Research into NAD+ covers an exceptionally wide range of diseases and disorders, including neurodegenerative diseases, cancer metabolism, kidney injury, mood disorders and addiction research.
In this article, we discuss the published research separately for each disease. We explain where the evidence is relatively stronger, where it remains preliminary, and where there is a practical lack of significant clinical data.
None of the following sections should be construed as medical advice for treating a specific condition. The aim is to present the current research landscape rather than to diagnose, prevent or treat diseases.
Does NAD+ cause or prevent cancer? What the research really shows
The relationship between NAD+ and cancer is complex. Current evidence does not allow for a simple conclusion that NAD+ causes or prevents cancer.
The biological effect appears to strongly depend on the context, including the tissue type, cancer subtype, metabolic state, and whether the studied cells are healthy or already malignant.
Mechanistic source of concern
Cancer cells, like other rapidly dividing cells, require large amounts of energy and materials necessary for the synthesis of new structures.
In many types of cancer, increased NAD+ metabolism activity has been observed, particularly the NAMPT-dependent salvage pathway, which may support tumour cell proliferation and survival. [1,2]
This is one of the reasons why NAMPT inhibitors are being investigated as potential anti-cancer drugs.
The basic concept relies on limiting the ability of cancer cells to regenerate NAD+, which could potentially reduce the availability of metabolic resources needed for their continued growth.
However, this does not mean that NAD+ itself is a carcinogenic substance for healthy cells.
Research suggests rather that pre-existing cancer cells can utilise NAD+ metabolism to satisfy their exceptionally high metabolic demands.
A specific study raising concern
In one preclinical study, a bioluminescent imaging probe was used to track nicotinamide riboside, or NR, in a mouse model of triple-negative breast cancer. [3]
Researchers noted that NR supplementation in this specific model was associated with a higher incidence of cancer and a greater number of brain metastases.
This is an important observation because it raises questions about whether NAD+ precursor supplementation can, under certain conditions, affect the biology of an existing tumour.
This result also serves as a reminder that the availability of an over-the-counter preparation should not be equated with safety in every clinical situation.
However, the scope of this study needs to be interpreted with caution.
It was an animal model concerning a specific cancer subtype. The result has not been confirmed in controlled clinical trials in humans.
The other side of research
Cancer research also encompasses the reverse direction.
Some tumours appear susceptible to NAD+ deficiency, which is why scientists are investigating strategies that disrupt its synthesis as a potential anti-cancer approach. [1,2]
At the same time, healthy cells need NAD+ for processes related to DNA repair.
Adequate NAD+ availability can support enzymes that respond to DNA damage, which in healthy cells can help maintain genome stability.
For this reason, the relationship between NAD+ and cancer cannot be reduced to the statement „more NAD+ is good” or „more NAD+ is bad”.
The same metabolic pathway can have different significance in a healthy cell, a stressed cell, or a pre-existing cancer cell.
Key takeaway
There is no simple, unidirectional answer to the question of whether NAD+ causes cancer.
Current research shows that NAD+ metabolism is strongly linked to cancer cell survival and proliferation, and at least one animal study indicates a potential risk associated with NR supplementation in a specific model of metastatic breast cancer. [1–3]
At the same time, NAD+ supports proper cellular processes, including DNA repair.
For people with a personal or family history of cancer, this is therefore more of an individual risk assessment issue than a typical wellness supplementation matter.
In such a situation, consultation with an oncologist or other appropriately qualified healthcare professional is more appropriate than relying on general supplement studies.
NAD+ and Alzheimer's disease: what is currently being researched?
Alzheimer's disease research is analysing NAD+ from several different perspectives.
Much of the interest stems from the observation that NAD+ metabolism changes with age and may be linked to mitochondrial dysfunction, neuroinflammation, and metabolic disorders observed in Alzheimer's disease.
Studies on mouse models
One study used the 3xTg Alzheimer's disease transgenic mouse model to analyse NAD+-related metabolism in brain tissue. [4]
Researchers found sex-dependent differences in the tryptophan–kynurenine pathway, which is involved in the de novo synthesis of NAD+, as well as alterations in salvage pathway metabolites.
The level of nicotinamide mononucleotide, or NMN, was markedly lower in both male and female mice with an Alzheimer's disease model compared to healthy control animals. [4]
This type of mechanistic research is important because it shows that NAD+ metabolism disturbances can indeed be measured in models of Alzheimer's disease.
They also point out that sex may influence these metabolic changes, which could be important when designing future clinical trials.
Research in people with mild cognitive impairment
Some human research focuses on mild cognitive impairment, or MCI, as this condition is often studied as a potential earlier stage preceding the development of Alzheimer's disease.
Studies using NAD+ precursors in this group have yielded mixed results.
