NMN Raises NAD+ — But Does It Actually Slow Ageing?

Few supplements have benefited more from the explosion of interest in longevity than nicotinamide mononucleotide, better known as NMN. It is a supplement that I personally take every single day and on a lot of metrics, it is one that has really moved the needle for me and one I would be loathe to remove from my protocol. It is marketed as an NAD+ booster and an anti-ageing supplement and, in some corners of the longevity industry, is presented as something approaching a means of turning back the biological clock. The scientific story behind these claims is considerably more interesting than much of the marketing, but it is also considerably more complicated.

There is a legitimate biological reason why researchers are interested in NMN. Nicotinamide adenine dinucleotide, or NAD+, is fundamental to cellular metabolism and participates in numerous processes involved in energy production, cellular signalling and maintenance. NAD+ metabolism can also change with ageing, while experiments in animals have produced intriguing results when NAD+ availability is manipulated. From these observations has emerged an extremely attractive hypothesis: if NAD+ availability becomes impaired as we age, perhaps restoring it could improve some of the physiological changes associated with ageing.

The difficulty arises when this hypothesis is quietly transformed into a conclusion. Increasing a molecule associated with ageing is not necessarily the same thing as slowing the ageing process, and changing an ageing-related biomarker does not automatically mean that someone has become biologically younger. A new randomised, double-blind, placebo-controlled trial published in npj Aging in September 2026 provides an unusually good opportunity to examine this distinction because researchers administered a substantial dose of NMN to older adults for six months and measured both its biochemical effects and a range of functional outcomes.

The results are fascinating precisely because NMN clearly did something biologically. Supplementation substantially increased NAD+ and related metabolites in the blood, demonstrating that the intervention successfully altered the pathway it was intended to target. What researchers did not find, however, was convincing evidence that this biochemical change translated into corresponding improvements in the principal measures of physical or physiological function they examined. This discrepancy between biomarker change and meaningful human outcome may ultimately tell us more about the current state of longevity science than another positive supplement trial ever could.

What exactly are NAD+ and NMN?

NAD+ is a molecule found throughout our cells and is involved in some of the most fundamental processes required to keep them functioning. One of its best-established roles is in energy metabolism, where NAD+ participates in redox reactions that allow energy derived from carbohydrate, fat and protein to be converted into forms that cells can use. Cellular energy metabolism cannot function normally without it.

Its importance extends well beyond energy production. NAD+ is also consumed by several families of enzymes involved in cellular regulation, including sirtuins and poly(ADP-ribose) polymerases, commonly known as PARPs. Sirtuins have attracted particular attention in ageing research because they participate in processes including metabolic regulation, mitochondrial function, cellular stress responses and gene regulation. PARPs use NAD+ during responses to DNA damage and repair, while another NAD+-consuming enzyme, CD38, participates in calcium signalling and immune function and has itself become an interesting target in ageing research.

NAD+ therefore sits at the intersection of metabolism, cellular maintenance, signalling and stress responses. The body can produce it through several biochemical routes, including pathways using forms of vitamin B3. NMN is one of the intermediates involved in NAD+ biosynthesis and can ultimately contribute to the cellular NAD+ pool.

This provides the biological rationale for supplementation. If NAD+ availability declines or its metabolism becomes disrupted with age, supplying additional NMN might theoretically increase NAD+ availability and influence some of the processes in which NAD+ participates. That is a perfectly reasonable scientific hypothesis and one that deserves investigation. It is not, however, evidence that NMN has already been demonstrated to slow human ageing.

Why has NAD+ become such a major target in longevity research?

Interest in NAD+ did not emerge from the supplement industry alone. A substantial body of preclinical research has linked changes in NAD+ metabolism with several biological processes associated with ageing. In experimental animals, manipulating NAD+ availability or supplying NAD+ precursors has produced effects on mitochondrial function, energy metabolism, insulin sensitivity, physical performance and other ageing-related processes.

