„Mental clarity”, „concentration support” and „NAD+ brain restoration therapy” are common terms used in cognitive marketing. These claims should be separated from research into specific conditions, such as Alzheimer's and Parkinson's disease, which we discuss in our disease research guide. This article focuses on what is currently known about NAD+ in the brain more broadly, including its role in neuronal energy metabolism, the scientific basis for concentration and mental clarity claims, whether „NAD+ brain restoration therapy” is an established treatment, and what research shows regarding sleep, anxiety and mood.
The role of NAD+ in neuronal energy metabolism
The brain is one of the organs with the highest metabolic demand in the human body. Although it makes up only a small fraction of total body weight, at rest it consumes a disproportionately large share of the body's energy. Neurons are largely dependent on the efficient functioning of mitochondria to meet this constant energy demand [1].
The fundamental role of NAD+ in energy metabolism is also directly relevant to brain tissue. NAD+ participates in electron transfer reactions associated with the production of ATP, which neurons constantly require for basic processes such as maintaining membrane potential, producing neurotransmitters, ion transport, and supporting synaptic signalling [1,2].
Apart from energy metabolism, NAD+ is also involved in several other cellular processes essential for the brain. It acts as a substrate for sirtuins and PARP enzymes, which are active in neurons and participate, amongst other things, in gene regulation, the cellular stress response and DNA repair [2].
The NAD+ level in the human brain can now be measured non-invasively using specialised magnetic resonance spectroscopy techniques, or MRS. Research using these methods has shown that the level of NAD+ in the brain appears to decrease with age, similarly to what is observed in several other tissues [3]. This measurable decline is one of the findings that has contributed to scientific interest in NAD+ metabolism and brain ageing.
What are the marketing claims of „mental clarity” and „concentration” based on?
Claims regarding „mental clarity” and „concentration” are often associated with NAD+ products, but the scientific evidence behind these specific terms is much less direct than their wording might suggest.
General reasoning usually starts with neuronal energy metabolism. Neurons need a large and steady amount of energy, and NAD+ is essential for the metabolic pathways involved in ATP production. On this basis, it is sometimes assumed that increasing the availability of NAD+ will improve brain energy metabolism and, consequently, also cognitive functions such as concentration, focus or mental clarity.
Such reasoning is biologically plausible, as the individual stages involve well-established biological processes. However, the combination of these mechanisms alone does not prove that NAD+ precursor supplementation improves subjective focus or mental clarity in humans.
No published, placebo-controlled, randomised human trials have been identified that use validated, standardised measurements of „concentration” or „mental clarity” as primary endpoints for NAD+ precursor supplementation in healthy adults.
The closest evidence comes from studies in specific clinical populations, including individuals with mild cognitive impairment or Parkinson's disease. These studies typically used objective cognitive tests, imaging, biomarkers, or disease-specific parameters rather than subjective assessments of „mental clarity”.
Importantly, some studies have shown that NAD+ precursors can increase NAD+ levels in the brain without simultaneously significantly improving all assessed cognitive functions. This distinction clearly illustrates the difference between changing a biomarker and demonstrating a meaningful cognitive benefit.
For this reason, claims that NAD+ products reliably improve concentration or mental clarity should not be regarded as established clinical effects unless supported by controlled human studies using appropriate cognitive endpoints.
What is NAD+ brain restoration therapy, and is it a recognised medical treatment?
„NAD+ brain restoration therapy is not a recognised medical treatment category defined in peer-reviewed clinical literature or by major regulatory agencies. It is primarily a commercial or marketing term.
This term is usually used to describe the intravenous or injectable administration of NAD+ promoted for cognitive or neurological purposes, including claims such as improving brain fog, slowing cognitive decline, supporting addiction recovery, or general „neurological restoration”.
There is real human research testing whether increasing NAD+ affects the brain in a measurable way, but the scope of this evidence is much narrower than the broad term „brain restoration” suggests.
One important example is the NADPARK Phase I trial. In this study, oral nicotinamide riboside was administered to people with Parkinson's disease. The researchers found that NR increased brain NAD+ levels and was associated with changes in several biological biomarkers and with minor clinical changes [4].
