NAD+ and Longevity: What the NMN and NR Trials Actually Show

No trial has shown that NAD+, NMN or nicotinamide riboside (NR) slows aging or extends life in people. None of the human trials measured lifespan, deaths, heart attacks or the onset of age-related disease; they ran for weeks or months and tracked surrogate markers.^[1] On those markers the record is consistent in one direction only. The pills raise NAD+ in the blood, often roughly doubling it.^[17][14] What they do to muscle, blood sugar, blood pressure and cognition is mostly nothing measurable, with a few small positive findings that have not been replicated. The 2026 meta-analysis of muscle trials in people over 60 found no benefit at all.^[18] Injected NAD+ has no outcome trials.

Why NAD+ became a longevity product

NAD+ (nicotinamide adenine dinucleotide) is a molecule every cell uses to turn food into energy and to run enzymes that repair DNA. Levels fall with age in animals, and raising them in mice and rats improved metabolic, mitochondrial and functional measures across many studies.^[1] That is the whole case. The jump from “NAD+ declines with age” to “restoring NAD+ reverses aging” is an inference, and it is the inference that the human trials were set up to test.

NAD+ itself is poorly suited to a pill, so most research uses precursors the body converts into it. NR and NMN are the two sold as supplements. Niacin (nicotinic acid) and nicotinamide are older forms of vitamin B3 that also feed the same pathway. A 2026 systematic review of the field from 2010 to late 2025 counted 33 human intervention studies, 28 of them randomized.^[1] That is the evidence base for every longevity claim on a label.

Raising NAD+ is easy. Changing outcomes is not.

The first half of the story holds up. Oral NR and NMN reliably raise NAD+ and its breakdown products in blood and in cells.^[1] A pharmaceutical-grade NMN called MIB-626 produced “substantial dose-related increases” in blood NAD+ in 32 adults aged 55 to 80 over two weeks.^[24] In a 2026 trial in people with mild cognitive impairment, NR doubled blood NAD+ in 12 weeks.^[17]

The second half does not follow. The same 2026 review found effects on function, metabolism and blood vessels were “heterogeneous and often null or endpoint-specific.”^[1] Two details from individual trials show why. In the best-known positive NMN trial, muscle NAD+ content did not change at all, even though blood levels did.^[7] In older men given NR for three weeks, the muscle NAD+ system was more active, but mitochondrial energy output was unchanged.^[6] Raising a number in the blood is a biochemical effect. It is not the same as a change in how a body ages.

The human trials on aging markers, one by one

Read down the right-hand column and a pattern appears. The trials whose main outcome was a hard physiological test, such as a glucose clamp, grip strength, cognition or blood pressure, mostly came back null. Most of the positive findings are secondary outcomes, within-group changes, or trends. Several of the positive NMN trials list company employees among their authors, which the papers disclose: staff of Mitsubishi Corporation Life Sciences on two Japanese trials,^[8][9] staff of Meiji on the walking and sleep trial,^[13] and staff of Abinopharm and Aba Chemicals on the dose trial.^[10]

Muscle and physical function

Muscle loss is the aging claim with the most trials behind it, and the answer is the clearest. A 2025 meta-analysis pooled randomized trials in adults whose average age was over 60. On NMN, none of grip strength, muscle mass, chair-stand time or gait speed changed significantly. Pooled gait speed changed by 0.01 m/s, with a confidence interval spanning zero. The authors’ conclusion was that current evidence does not support NMN or NR for preserving muscle mass and function in this age group.^[18]

The individual trials fit that picture. In 14 men around 81 years old with diabetes and weak grip or slow walking, six months of NMN did not improve either.^[12] Older men in a 2022 trial showed only “nominally significant” gains in gait speed and one hand’s grip, and no change in body composition; its authors asked for larger studies.^[8] In the 108-person Japanese trial, chair-stand times got better in all four groups, including both placebo groups, which points to a practice effect rather than a supplement effect.^[9] In the NR trial in mild cognitive impairment, walking speed improved on placebo and not on NR.^[14]

Endurance is the one physical measure that holds up somewhat better. A 2026 network meta-analysis of 27 studies found NMN improved endurance-type exercise tests, with standardized effects of 0.66 at medium doses and 1.02 at high doses, but strength did not change and no precursor improved perceived fatigue or sleep quality.^[22] Those pooled studies were small, short and often in young or trained people, like the runners in the 2021 Chinese trial whose maximum oxygen uptake did not change.^[30] If you are on a GLP-1 and feel worn out, the common causes have nothing to do with NAD+; see fatigue on a GLP-1.

