Research on 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 virtually a lack of relevant clinical data.
None of the following sections should be construed as medical advice for treating a specific disease. The purpose is to present the current state of research, not 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 be strongly context-dependent, 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 activity of NAD+ metabolism has been observed, particularly the NAMPT-dependent salvage pathway, which may support tumor cell proliferation and survival. [1,2]
This is one of the reasons why NAMPT inhibitors are being investigated as potential anticancer drugs.
The basic concept involves 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 rather shows that pre-existing cancer cells can utilize NAD+ metabolism to meet 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 supplementation with NAD+ precursors can, under certain conditions, affect the biology of an existing tumor.
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 must be interpreted with caution.
This was a single animal model concerning a specific subtype of cancer. The result has not been confirmed in controlled clinical trials in humans.
The other side of research
Cancer research also includes the opposite direction.
Some tumors appear susceptible to NAD+ deficiency, so researchers 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.
Because of this, 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 an already existing cancer cell.
Key conclusion
There is no simple, one-way 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 metastatic breast cancer model. [1–3]
At the same time, NAD+ supports proper cellular processes, including DNA repair.
For individuals 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 properly qualified healthcare professional is more appropriate than relying on general supplementation studies.
NAD+ and Alzheimer's disease: what is currently being researched?
Alzheimer's disease research analyzes 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
In one study, a 3xTg mouse model of Alzheimer's disease was used to analyze NAD+-related metabolism in brain tissue. [4]
Researchers found sex-dependent differences in the tryptophan-kynurenine pathway, which is involved in de novo NAD+ synthesis, as well as changes in metabolites of the salvage pathway.
The level of nicotinamide mononucleotide, or NMN, was markedly lower in both male and female mice with the Alzheimer's disease model compared to healthy control animals. [4]
This type of mechanistic research is important because it shows that NAD+ metabolism disorders can indeed be measured in Alzheimer's disease models.
They also indicate that sex may influence these metabolic changes, which could be important when designing future clinical trials.
Studies in people with mild cognitive impairment
Some human studies focus on mild cognitive impairment, or MCI, as this condition is often studied as a potential early stage preceding the development of Alzheimer's disease.
Studies using NAD+ precursors in this group have yielded mixed results.
A key observation is that scientists have sometimes succeeded in increasing NAD+-related biomarker levels in the blood or brain without a simultaneous improvement in cognitive function.
This is an important, recurring pattern.
Changing a 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 this?
Research on NAD+ in Alzheimer's disease remains at a relatively early stage.
Most of the evidence is mechanistic, preclinical, 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 fruit fly models with the genetic form of Parkinson's disease associated with the GBA gene analyzed the effects of nicotinamide riboside. [5]
In these models, NR ameliorated certain mitochondrial disorders and reduced neuronal loss.
In studies on fruit flies, protection against age-related loss of dopaminergic neurons and motor function decline was also observed. [5]
These preclinical results helped justify the transition to human clinical trials.
Phase I NADPARK study
A randomized, 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 several basic early-phase questions.
Scientists wanted to determine whether NR is safe, whether it can increase NAD+ in the brain and not 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 NAD+ levels in the brain. [6]
A mild clinical improvement and changes in cerebrospinal fluid markers related to Parkinson's disease pathology and inflammation were also noted.
However, it was a Phase I study.
Its main objective was to assess safety and confirm the biological mechanism of action, rather than to demonstrate definitive clinical efficacy.
The authors emphasized the need for larger and longer placebo-controlled trials specifically designed to evaluate clinical outcomes.
Important caveat from other mechanistic studies
Not all research on NAD+ and Parkinson's disease paints a clearly positive picture.
Separate mechanistic studies have shown that simply restoring mitochondrial NAD+ regeneration may not correct dopaminergic neuron impairments if the underlying problem involves complex I of the mitochondrial electron transport chain.
This suggests that a specific type of bioenergetic defect matters.
Restoring NAD+ does not automatically fix all mitochondrial impairments involved in neurodegeneration in Parkinson's disease.
Key conclusion
Parkinson's disease currently has some of the most promising early human NAD+ data among the conditions discussed here.
Nevertheless, 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 mere NAD+ replenishment may not be sufficient to affect all processes involved in neurodegeneration in Parkinson's disease.
NAD+, ADHD, and cognitive functions: is there a real connection?
Evidence in this area is exceptionally limited.
Practically no dedicated human clinical trials show that NAD+ or NAD+ precursor supplementation treats ADHD.
This places ADHD in a completely different evidentiary category than Alzheimer's or Parkinson's disease, for which there are at least disease-specific tests.
What does a biologically plausible, yet untested hypothesis look like?
NAD+ plays well-known roles in cellular energy metabolism and mitochondrial function.
