Ketogenic Diet and Cancer?

The War Is On

Can what you eat affect whether you get cancer or succumb to cancer? How about ketogenic diets and cancer? Let’s talk about that.

Does the “C” Word Scare You?

The “C” word certainly scares me. Every time I get a mammogram, I can’t sleep the night before and I worry each day until I get a clean result. Then, I feel elated. I escaped again!

The most amazing and important fact about following a ketogenic diet and inducing a state of ketosis in the body is the startling effect this diet has on cancer cells. I’d already had success in losing weight by following a ketogenic diet when I discovered the many health benefits of the ketogenic lifestyle.

What You Eat Makes a Big Difference

When I researched the impact of eating a ketogenic diet on health and longevity for our book on carbohydrate addiction, I wanted to shout. Not only did cutting out carbs help me lose weight, but I was reducing my risk of a number of illnesses. The most important illness among these was cancer. Find link to Confessions of a Carbohydrate Addict here. https://carbohydrateconfessions.com/

What I learned made me a fan of low carbohydrate diets forever. Let’s look at why.

Cancer Cells Need Sugar

Cancer cells metabolize sugar or glucose to grow and (Ugh!) multiply. They thrive on the stuff. In fact, you might say, cancer cells are “addicted to” or dependent on carbohydrates as their primary energy source. Take away their carbohydrate energy source, and cancer cells don’t thrive.

I could never understand why being significantly overweight increased our risks of so many types of cancer. Now I do.

The Enemy of My Enemy Is My Friend

Image of a model of one of the ketone body types.

Ketone bodies and cancer cells are enemies.

Is the Ketogenic Diet Harmful?

What about my body? Won’t my body suffer too if I stop eating carbohydrates? The wonderful answer is, “No”. The cells in our bodies can use ketone bodies as an alternate energy source.

Why Didn’t My Doctor Tell Me?

If the ketogenic diet is as great as you say, why didn’t my doctor tell me about it? There are at least two reasons. First, physicians are a conservative lot, and paradigm shifts are difficult for them. Viewing diet as a treatment is a paradigm shift in medicine. Physicians put diet “over there”– something for other disciplines to deal with. In other words, diet wasn’t really important. Thus, some physicians are still reluctant to use a ketogenic diet with cancer patients despite growing evidence of its utility (Cohen et al., 2018).

Medical School Curricula Are Woefully Lacking in Nutrition Education

Despite the fact that the US Burden of Disease Collaborators identified poor-quality of diet as the leading cause of death in the United States (Devries, Willett, & Bonow, 2019), medical students spend a total of 19 hours studying nutrition. Think about it! 19 hours! That translates into two days in the entire medical curriculum. As a result, nutrition education is minimal or missing in most residencies and medical schools.

How Does the Ketogenic Diet Affect Cancer Cells?

Ketogenic diets promote metabolic health and protection against cancer through multiple mechanisms that include

  • Lowering insulin levels
  • Enhancing mitochondrial substrate oxidation resulting in a sustained mild elevation of mitochondrial reactive oxygen species production and hermetic anti-oxidative adaptation
  • Specific anti-oxidative and anti-inflammatory effects of the ketone body beta-hydroxy butyrate which is a compound like butyrate (Klement, 2019).

The Warburg Effect, Ketogenic Diet, and Cancer

Microscopic Image of Cancer Cells
Image from Pixabay.com

In cancer cells, most energy comes from glucose even when oxygen is present. The shift from oxidative (oxygen using) phosphorylation to glycoloysis is called the Warburg effect. Early in the generation of a tumor, there are several characteristic changes– decreased tricarboxylic acid cycle and oxidative phosphorylation (Weber, 2019).

Eating a fat-rich, low-carbohydrate diet cuts glucose levels and induces a state of ketosis. Since cancer cells rely on the breakdown of glucose to obtain energy to survive and grow, they have the metabolic machinery needed to metabolize glucose. Cancer cells can’t get energy from ketone bodies because they lack the enzymes needed to use them as fuel.

Ketogenic Diets Starve Cancer Cells

Thus, a ketogenic diet starves cancer cells while the normal cells adapt their metabolism, use the available ketone bodies, and survive (Weber, Aminazdeh-Gohari, & Kofler, 2018).

Ketogenic Diet Targets Early Cancer Cell Alterations

Many medical researchers now view the ketogenic diet as a promising opportunity to target the early biochemical alterations in tumor cells. The ketogenic diet can have a tumor growth-limiting effect, protect healthy cells from damage by chemotherapy or radiation, accelerate chemotherapeutic toxicity toward cancer cells, and lower inflammation.

