NAD+ Benefits: What Supplements and IV Drips Actually Do in Human Trials

The short answer. NAD+ (nicotinamide adenine dinucleotide) is a coenzyme every cell uses to turn food into energy. The best-replicated finding in people is that its precursors, nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), reliably raise NAD+ levels in blood. Whether that rise produces better energy, metabolism, muscle or longevity is far less settled: across dozens of human trials, functional results are mixed and often null. Intravenous NAD+ has even less outcome evidence than the oral precursors. Our NAD+ therapy page covers the basics; this article is about what the trials actually measured.

NAD+ is one of the most heavily marketed compounds in longevity. It is also one of the more honestly studied ones. That combination makes it a useful case study in a gap that shows up across wellness: the distance between moving a biomarker and changing an outcome.

NAD+ benefits: what the trials actually measured

Start with the finding that holds up. In a randomized, double-blind, placebo-controlled crossover trial, 24 healthy adults aged 55 to 79 completed six weeks of oral NR and six weeks of placebo. NR raised NAD+ in blood cells by roughly 60% compared with placebo, and it was well tolerated with no serious adverse events (Martens et al., Nature Communications, 2018).

That result has been repeated many times. A 2026 systematic review of NAD-related interventions identified 33 human intervention studies, 28 of them randomized, and found that oral NR and NMN "consistently demonstrated biochemical target engagement" (Gallagher and Emmanuel, Ageing Research Reviews, 2026). In other words, the supplements get into the body and raise the marker they are supposed to raise.

The same review is just as clear about the next step. Effects on "functional, metabolic, vascular, and other healthspan-relevant outcomes were heterogeneous and often null or endpoint-specific," and clinical effectiveness for anti-aging or wellness outcomes "remains inconclusive."

Even the 2018 trial shows the pattern. Its authors flagged lower systolic blood pressure and aortic stiffness as the most promising signals, but treated them as exploratory hypotheses for a larger trial, not as findings (Martens et al., 2018).

Do NAD supplements work for metabolism and muscle?

The metabolic trials are where the marketing and the data diverge most.

In a 12-week randomized, placebo-controlled trial, 40 sedentary men with obesity aged 40 to 70 took NR or placebo. NR appeared safe, but it did not improve insulin sensitivity, glucose metabolism, resting energy expenditure, fat burning or body composition, measured with clamp studies, DXA and MRI (Dollerup et al., American Journal of Clinical Nutrition, 2018).

The most cited positive result is a 10-week randomized, double-blind trial of NMN in postmenopausal women with prediabetes who were overweight or obese. Muscle insulin sensitivity and insulin signaling improved with NMN and did not change with placebo (Yoshino et al., Science, 2021). It was a small trial of 25 women (Alangari et al., Frontiers in Aging, 2026), and the result has not been shown to generalize.

When trials are pooled, the effect largely disappears. A meta-analysis of eight randomized NMN trials covering 342 adults found no significant benefit on fasting glucose, fasting insulin, HbA1c or blood lipids, even though five of the eight trials reported higher blood NAD+ (Chen et al., Current Diabetes Reports, 2024). The authors concluded their findings "do not support the use of NMN supplementation among general population to improve glucose and lipid metabolism."

Muscle tells the same story. In 12 older men, three weeks of NR raised the NAD+ metabolome inside muscle tissue and lowered circulating inflammatory cytokines, but did not change mitochondrial bioenergetics (Elhassan et al., Cell Reports, 2019). A 2025 meta-analysis of 10 randomized trials in adults with a mean age over 60 found no significant effect of NMN or NR on muscle mass, grip strength or gait speed, and concluded current evidence "does not support" either for preserving muscle mass and function (Prokopidis et al., Journal of Cachexia, Sarcopenia and Muscle, 2025).

NMN vs NR

The two precursors take slightly different routes to the same molecule, and both are sold as supplements. In practice, the human evidence does not separate them on outcomes. The 2025 muscle meta-analysis analysed six NMN trials and four NR trials and found neither improved the primary outcomes (Prokopidis et al., 2025).

