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Is the Ketogenic Diet Relevant to People with Cancer?

By Michael McCulloch, LAc, MPH, PhD
December 2023

If you’re not sure whether Keto is helpful or appropriate for a person with cancer, this article provides up-to-date core details which may be useful. Frequently, people with cancer are not sure whether online claims are valid, and their doctors not convinced it’s helpful or safe.

Quick Start Guide:
Ketogenic Diet and Cancer: How do we Know it Works?

We now have strong data available from several well-designed randomized trials, published in reputable journals:

In the first study, 80 patients with locally advanced or metastatic breast cancer were randomly assigned during the course of their chemotherapy to KD or control group for 12 weeks. Among the locally advanced patients, reductions among the Keto group were seen in tumor size, cancer stage, and blood levels of TNF-α and insulin, when compared to non-keto controls. Among the metastatic patients, no significant differences in response rate were observed.[1]

In the second, a study of feasibility and acceptability of Keto, ovarian and endometrial cancer patients were randomly assigned to either a KD (70% fat, 25% protein, 5% carbohydrate), or the American Cancer Society diet (high-fiber and lower-fat), no adverse effect on cholesterol levels were seen in the Keto group, and the ability to stick to Keto ranged between 57% to 80%.[2]

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Personalizing and monitoring a ketogenic diet:
Success with Keto involves considering factors like age, physical activity level, health status, and specific health goals.

  • Assessment of Individual Needs: Before starting a ketogenic diet, a thorough assessment of individual dietary preferences, nutritional requirements, and health goals is necessary. Adapting the diet to meet individual calories and protein needs can be efficiently organized with the Carb Manager phone app.
  • Macronutrient Ratios: The standard ketogenic diet typically consists of about 70-75% fat, 20-25% protein, and 5-10% carbohydrates. However, these ratios can be adjusted based on personal goals and responses. For instance, athletes or individuals undergoing cancer treatment will require more protein. A weight gain calculator is an essential tool for ensuring caloric adequacy.
  • Monitoring Ketone Levels: Monitoring blood ketone levels is crucial for ensuring the diet’s effectiveness. Nutritional ketosis is generally achieved when blood ketone levels are between 0.5 to 3.0 mmol/L. Maintaining these levels can be monitored through blood ketone meters. The Abbott Laboratories Precision Xtra can measure both glucose and ketones.
  • Regular Health Check-ups: Regular consultations with healthcare professionals are vital, especially for individuals with pre-existing conditions like diabetes or heart disease. Blood tests and health check-ups can help monitor the diet’s impact on overall health.
  • Adjustments Based on Feedback: The diet should be regularly adjusted based on individual feedback and health outcomes. For instance, if a person experiences fatigue, weight loss or nutrient deficiencies, dietary adjustments may be required.

Ketogenic Diet and Cancer: How do we Know it Works?
We now have strong data available from several well-designed randomized trials, published in reputable journals:


In the first study, 80 patients with locally advanced or metastatic breast cancer were randomly assigned during the course of their chemotherapy to KD or control group for 12 weeks. Among the locally advanced patients, reductions among the Keto group were seen in tumor size, cancer stage, and blood levels of TNF-α and insulin, when compared to non-keto controls. Among the metastatic patients, no significant differences in response rate were observed.[1]

In the second, a study of feasibility and acceptability of Keto, ovarian and endometrial cancer patients were randomly assigned to either a KD (70% fat, 25% protein, 5% carbohydrate), or the American Cancer Society diet (high-fiber and lower-fat), no adverse effect on cholesterol levels were seen in the Keto group, and the ability to stick to Keto ranged between 57% to 80%.[2]

The History of Modern Keto Research
A defining feature of the dysfunctional metabolism in cancer cells is their increased ability to shift their primary energy source to fermentation of blood glucose (aerobic glycolysis), also called the Warburg effect.[3, 4] The benefits of a ketogenic diet (Keto) in cancer care are provided by (1) reducing the harms of carbohydrate intake by making blood glucose less available to cancer cells, and (2) providing the benefits of elevated blood ketone levels by achieving ketosis from dietary fats. Understanding ketosis, particularly its different types—nutritional and therapeutic—is crucial in the context of cancer treatment.

Keto has been in continuous use for both epilepsy[5, 6] and diabetes since the early 1920s, with a design quite similar to today’s version (5% of energy from carbohydrates, 20% from protein, and 75% from fat).[7] The first peer-reviewed paper on Keto specific to cancer was a 1981 study showing ketones interfered with cancer cells’ ability to metabolize sugar.[8] That core detail, together with the more recently discovered anti-tumor effect of reducing available blood sugar through carbohydrate restriction, provide the foundation for understanding why Keto is a useful tool across a wide range of cancers.

Modern approaches to care of people with cancer are usually combinatorial, bringing together multiple complementary modes of action. Very few FDA approved drugs work directly on the metabolic vulnerability of cancer cells.[9] Keto provides a low-cost way to help optimize the metabolism, thereby complement front-line standard-of-care for cancer.

