You have had the labs. They came back normal. Someone suggested an NAD+ infusion, and maybe you tried one, or three. Perhaps something shifted. Perhaps nothing did, and now you are reading accounts online from people who say it changed their life sitting right next to accounts from people who say it did nothing.
A network meta-analysis published in September 2026 goes a long way toward explaining how both groups can be telling the truth. The short version: fatigue is not one thing, and NAD+ precursors do not act on it as though it were.
What the September 2026 analysis actually did
Researchers pooled 27 studies covering 1,599 adults — 25 randomized controlled trials and 2 quasi-experimental studies — and compared four NAD+ precursors against one another: nicotinamide riboside, nicotinamide mononucleotide, NADH, and nicotinamide. The review was registered in advance with PROSPERO and followed PRISMA reporting standards for network meta-analyses.
The design choice that matters is what they did next. Instead of asking the usual question — does NAD+ help fatigue — they broke fatigue into the domains clinicians actually distinguish: perceived fatigue, meaning how tired you feel; cognitive performance; and exercise performance, split into endurance and strength. Quality of life and sleep were tracked separately. Then they ranked the precursors within each domain rather than lumping the outcomes together.
The finding that explains the disagreement
Across the whole analysis, no precursor significantly improved perceived fatigue. None improved sleep quality either.
That is the most useful sentence in the paper for anyone deciding whether to spend money on this, and it is worth sitting with. Perceived fatigue is the reason almost everyone walks through the door. It is the complaint. And in the pooled randomized evidence, it is the outcome that did not move.
If you took NAD+ hoping to stop feeling tired and you still feel tired, you are not an outlier and you did not do it wrong. You got the result the published evidence would predict.
What did move
The same analysis found real, statistically significant effects. They are simply not in the place the marketing points.
Endurance, and it tracked with dose
Nicotinamide mononucleotide improved endurance performance, and the effect grew with dose: a standardized mean difference of 0.66 at a medium dose and 1.02 at a high dose. Neuromuscular strength did not change. Quality of life improved moderately, again mainly with nicotinamide mononucleotide, at both low and high doses.
Cognition, with a caveat the authors flag themselves
NADH produced the largest single effect in the analysis on cognitive performance, and that effect was strongest in groups who already had cognitive impairment. The authors note it was sensitive to influential studies, meaning that removing one or two trials changes the result substantially. That is a reason to hold the finding loosely rather than quote it as settled, and the authors say so themselves.
A second line of evidence pointing the same way
If the NAD+ result were a one-off it would be easy to set aside. It is not. A separate 2026 systematic review and meta-analysis examined coenzyme Q10 — a different mitochondrial cofactor, a different research group, a different set of patients — and landed in a similar place. Across five randomized trials and 474 participants, coenzyme Q10 was associated with a moderate improvement in depressive symptoms. For fatigue, the pooled result was not statistically significant, drawn from only two trials with very high variability between them, and the authors described the evidence as inconclusive.
Two independent analyses, two different molecules aimed at the same cellular machinery, and subjective fatigue is the outcome that resists both.
Every one of those trials used a pill, not an IV
This is where being straight with you matters more than positioning. The precursors in that network meta-analysis are oral compounds. Intravenous NAD+, which is what is actually sold in infusion clinics, was not the intervention being tested in it.
A July 2026 review in Molecular Biology Reports puts the position plainly: oral precursors can raise circulating NAD+, while intravenous NAD+ administration is less well characterized and lacks robust clinical validation. The same review describes NAD+ responses as nonlinear and shaped by dose, age, metabolic state and route of administration, operating within a regulatory system that includes feedback and biological saturation — which is a technical way of saying that more is not automatically better.
The most detailed intravenous NAD+ pharmacology published this year is preclinical work in cell lines and animals on an investigational formulation, not the product given in clinics. That is a legitimate stage of research. It is not human outcome evidence, and it should not be presented as though it were. NAD+ IV therapy is not FDA-approved for fatigue, energy, or cognitive performance.
Tired is a symptom, not a diagnosis
None of this means your fatigue is imaginary or that nothing can be done about it. It means a molecule aimed at cellular energy production is one hypothesis about your tiredness among several, and the pooled evidence does not support making it the first one.
Persistent fatigue in adults commonly involves sleep-disordered breathing, iron or B12 status, thyroid function, blood sugar regulation, medication effects, mood, post-viral illness such as Long COVID, or autonomic dysfunction — and frequently more than one at the same time. Those are findable. Several of them have considerably stronger treatment evidence behind them than any infusion does.
Questions worth asking before you book an infusion anywhere
These apply to any clinic in the Oklahoma City metro, including this one. They are the questions that separate a treatment plan from a package price.
- What specifically are we expecting to change, and how will we measure it?
- What has been ruled out first, which labs were run, and what did they show?
- Is the plan oral, intravenous, or both — and what is the reasoning behind that choice?
- What is the dose, how many sessions, and at what point do we stop if nothing has changed?