The key observation is that scientists have sometimes succeeded in increasing the levels of NAD+-associated biomarkers in the blood or brain without a simultaneous improvement in cognitive function.
This is an important, recurring pattern.
Changing the biochemical target does not automatically mean an improvement in memory, executive functions or other clinical outcomes.
In other words, a higher NAD+ level does not necessarily mean better cognitive function.
What follows from that?
Research into NAD+ in Alzheimer's disease remains at a relatively early stage.
Most of the evidence is mechanistic or preclinical in nature, or comes from small human studies rather than large trials confirming efficacy.
No large, definitive clinical trial has been conducted to show that NAD+ precursors effectively treat or prevent Alzheimer's disease.
Current data justify further research, but do not yet allow for clinical conclusions.
NAD+ and Parkinson's disease
Among neurodegenerative diseases, Parkinson's disease has one of the more developed human research bases regarding NAD+ precursors.
One of the reasons is the strong link between mitochondrial dysfunction and the biology of Parkinson's disease, as well as the central role of NAD+ in mitochondrial energy metabolism.
Cellular and animal studies
Laboratory studies using patient-derived stem cells and Drosophila models of the genetic form of Parkinson's disease associated with the GBA gene have analysed the effects of nicotinamide riboside. [5]
In these models, NR ameliorated certain mitochondrial disorders and reduced neuronal loss.
Studies on fruit flies also observed protection against age-related degeneration of dopaminergic neurons and deterioration of motor functions. [5]
These preclinical results helped justify the progression to human clinical trials.
Phase I NADPARK study
The randomised, double-blind phase I clinical trial named NADPARK evaluated oral nicotinamide riboside in people with Parkinson's disease. [6]
The study was primarily intended to answer a few fundamental early-phase questions.
Scientists wanted to determine whether NR is safe, whether it can increase NAD+ in the brain rather than just in the blood, and whether measurable changes in brain metabolism can be detected.
The study found that NR was generally well tolerated and increased brain NAD+ levels. [6]
A mild clinical improvement was also noted, along with changes in cerebrospinal fluid markers associated with Parkinson's disease pathology and inflammation.
However, it was a phase I study.
Its primary aim was to assess safety and confirm the biological mechanism of action, rather than to demonstrate definitive clinical efficacy.
The authors emphasised the need for larger and longer placebo-controlled trials, designed specifically to evaluate clinical outcomes.
Important caveat from other mechanistic studies
Not all research into NAD+ and Parkinson's disease paints a unequivocally positive picture.
Separate mechanistic studies have shown that restoring mitochondrial NAD+ regeneration alone may not correct dopaminergic neuronal impairment if the underlying issue involves complex I of the mitochondrial electron transport chain.
This suggests that the specific type of bioenergetic defect matters.
Restoring NAD+ does not automatically fix all mitochondrial defects involved in neurodegeneration in Parkinson's disease.
Key takeaway
Parkinson's disease currently has some of the most promising early human NAD+ data among the conditions discussed here.
Even so, the research is still at an early stage.
Available data more strongly support safety and confirmation of the mechanism than proven therapeutic efficacy.
Mechanistic studies also suggest that NAD+ supplementation alone may not be sufficient to influence all the processes involved in neurodegeneration in Parkinson's disease.
NAD+, ADHD and cognitive function: is there a real connection?
Evidence in this area is exceptionally limited.
Virtually no dedicated clinical studies in humans show that NAD+ or NAD+ precursor supplementation treats ADHD.
This puts ADHD in a completely different evidentiary category to Alzheimer's or Parkinson's disease, for which there are at least disorder-specific tests.
What does a biologically plausible but untested hypothesis look like?
NAD+ plays well-known roles in cellular energy metabolism and mitochondrial function.
Because some research into ADHD analyses metabolic and mitochondrial factors, and dopamine plays a key role in the biology of ADHD, speculation sometimes arises regarding a possible link with NAD+.
Imaging studies also show that NAD+ levels in the human brain can be measured non-invasively and that they may decline with age.
This confirms that the level of NAD+ in the brain is a real biological variable.
However, this has not translated into significant clinical trials regarding NAD+ supplementation in ADHD.
What does this mean in practice?
Currently, claims that NAD+ supplementation improves ADHD symptoms are not supported by dedicated clinical data.
Such claims are based on general mechanistic plausibility rather than research conducted in individuals with ADHD.
This distinction is key.
A biologically plausible mechanism is not the same as demonstrated clinical efficacy.
At the current stage, NAD+ and ADHD should be treated as an open and largely unresearched question, rather than an established or even well-evidenced application.
NAD+ and anxiety and depression: current state of research
Direct clinical evidence regarding NAD+ precursors as treatments for anxiety or depression is also limited.
