The Keto Diet and Cancer
The ketogenic diet (KD) is being explored as a potential adjuvant therapy in cancer treatment due to its unique metabolic effects on cancer cells. Here are some reasons why the ketogenic diet is considered for use in cancer therapy:
Mechanisms of Action
1. Starving Cancer Cells: The ketogenic diet is high in fats and low in carbohydrates, which induces a state of ketosis where the body burns fat for energy instead of glucose. Many cancer cells rely heavily on glucose for energy due to the Warburg effect, which involves the preference for glycolysis over oxidative phosphorylation even in the presence of oxygen[2][4]. By reducing glucose availability, a ketogenic diet may starve cancer cells while normal cells adapt to use ketone bodies[2].
2. Inhibition of Growth Pathways: Ketogenic diets can reduce insulin and insulin-like growth factor levels, which are important for cancer cell proliferation[2][5]. Additionally, they may inhibit pathways such as PI3K/Akt/mTOR that are involved in tumor growth and survival[5].
3. Induction of Ferroptosis: Research has shown that ketogenic diets can lead to the accumulation of toxic lipid byproducts that induce ferroptosis, a type of cell death, in cancer cells[1].
4. Slowing glycolysis: Secondary to the Warburg Effect cancers thrive on glucose. Ketones block Aldolase, one of the enzymes in the glycolytic (glucose breakdown) pathway[10].
Potential Benefits
Slowing Tumor Growth: Preclinical studies have shown that ketogenic diets can slow the growth of various tumors and may enhance the effectiveness of chemotherapy and radiotherapy[6].
Improving Survival: Some studies suggest that long-term adherence to a ketogenic diet may improve survival rates in certain types of cancers[9].
Enhancing Drug Efficacy: Combining a ketogenic diet with specific cancer therapies has shown promise in preclinical models. For example, in pancreatic cancer, the combination of a ketogenic diet with a drug that blocks fat metabolism led to tumor shrinkage[3].
Challenges and Considerations
Cachexia Risk: In some cases, particularly with advanced cancers like pancreatic or colorectal cancer, a ketogenic diet may exacerbate cachexia—a wasting syndrome associated with severe weight loss and muscle atrophy—unless paired with interventions like corticosteroids[1].
Limited Human Data: Most evidence supporting the use of ketogenic diets in cancer comes from animal studies or small human trials. Larger randomized controlled trials are needed to confirm these findings and determine which cancers might benefit most from this dietary approach[2][4].
Individual Variability: The effectiveness of a ketogenic diet may vary depending on the type and stage of cancer, as well as individual patient factors. Some cancers might not respond or could even be worsened by such dietary interventions[4].
In summary, while there is promising evidence supporting the potential benefits of the ketogenic diet as an adjunct therapy in cancer treatment, more research is needed to fully understand its efficacy and safety across different cancer types. Patients considering this dietary approach should do so under medical supervision to manage potential risks and ensure it complements their overall treatment plan.
Citations:
[1] https://www.cshl.edu/the-latest-weapon-against-cancer-is-a-keto-diet/
[2] https://pmc.ncbi.nlm.nih.gov/articles/PMC5842847/
[4] https://www.webmd.com/cancer/keto-diet-cancer-link
[5] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6375425/
[6] https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2021.594408/full
[7] https://www.mdpi.com/1467-3045/43/2/42
[8] https://www.mdpi.com/2072-6643/15/20/4357
[10] https://www.nature.com/articles/s42255-024-01093-w#citeas
Fasting for up to 72 hours prior to chemotherapy attenuates toxic side effects to normal cells and may sensitize cancer cells to the effects of the chemotherapeutic agent.
Plotti F, Terranova C, Luvero D, et al. Diet and Chemotherapy: The Effects of Fasting and Ketogenic Diet on Cancer Treatment. Chemotherapy. 2020;65(3–4):77–84.
“All comparatives studies have demonstrated that even fasting then KD results in a reduction of collateral effects of adjuvant chemotherapy (due to reduction of drugs toxicity) and a better QoL than in patients that follow no diet. Unfortunately, despite the fact that various laboratory and animal studies confirm advantages from KD and fasting, few data are today disposable on humans: further studies are needed to confirm data exposed in this review.“
Dorff TB, Groshen S, Garcia A, et al. Safety and feasibility of fasting in combination with platinum-based chemotherapy. BMC Cancer. 2016;16(1):360.