This research forms part of a much broader change in the way ageing is studied. Rather than viewing ageing simply as the passive accumulation of years, researchers increasingly investigate biological processes that change across the lifespan and may contribute to functional decline and disease. These include cellular senescence, mitochondrial dysfunction, altered nutrient sensing, epigenetic change, chronic low-grade inflammation, impaired protein homeostasis and changes in cellular repair mechanisms. NAD+ intersects with several of these areas, which makes it an entirely legitimate and potentially important research target.

The commercial interpretation has moved considerably faster than the clinical evidence. The fact that a molecule participates in ageing biology does not mean that increasing its concentration will necessarily slow ageing. Human physiology is rarely governed by simple relationships in which increasing an important molecule automatically produces a better outcome. Glucose, insulin, cortisol and cholesterol are all essential to normal physiology, yet their biological importance tells us very little about whether deliberately increasing them would improve health.

NAD+ needs to be approached with the same intellectual discipline. The relevant question is not whether NAD+ is important, because there is little doubt that it is. The relevant question is whether increasing NAD+ availability through supplementation produces meaningful improvements in human health, function or the trajectory of ageing. That requires human intervention studies measuring outcomes that extend beyond the concentration of NAD+ itself.

The new trial put NMN to a more substantial test

The new study is particularly useful because it addresses several limitations of earlier NMN research. Researchers recruited healthy adults aged 65 years or older and randomly assigned them to receive either NMN or placebo. Participants in the intervention group consumed 1,250 mg of NMN every day for 24 weeks, providing both a substantial daily dose and a longer intervention period than many previous human trials.

The randomised, double-blind, placebo-controlled design is important because it substantially strengthens our ability to determine whether differences between the groups were genuinely caused by NMN. The primary outcome was a measure of auditory function, but researchers also investigated a broader collection of ageing-related outcomes including physical function, blood biomarkers, exercise tolerance, body composition, quality of life and other physiological measures. NAD+ and related metabolites were also measured, allowing the researchers to establish whether the supplement was successfully altering its intended biochemical target.

On that final measure, the result was clear. NMN supplementation significantly increased circulating NAD+ and related metabolites over the 24-week intervention. This is important because it demonstrates biological activity: the supplement was absorbed and produced a measurable alteration in NAD+ metabolism. The more important question, however, was whether successfully changing that pathway produced corresponding improvements in the people taking it.

Raising NAD+ did not produce convincing functional rejuvenation

Despite the substantial effect on NAD+ metabolism, NMN did not significantly improve the study's primary outcome of auditory function. Researchers also failed to identify significant improvements in the principal physical-performance measures. There were nominal changes in some measures relating to body composition, lipid metabolism and dietary behaviour, but these did not remain statistically significant after correction for multiple comparisons and therefore need to be regarded as exploratory rather than established treatment effects.

This is an extremely important distinction in longevity research. A biomarker can move considerably without demonstrating that the health or functional state of the person has meaningfully changed. If an intervention increases a molecule associated with mitochondrial function, for example, we can conclude that the intervention altered that molecule. We cannot automatically conclude that mitochondrial function has improved sufficiently to enhance physical performance, reduce disease risk or extend healthy lifespan. Each step along that chain requires its own evidence.

The new trial therefore gives us two different findings that should not be conflated. NMN appears capable of substantially increasing NAD+ and related metabolites in older humans, which supports the proposed biochemical action of the supplement. The study does not provide similarly convincing evidence that producing this increase results in broad functional rejuvenation. This difference between biochemical efficacy and clinical or functional efficacy is central to understanding not only NMN, but much of the current longevity supplement market.

This does not mean NMN has been proven useless

It would be equally inappropriate to interpret a largely neutral trial as evidence that NMN has no biological effects or could never have a useful application. Scientific evidence rarely develops through one decisive experiment, particularly in a relatively young field. Earlier human studies have produced several interesting signals, although many have involved relatively small samples, short intervention periods or exploratory outcomes.