Oxidative Stress and Insulin Growth Factor, Ketogenic Diet, and Cancer

Another fun thing about ketogenic diet and cancer is the side effect of oxidative stress. The restricted access to glucose during a ketogenic diet increases oxidative stress in cancer cells. Doesn’t it feel good to think about stressing cancer cells? Turn about is fair play.

Ketogenic diets reduce insulin levels. Insulin growth factors drive cancer cell spread and multiplication.

Toward a Definition of the Ketogenic Diet

Let’s back up for a moment and define ketogenic diet. The ketogenic diet you follow may not be the diet used by your friend down the street (Veyrat-Durebex et al., 2018). Ketogenic diet usually means a high-fat, low-carbohydrate, and adequate-protein diet (Zhang, Xu, Zhang, Yang, & Li, 2018).

Most ketogenic diets limit carbohydrates to 20 to 30 grams per day or less than 5% of total daily calories (Bosco et al., 2018). To make up for the energy deficit caused by reduced carbohydrate intake, fatty foods are added to the diet. When this low carbohydrate state is maintained for more than 45 days, the liver begins to produce ketone bodies from fatty acids by a process called ketosis. See this post for more information. https://carbohydrateconfessions.com/the-history-of-fasting-ketosis-and-the-ketogenic-diet/

How Do I Know If My Body Is in Ketosis?

Ketone levels can be measured in your blood, urine, or breath. Ketone levels range between .5 to 3.0 mM in physiologic ketosis. Contrast these levels with the unhealthy condition of ketoacidosis. In ketoacidosis, blood concentrations are greater than 10 mM.

You certainly can’t get a blood draw whenever you want to know whether you are in ketosis. Instead, you can track ketosis through its breakdown products in your urine or breath. For example, it is well known that a body state of ketosis can cause unpleasant breath and a keto taste. These are caused by the release of acetone as a byproduct of ketone body production and its removal through the respiratory and urinary systems.

Tools to Detect Ketosis

The image shows one type of urine strip that can be used to test ketone levels in the urine.
Ketone Urine Testing Strips

You can purchase strips or instruments that pick up the breakdown products of ketone body production. The most popular and least expensive method is urine testing strips. You can also purchase a breath analyzer. Although the accuracy of the measurements is limited, you can get a general idea of how well you’re doing in maintaining ketosis using either method.

The image shows one type of breath analyzer that can detect ketone breakdown products.
Ketone Breath Analyzer

Cancer Research Definitions of a Ketogenic Diet

When you read the literature on the ketogenic diet and cancer, the diets used do vary from study to study. The two most common ketogenic diets are the Atkins Diet and the Modified Atkins Diet. Paleolithic diets and Mediterranean diets have also been studied. I’ll focus on Ketogenic and Paleolithic diets in this post. I’ll cover the Mediterranean diet later.

For more on the differences among the MAD, the Atkins Diet, and the Paleolithic Diet, see more https://carbohydrateconfessions.com/what-is-a-ketogenic-diet/.

Ketogenic Diets Do Not Replace Other Cancer Treatments

No one can or should suggest that a ketogenic diet is a freestanding cancer treatment. Although ketogenic diets are “gaining traction” as adjuvant or supportive treatments for several types of cancer (Ok et al., 2018), the ketogenic diet does not replace other treatments, and it is used as a supplement.

Glioblastomas Have A High Death Rate

Image shows nursing students watching while their teacher dissects a brain. Such focus.
Image from the Library of Congress

The brain has two main cell types– neurons and glia. Neurons carry information from one cell to another. Glial cells are support cells. They have many functions including providing nutrition, maintaining neurons, and removing waste. Glioblastomas are tumors made up of cancerous glial cells.

Using Diet to Fight Brain Cancer

Of the cancers, the evidence for diet as a supplementary treatment for brain cancer is the strongest. Following a ketogenic diet is an important supplementary therapy for cancer of the glial cells of the brain (Martin-McGill, Marson, Tudur Smith, & Jenkinson, 2018).

Santos et al. used a ketogenic diet versus a standard diet with patients who had been diagnosed with high grade glioblastomas (Santos et al., 2018). The results were striking. The positive response rate of patients on the ketogenic diet was approximately 78%, but the response rate of patients on the standard diet was only 25%. Progressing disease was 11% in ketogenic diet patients, but it was much higher in standard diet patients (50%).

