NAD⁺ precursors and cancer
Cancer is a group of diseases that may affect anyone at any point in life and can lead to long-lasting changes in our lives. My uncle was diagnosed with melanoma at the age of 33 and passed away seven years later, shortly after his 40th birthday. Since his death, I have been wondering: would it have been possible to do something before his diagnosis?
NAD+ and cancer are not directly related at first sight. On the one hand, NAD+ is a cofactor required for multiple enzymatic functions, divided into three classes: sirtuins 1-7 (proteins regulating cellular function), PARPs (DNA repair proteins), and CD38 (protein regulating NAD+ levels) (Zapata‐Pérez et al., 2021). On the other hand, cancer is defined as a group of diseases involving aberrant cell growth, which can spread to different parts of the body and ultimately lead to organ failure and subsequent death (What Is Cancer? – NCI, n.d.). Notably, cancer is one of the leading causes of death in the world, accounting for nearly one in six deaths (World Health Organization, 2025).
What is the relationship between NAD+ and cancer?
Due to their roles involved in cell functions, sirtuins and PARPs, by consuming NAD+, are tightly involved in cancer regulation: sirtuins prevent the emergence of mechanisms that would promote cancer in the cells, and PARPs repair DNA that otherwise would lead to mutations and then cancer growth (Podyacheva & Toropova, 2023). For instance, increased SIRT3 expression may increase tumor growth arrest and cancer cell death (Alhazzazi et al., 2011; Allison & Milner, 2007). Similarly, SIRT6 and 7 control DNA repair mechanisms, protecting the DNA against further damage and potential cancer emergence (Imai & Guarente, 2016; Kane & Sinclair, 2018).
However, it has been proven that tumors are prone to turning the defensive mechanisms of the cells to their advantage. As a consequence, cancer cells are capable of reprogramming the cell metabolism and thereby utilize sirtuin activity to enhance cell growth, prevent cell death, and promote proliferation (Phan et al., 2014). An example of this is SIRT1, which may promote cell growth and prevent cell death, driving cancer cell proliferation (Karbasforooshan et al., 2018). Also, SIRT6 expression is increased in aggressive tumors (Bae et al., 2016). Likewise, PARPs activity prevents further genomic instability in cancer cells by repairing DNA breaks caused by the high rate of mutations within tumors (Navas & Carnero, 2021; Podyacheva & Toropova, 2023). All in all, cancer and NAD+ are closely interacting due to the heavy role of NAD+ in cell functions that cancer relies on to grow and spread.
NAD+ augmentation and cancer risk
Given the duality of the NAD+ metabolism, on the one hand, NAD+ supplementation can reduce cancer risk (Chiarugi et al., 2012) mainly through the DNA repair pathway upregulation (Surjana et al., 2013; Thompson et al., 2014). On the other hand, it might support the metabolism of cancer cells (such as the Warburg Effect (Phan et al., 2014)), enable tumor progression and survival (Navas & Carnero, 2021), and promote resistance to cancer treatments (Maric et al., 2023). Additionally, increasing NAD+ levels may upregulate the inflammatory effect of senescent cells, which can, in some contexts, be tumorigenic (Nacarelli et al., 2019). In summary, the effects of NAD+ augmentation can either increase or decrease the risk of cancer development, but mostly worsen the phenotypes of already preexisting cancers.
Conclusion
This leads us to conclude that NAD+ supplementation may either reduce or increase cancer risk. As cancer is a heterogeneous disease (each cancer in each patient is unique), it is inadequate to characterize NAD+ precursors as pro- or anti-oncogenic compounds because they require a personalized approach to determine their impact on cancer risk. More studies are needed to better understand whether NAD+ supplementation would help in cancer prevention. As of today, I still do not know if NAD+ precursors could have helped my uncle in avoiding cancer.
References:
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