A previous randomised trial in older men using 250 mg of NMN daily for up to 12 weeks demonstrated increased blood NAD+ concentrations and reported nominal improvements in gait speed and left-hand grip strength. These findings were potentially interesting but required confirmation in larger and more rigorous trials. Other studies have investigated glucose metabolism, exercise performance, sleep, body composition and various metabolic outcomes, with occasional favourable signals but no consistent picture of broad clinical benefit.

This is typical of an emerging area of clinical research. Small studies often identify possible effects that subsequently need to survive replication in larger, longer and better-powered trials. Some eventually prove to be real, while others become smaller or disappear entirely as the quality and quantity of evidence improves. The appropriate response is therefore neither to dismiss NMN as worthless nor to declare it a longevity breakthrough. It is to continue testing specific hypotheses while ensuring that public claims remain proportionate to what those experiments have actually demonstrated.

What does the wider human evidence tell us?

Looking beyond individual trials makes the current position clearer. Systematic reviews and meta-analyses of randomised controlled trials have consistently found that NMN supplementation can increase NAD+-related biomarkers, but evidence for substantial improvements in conventional metabolic outcomes remains considerably weaker.

One systematic review and meta-analysis examining randomised controlled trials of NMN and glucose and lipid metabolism included eight trials involving 342 predominantly middle-aged and older adults. Doses ranged from 250 to 2,000 mg per day, with intervention periods ranging from two to 12 weeks. The pooled analysis found no significant improvement in fasting glucose, fasting insulin, HbA1c, insulin resistance or blood lipids.

Another systematic review and meta-analysis included 12 studies involving 513 participants. Once again, NMN significantly increased blood NAD+ concentrations, while most clinically relevant metabolic outcomes were not significantly different from those observed in control groups. The authors also identified methodological concerns within the existing evidence base and cautioned that the benefits attributed to NMN may have been overstated.

Research examining muscle function has produced a similarly restrained picture. A systematic review and meta-analysis examining NAD+ precursors in older adults found no convincing evidence that NMN improved skeletal muscle index, grip strength, gait speed or several other measures of muscular function. A more recent network meta-analysis examining different NAD+ precursors identified possible improvements in some endurance-related outcomes with NMN, while strength remained unchanged and the evidence differed substantially according to the outcome, dose and population being examined.

Taken together, these studies suggest that NMN is biologically active and capable of altering NAD+ metabolism, but that the downstream human consequences of doing so remain uncertain. That is a considerably more nuanced conclusion than either the marketing claim that NMN has already been shown to slow ageing or the opposing claim that it does absolutely nothing.

Changing an age-related pathway is not the same as correcting a deficiency

There is another conceptual issue that is often overlooked in discussions about longevity supplements. If somebody is genuinely deficient in an essential nutrient, correcting that deficiency can produce profound improvements. Vitamin B12 given to somebody with severe B12 deficiency, iron used appropriately in iron-deficiency anaemia or vitamin C provided to somebody with scurvy addresses a defined physiological problem for which the missing nutrient has a well-established causal role.

The situation with NAD+ precursors is considerably more complicated. The observation that NAD+ metabolism changes with age does not mean that older adults have an NMN deficiency in the same sense that somebody can have an iron or vitamin B12 deficiency. Ageing alters thousands of biological variables simultaneously, and not every age-associated change is necessarily a useful therapeutic target. Some changes may contribute directly to dysfunction, some may represent adaptive responses to other physiological changes, and others may accompany ageing without being major causal drivers of functional decline.

Even when an age-associated biological change is genuinely contributing to dysfunction, restoring one component of that pathway does not necessarily restore the entire physiological system. Human ageing emerges from interactions between genetics, cellular damage, metabolism, immune function, vascular health, body composition, environmental exposures, behaviour and disease accumulated over decades. It would therefore be extraordinary if manipulating one metabolic intermediate reliably reversed this entire network of changes.

This is one reason surrogate biomarkers need to be treated cautiously in longevity research. A supplement can successfully manipulate one measurable component of ageing biology while producing little detectable difference in the health or function of the person taking it. The new NMN trial provides a particularly useful illustration because the biochemical target responded so clearly while the major functional outcomes did not.