This study used controlled clinical methods and direct measurements of brain NAD+ metabolism. However, it was conducted in a specific population of people with the disease and used oral nicotinamide riboside, rather than intravenously or injectably administered NAD+.
In a separate Phase I pharmacokinetic study, changes in blood and brain NAD+ levels were evaluated during repeated oral administration of the precursor. Blood NAD+ levels increased earlier, whereas measurable changes in brain NAD+ developed more slowly and became detectable after approximately four weeks of regular use [5].
These results provide evidence that oral NAD+ precursors can alter measurable brain NAD+ levels over time.
However, they do not support „NAD+ brain restoration therapy” as a general treatment for brain fog, cognitive decline, concentration issues, or neurological recovery. Nor do they prove that intravenous or injectable NAD+ produces equivalent effects in the brain.
Controlled evidence from human studies regarding increasing NAD+ levels in the brain largely comes from precisely defined research conditions, specific populations, oral administration of precursors, and objective imaging or biomarker assay methods. This differs significantly from the broad claims often associated with commercial „brain restoration” programmes.
Does NAD+ affect sleep, anxiety or mood?
Sleep has been evaluated in at least one significant controlled human trial.
In a randomised, placebo-controlled, double-blind study, 250 mg of NMN per day was administered for 12 weeks to older adults. Physical performance, blood NAD+-related metabolites, and several additional outcomes related to sleep and stress were evaluated [6].
The primary endpoint, involving the step test, showed no significant difference between the groups. However, walking speed was maintained in participants receiving NMN, whereas a decrease was observed in the placebo group, and an improvement in sleep quality was also noted in the NMN group as a secondary outcome [6].
This constitutes controlled human trial evidence relevant to sleep, but the interpretation should remain cautious. Sleep quality was a secondary rather than a primary endpoint, meaning the study was not designed or adequately powered primarily to establish the efficacy of NMN on sleep issues.
This result would therefore need to be replicated in studies designed specifically to assess sleep, using validated sleep measures as pre-specified primary endpoints.
Evidence regarding anxiety and mood is more indirect.
Studies analysing genetic data from the Taiwan Biobank have shown associations between variants of genes involved in metabolic pathways related to NAD+, including the kynurenine pathway and nicotinate metabolism, and the risk of major depressive disorder [7].
This suggests that NAD+-related metabolism may be linked to vulnerability to depression or related biological pathways in some individuals.
However, these were genetic association studies. They do not prove that increasing NAD+ through supplementation improves symptoms of depression, anxiety or mood disorders.
No published, placebo-controlled, randomised human trial has been identified that evaluates the NAD+ precursor specifically as a treatment for anxiety or depression.
Therefore, evidence linking NAD+ to mood disorders remains largely mechanistic, genetic or associative, rather than interventional.
What has actually been researched and what remains anecdotal?
Current evidence can be divided into several levels of confirmation.
Controlled human studies have directly analysed age-related changes in brain NAD+ levels using specialist MRS imaging [3].
Human pharmacokinetic studies have also shown that oral NAD+ precursors can increase NAD+ levels in the blood, and more slowly also in the brain [5].
The Phase I NADPARK trial demonstrated an increase in brain NAD+ levels in individuals with Parkinson's disease, alongside related biomarker changes and minor clinical changes [4].
One 12-week NMN study in older adults also showed improvements in sleep quality as a secondary outcome [6].
At another level of evidence, genetic studies have shown links between metabolic pathways associated with NAD+ and the risk of major depressive disorder [7]. These findings are useful for understanding possible biological relationships, but they do not confirm therapeutic effects.
In turn, several popular claims directed at consumers have not been directly confirmed in controlled human studies.
This relates to the reliable improvement of „concentration”, „mental clarity” or similar subjective cognitive functions in healthy adults.
This also applies to the use of NAD+ precursors as a proven treatment for anxiety or depression.
„NAD+ brain restoration therapy” also remains a marketing term rather than a validated clinical treatment category.