Insulin sensitivity and blood sugar

The 2021 Science trial is the strongest single NMN result. Thirteen postmenopausal women with prediabetes took 250 mg of NMN a day for 10 weeks. Insulin-driven glucose uptake into muscle, measured by the gold-standard clamp method, rose 25% within the NMN group and did not change on placebo.^[7] It is a real, carefully measured finding. It is also narrow. Liver and fat-tissue insulin sensitivity, blood glucose, insulin, body composition and blood pressure did not change, and neither did muscle strength or mitochondrial capacity.^[7]

NR has not matched it. In 40 men with obesity, 2,000 mg of NR a day for 12 weeks did not improve insulin sensitivity measured the same way.^[4] A six-week crossover in 13 adults also found no change.^[5] Pooled across eight NMN trials in 342 mostly non-diabetic adults, a 2024 meta-analysis found no significant benefit on fasting glucose, fasting insulin, HbA1c, insulin resistance or cholesterol.^[19] A 2026 meta-analysis of 15 NMN trials reached the same result for weight, BMI, glucose, HbA1c and lipids.^[21]

Blood pressure and arterial stiffness

Blood pressure is where the NAD+ field has its most cited hint. In the 2018 NR trial, systolic pressure fell 3.9 mmHg on average, but the result did not survive correction for multiple comparisons. A follow-up look at the 13 people with elevated or stage 1 blood pressure found a 9 mmHg drop; the authors stated that because this analysis was exploratory, “no statistical inferences can be made.”^[3]

When that idea was tested directly, it failed. A 2025 trial randomized 54 adults aged 55 and over with high blood pressure to NR plus supervised walking, placebo plus walking, or NR alone. Adding NR to exercise did not reduce daytime systolic pressure beyond what placebo plus exercise achieved.^[16] The 2026 cognitive-impairment trial also found no blood-pressure effect.^[17] Arterial stiffness trended lower in a 12-week NMN trial, without a significant difference from placebo.^[11]

Meta-analyses give a small signal. A 2026 pooling of 10 NMN trials with 349 people found diastolic pressure 2.15 mmHg lower than placebo; systolic pressure did not differ overall, though a subgroup aged 60 and over showed a 3.94 mmHg drop. The authors called this “preliminary and suggestive.”^[20] A 2023 meta-analysis that reported larger effects pooled all NAD+ precursors, including niacin, and found the biggest effects with niacin.^[23] That result says little about NMN or NR capsules.

Epigenetic clocks and “biological age”

Claims that NMN “reverses aging” usually trace to a clock: a statistical model that estimates age from blood tests or DNA methylation. Clocks are surrogate markers. None has been shown to work as a stand-in for living longer when a drug or supplement moves it, a point our semaglutide and aging review covers in detail.

• Yi 2023 (NMN): a blood-test age score from an online calculator rose on placebo over 60 days and stayed flat on NMN. It is a secondary outcome, and several co-authors were company employees.^[10]
• Orr 2024 (NR): an exploratory analysis in 20 people with mild cognitive impairment reported lower PhenoAge and GrimAge readings after 10 weeks.^[14]
• Johnson and Sinclair 2026: a review of 41 human studies on next-generation clocks listed NR among interventions that showed “no detectable effect.”^[2]

That last finding is notable because its senior author is among the most prominent public advocates of NAD+ boosting. Twenty people for 10 weeks cannot settle a question about aging, and no clock result has been tied to a later change in health.