What about sirtuins and the supposed “longevity pathways”?

NAD+ is frequently discussed alongside sirtuins, particularly SIRT1, because these enzymes require NAD+ for their activity. This relationship has helped generate the popular narrative that increasing NAD+ somehow “activates longevity genes”, but that description considerably oversimplifies the underlying biology.

Sirtuins are a family of enzymes involved in numerous aspects of cellular regulation, including metabolism, mitochondrial biology, stress responses and gene expression. Their activity depends on cellular context, tissue type, metabolic state and the availability of substrates and regulatory factors. They are not simple switches controlling ageing, and increasing one of the molecules involved in their activity cannot automatically be assumed to produce a clinically meaningful anti-ageing effect.

The same reductionism appears repeatedly in longevity nutrition. mTOR can be described as though it were an ageing switch that simply needs to be suppressed, AMPK as though activating it automatically promotes longevity, and autophagy as though it were a cellular cleaning programme that can be predictably activated by fasting for a prescribed number of hours. Each of these concepts originates in legitimate and fascinating biology, but the translation into consumer language frequently removes most of the complexity that determines what actually happens in a living human organism.

Increasing NAD+ may influence sirtuin activity under particular physiological circumstances, and understanding that relationship remains an important area of research. What it does not currently allow us to say is that taking NMN activates a human longevity programme or produces a predictable reduction in biological ageing.

Does NMN actually slow biological ageing?

This is ultimately the question that matters, and it is also the question that current research cannot answer with confidence. The new trial did not demonstrate that NMN extends human lifespan, reduces cardiovascular disease, prevents dementia, lowers cancer incidence or delays the development of frailty. Nor did it provide convincing evidence of broad improvements in physical function that could reasonably be interpreted as functional rejuvenation.

This should not be regarded as a failure of the research. Good science is not designed to validate an attractive biological story; it is designed to test whether that story survives experimental scrutiny. One of the recurring problems within the modern longevity industry is that mechanistic plausibility, animal experiments, biomarker changes and demonstrated improvements in human ageing are often discussed as though they represented different ways of describing the same evidence. They do not.

Animal and cellular studies can identify mechanisms and generate hypotheses. Biomarker studies can demonstrate that an intervention reaches or modifies a biological target. Short-term human trials can begin establishing safety and investigate physiological outcomes. Longer and larger clinical studies are then required to determine whether those changes translate into reductions in disease, disability, frailty or other outcomes that genuinely matter to human healthspan.

NMN has progressed some distance along that evidential pathway, but it has not reached the end of it. We have increasingly good evidence that oral NMN can alter NAD+ metabolism in humans. We have much less evidence that doing so produces the kind of substantial improvements in health and function that would justify describing NMN as a proven anti-ageing intervention.

Safety requires a much longer view

The 1,250 mg daily dose used in the new trial was generally well tolerated over 24 weeks, with no significant adverse effects attributed to NMN. This is reassuring, particularly because the dose was considerably higher than that used in several previous trials. It does not, however, establish the long-term safety profile that would be required for a supplement intended for chronic use.

This distinction matters because people interested in longevity supplements are rarely considering taking them for only six months. The implicit proposition is often that supplementation will continue for years or potentially decades. An intervention that appears well tolerated during a six-month trial may still have uncommon adverse effects that require much larger populations to identify, or consequences of prolonged exposure that short-term studies cannot detect.

There is also a relevant issue of research transparency. The new trial was funded by MIRAILAB BIOSCIENCE Inc., which also supplied the NMN, and several authors were employees of the company. The publication states that the company was not involved in the study design, clinical data collection, statistical analysis, interpretation of the results or decision to publish. Industry involvement does not invalidate research, and commercial funding is commonplace across pharmaceutical and nutritional science, but potential competing interests should always be transparent when evidence is being interpreted.