However, there is more genetic and mechanistic research linking NAD+-related metabolism to mood disorders than there is for ADHD.
However, it is worth interpreting them with caution.
Genetic testing
In one study using Taiwan Biobank data, it was analysed whether genetic variants in NAD+-related metabolic pathways were associated with the risk of major depression. [7]
Scientists focused primarily on the kynurenine pathway and nicotinate metabolism.
In the studied Taiwanese case-control population, several genetic variants in these pathways were associated with the risk of depression. [7]
This may suggest that inherited differences in NAD+-related metabolism could influence susceptibility to depression in some people.
However, it was a genetic association study.
It did not check whether the use of NMN, NR, NAD+ or another precursor alleviates symptoms of depression.
Trauma and stress research
Separate extensive genetic studies analysed the potential links between anxiety disorders, PTSD, accelerated biological ageing, NAD+ metabolism and sirtuin pathways. [8]
For PTSD, a proposed biological pattern involving NAD+ metabolism and the mitochondrial sirtuin SIRT3 has been described.
The studies also described a specific pattern of vulnerability in nerve fibres.
However, the author characterised these proposed subtypes as hypotheses requiring further verification.
These are not established clinical categories and should not serve as the basis for diagnosis or therapeutic decisions.
What else is missing?
There is no published, randomised, placebo-controlled clinical trial in which an NAD+ precursor has been tested specifically for the treatment of anxiety or depression as a primary endpoint.
The kynurenine pathway is important here because it is involved in both the synthesis of NAD+ and the production of several neuroactive metabolites studied independently in psychiatry.
This partly explains why NAD+ metabolism and mood disorders appear together in the scientific literature.
It does not prove, however, that increasing NAD+ treats anxiety or depression.
Key takeaway
Real genetic and mechanistic data exist indicating that NAD+-related pathways intersect with the biology of depression, stress and post-traumatic stress disorder. [7,8]
However, this has not yet translated into clinical trials showing that NAD+ supplementation improves symptoms of anxiety or depression.
Individuals with these disorders should base their treatment on proven methods and collaboration with qualified mental health professionals, rather than replacing established therapies with NAD+-related supplementation.
Other researched areas: kidney disease, addictions and Cushing's disease
Kidney diseases
Kidney diseases are one of the better-developed areas of NAD+ research outside of neurodegeneration.
In many experimental studies, a decrease in NAD+ in kidney tissue has been linked to acute kidney injury.
In various animal models, a protective effect has also been observed when restoring or maintaining NAD+ metabolism.
One study analysed a traditional Chinese herbal formula in two rat models of chronic kidney disease. [9]
The intervention was associated with a reduction in kidney damage and changes in the pathway involving QPRT, NAD+, and the mitochondrial enzyme SIRT3.
Researchers also noted an improvement in the balance between mitochondrial fission and fusion, which was impaired in chronic kidney disease models. [9]
This fits into a broader direction of nephrological research.
Protecting or restoring NAD+ metabolism is an active and potentially important area of preclinical research.
However, randomised human trials involving NAD+ precursors as a treatment for kidney diseases remain considerably more limited than data from animals.
Addiction
Intravenous NAD+ has for many years been promoted as a method aimed at reducing withdrawal symptoms and supporting recovery from addiction to alcohol, opioids and other substances.
Such a commercial application appeared before the recent increase in interest in research on NR and NMN.
It is based mainly on older clinical reports rather than modern randomised placebo-controlled trials, which are expected when confirming the efficacy of a treatment.
No solid base of contemporary, peer-reviewed randomised studies has been established to show that intravenous NAD+ is an effective treatment for addictions or withdrawal symptoms.
This is an area where the difference between marketing and controlled clinical evidence appears to be particularly large.
Individuals considering NAD+ for addiction treatment should bear in mind that there are already well-researched and effective treatments for substance use disorders.
Therapeutic decisions should therefore be discussed with an addiction medicine specialist, rather than being based on clinic promotional materials.
Cushing's disease
Dedicated research on the relationship between NAD+ or its precursors and Cushing's disease appears to be exceptionally limited.
Cushing's disease is associated with the excessive production of cortisol, usually due to a pituitary tumour.
No extensive human or animal research base has been identified showing that NAD+ supplementation has an established role in this condition.
It appears to be indeed a poorly researched issue rather than a well-developed field that is simply rarely talked about.
If claims arise that NAD+ can treat Cushing's disease, the appropriate approach is to ask for specific scientific evidence.
Currently, there does not appear to be an established base of clinical research for such an application.
Limitations of current evidence
A significant portion of research on NAD+ in the context of specific diseases comes from cell cultures and animal models.
This is particularly true for cancer, Alzheimer's disease and kidney diseases, where mechanistic literature is much more extensive than human clinical data. [1,3,4,9]
Where human studies exist, they are often Phase I trials, small pilot studies or exploratory projects rather than large, efficacy-confirmatory studies.
