMN trials in adults, at 250–2,000 mg a day for 14 days to 24 weeks, again found no clear effect on weight, fasting blood sugar, HbA1c or blood fats, though diastolic (bottom-number) blood pressure fell slightly.^[8]

Muscle and blood pressure: no reliable gain

Pooled trials in adults averaging over 60 found no gain in muscle mass, grip strength, walking speed or chair-rise time with either NMN or NR, and NR was linked to worse physical-performance scores and slower chair rises in people with mild cognitive impairment.^[9]

The blood-pressure story followed the same arc. A small 2018 trial in healthy middle-aged and older adults saw systolic (top-number) blood pressure fall on 1,000 mg of NR only in a subgroup with above-normal readings, picked out after the fact, and the authors said no conclusions could be drawn from it.^[10] When the same group tested it directly in people with high blood pressure, adding NR to a walking programme lowered blood pressure no more than walking alone.^[11]

The trial most often quoted for a benefit in healthy people is weaker than it sounds. In 80 healthy middle-aged adults over 60 days, NMN raised blood NAD+ and lengthened six-minute walking distance, with benefits peaking at the middle dose (600 mg a day). It was fully funded by the companies that make the NMN tested. Its "biological age" score, calculated from routine lab markers rather than a methylation clock, held steady on NMN, but the contrast rests mostly on the placebo group's score jumping from 39.8 to 45.4 years within 60 days, which points to a noisy measure.^[12]

Raising blood NAD+ is real; the downstream benefit is what keeps failing to appear.

Two newer trials in patients

• Long COVID: a null. In a 58-person trial in people with long COVID, 2,000 mg a day of NR raised blood NAD+ about 2.6- to 3.1-fold within 5 to 10 weeks but did not significantly improve cognition, fatigue, sleep or mood compared with placebo. About half of those taking it from the start had dropped out by 20 weeks.^[13]
• Werner syndrome: a small hopeful signal. Werner syndrome is an inherited DNA-repair disorder that causes premature aging. Nine patients took 1,000 mg of NR a day and a placebo for 26 weeks each, in turn. No serious side effects were seen on NR; it modestly reduced arterial stiffness and shrank skin ulcers, although one blood-flow measure in the right leg got worse. Only six patients finished and the supplement maker supplied the capsules, so this is a hopeful signal for people whose repair machinery is broken, not evidence for anyone else.^[14]

The wider case for NAD+ precursors as DNA-repair aids is covered on genomic instability.

Safety: an open question

The 2-PY/4-PY signal. NR and NMN, like niacin, raise blood levels of 2-PY and 4-PY, the end products of NAD+ breakdown. In observational studies of heart patients, people with higher levels had more major cardiovascular events (heart attack, stroke or death) over three years, and 4-PY inflamed blood-vessel walls in mice.^[15] Whether supplement-driven rises cause harm is unknown; no trial has shown that raising them does.

NMN's short-term tolerability looks fine. In the 2026 pooling, NMN did not increase side effects in the 10 trials with safety data, but no trial in it ran longer than 24 weeks.^[16]

No long-term data. The honest caution is not a known toxicity but an unknown one: there are no long-term human safety data, and a theoretical concern that boosting NAD+ could feed an existing, undetected cancer has not been resolved either way.

Legal status in the US

NMN's status has been unstable. In late 2022 the US Food and Drug Administration (FDA) concluded NMN was excluded from the dietary-supplement definition, because it had earlier been authorised for investigation as a new drug (the filing behind the pharmaceutical candidate MIB-626). That threw its US over-the-counter availability into legal limbo. After an industry lawsuit the agency suspended enforcement in late 2024, and in September 2025 it reversed itself: NMN is no longer barred from supplements, though as a new dietary ingredient its makers must still notify the FDA.^[17] NR has been on stable footing throughout. Being legal to sell does not make either effective.

What to do

1. Don't buy them for longevity. The one encouraging metabolic trial has not been borne out by the pooled evidence.
2. If you take one anyway, remember it is not separate from high-dose niacin as far as 2-PY and 4-PY go, and that no long-term safety data exist.
3. Spend the money on what works: exercise, sleep and the core supplements on Supplements.

Further reading

• Yoshino M et al. Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science 2021.^[18]
• Ferrell M et al. A terminal metabolite of niacin promotes vascular inflammation and contributes to cardiovascular disease risk. Nat Med 2024.^[19]
• Dollerup OL et al. A randomized placebo-controlled clinical trial of nicotinamide riboside in obese men: safety, insulin-sensitivity, and lipid-mobilizing effects. Am J Clin Nutr 2018.^[20]
• Chen F et al. 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.^[21]
• Prokopidis K et al. The Effect of Nicotinamide Mononucleotide and Riboside on Skeletal Muscle Mass and Function: A Systematic Review and Meta-Analysis. J Cachexia Sarcopenia Muscle 2025.^[22]
• Yang W et al. Safety and Metabolism-Related Outcomes of Oral Nicotinamide Mononucleotide Supplementation in Adults: A Systematic Review and Meta-Analysis. Nutrients 2026.^[23]
• Trętowicz MM et al. Human whole-blood NAD(+) levels do not vary with age or lifestyle interventions. Nat Metab 2026.^[24]
• Shoji M et al. Nicotinamide Riboside Supplementation Benefits in Patients With Werner Syndrome: A Double-Blind Randomized Crossover Placebo-Controlled Trial. Aging Cell 2025.^[25]