The appropriate conclusion from the current safety evidence is therefore relatively straightforward. Human trials provide some reassurance that NMN can be tolerated over the periods and doses studied so far, but they cannot yet tell us everything we would want to know about taking high-dose NMN continuously for many years.

Where does this leave somebody considering NMN?

The decision becomes much clearer once the desired outcome is defined. If the objective is simply to increase circulating NAD+ and related metabolites, human trials suggest that NMN is capable of doing this. If the objective is to improve physical function, prevent age-related disease, extend healthy lifespan or meaningfully slow the overall ageing process, the evidence is substantially less convincing.

That distinction should determine the language used around NMN. At present, I do not think the evidence justifies describing it as a proven anti-ageing supplement. There is interesting biology, increasingly useful human research and sufficient evidence of biological activity to justify continued investigation. Future studies may identify particular populations that benefit, specific outcomes that respond or circumstances in which NMN becomes clinically useful. Those possibilities are scientifically legitimate, but they remain possibilities rather than established anti-ageing effects.

This is also why the question “does NMN work?” is not particularly useful without specifying what we mean by “work”. Does it increase NAD+? The evidence increasingly suggests that it does. Does it reliably improve glucose regulation, muscle strength, physical performance or other established health outcomes? The evidence is inconsistent and often neutral. Does it slow human ageing or extend healthy lifespan? We simply do not have the evidence required to make that claim.

The problem is therefore not that the entire NMN story is fabricated. It is that the commercial narrative frequently takes the most firmly established part of the evidence, namely the increase in NAD+ metabolites, and allows consumers to assume that the much larger claims about ageing naturally follow from it.

The hierarchy of healthy-ageing interventions still matters

The extraordinary interest in longevity biology can sometimes distort our perception of where the greatest opportunities for improving healthspan currently lie. It is entirely possible to become preoccupied with NAD+, sirtuins, autophagy, mTOR and increasingly sophisticated biological-age measurements while paying insufficient attention to risk factors that have far more established relationships with disease, disability and premature mortality.

Cardiovascular risk remains enormously important. Maintaining appropriate blood pressure, controlling atherogenic lipoproteins, avoiding smoking and supporting vascular health addresses diseases that continue to account for a substantial proportion of morbidity and mortality. Metabolic health matters just as much, particularly the prevention or appropriate management of insulin resistance, type 2 diabetes, excess visceral adiposity and fatty liver disease.

Physical capacity also becomes increasingly important as we age. Maintaining skeletal muscle, strength, cardiorespiratory fitness and bone health influences whether additional years of life are spent active and independent or increasingly limited by frailty and loss of function. Nutrition contributes to each of these areas through adequate protein and micronutrient intake, dietary fibre, unsaturated fats, plant foods and an overall dietary pattern that supports an appropriate body composition and metabolic health.

None of this makes molecular ageing research irrelevant. Understanding cellular senescence, mitochondrial biology, epigenetic change, nutrient sensing, immune ageing and NAD+ metabolism may eventually lead to interventions that substantially alter human healthspan. The important point is that emerging interventions should sit on top of established health behaviours rather than replacing them. A supplement capable of increasing NAD+ cannot compensate for uncontrolled hypertension, severe dyslipidaemia, poor glucose regulation, smoking, physical inactivity or progressive loss of muscle.

This hierarchy is particularly important because novelty has a powerful psychological effect. A newly identified molecular pathway feels more sophisticated than eating well, exercising and managing established cardiovascular risk factors, even when the evidence supporting those conventional interventions is vastly stronger. Longevity science becomes most useful when it adds to established preventive medicine rather than distracting us from it.

What NMN teaches us about the wider longevity industry

Perhaps the most interesting lesson from the new trial extends beyond NMN itself. Modern biomedical science has become extraordinarily good at measuring biological processes associated with ageing. Researchers can quantify metabolites, proteins, inflammatory signals, gene expression, DNA methylation patterns and increasingly sophisticated molecular signatures. This is transforming our understanding of what happens to the human body across the lifespan and may eventually allow us to intervene in ageing biology with much greater precision.