The overall picture of the evidence is therefore inconclusive. There is significant human research concerning brain NAD+ metabolism, particularly with regard to cerebral pharmacokinetics, age-related changes, and selected disease contexts. However, many frequently repeated claims regarding general improvements in cognitive ability, concentration, mental clarity, or broadly defined neurological recovery remain considerably less directly substantiated.
Realistic expectations regarding cognitive effects
The role of NAD+ in neuronal energy metabolism is well documented. Neurons require NAD+-dependent metabolic pathways for ATP production, and NAD+ is also involved in cellular functions encompassing sirtuins, PARPs, the stress response, and DNA repair [1,2].
Controlled human studies have also shown that oral NAD+ precursors can increase NAD+ levels in the blood, and more gradually in the brain as well [5].
Under specific conditions, additional outcomes were also noted. These include an increase in brain NAD+ and associated biomarker changes or minor clinical changes in Parkinson's disease studies [4], as well as an improvement in sleep quality as a secondary outcome in one NMN study in older adults [6].
These results are scientifically significant, but have a much narrower scope than general claims about the improvement of cognitive function.
Current research does not show that NAD+ precursor supplementation reliably improves concentration, mental clarity, focus, memory, or overall cognitive performance in healthy adults.
They also do not endorse „NAD+ brain restoration therapy” as a validated treatment category for cognitive decline, brain fog, mood disorders, or neurological recovery.
It is particularly important to distinguish between measurable changes in brain NAD+ levels and a clinically significant improvement in cognitive function. Increasing a biomarker does not automatically mean an improvement in cognitive function.
Similarly, results obtained in specific patient populations should not be automatically extrapolated to healthy adults seeking to improve their cognitive abilities.
Individuals considering NAD+ supplementation due to persistent cognitive issues, sleep disturbances, anxiety, or mood changes should also bear in mind that these symptoms can have multiple potential causes. An evidence-based medical or psychological assessment may be more appropriate than assuming the symptoms stem from NAD+ levels.
Limitations of current evidence
- No published controlled human studies using validated measures of „concentration” or „mental clarity” as primary endpoints for NAD+ precursor supplementation in healthy adults have been identified.
- The strongest evidence regarding the human brain, including pharmacokinetic data on brain NAD+ and biomarker studies in Parkinson's disease, comes from relatively small studies and strictly defined clinical populations. These results cannot be automatically extrapolated to healthy adults seeking a general cognitive enhancement [4,5].
- Proof that oral NAD+ precursors can increase NAD+ levels in the brain does not mean that such an increase improves memory, attention, concentration, executive function or subjective mental clarity.
- The discussed improvement in sleep quality was a secondary rather than a primary endpoint. Therefore, it requires confirmation in studies specifically designed and appropriately powered from a statistical standpoint to assess sleep parameters [6].
- The evidence linking NAD+ metabolism to depression is mainly genetic and associative rather than interventional. Such results do not prove that NAD+ supplementation treats depression or anxiety [7].
- No randomised, placebo-controlled human study confirming an NAD+ precursor as a treatment for anxiety or depressive disorders has been identified.
- The results of Parkinson's disease research should not be generalised to other neurological diseases, healthy ageing or general cognitive enhancement without appropriate studies in those populations [4].
- „NAD+ brain restoration therapy” is neither a defined nor recognised category of treatment in peer-reviewed medical literature, and the term should not be interpreted as evidence of the existence of a validated neurological therapy under such a name.
- Controlled evidence showing that oral NAD+ precursors affect brain NAD+ levels does not automatically support equivalent claims for intravenous, intramuscular, subcutaneous, sublingual, or other routes.
- Changes in NAD+ biomarkers, imaging measurements, inflammatory markers or other biological signals do not in themselves prove a clinically significant improvement in cognitive function, mood, sleep or neurological health.
- Subjective reports concerning improvements in concentration, mental clarity or mood can be influenced by the placebo effect, sleep, stress, caffeine intake, medication, physical activity, diet, underlying medical conditions and other factors that are difficult to control outside of clinical trials.
Disclaimer
The article is strictly educational and summarises scientific research. It does not constitute medical, neurological, psychiatric or psychological advice.