- What would make you tell me this is not the right treatment for me?
A clinic that answers these comfortably is a clinic paying attention. You can read more about how we approach NAD+ IV therapy and the rest of our alternative and functional medicine services before you call.
Who is generally not a good candidate
Candidates are typically evaluated for several things before an infusion is considered a reasonable next step. In general, this is not the right starting point for someone who:
- has not yet had a basic medical workup for fatigue
- is pregnant or breastfeeding
- has significant kidney or liver impairment
- has an active infection, or an unstable cardiac or blood pressure condition
- is looking for a substitute for treating a diagnosed condition rather than an addition to it
- expects a single visit to resolve symptoms that have been present for years
This is a starting point for a conversation, not a screening tool. Whether any therapy is appropriate is determined during a consultation, and some people are told that it is not.
Frequently asked questions
Does NAD+ therapy help fatigue?
In the pooled randomized evidence, not for the symptom most people mean by fatigue. The September 2026 network meta-analysis in Frontiers in Nutrition found that no NAD+ precursor significantly improved perceived fatigue, which is the subjective feeling of being tired. The same analysis did find significant improvements in endurance performance and in some cognitive measures. Results vary between individuals, and these findings describe averages across groups, not predictions about any one person.
Why do some people say NAD+ changed their energy levels?
Because energy is a word that covers several different things. A person whose endurance during exercise improved and a person whose background tiredness never lifted may both be describing their experience accurately. The 2026 analysis found the effects were domain-specific, which means the treatment can move one measure and leave another untouched. Individual factors such as baseline nutritional status, sleep, and untreated medical conditions also differ widely from person to person.
Is IV NAD+ better than oral NAD+ supplements?
The published comparison does not exist yet. Every precursor in the 2026 network meta-analysis was given orally. A July 2026 review in Molecular Biology Reports states that oral precursors can raise circulating NAD+ while intravenous NAD+ is less well characterized and lacks robust clinical validation. Anyone telling you the intravenous route is proven to work better is going beyond what has been published.
Is NAD+ therapy FDA-approved?
No. NAD+ IV therapy is not FDA-approved for fatigue, energy, cognitive performance, or anti-aging. Oral NAD+ precursors are sold as dietary supplements, which are not FDA-approved to treat any condition either. This is worth knowing before you spend money on it, and any clinic that is not clear about it is not being straight with you.
How many sessions before you know whether it is working?
That should be agreed before the first one, not after the fifth. A reasonable plan names what is being measured, how often it will be checked, and the point at which the approach is reconsidered if nothing has changed. Open-ended packages with no stopping rule are a warning sign rather than a treatment plan.
What should I do first if I am always tired?
Get the common causes looked for properly before paying for an infusion. Persistent fatigue in adults frequently involves sleep-disordered breathing, iron or B12 status, thyroid function, blood sugar regulation, medication effects, mood, post-viral illness, or autonomic dysfunction, and often more than one at once. Those are identifiable, and several have much stronger treatment evidence behind them than any infusion.
Talking it through in Oklahoma City
If you are tired and have been told your labs are normal, the useful next step is an evaluation that looks for a cause, not a menu of infusions. Venturis Clinic offers regenerative, functional, and alternative medicine care in Oklahoma City, and we would rather tell you that an infusion is not your answer than sell you one. Patients may experience different results, and no outcome is guaranteed.
Venturis Clinic
7917 N May Ave, Suite B
Oklahoma City, OK 73120
(405) 848-7246
This content is for educational purposes only and is not medical advice, diagnosis, or treatment. Individual results vary and no outcome is guaranteed. Venturis Clinic offers regenerative, functional, and alternative medicine services; some therapies discussed are not FDA-approved for the uses described. Talk with a qualified healthcare provider about your specific situation before beginning any treatment.
Sources
- Gao Y, Li S, Guan J, Yin Y, Kong X, Yu L. Domain-specific effects of NAD+ precursors on fatigue and functional performance: a systematic review and network meta-analysis. Frontiers in Nutrition. 2026;13:1890335. DOI: 10.3389/fnut.2026.1890335
- Magalhães PLM, da Silva AMP, Maximiano MLB, et al. Effects of Coenzyme Q10 Supplementation on Depressive Symptoms and Fatigue: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Journal of Clinical Psychopharmacology. 2026;46(1):93–100. DOI: 10.1097/JCP.0000000000002112
- Pandolfi S, Ghezzi C, Björklund G, Metalla M, Paone FM, Chirumbolo S. NAD+ biology and supplementation: from mechanisms to clinical perspectives. Molecular Biology Reports. 2026;53(1). DOI: 10.1007/s11033-026-12351-3
- Ghosh A, Pranesh G, Zachariah N, et al. Pharmacological profiling of intravenous MP-04: sustained NAD+ augmentation, immune modulation, and renal protection in preclinical models. Frontiers in Pharmacology. 2026;17:1832979. DOI: 10.3389/fphar.2026.1832979