“…brief cycles of STS [short term starvation, i.e. fasting] lead to profound changes in gene expression and cellular metabolism that render normal cells more resistant to oxidative stress…”
Mehdi Sadeghian, Sepideh Rahmani, Saman Khalesi, Ehsan Hejazi, A review of fasting effects on the response of cancer to chemotherapy, Clinical Nutrition, Volume 40, Issue 4, 2021, Pages 1669-1681, ISSN 0261-5614
“Fasting potentially improves the response of tumor cells to chemotherapy by (1) repairing DNA damage in normal tissues (but not tumor cells); (2) upregulating autophagy flux as a protection against damage to organelles and some cancer cells; (3) altering apoptosis and increasing tumor cells' sensitivity to the apoptotic stimuli, and preventing apoptosis-mediated damage to normal cells; (4) depleting regulatory T cells and improving the stimulation of CD8 cells…”
Klement RJ. Fasting, Fats, and Physics: Combining Ketogenic and Radiation Therapy against Cancer. Complement. Med. Res. 2018;25(2):102–113.
“The first effect relates to the metabolic shift from glycolysis towards mitochondrial metabolism, which selectively increases reactive oxygen species (ROS) production and impairs adenoside triphosphate (ATP) production in tumor cells. The second effect is based on the differential stress resistance phenomenon describing the reprogramming of normal cells, but not tumor cells, from proliferation towards maintenance and stress resistance when glucose and growth factor levels are decreased and ketone body levels are elevated. Underlying both effects are metabolic differences between normal and tumor cells. Ketogenic therapy is a non-toxic and cost-effective complementary treatment option that exploits these differences and deserves further clinical investigation.”
Research Info
Seyfried TN, Mukherjee P, Iyikesici MS, et al. Consideration of Ketogenic Metabolic Therapy as a Complementary or Alternative Approach for Managing Breast Cancer. Front. Nutr. 2020;7:21.
Seyfried TN, Shivane AG, Kalamian M, et al. Ketogenic Metabolic Therapy, Without Chemo or Radiation, for the Long-Term Management of IDH1-Mutant Glioblastoma: An 80-Month Follow-Up Case Report. Front. Nutr. 2021;8:682243.
Seyfried TN, Shelton L, Arismendi-Morillo G, et al. Provocative Question: Should Ketogenic Metabolic Therapy Become the Standard of Care for Glioblastoma? Neurochem. Res. 2019;44(10):2392–2404.
Seyfried TN, Mukherjee P, Lee DC, et al. Case report: Resolution of malignant canine mast cell tumor using ketogenic metabolic therapy alone. Front. Nutr. 2023;10:1157517.
Li J, Zhang H, Dai Z. Cancer Treatment With the Ketogenic Diet: A Systematic Review and Meta-analysis of Animal Studies. Front. Nutr. 2021;8:594408.
Evangeliou AE, Spilioti MG, Vassilakou D, et al. Restricted Ketogenic Diet Therapy for Primary Lung Cancer With Metastasis to the Brain: A Case Report. Cureus. 2022;14(8):e27603.
Lane J, Brown NI, Williams S, et al. Ketogenic Diet for Cancer: Critical Assessment and Research Recommendations. Nutrients. 2021;13(10):3562.
Money ME, Matthews CM, Tan-Shalaby J. Review of Under-Recognized Adjunctive Therapies for Cancer. Cancers. 2022;14(19):4780.
Tan-Shalaby JL, Carrick J, Edinger K, et al. Modified Atkins diet in advanced malignancies - final results of a safety and feasibility trial within the Veterans Affairs Pittsburgh Healthcare System. Nutr. Metab. 2016;13(1):52.
Tan-Shalaby J. Ketogenic Diets and Cancer: Emerging Evidence. Fed Pract. 2017 Feb;34(Suppl 1):37S-42S. PMID: 30766299; PMCID: PMC6375425.
Qin, J., Huang, X., Gou, S. et al. Ketogenic diet reshapes cancer metabolism through lysine β-hydroxybutyrylation. Nat Metab 6, 1505–1528 (2024). https://doi.org/10.1038/s42255-024-01093-w
Yang L, TeSlaa T, Ng S, et al. Ketogenic diet and chemotherapy combine to disrupt pancreatic cancer metabolism and growth. Med. 2022;3(2):119-136.e8.
Evangeliou AE, Spilioti MG, Vassilakou D, et al (2022) Restricted Ketogenic Diet Therapy for Primary Lung Cancer With Metastasis to the Brain: A Case Report. Cureus 14:e27603. https://doi.org/10.7759/cureus.27603
İyikesici MS, Slocum AK, Slocum A, et al. Efficacy of Metabolically Supported Chemotherapy Combined with Ketogenic Diet, Hyperthermia, and Hyperbaric Oxygen Therapy for Stage IV Triple-Negative Breast Cancer. Cureus. 2017;9(7):e1445.
Additional Resources
Excellent book and Audible recording on the history of cancer research and how research got led astray