The challenge is that every measurable biomarker creates the possibility of confusing measurement with outcome. If a particular marker declines with age and a supplement increases it, the story feels intuitively complete. Yet the biological system in which that marker operates may be vastly more complicated. Restoring one measurement to a more youthful value does not necessarily restore the surrounding physiology to a younger state, and a biomarker can change without producing a meaningful improvement in disease risk, physical function or quality of life.

This distinction is already familiar elsewhere in medicine. Clinical research has repeatedly shown why surrogate outcomes need validation against endpoints that actually matter. Longevity research should be held to the same standard. If an intervention is eventually going to be described as slowing ageing, we should expect evidence that extends beyond changing a molecule associated with ageing.

The new NMN trial is therefore valuable precisely because it separates these two ideas. Six months of high-dose supplementation successfully altered NAD+ metabolism in older adults, yet this biochemical success was not accompanied by convincing improvements across the major functional outcomes examined. Rather than undermining the science of NAD+, this tells us where the science currently stands and what the next generation of research needs to establish.

NMN remains interesting, but the anti-ageing claim remains unproven

NMN deserves continued scientific attention. NAD+ biology is important, the mechanistic rationale is substantial, human supplementation clearly alters NAD+ metabolism and there are enough preliminary signals in some areas to justify further clinical trials. Larger studies, longer follow-up and better-defined outcomes may yet reveal useful applications, particularly if researchers can identify populations in whom NAD+ metabolism is genuinely limiting physiological function.

What the existing evidence does not justify is collapsing all of that uncertainty into the simple claim that NMN slows human ageing. Raising NAD+ is not synonymous with extending lifespan, preventing age-related disease or preserving physical function. The new trial demonstrates the first of those effects particularly well while providing little evidence for the broader outcomes that consumers are ultimately interested in.

That distinction should not make longevity research less exciting. If anything, it makes the subject more interesting because it forces us to confront how extraordinarily complex human ageing really is. There is unlikely to be one molecular switch that determines whether we age well, just as there is unlikely to be one supplement capable of overriding the accumulated effects of genetics, cardiovascular health, metabolic health, body composition, physical activity, diet, environmental exposures and disease across an entire lifetime.

For now, NMN is best understood as an intriguing experimental approach to manipulating one important component of ageing biology rather than an established method of slowing the ageing process itself. That may sound less dramatic than the claims made in parts of the longevity industry, but it is a far more accurate reflection of what human research currently allows us to say.

References

Igarashi, M., Naruse, K., Takaoka, Y. et al. (2026) ‘Sustained NAD+ augmentation by high-dose nicotinamide mononucleotide supplementation in older adults: a 24-week randomized, double-blind, placebo-controlled trial’, npj Aging. doi: 10.1038/s41514-026-00482-7.

Igarashi, M., Miura, M., Williams, E. et al. (2022) ‘Chronic nicotinamide mononucleotide supplementation elevates blood nicotinamide adenine dinucleotide levels and alters muscle function in healthy older men’, npj Aging, 8, 5.

‘Effects of nicotinamide mononucleotide on glucose and lipid metabolism in adults: a systematic review and meta-analysis of randomised controlled trials’ (2024). Available at: https://pubmed.ncbi.nlm.nih.gov/39531138/

‘Efficacy of oral nicotinamide mononucleotide supplementation on glucose and lipid metabolism for adults: a systematic review with meta-analysis on randomized controlled trials’ (2024). Available at: https://pubmed.ncbi.nlm.nih.gov/39116016/

‘The effect of nicotinamide mononucleotide and riboside on skeletal muscle mass and function: a systematic review and meta-analysis’ (2025). Available at: https://pubmed.ncbi.nlm.nih.gov/40275690/

‘Domain-specific effects of NAD+ precursors on fatigue and functional performance: a systematic review and network meta-analysis’ (2026). Available at: https://pubmed.ncbi.nlm.nih.gov/42774067/