NMN also had a regulatory detour. FDA said in November 2022 that NMN could not be sold as a dietary ingredient because it had first been investigated as a drug. In September 2025, responding to a citizen petition, FDA concluded that NMN "is not excluded from the definition of dietary supplement" because it was marketed as a supplement before that drug authorization (NutraIngredients, 2025).

Being lawful to sell is a low bar. Under federal law FDA "does not have the authority to approve dietary supplements before they are marketed," and manufacturers carry the initial responsibility for safety (FDA). No supplement label can claim to treat, cure or prevent a disease.

NAD+ IV benefits: what the infusion studies show

Intravenous NAD+ is the most heavily promoted version of the idea and the least studied one. The 2026 systematic review found no eligible outcome trials of intravenous or intramuscular NAD+ itself for anti-aging or wellness indications (Gallagher and Emmanuel, 2026).

What exists is pharmacology. In a controlled pilot of 11 healthy men, eight received a six-hour NAD+ infusion and three received saline (Alangari et al., 2026). For at least the first two hours, NAD+ was "rapidly and completely removed from the plasma," with no change in plasma NAD+ or its metabolites until after that point (Grant et al., Frontiers in Aging Neuroscience, 2019).

A 2026 narrative review of IV NAD+ and its precursors catalogued the remaining human data: an uncontrolled pilot of eight older adults, a single-patient case report, a small open-label study of IV NMN, and a retrospective comparison of 14 clinic patients (Alangari et al., 2026). The review lists the eight-person pilot's problems plainly: no control or placebo arm, no randomisation or blinding, and follow-up limited to the six-day infusion window. In that comparison, patients given IV NAD+ experienced moderate-to-severe infusion symptoms, including nausea, cramps and chest discomfort. Their infusions averaged 97 minutes, against mild, short-lived effects and 37-minute infusions for IV NR.

None of these studies was designed to show that an infusion makes you feel, perform or age differently. That is the question most people are actually asking, and nobody has tested it properly yet.

Where the evidence runs out

Small and short. Most human NAD+ trials enrol a few dozen people for weeks, not years. The pooled NMN meta-analysis noted that both the number of trials and their sample sizes were small (Chen et al., 2024).

Mostly healthy volunteers. Healthy adults may have little room to improve. The 2018 NR trial authors said their healthy cohort "may have reduced the likelihood" of seeing functional improvements (Martens et al., 2018). People with genuine NAD+ deficits are under-studied.

Industry ties are common. The 2018 NR trial received study pills and partial funding from the supplement's manufacturer (Martens et al., 2018). A co-author of the muscle study holds patents licensed to an NR supplier (Elhassan et al., 2019), and authors of the NMN insulin study disclosed NMN patent interests (Yoshino et al., 2021). That does not make the results wrong, but it is worth knowing.

Animals are not people. Much of the excitement comes from rodent work, where NAD+ augmentation frequently improved metabolic and functional outcomes. Human results have been far more modest (Gallagher and Emmanuel, 2026).

IV is the biggest gap. The reviews call for larger, longer randomized trials with clinically meaningful endpoints, "particularly for parenteral approaches."

What this means at Aeon

Aeon offers NAD+ by injection and by IV infusion. We would rather you hear the evidence on both from us than from a brochure: a real biological pathway, a reliable way to raise a blood marker, and an unproven route to benefits you would notice. The injected and infused forms in particular have the least outcome research behind them, and we say so before anyone books one.

Three things follow. Fundamentals come first. Resistance training, sleep and nutrition have far stronger outcome evidence than any NAD+ product. A licensed provider decides whether NAD+ fits you at all, and in which form, after a consultation and, where relevant, clinic lab work. Expectations are stated up front, including the chance that it changes a number on a lab report and nothing else.

If you want to understand where NAD+ fits in your own plan, start with our NAD+ therapy page.