It’s Hard to Believe, But…

Some glioblastoma patients have apparent brief disappearance of tumor tissue. How great is that?

The Ketogenic Diet and Brain Cancer Growth

Schwartz et al. examined the enzyme structures of cancer cells in 17 patients with glioblastoma (Schwartz, Noel, Nikolai, & Chang, 2018). The brain cancer cells did not have the enzymes they needed to break down ketone bodies and use them as energy, and there were ketone bodies in the brain tumors of the patients who were being treated with a ketogenic diet. The ketone bodies had penetrated the cancer cells.

The growth of a neuroblastoma was reduced by a ketogenic diet (Weber et al., 2018). They found that an ad lib ketogenic diet 8:1 ratio produced a very strong anti-tumor effect. To learn what the ratio means, see this post. https://carbohydrateconfessions.com/what-is-a-ketogenic-diet/

What Do Patients Think About the Ketogenic Diet?

Patients with glioblastoma don’t reject the ketogenic diet. Many of them like the diet (Schwartz et al., 2018; Shai et al., 2008), and there are no negative effects on patient health.

Other Types of Brain Cancer and Ketogenic Diet

The jury is still out for other types of brain cancer, and Weber said the effect of a ketogenic diet on astrocytoma and medulloblastoma is less promising (Weber et al., 2018).

Pancreatic Cancer

Following a ketogenic diet may also be important for patients with pancreatic-biliary cancer. This is another cancer which claims many victims.

Ketogenic diets haven’t been shown to increase your chance of surviving pancreatic cancer. Eating a ketogenic diet does make recovery easier for patients who’ve had surgery because they can eat more calories, have more energy, and feel more satisfied (Ok et al., 2018).

Prostate Cancer

Prostate cancer is the second leading cause of cancer related deaths in the United States. Men in Western countries have a six-times greater rate of prostate cancer than do men in China and Japan. Could the diets of men in China and Japan versus those of men in the United States explain the difference in cancer rates?

Animal Studies Show Diet Changes Prostate Tumor Progression

We must turn to the animal literature to get information about eating a ketogenic diet and prostate cancer. Here is a typical study result.

If you feed mice a no-carbohydrate or ketogenic diet, prostate tumors grow more slowly, and more mice survive. Mice fed a Western diet or low-fat diet don’t fare well. This effect is true for mice fed several low carbohydrate diets including the Modified Atkins Diet.

The Bottom Line on Ketogenic Diet and Prostate Cancer

The bottom line is this, eating a less-restrictive low carbohydrate diet such as the Modified Atkins Diet might have the same benefits for human patients (Weber et al., 2018).

Ovarian and Endometrial Cancer

For patients with endometrial or ovarian cancer, using a ketogenic diet can improve quality of life. Patients with these cancers sleep better, have more energy, and have fewer cravings (Cohen, Fontaine, Arend, Soleymani, & Gower, 2018).

Melanoma

Patients with advanced melanomas don’t survive more than a few months. If advanced melanoma patients follow a Modified Atkins ketogenic diet, they live longer.

Pairing the Modified Atkins Diet with perillyl alcohol treatment improves the patients life span even more. When compared with a control group, the tumors of patients on the MAD diet didn’t progress to the same extent (Klement, 2019).

Perillyl Alcohol

Perillyl alcohol is found in certain plants such as lavender and citrus fruits. People take perillyl alcohol for cancers including lung cancer, breast cancer, colon cancer, prostate cancer, pancreatic cancer, and brain cancer.

Colon Cancer

Here we must rely on animal research. When colon cancer tumor cells are injected into mice and the mice are fed a ketogenic diet rich in Omega 3 or a ketogenic diet with lard, colon tumor growth is slowed. The standard Western diet has no effect on tumor growth rate (Hao et al., 2015).

Breast, and Liver Cancer

There is no support for the use of a ketogenic diet as an adjunctive treatment for these cancers (Weber et al., 2018). We simply don’t know whether eating a ketogenic diet will help you recover from breast and liver  cancer or not.

Stomach Cancer

I could find only indirect evidence of the impact of eating a ketogenic diet on stomach cancer. Because a ketogenic diet relies heavily upon vegetables and reduces the intakes of carbohydrates, I looked at which dietary styles were associated with stomach cancer incidence.

Stomach Cancer Incidence Varies by Country

Image of some parts of S. E. Asia where stomach cancer is more common.

