NAD+ Infusions: What the Evidence Actually Shows
Abstract: NAD+ intravenous infusions are being sold in wellness clinics worldwide for anti-ageing, fatigue, addiction recovery, and cognitive performance. The underlying biology is real. NAD+ is a critical coenzyme in cellular metabolism, and levels do decline with age. But a plausible mechanism is not the same as a demonstrated clinical benefit. The human evidence for intravenous NAD+ therapy is limited to small pilot studies, most of which assessed tolerability and biomarker changes rather than clinical outcomes. No adequately powered, placebo-controlled trials have confirmed meaningful benefits for any of the conditions being marketed. People are paying several hundred to several thousand pounds for a treatment that has not cleared a basic evidential bar.
The biology is not the problem
NAD+ nicotinamide adenine dinucleotide is a coenzyme present in every cell of the body. It plays a central role in energy metabolism, DNA repair, and the regulation of proteins involved in cellular stress responses. There is genuine scientific interest in the observation that NAD+ concentrations in some tissues decline with age, and a substantial body of preclinical work suggests that maintaining or restoring NAD+ levels may have protective effects in the context of ageing and metabolic disease.
This is legitimate science. The question is not whether NAD+ matters biologically. It clearly does. The question is whether infusing it intravenously into a generally healthy person produces the clinical outcomes being advertised. These are very different questions, and conflating them is a common assumption underlying commercial claims about this treatment that the evidence does not support.
Understanding the gap between them requires looking at what the evidence actually shows, starting with the most basic question: what happens when you infuse NAD+ directly into the bloodstream?
What happens when you infuse NAD+
One of the central selling points of intravenous NAD+ therapy is that it bypasses the gut and delivers the molecule directly into circulation. This is presented as superior to oral supplementation. The claim sounds pharmacologically intuitive, but the underlying biology complicates it considerably.
NAD+ is a large, charged molecule. It does not cross cell membranes freely. When infused intravenously, it encounters a range of enzymes in the bloodstream, including CD38, an NAD-degrading enzyme expressed on immune cells, that break it down before it can enter tissues. A pilot study published in Frontiers in Aging found that plasma NAD+ levels did not begin to rise until two hours into a six-hour infusion, and that the increases observed were accompanied by large rises in metabolites, particularly nicotinamide and ADP-ribose, suggesting substantial breakdown of the infused molecule rather than intact delivery to tissues. Urinary excretion of NAD+ metabolites increased sharply after the infusion stopped, consistent with the body clearing what it could not use. No clinical benefits or long-term safety outcomes were reported.
A 2025 review published in Nature Aging noted that the dynamics and kinetics of NAD+ after intravenous administration remain poorly understood, and that tracer studies in humans, the kind of work needed to track where infused NAD+ actually goes, have not been done. The available evidence suggests that intravenously administered NAD+ is likely subject to substantial extracellular metabolism before reaching intracellular targets, though the precise magnitude of this effect in humans has not been quantified.
This is the pharmacokinetic problem that the industry does not advertise. The argument for intravenous delivery rests on bioavailability, but the bioavailability of intact NAD+ at the intracellular level, which is where it needs to be, has not been demonstrated in humans.
What the clinical evidence actually shows
A 2020 systematic review of NAD-related clinical trials identified only two adequately powered completed studies across the entire literature. Neither was a trial of intravenous NAD+ for the conditions currently being marketed. The broader trial landscape at the time consisted of small, poorly controlled studies with heterogeneous designs and endpoints.
That picture has improved modestly since, but not substantially. One of the more structured recent human studies on intravenous NAD+ is a randomised, placebo-controlled pilot published as a preprint in 2024, which compared 500mg of intravenous NAD+, 500mg of intravenous nicotinamide riboside (NR), oral NR, and a saline placebo in healthy adults. The primary outcomes were safety, tolerability, and blood NAD+ levels, not clinical endpoints. No assessment of energy, cognitive function, ageing biomarkers, or any of the conditions routinely marketed was included. As a preprint, the study has not yet completed peer review and should not be used to support clinical claims.
On the specific claims made by clinics, the evidence is either absent or insufficient. Anti-ageing: there are no published human trials showing that NAD+ infusions slow, reverse, or meaningfully modify any validated marker of biological ageing. Energy and fatigue: the available reviews of NAD-related supplementation, including broader assessments of NAD precursor literature, have generally found insufficient evidence that intravenous NAD+ improves fatigue or energy levels in healthy adults, with most available data coming from self-reported outcomes without placebo controls; a fully specified systematic review restricted to intravenous NAD+ alone has not been identified in the published literature. Addiction treatment: interest in NAD+ for addiction dates to case reports from the 1960s, but a 2022 commentary in JAMA Psychiatry noted that claims of addiction recovery are not supported by current clinical data, and modern randomised trials are lacking. Cognitive function: animal data showing NAD+ precursors can improve mitochondrial function and cognitive markers are well-documented, but these results come from oral precursor supplementation, not intravenous NAD+ , and human translation has not been established.