IV and injected NAD+: what happens to it

Drip clinics argue that infusing NAD+ bypasses the gut and puts more into cells. The one pharmacokinetic study in people points the other way. During a six-hour infusion, blood NAD+ did not rise at all for the first two hours; the infused molecule was “rapidly and completely removed from the plasma,” broken down by enzymes, with NAD+ and a breakdown product showing up in urine.^[25] Whether any intact NAD+ reaches cells this way is unknown.

A 2026 chart review from a commercial wellness chain, written by its employees, compared four daily 500 mg infusions of NAD+ or NR. People on NAD+ drips reported moderate to severe stomach symptoms, a faster heart rate and chest pressure, which stretched infusions to 97 minutes on average against 37 for NR.^[26] It had no placebo group and no aging outcome. No outcome trial of IV or intramuscular NAD+ for anti-aging turned up in the 2026 systematic review,^[1] and a 2026 critical review concluded that IV longevity therapy should be treated as experimental.^[27] Our NAD+ injections page covers how clinics sell it.

The only NAD+ precursor tested on hard outcomes

One vitamin B3 form has been through the kind of large trials that longevity claims would need: niacin, tested for decades as a cholesterol drug. A 2019 meta-analysis of 17 trials and 35,760 patients found no preventive effect on cardiovascular outcomes in people with heart disease, and the benefits seen in people not on statins came mainly from two trials run in the 1970s and 1980s.^[28] Niacin was studied for lipids, not as an NAD+ booster, so this does not test NR or NMN directly. It does show how a plausible biomarker story can fail once events are counted. No NR or NMN trial has counted them.

Is NMN legal as a supplement? FDA’s reversal

In October 2022 FDA told a company that had filed a new-ingredient notification for NMN that the ingredient was excluded from the legal definition of a dietary supplement. A substance first authorized for investigation as a new drug cannot later be sold as a supplement unless it was on the market as one first. FDA found that “NMN was not marketed as a dietary supplement, except unlawfully without an NDI notification, or as a food before FDA authorized it for investigation as a new drug,” and sent similar letters to every company that had filed for NMN.^[29]

Trade groups petitioned, and on September 29, 2025, FDA changed course. It dropped its view that earlier supplement sales had to be lawful to count, said it had evidence NMN was sold as a supplement in the US “as early as 2017,” before the drug authorization, and concluded:^[29]

“Accordingly, we now conclude that NMN is not excluded from the dietary supplement definition under section 201(ff)(3)(B).”^[29]

— FDA response to citizen petition FDA-2023-P-0872, September 29, 2025

Two limits matter. FDA said it cannot disclose when the drug authorization happened, because information about investigational drugs is confidential.^[29] And supplement status is not an endorsement. A dietary supplement does not go through FDA review for effectiveness, and the same letter notes that FDA’s acknowledgment of a new-ingredient notification is not a finding that the ingredient is safe.^[29] NMN went from “not a supplement” to “a supplement” on a legal reading of a 1994 statute. Nothing about the evidence changed.

Marketing claims against the trial data

Safety

In the short run, oral precursors look benign. A 2026 meta-analysis of NMN trials using 250 to 2,000 mg a day for two weeks to 24 weeks found no increase in adverse events, serious adverse events, dropouts or liver enzymes.^[21] That covers months, not the decades a longevity supplement implies. IV NAD+ is a different matter: infusion symptoms are common enough to slow the drip.^[26] Anyone on a GLP-1 or another prescription drug should tell the prescriber about any supplement or infusion.

Where NAD+ fits in the longevity picture

NAD+ biology is real science, and a few signals, in muscle insulin sensitivity, walking distance in artery disease and endurance testing, deserve larger trials. None of that amounts to a longevity drug. For comparison, the drugs with the strongest claim to extend healthy life in people are the ones with hard-outcome trials behind them, which our GLP-1s as longevity drugs review sets out. Peptides sold on the same anti-aging menus have even less: see the evidence on epitalon and MOTS-c, and our count of which peptides have human trials.