The incidence of stomach cancer is much greater in some countries and in some regions within countries. Countries with high incidences of stomach cancer are China, Japan, Poland, and Korea.

Eat Your Veggies

The findings were near universal for countries including the United States, Greece, Turkey, Poland, Japan, China, and Korea. When the diets of those who have developed stomach cancer are examined, eating more vegetables (both green and cruciferous) is protective against cancer (Ahn, 1997; Chyou, Nomura, Hankin, & Stemmermann, 1990; Demirer, Icli, Uzunalimoglu, & Kucuk, 1990; Hirohata & Kono, 1997; Hoshiyama & Sasaba, 1992; Hu et al., 1988; Lissowska et al., 2004; McCullough et al., 2001; Trichopoulos et al., 1985; You et al., 1988).

Eating fruit may also be protective, but this finding wasn’t universal.

Eating Carbs May Increase Your Risk

On the flip side, carbohydrate loaded foods increased the risk of developing stomach cancer in some international studies (Hoshiyama & Sasaba, 1992; Lissowska et al., 2004; Trichopoulos et al., 1985).

The Good News

“The ketogenic diet creates an unfavorable metabolic environment for cancer cell proliferation, and thus, represents a promising adjuvant for a multifactorial patient-specific therapeutic regime” (Weber et al., 2019). The strongest scientific finding thus far is that following a ketogenic diet increases the response to cancer treatment drugs.

How does that finding translate into real life? It means that you will need fewer doses of radiation and less chemotherapy to achieve the same result.

How Much Ketosis Do You Need to Fight Cancer?

Another important question is whether a patient needs to follow the ketogenic diet at all meals or if there is a degree of flexibility. Klement and colleagues are doing a clinical trial looking at whether a part-time ketogenic diet, e.g., ketogenic breakfast after radiation treatment, is helpful to patients undergoing radiographic treatment for head, neck, and breast cancers (Klement, 2016). Their preliminary results are favorable.

The Future

The promise of the ketogenic diet in the treatment of cancer won’t be realized until dietary programs are standardized across studies, and study designs are optimized. Large scale clinical trials are ongoing. https://clinicaltrials.gov/

References

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Chyou, P. H., Nomura, A. M., Hankin, J. H., & Stemmermann, G. N. (1990). A case-cohort study of diet and stomach cancer. Cancer Res, 50(23), 7501-7504.

Bosco, G., Rizzato, A., Quartesan, S., Camporesi, E., Mangar, D., Paganini, M., Paoli, A. (2018). Effects of the Ketogenic diet in overweight divers breathing Enriched Air Nitrox. Sci Rep, 8(1), 2655. doi:10.1038/s41598-018-20933-w

Cohen, C. W., Fontaine, K. R., Arend, R. C., Soleymani, T., & Gower, B. A. (2018). Favorable Effects of a Ketogenic Diet on Physical Function, Perceived Energy, and Food Cravings in Women with Ovarian or Endometrial Cancer: A Randomized, Controlled Trial. Nutrients, 10(9). doi:10.3390/nu10091187

Devries, S., Willett, W., & Bonow, R. O. (2019). Nutrition Education in Medical School, Residency Training, and Practice. JAMA. doi:10.1001/jama.2019.1581

Demirer, T., Icli, F., Uzunalimoglu, O., & Kucuk, O. (1990). Diet and stomach cancer incidence. A case-control study in Turkey. Cancer, 65(10), 2344-2348. doi:10.1002/1097-0142(19900515)65:10<2344::aid-cncr2820651030>3.0.co;2-h

Hirohata, T., & Kono, S. (1997). Diet/nutrition and stomach cancer in Japan. Int J Cancer, Suppl 10, 34-36. doi:10.1002/(sici)1097-0215(1997)10+<34::aid-ihc9>3.0.co,2-a

Hao, G. W., Chen, Y. S., He, D. M., Wang, H. Y., Wu, G. H., & Zhang, B. (2015). Growth of human colon cancer cells in nude mice is delayed by ketogenic diet with or without omega-3 fatty acids and medium-chain triglycerides. Asian Pac J Cancer Prev, 16(5), 2061-2068.