Another recurring limitation is the difference between biomarker change and actual clinical benefit.
Several human studies have shown that NAD+ precursors can increase NAD+ levels in the blood or brain without a statistically significant improvement in the evaluated clinical outcome.
This is one of the most important patterns observed in this field.
There are no dedicated clinical trials confirming the use of NAD+ or its precursors in ADHD.
In the case of anxiety and depression, current data are predominantly genetic or mechanistic rather than interventional.
The cancer warning discussed in this article comes from one specific animal model and has not been confirmed in humans.
At the same time, broader oncological literature shows that NAD+ metabolism can play different roles depending on the tumour type, tissue, and cellular context.
There are also no robust contemporary randomised controlled trials confirming NAD+ as a treatment for addictions.
Similarly, no significant body of research was identified indicating a specific therapeutic role for NAD+ in Cushing's disease.
Disclaimer
This article is for educational and scientific-informational purposes only. It does not constitute medical advice, a diagnosis, treatment guidance, dosage instructions, or a recommendation for the use of NAD+, NMN, NR, or other NAD+-related compounds in the case of cancer, Alzheimer's disease, Parkinson's disease, ADHD, anxiety, depression, kidney disease, addiction, Cushing's disease, or any other medical conditions.
Research on NAD+ involves well-understood biochemical mechanisms, as well as the results of cellular, animal, genetic and clinical studies of very varying degrees of reliability. Changes in NAD+ metabolism, mitochondrial function, sirtuin signalling, DNA repair or other cellular pathways should not be interpreted as proof that increasing NAD+ prevents, treats, slows down or reverses any disease.
For several of the conditions discussed here, the strongest available data remain preclinical or come from early-phase studies, while direct clinical evidence regarding treatment remains limited or non-existent. Increasing NAD+ levels in the blood or brain should not automatically be equated with clinical benefit simply because a specific biological pathway is altered. Individuals with cancer, a personal or family history of cancer, neurological diseases, mental health disorders, kidney disease, substance use disorders, endocrine disorders or other serious health problems should discuss NAD+ supplements and interventions with a suitably qualified doctor or relevant specialist. NAD+ products should not replace proven oncological, neurological, psychiatric, nephrological or addiction treatments, or other evidence-based methods.
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] Maric, T., Bazhin, A., Khodakivskyi, P., Mikhaylov, G., Solodnikova, E., Yevtodiyenko, A., Giordano Attianese, G. M. P., Coukos, G., Irving, M., Joffraud, M., Cantó, C., & Goun, E. (2023). A bioluminescent-based probe for in vivo non-invasive monitoring of nicotinamide riboside uptake reveals a link between metastasis and NAD+ metabolism. Biosensors and Bioelectronics, 222, 114826. https://doi.org/10.1016/j.bios.2022.114826
[4] van der Velpen, V., Rosenberg, N., Maillard, V., Teav, T., Chatton, J.-Y., Gallart-Ayala, H., & Ivanisevic, J. (2021). Sex-specific alterations in NAD+ metabolism in 3xTg Alzheimer’s disease mouse brain assessed by quantitative targeted LC-MS. Journal of Neurochemistry, 159(2), 378–388. https://doi.org/10.1111/jnc.15367
[5] Schöndorf, D. C., Ivanyuk, D., Baden, P., Sanchez-Martinez, A., De Cicco, S., Yu, C., Giunta, I., Schwarz, L. K., Di Napoli, G., Panagiotakopoulou, V., Nestel, S., Keatinge, M., Pruszak, J., Bandmann, O., Heimrich, B., Gasser, T., Whitworth, A. J., & Deleidi, M. (2018). The NAD+ precursor nicotinamide riboside rescues mitochondrial defects and neuronal loss in iPSC and fly models of Parkinson’s disease. Cell Reports, 23(10), 2976–2988. https://doi.org/10.1016/j.celrep.2018.05.009
[6] 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
[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
[8] Cheung, N. (2026). Posttraumatic stress disorder (PTSD) NAD/sirtuin deficiency and SARM1-mediated synaptic vulnerability: Evidence for accelerated brain ageing subtypes. Cureus, 18(6), e110755. https://doi.org/10.7759/cureus.110755
[9] Liu, X., Liu, S., Zhang, B., Luo, D., Huang, S., Wang, F., Zheng, L., Lu, J., Chen, J., & Li, S. (2021). Jian-Pi-Yi-Shen formula alleviates chronic kidney disease in two rat models by modulating QPRT/NAD+/SIRT3/mitochondrial dynamics pathway. Evidence-Based Complementary and Alternative Medicine, 2021, 6625345. https://doi.org/10.1155/2021/6625345