Is it safe to eat 'NMN'?
[Highlight]
"Although NMN intake should be considered with caution in patients with certain cancers, such as breast or ovarian cancer, it may actually help prevent cancer in those without the condition."
NMN (Nicotinamide mononucleotide) is a derivative of vitamin B3. It stimulates the biosynthesis of NAD+ (Nicotinamide adenine dinucleotide), a coenzyme essential for various physiological processes in the body, including energy metabolism, DNA repair, and cell growth. Concerns surrounding the use of NMN sometimes arise regarding its carcinogenicity. Why do these concerns arise? So, does NMN cause cancer? In this episode, we will examine the reasons for these concerns and determine whether NMN actually causes cancer.
Why NMN's Carcinogenicity Concerns Are Raised
When researching NMN, you will occasionally come across claims like, "NMN can cause cancer, so don't eat it!"
"Then why does NMN cause cancer?"
1) NAD+ promotes PARP enzyme.
The basis for the claim that NMN causes cancer is that NAD+ promotes the enzyme PARP (Poly ADP-ribose polymerase) . Anticancer drugs such as Lynparza inhibit PARP, but when NMN is taken, it increases PARP levels in the opposite way that anticancer drugs work, so the claim is that taking NMN can cause cancer. However, PARP is an enzyme that repairs DNA and promotes cell differentiation when there are no cancer cells in our body, so it is essential for us. Inhibiting PARP only produces an anticancer effect in patients with certain cancers, such as breast or ovarian cancer. Therefore, while NMN may be problematic for patients with certain cancers, it is not a problem at all for healthy people. In people without cancer, PARP is an enzyme that can actually prevent cancer.
* PARP (Poly ADP-ribose polymerase): An enzyme that recognizes and repairs damaged DNA.
* Lynparza: A representative anticancer drug that inhibits PARP and prevents the growth of cancer cells as a treatment for ovarian cancer or breast cancer with BRCA abnormalities.
Figure 1. DNA repair according to PARP
2) NMN can fuel cancer cells by enhancing NAD+.
NMN can fuel cells by enhancing NAD+, thereby promoting cell growth. Another argument for NMN's carcinogenicity is that NMN fuels cancer cells as well as normal cells by enhancing NAD+, thereby promoting cancer cell growth . So, does injecting NMN into cancer cells actually accelerate their growth? To confirm this, let's introduce two experiments.
2-1) Animal testing
In animal experiments, mice were injected with NMN and cancer cells to determine whether NMN stimulates cancer cell growth. C57 mice were injected intraperitoneally with NMN daily for two weeks, and lung cancer cells were then injected subcutaneously. Three weeks later, tumor size and volume were measured, and there was little difference between the saline-treated control group and the NMN group. Furthermore, there was no statistical difference in tumor incidence between the two groups. These experimental results suggest that NMN does not fuel lung cancer cells or promote lung cancer. Rather, NMN-treated mice showed elevated levels of tumor-associated immune factors, such as IL-1β, IL-6, TNF-α, and CXCL-12, and weight loss, demonstrating the anti-inflammatory and weight-loss effects of NMN.
* IL-1 β (Interleukin 1 beta), IL-6 (Interleukin 6), TNF-α (Tumor necrosis factor alpha): A type of cytokine secreted by activated immune cells that plays an immune regulatory role, such as suppressing tumor formation and virus replication.
* CXCL-12: A type of chemokine protein that plays an immune-regulating role by attracting CXCR4+ T cells and monocytes. 
Graph 1. Comparison of tumor incidence and tumor size between mice administered NMN and mice administered NACl (saline solution).
2-2) Clinical trials
We previously administered NMN to mice to determine its carcinogenic potential. Now, to see what effect NAM has on actual cancer patients, we will administer NAM to 386 people who had skin cancer to determine whether NAM promotes cancer.
*NAM is a precursor that is converted to NMN in the NAD⁺ biosynthetic pathway, ultimately producing NAD⁺.
People who had suffered from skin cancer in the past five years were given 500 mg of NAM twice a day for 12 months. As a result, those who took NAM had a 23% lower risk of skin cancer than those who did not.
Graph 2. Difference in the number of actinic keratoses (no.) between the group receiving NAM and the control group.
Additionally, skin cancer patients who took NAM for 12 months had fewer actinic keratoses than those who did not take NAM , and the difference between patients increased over time. This confirms that oral NAM intake prevents skin cancer and reduces actinic keratoses in high-risk patients.
* Actinic keratosis: Pink or red spots that develop on the skin due to constant exposure to sunlight, and are an early stage that can develop into skin cancer.
Patients with certain cancers, such as breast or ovarian cancer, should exercise caution when taking NMN and are advised to consult with their physician before deciding to take it. However, for those without these specific cancers, NMN does not cause or promote cancer. Rather, it can help prevent cancer with its anti-inflammatory and anti-aging properties, so they can take it with confidence.
[References and Figure Source]
[1] NAD+ promotes PARP enzyme.
https://www.youtube.com/watch?v=Vzyt-mD5vio
[2] NAD+ promotes PARP enzyme.
https://www.sciencedirect.com/science/article/pii/S0753332219352837
[3] Results of animal experiments on NMN
https://www.youtube.com/watch?v=DhF2blHlHCQ
[4] Results of animal experiments on NMN
https://www.x-mol.net/paper/article/1337143058528067584
[5] Results of clinical trials of NMN
https://pubmed.ncbi.nlm.nih.gov/26488693/
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