Hoshiyama, Y., & Sasaba, T. (1992). A case-control study of stomach cancer and its relation to diet, cigarettes, and alcohol consumption in Saitama Prefecture, Japan. Cancer Causes Control, 3(5), 441-448. doi:10.1007/bf00051357

Hu, J. F., Zhang, S. F., Jia, E. M., Wang, Q. Q., Liu, S. D., Liu, Y. Y., . Cheng, Y. T. (1988). Diet and cancer of the stomach: a case-control study in China. Int J Cancer, 41(3), 331-335. doi:10.1002/ijc.2910410302

Klement, R. J., Sweeney, R. A. . (2016). Impact of a ketogenic diet interention during radiotherapy on body composition: II. Protocol of a randomized phase I study (KETOCOMP). Clinical Nutrition, 12, e1-e6.

Lissowska, J., Gail, M. H., Pee, D., Groves, F. D., Sobin, L. H., Nasierowska-Guttmejer, A., .Chow, W. H. (2004). Diet and stomach cancer risk in Warsaw, Poland. Nutr Cancer, 48(2), 149-159. doi:10.1207/s15327914nc4802_4

Martin-McGill, K. J., Marson, A. G., Tudur Smith, C., & Jenkinson, M. D. (2018). The Modified Ketogenic Diet in Adults with Glioblastoma: An Evaluation of Feasibility and Deliverability within the National Health Service. Nutr Cancer, 70(4), 643-649. doi:10.1080/01635581.2018.1460677

McCullough, M. L., Robertson, A. S., Jacobs, E. J., Chao, A., Calle, E. E., & Thun, M. J. (2001). A prospective study of diet and stomach cancer mortality in United States men and women. Cancer Epidemiol Biomarkers Prev, 10(11), 1201-1205.

Ok, J. H., Lee, H., Chung, H. Y., Lee, S. H., Choi, E. J., Kang, C. M., & Lee, S. M. (2018). The Potential Use of a Ketogenic Diet in Pancreatobiliary Cancer Patients After Pancreatectomy. Anticancer Res, 38(11), 6519-6527. doi:10.21873/anticanres.13017

Santos, J. G., Da Cruz, W. M. S., Schonthal, A. H., Salazar, M. D., Fontes, C. A. P., Quirico-Santos, T., & Da Fonseca, C. O. (2018). Efficacy of a ketogenic diet with concomitant intranasal perillyl alcohol as a novel strategy for the therapy of recurrent glioblastoma. Oncol Lett, 15(1), 1263-1270. doi:10.3892/ol.2017.7362

Schwartz, K. A., Noel, M., Nikolai, M., & Chang, H. T. (2018). Investigating the Ketogenic Diet As Treatment for Primary Aggressive Brain Cancer: Challenges and Lessons Learned. Front Nutr, 5, 11. doi:10.3389/fnut.2018.00011

Shai, I., Schwarzfuchs, D., Henkin, Y., Shahar, D. R., Witkow, S., Greenberg, I., Dietary Intervention Randomized Controlled Trial, G. (2008). Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet. N Engl J Med, 359(3), 229-241. doi:10.1056/NEJMoa0708681

Trichopoulos, D., Ouranos, G., Day, N. E., Tzonou, A., Manousos, O., Papadimitriou, C., & Trichopoulos, A. (1985). Diet and cancer of the stomach: a case-control study in Greece. Int J Cancer, 36(3), 291-297.

Veyrat-Durebex, C., Reynier, P., Procaccio, V., Hergesheimer, R., Corcia, P., Andres, C. R., & Blasco, H. (2018). How Can a Ketogenic Diet Improve Motor Function? Front Mol Neurosci, 11, 15. doi:10.3389/fnmol.2018.00015

Weber, D. D., Aminazdeh-Gohari, S., & Kofler, B. (2018). Ketogenic diet in cancer therapy. Aging (Albany NY), 10(2), 164-165. doi:10.18632/aging.101382

Weber, D. D., Aminzadeh-Gohari, S., Tulipan, J., Catalano, L., Feichtinger, R. G., & Kofler, B. (2019). Ketogenic diet in the treatment of cancer – Where do we stand? Mol Metab. doi:10.1016/j.molmet.2019.06.026

You, W. C., Blot, W. J., Chang, Y. S., Ershow, A. G., Yang, Z. T., An, Q., . . . Wang, T. G. (1988). Diet and high risk of stomach cancer in Shandong, China. Cancer Res, 48(12), 3518-3523.

Zhang, Y., Xu, J., Zhang, K., Yang, W., & Li, B. (2018). The Anticonvulsant Effects of Ketogenic Diet on Epileptic Seizures and Potential Mechanisms. Curr Neuropharmacol, 16(1), 66-70. doi:10.2174/1570159X15666170517153509

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