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Cancer Immunotherapy & the Ketogenic Diet: New Research Reveals Potential Anticancer Mechanisms

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  Published on February 22nd, 2021
  Reading time: 5 minutes
  Last modified April 15th, 2021
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Interest in the ketogenic diet as nutritional therapy for cancer has rapidly increased as preliminary studies (and individual case studies) have suggested anti-tumor benefits in having reduced blood glucose levels. Up until this point, a reduction in glucose levels, as well as increased sensitivity of cancer cells to chemotherapy, has been investigated and the drivers behind the benefits of a ketogenic diet in cancer cases. A new study on cancer immunotherapy, however, points towards another possible beneficial mechanism. (1)

In order to understand this new research, let’s breakdown what cancer is exactly and how the ketogenic diet may be beneficial.

What is Cancer?

Cancer cells are just normal cells that have grown abnormally.

cancer cells growth and cancer immunotherapy

These cells evade checkpoints set in place to prevent abnormal cell growth and have the potential to spread to other parts of the body and cause damage to vital organs and tissues. (2)

Keto and Cancer

The primary reason going keto has been investigated for its cancer-preventing or reducing properties has to do with a phenomenon known as the Warburg effect. This phenomenon describes how cancer cells use glycolysis (the breakdown of glucose) to produce energy. (3) Cancer cells use glucose as an energy source, but can not use ketone bodies. (4)
The goal of cancer cells is to grow, but if there is limited glucose available (i.e. through a diet low in carbohydrates), cancer cells will have less fuel. The idea behind using the ketogenic diet as nutritional therapy for cancer stems from this idea that less glucose available means less fuel for cancer cells and thus less growth.

For more information on the Warburg effect and how cancer uses glucose to grow and spread, check out some of our other articles on keto and cancerA study titled Ketogenic diet and ketone bodies enhance the anticancer effects of PD-1 blockade was published this past December indicating 3HB, the primary ketones produced in the body when in a state of ketosis, may play a larger role in reducing cancer growth. (1)

What is Cancer Immunotherapy?function of cytotoxic t cells

One way that scientists are looking to prevent cancer is by looking at how cancerous cells evade the immune system. Cells of the immune system, and specifically T-cells, look for abnormal or foreign bodies. These cells are then killed and removed and memory is stored to allow the immune system to respond more quickly to this same type of cell in the future.

Researchers have spent years trying to figure out how exactly cancer cells evade detection by T-cells and have discovered a special molecule present on cancer cells. PDL-1 (programmed death-ligand 1) is a ligand present on the surface of cancer cells that binds to PD-1 receptors present on T-cells and prevents being flagged as a harmful cell. Think of PDL-1 as a disguise the cancer cells wear to prevent recognition. (5)

What Does Cancer Immunotherapy Have to Do With The Ketogenic Diet?

Numerous case studies have shown the benefits of a ketogenic diet for reducing tumor growth, but up until this point, it was believed to be caused by either a reduction in glucose availability (cancer cells can use glucose but not ketones for fuel) or increased sensitivity of cells to chemotherapy caused by BHB (the primary ketone produced in the body). (4,5,6)

This paper aforementioned looked at the effects of 3-HB (beta-hydroxybutyrate or BHB) and how it upregulates CD8+ and CXCR3+ expansion while downregulating PDL-1 activity by antigen-presenting cells (APC).  (1)

 

The researchers found the following:

“Importantly, KD and 3HB slowed natural tumor progression in the absence of additional therapeutic intervention, but they also accelerated and improved the efficacy of cICB against established and aggressive orthotopic melanoma, lung, and renal cell cancers. This anticancer effect was blunted by sucrose supplementation (in the case of KD) or by blocking the 3HB receptor (for both KD and 3HB). Indeed, T cells and GPR109A engagement were mandatory for the full-blown anticancer properties of 3HB, paving the way to the accelerated efficacy of ICB.” (1)

This means that the ketogenic diet and BHB specifically reduced tumor growth, without any additional therapy, and was confirmed because when sucrose (table sugar) was added back, into the equation, this effect was reduced.

 

Concluding Thoughts

More research is needed to fully investigate this mechanism, but the idea that the ketone body BHB can have anti-cancer effects through cancer immunotherapy is a fascinating new discovery.

 

If you are interested in the more complex biochemical intricacies of cancer and how the ketogenic diet may be beneficial, check out our Keto Mastery program. This intensive, Nationally recognized course, has an entire section dedicated to complex research behind just how a ketogenic diet may be physiologically beneficial for cancer patients or those at risk for cancer.

 

References

1. Ferrere G, Tidjani Alou M, Liu P, Goubet AG, Fidelle M, Kepp O, Durand S, Iebba V, Fluckiger A, Daillère R, Thelemaque C, Grajeda-Iglesias C, Alves Costa Silva C, Aprahamian F, Lefevre D, Zhao L, Ryffel B, Colomba E, Arnedos M, Drubay D, Rauber C, Raoult D, Asnicar F, Spector T, Segata N, Derosa L, Kroemer G, Zitvogel L. Ketogenic diet and ketone bodies enhance the anticancer effects of PD-1 blockade. JCI Insight. 2021 Jan 25;6(2):145207.

2. US), National Institutes of Health. “Understanding Cancer.” NIH Curriculum Supplement Series [Internet]., U.S. National Library of Medicine, 1 Jan. 1970.

3. Epstein, Tamir et al. “The Warburg effect as an adaptation of cancer cells to rapid fluctuations in energy demand.” PloS one vol. 12,9 e0185085. 18 Sep. 2017, doi:10.1371/journal.pone.0185085

4. Weber, Daniela D et al. “Ketogenic diet in cancer therapy.” Aging vol. 10,2 (2018): 164-165. doi:10.18632/aging.101382

5. Salmaninejad A, Valilou SF, Shabgah AG, Aslani S, Alimardani M, Pasdar A, Sahebkar A. PD-1/PD-L1 pathway: Basic biology and role in cancer immunotherapy. J Cell Physiol. 2019 Aug;234(10):16824-16837. doi: 10.1002/jcp.28358. Epub 2019 Feb 19. PMID: 30784085.

6. Wang, Y., Jing, M. X., Jiang, L., Jia, Y. F., Ying, E., Cao, H., Guo, X. Y., & Sun, T. (2020). Does a ketogenic diet as an adjuvant therapy for drug treatment enhance chemotherapy sensitivity and reduce target lesions in patients with locally recurrent or metastatic Her-2-negative breast cancer? Study protocol for a randomized controlled trialTrials21(1), 487. https://doi.org/10.1186/s13063-020-04429-5

7. Smyl C. “Ketogenic Diet and Cancer- a perspective.” Recent results in cancer research. Vol. 207 (2016): 233-40. doi: 10.1007/978-3-319-42118-6_11

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