There is an important distinction running through all of this. Much of the preclinical and some of the human biomarker evidence relates to oral NAD+ precursors, primarily nicotinamide riboside and nicotinamide mononucleotide, not to intravenous NAD+ itself. The clinical profile for oral NR, in particular, is more developed: there are multiple randomised trials demonstrating that it raises blood NAD+ levels, and some evidence of modest effects on metabolic parameters in specific populations. Extrapolating that evidence to intravenous NAD+ is not scientifically justified. The route of administration, the molecule, and the dose are all different, and none of them have been directly compared against clinical outcomes in a powered trial.
Why intravenous delivery does not resolve the problem
The logic offered by clinics is essentially this: oral NAD+ precursors work by raising NAD+ levels, so a more direct method of raising NAD+ levels should work better or faster. This argument is wrong in at least two respects.
First, as discussed above, intravenous NAD+ does not reliably raise intracellular NAD+ levels. The molecule is subject to extracellular degradation. In the 2024 preprint, which should be interpreted cautiously given its unpublished status, intravenous NR produced higher and faster rises in whole blood NAD+ than intravenous NAD+ itself. It is worth noting that whole blood NAD+ is not a validated surrogate for intracellular NAD+ availability or clinical outcomes; the finding nonetheless raises questions about the delivery rationale for the form most widely used in clinics. Tolerability also differed substantially: participants receiving intravenous NAD+ reported moderate to severe abdominal cramping, diarrhoea, nausea, vomiting, and elevated heart rate. These are not trivial adverse effects for an intervention with no demonstrated clinical benefit, and they compound the safety uncertainty that already exists around repeated infusion, including risks of phlebitis, infection, and the absence of standardised dosing protocols across providers.
Second, and more fundamentally, the assumption that raising blood NAD+ produces clinical benefits has not been validated in humans at the level required to justify these claims. The pharmacokinetic uncertainty outlined above does not by itself establish that intravenous NAD+ is ineffective. Absence of evidence is not evidence of absence. But it does mean the mechanistic rationale for the treatment remains unconfirmed at the level of tissue delivery. The step from "NAD+ levels in some tissues decline with age" to "artificially raising NAD+ via infusion will produce meaningful clinical improvements in healthy adults" requires a chain of evidence that has not been assembled. Mechanism is not outcome. The pathway is biologically plausible. The clinical benefit remains undemonstrated.
There is also a regulatory dimension worth noting. Intravenous NAD+ is not approved for any of the indications being marketed, anti-ageing, fatigue, addiction, or cognitive performance, by any major regulatory body. It is administered as a compounded preparation, meaning formulations and dosing protocols vary across clinics without the standardisation or oversight applied to licensed medicines. Sessions are typically priced between a few hundred and several thousand pounds, a cost that is difficult to justify against an evidence base that has not established benefit over placebo for any of these outcomes.
What it would take to change this assessment
It would be wrong to suggest that NAD+ biology is uninteresting or that intravenous applications could never be clinically useful. The biology is compelling, and it is genuinely possible that future well-designed trials could identify populations, contexts, or conditions where this approach offers meaningful benefit. Some research groups are investigating NAD+ in the context of specific diseases, Parkinson's, cardiac ischaemia, certain metabolic conditions, where the rationale is more developed and the study design more rigorous.
But that is not what is being sold in wellness clinics. What is being sold is a broadly applicable treatment for ageing, fatigue, cognitive decline, and addiction in generally healthy adults, at prices ranging from a few hundred to several thousand pounds per session, without the clinical evidence to support any of those claims.
For this assessment to change, what would be needed is straightforward: adequately powered, randomised, placebo-controlled trials in humans, measuring clinical outcomes, not just biomarker changes, with sufficient follow-up to assess both efficacy and long-term safety. Those trials have not been done.
Until they are, the appropriate conclusion is that the biological rationale for NAD+ supplementation is plausible, that oral precursor supplementation has a developing evidence base for some outcomes in some populations, and that intravenous NAD+ therapy as currently marketed occupies a different evidential category: an intervention that has expanded commercially well ahead of the controlled human data needed to support its claims. Where evidence is limited or outcomes are uncertain, conclusions should be treated as provisional and subject to revision as the evidence base develops.
Further reading
For a detailed review of the evidence on oral NAD+ precursors, including NMN and NR, see the Evidentia Nutrition entry on NMN (Nicotinamide Mononucleotide).
Evidentia Nutrition evaluates supplements and nutrition interventions against the published evidence. Entries and articles are reviewed against primary literature and updated as the evidence base develops.