NAD+ & NAD+ Precursors Effect on Cancer Cells

CalerieHealth™ Nutritionalist

NAD+ and its precursors have multiple benefits. Although, there is currently a controversy if NAD+ precursors increase the growth of cancer cells. There is mostly laboratory in vitro work and some animal studies, and zero human clinical from what I was able to find. I spent time reviewing research and wrote this report, but if needed per your request, I can provide a full review, doing an exhaustive literature review to find all research.

Cancer Cells Pathway

It has been shown that cancer cells go through aerobic glycolysis. Glycolysis is a metabolic pathway in the body to generate energy. So cancer cells receive the majority of their energy from the glycolysis pathway, where glucose is converted to lactate for energy, and then it is followed by lactate fermentation (Liberti MV, Locasale JW, 2016). This is called the Warburg Effect and has been studied for over 90 years.

Glucose is metabolized and is able to be used for energy in the form of ATP, which is necessary for life. This process produces lactate or when glucose is fully oxidized, it goes through the respiration pathway in the mitochondria and  CO2 is produced.

Tumors and other types of cells that multiply increase the rate of the amount of glucose being taken up quickly, and fermentation occurs, producing lactate. Research has shown that if cancer cells were suppressed in performing fermentation, it might reduce cancer cells.

In a laboratory setting, scientists took a compound that forced cancer cells to turn away pyruvate from entering into the fermentation pathway and instead go into the aerobic respiration pathway. The research demonstrated that if this stage of fermentation could be blocked, it would slow down the growth of cancer cells.

Research began to evaluate cancer cell fermentation and NAD+ (Luengo A et al, 2020). A particular compound was used to stimulate NAD+ production in the cells. This caused the cells to proliferate again but without executing fermentation quickly. It was shown that the cells actually need more NAD+ and less ATP. It was believed that when there was too much ATP, it would slow down the respiration pathway and the production of NAD+.

It has been stated that compounds that force cancer cells to switch back to aerobic respiration instead of fermentation could offer a possible way to treat tumors. Although it also stated that compounds that inhibit NAD+ production could also have a beneficial effect.

NMN & Cancer Cells 

Pan F, Kang S, Zhao Y et al. Effect of β-nicotinamide mononucleotide on tumor formation and growth in a lung cancer mouse model. Materials Chemistry Frontiers. 2021;Issue 2.

In one animal study with mice, the role of NMN in the oncogenesis of lung cancer was investigated. The animals were intraperitoneally injected with NMN daily for two weeks, followed by subcutaneous injection of mouse lung cancer cells (LLC).

Three weeks later, the tumor incidence and tumor size and volume were measured. To verify whether NMN can inhibit tumor growth, a xenograft model was constructed in nude mice.

After intraperitoneal injection with NMN for three weeks, the mice’s weight and tumor volume were measured. After NMN treatment, the tumor formation rates in the two C57 mouse groups were both 100%. The tumor volume has no statistical difference between the NaCl control group and the NMN treatment group.

Immunohistochemical study of Ki67 in tumor sections from the two groups indicated that NMN does not affect the proliferation of tumor cells. The tumor volume in nude mice has no statistical difference either between the NaCl control group and the NMN treatment group.

NMN does not affect the proliferation of tumor cells in mouse subcutaneous tumors. Carcinoembryonic antigens (CEA), interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and stromal cell-derived factor 1 (CXCL-12) have no significant difference between the two groups.

The conclusion of investigators had mixed results: “Our findings indicate that NMN does not prevent the formation of lung cancer or restrain tumor growth in a mouse xenograft model, nor does it promote tumor growth.”

In other words, the investigators couldn’t show that NMN prevented cancer or held back tumor growth. On the other hand, the research didn’t show NMN increased tumor growth.

Charles Brenner, the chief scientific advisor for ChromaDex, stated, “higher-than-normal NAMPT levels in many cancers do not prove that high NAD+ levels actually promote cancer growth, he notes. He contends that studies that kill cancer cells by suppressing the NAD+-producing enzyme also do not properly address the issue. “Whether low NAD+ would block cancer and whether high NAD+ would promote cancer are two separate questions.”

One review included only the abstract. If you would like the full article, I could order it. If you want it let me know. The review stated:

“Administration of NAD+ precursors such as nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) offer promising therapeutic strategies to improve health, progeria comorbidities, and cancer therapies (Demarest TG et al, 2019).”

It is possible that this review includes research demonstrating that NAD+ precursors have a negative effect on cancer growth.

In summary, there is controversy on if NAD+ has an effect on the proliferation of cancer cells. I was only able to find some laboratory and animal studies. Further investigation would need to be done to determine what other research is available to support theories.

This article is for educational purposes only and is not intended to diagnose, treat, cure or prevent any disease.

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