NAD+ and its precursors should not be presented as FDA- or EMA-approved treatments for cognitive impairment, brain fog, anxiety, depression, sleep disorders, Parkinson's disease, Alzheimer's disease, or any other neurological or psychiatric conditions, unless referring to a specific approved medicinal product and indication.
The evidence summarised here includes basic neurobiology, biomarker studies, pharmacokinetic studies, genetic association studies and early human clinical trials. Changes in brain NAD+ levels, biomarkers or other biological measurements should not be interpreted as evidence of cognitive improvement or treatment efficacy.
Persistent problems with memory, concentration, sleep, anxiety, mood, or other cognitive symptoms can have many possible causes, including neurological, psychiatric, endocrinological, cardiovascular, metabolic, medication-related, nutritional, or sleep-related ones.
Individuals experiencing persistent or worsening cognitive problems, sleep disturbances, anxiety or mood disorders should seek an assessment from an appropriately qualified healthcare professional or mental health specialist rather than relying solely on NAD+ supplementation. Before starting any new supplement or therapy, you should consult a qualified healthcare professional, particularly during pregnancy or breastfeeding, when receiving treatment for a chronic physical or mental illness, or when taking prescription medications concurrently.
References
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[2] Covarrubias, A. J., Perrone, R., Grozio, A., & Verdin, E. (2021). NAD+ metabolism and its roles in cellular processes during ageing. Nature Reviews Molecular Cell Biology, 22(2), 119–141. https://doi.org/10.1038/s41580-020-00313-x
[3] Bagga, P., Hariharan, H., Wilson, N. E., Beer, J. C., Shinohara, R. T., Elliott, M. A., Baur, J. A., Marincola, F. M., Witschey, W. R., Haris, M., Detre, J. A., & Reddy, R. (2020). Single-voxel ¹H MR spectroscopy of cerebral nicotinamide adenine dinucleotide (NAD+) in humans at 7T using a 32-channel volume coil. Magnetic Resonance in Medicine, 83(3), 806–814. https://doi.org/10.1002/mrm.27971
[4] Brakedal, B., Dölle, C., Riemer, F., Ma, Y., Nido, G. S., Skeie, G. O., Craven, A. R., Schwarzlmüller, T., Brekke, N., Diab, J., Sverkeli, L., Skjeie, V., Varhaug, K., Tysnes, O.-B., Peng, S., Haugarvoll, K., Ziegler, M., Grüner, R., Eidelberg, D., & Tzoulis, C. (2022). The NADPARK study: A randomised phase I trial of nicotinamide riboside supplementation in Parkinson’s disease. Cell Metabolism, 34(3), 396–407.e6. https://doi.org/10.1016/j.cmet.2022.02.001
[5] Berven, H., Svensen, M., Eikeland, H., Tvedten, N., Sheard, E. V., Amdahl Af Geijerstam, S., Søgnen, M., McCann, A., Arnsten, L., Årseth, O., Skjeie, V., Hjellbrekke, A., Skeie, G.-O., Torres Cleuren, Y. N., Nido, G. S., Haugarvoll, K., Riemer, F., Tzoulis, C., & Dölle, C. (2026). The NAD-brain pharmacokinetic study of NAD augmentation in blood and brain using oral precursor supplementation. iScience, 29(3), 114764. https://doi.org/10.1016/j.isci.2026.114764
[6] Morifuji, M., Higashi, S., Ebihara, S., & Nagata, M. (2024). Ingestion of β-nicotinamide mononucleotide increased blood NAD levels, maintained walking speed, and improved sleep quality in older adults in a double-blind randomised, placebo-controlled study. GeroScience, 46(5), 4671–4688. https://doi.org/10.1007/s11357-024-01204-1
[7] Chen, D. T.-L., Cheng, S.-W., Chen, T., Chang, J. P.-C., Hwang, B.-F., Chang, H.-H., Chuang, E. Y., Chen, C.-H., & Su, K.-P. (2022). Identification of genetic variations in the NAD-related pathways for patients with major depressive disorder: A case-control study in Taiwan. Journal of Clinical Medicine, 11(13), 3622. https://doi.org/10.3390/jcm11133622