Since some ADHD research analyzes metabolic and mitochondrial factors, and dopamine plays a key role in the biology of ADHD, speculation sometimes arises regarding a possible link to 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 did not translate into significant clinical studies regarding NAD+ supplementation in ADHD.
What does that 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 crucial.
A biologically plausible mechanism is not the same as demonstrated clinical efficacy.
At the present stage, NAD+ and ADHD should be treated as an open and largely unexplored research question, rather than an established or even well-supported 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, they should be interpreted with caution.
Genetic testing
One study using Taiwan Biobank data analyzed 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 hereditary differences in NAD+-related metabolism may 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 studies
Separate large-scale genetic studies analyzed possible links between anxiety disorders, PTSD, accelerated biological aging, NAD+ metabolism, and sirtuin pathways. [8]
In the case of PTSD, a proposed biological pattern involving NAD+ metabolism and the mitochondrial sirtuin SIRT3 has been described.
Studies also described a specific pattern of nerve fiber vulnerability.
However, the author characterized 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, randomized, placebo-controlled clinical trial in which an NAD+ precursor was tested specifically for the treatment of anxiety or depression as the primary endpoint.
The kynurenine pathway is important here because it participates 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 conclusion
There is actual genetic and mechanistic data indicating that pathways associated with NAD+ 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 studied 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 preserving NAD+ metabolism.
One study analyzed a traditional Chinese herbal formula in two rat models of chronic kidney disease. [9]
The intervention was associated with a reduction in kidney injury and changes in the pathway involving QPRT, NAD+, and the mitochondrial enzyme SIRT3.
The researchers also noted an improvement in the balance between mitochondrial fission and fusion, which had been disrupted 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.
Randomized human trials on NAD+ precursors as a kidney disease therapy, however, remain much more limited than animal data.
Addictions
Intravenous NAD+ has been promoted for many years as a method to reduce withdrawal symptoms and support recovery from addiction to alcohol, opioids, and other substances.
Such commercial use appeared before the recent surge in research interest in NR and NMN.
It is based mainly on older clinical reports rather than modern randomized, placebo-controlled trials, which are expected when confirming the efficacy of a treatment.
A solid foundation of contemporary, peer-reviewed randomized trials demonstrating that intravenous NAD+ is an effective treatment for addiction or withdrawal symptoms has not been established.
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 keep in mind that well-researched and effective treatments for substance use disorders already exist.
Therapeutic decisions should therefore be discussed with an addiction medicine specialist rather than relying 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 excessive cortisol production, usually due to a pituitary tumor.
No extensive body of human or animal research has been identified showing that NAD+ supplementation has an established role in this disease.
It seems to be indeed a poorly researched issue rather than a well-developed field that is simply rarely talked about.
If claims are made 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 clinical research base for such an application.
Limitations of current evidence
Much of the research on NAD+ in the context of specific diseases comes from cell cultures and animal models.
This applies particularly to cancer, Alzheimer's disease, and kidney diseases, where the mechanistic literature is much more extensive than clinical data in humans. [1,3,4,9]
Where human studies exist, they are often Phase I trials, small pilot studies, or exploratory projects rather than large confirmatory efficacy studies.
Another recurring limitation is the discrepancy 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 studies 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 oncology literature shows that NAD+ metabolism can play different roles depending on the tumor type, tissue, and cellular context.
There are also no robust contemporary randomized controlled trials confirming NAD+ as a treatment for addiction.
Similarly, no significant body of research indicating a specific therapeutic role of NAD+ in Cushing's disease has been identified.
Disclaimer
This article is for educational and scientific-informational purposes only. It does not constitute medical advice, a diagnosis, treatment guidelines, dosage instructions, or a recommendation for the use of NAD+, NMN, NR, or other NAD+-related compounds in cases 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+ encompasses well-understood biochemical mechanisms as well as the results of cellular, animal, genetic, and clinical studies with varying levels of credibility. Changes in NAD+ metabolism, mitochondrial function, sirtuin signaling, 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 diseases discussed here, the strongest available data remain preclinical or come from early-phase studies, while direct clinical evidence regarding treatment remains limited or does not exist. An increase in 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 disorders, psychiatric disorders, kidney disease, substance use disorders, endocrine disorders, or other serious health problems should discuss NAD+ supplements and interventions with a properly qualified physician or appropriate specialist. NAD+ related products should not replace proven oncological, neurological, psychiatric, nephrological, addiction treatment, or other evidence-based methods.
References
[1] Yoshino, J., Baur, J. A., & Imai, S. (2018). NAD+ intermediates: The biology and therapeutic potential of NMN and NR. Cell Metabolism, 27(3), 513–528. https://doi.org/10.1016/j.cmet.2017.11.002
[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 randomized 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 aging 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