A range of genetic, epigenetic, environmental and lifestyle factors contribute to breast cancer occurrence and progression. Diet also plays a role, primarily through increasing blood sugar and body fat, and dysregulating hormonal balance.[10] Elevated levels of glucose in the blood – primarily driven by diet – increase availability of energy for tumor cell growth.[10] The understanding of the role metabolic health plays in cancer has increased substantially in the past five years. The altered energy metabolism described in the Warburg Effect is a key factor in cancer cell growth.[11] A key link between metabolic health and cancer is ILT4, an immunosuppressive protein found in solid tumor cells.[12] For example, in breast cancer, particularly triple-negative,[13] ILT4 promotes tumor formation and immune evasion.[14]

The anticancer effects of a ketogenic diet are related both to the avoidance of high carbohydrates and the achievement of ketosis. Most cancer cells consume much more glucose than normal non-cancerous cells, therefore reducing glucose availability is key. Nevertheless, even if reduced carbohydrate intake doesn’t lower blood glucose levels, one can still achieve reduced blood levels of insulin, lowered inflammation markers, and higher levels of ketone bodies.[3]

Ketogenic diet: Definition
Fundamentally, ketogenic diet is defined by a reduction of carbohydrate intake to less than 20% of the daily total calories (i.e. reducing ingested carbohydrates, keeping protein normal, and increasing dietary fat).This nutritional fat adaptation prompts the metabolism to get energy from fat instead of carbohydrates. The liver transforms fatty acids into ketone bodies, providing energy to body cells and improving blood glucose control,[15] which in the context of cancer can reduce cell growth promotion.

Keto can have an adjunctive or supportive role in cancer care, however people with a cancer diagnosis need to be very mindful of avoiding weight loss. Therapeutic use of ketogenic diet is more likely to be successful with a clear and specific plan, discipline in sticking to the plan, and creativity in cooking to make it enjoyable.

What are the different types of Keto?
In general Keto is composed of very low carbohydrates, moderate protein, and high fat, there are different sub-types: Modified Atkins, MCT diet, and standard Ketogenic.

Modified Atkins Diet
Daily Fat: Not specifically provided
Daily Net Carbohydrates: 10 to 20 grams
Daily Protein: Moderate, to meet physiological needs
Source: Boston Medical Center

Standard Ketogenic Diet
Daily Fat: About 165 grams
Daily Net Carbohydates: Less than 50 grams, can be as low as 20
Daily Protein: About 75 grams
Source: Boston Medical Center

MCT Diet
Daily Fat: Begins at 30% of calories from MCT oil, may increase to 40-50% for ketosis
Daily Net Carbohydates: Not specifically provided
Daily Protein: Not specifically provided
Source: Epilepsy Foundation

Notes:

1. Net carbohydrates: are simply “Total carb grams” minus “Fiber grams”.

2. Low-Glycemic Index Diet: the specific daily grams of fat, net carbohydrates, and protein are not provided, as this diet focuses more on the type of carbohydrates (low-GI) rather than specific macronutrient ratios.

3. Macronutrient gram amounts: These are averages. Adjustments should be made based on body weight and activity level.

Is there an ideal target for blood ketone levels?

  • Nutritional ketosis: this occurs when the body starts using ketones for energy due to reduced carbohydrate intake. Blood ketone levels in this state typically range between 0.5 to 3.0 mmol/L. This type of ketosis is associated with various health benefits, including weight loss, improved insulin sensitivity, and better lipid profiles.[16]
  • Therapeutic ketosis: is employed to manage specific health conditions, including epilepsy, neurological disorders, and cancer. It often requires maintaining higher ketone levels than those in nutritional ketosis. For epilepsy, ketone levels around 4.0 mmol/L have been shown to be effective in reducing seizure frequency.

Ketosis in Cancer Care
A ketogenic diet, by limiting glucose availability, might inhibit tumor growth by restricting energy supply to tumors.[17] Research on the relevance of ketosis to brain tumors has suggested that higher ketone levels, potentially above 3.0 mmol/L, could be effective in starving cancer cells while providing energy to normal cells.[17] This may be enhanced by the inclusion of MCT oil, which due to its efficiency in raising ketone levels could be additionally beneficial in ketogenic diets for cancer patients, possibly enhancing the diet’s core anti-cancer effects.[18]

What about safety, i.e. ketoacidosis?
Nutritional or therapeutic ketosis are very distinct from Ketoacidosis, a dangerous metabolic condition that usually occurs in type 1 diabetes. Ketoacidosis occurs when the body produces excessively high levels of ketones, combined with high blood sugar levels, leading to a highly acidic environment in the blood. Monitoring with readily available blood spot meters is essential, especially in diabetic patients or those following a ketogenic diet. Of the 22 Adverse Event reports published in the peer-reviewed literature to date:

  • 8 breastfeeding women,[19-22] of which 2 were non-diabetic;[23, 24]
  • 7 cases of ketoacidosis linked to Keto occurred in people using the SGLT2-inhibitor class of medications: Brenzavvy (bexaglifloxin), Invokana (canagliflozin), Farxiga (dapagliflozin), Jardiance (empagliflozin)[25-27] Steglatro (ertugliflozin), or the particular SGLT2-inhibitor medicine not specified;[26, 28, 29]
  • 3 persons with previously undiagnosed Type 1 Diabetes;[25, 30, 31]
  • 2 persons who combined Keto diet with extended fasting and exogenous ketone salts, in the setting of type II diabetes, and developed starvation ketoacidosis;[32, 33]
  • 1 person combining Keto with Intermittent Fasting;[34] and,
  • 1 pregnant woman.[35]

It has been suggested that the SGLT-2 inhibitors may also have their own ketogenic effect.

What if intensive carbohydrate restriction is not feasible or desirable?
MCT Oil and Nutritional Ketosis: The inclusion of MCT oil in the diet has been shown to facilitate the achievement of nutritional ketosis, potentially increasing ketone levels within or beyond the 0.5 to 3.0 mmol/L range.

What is known from clinical trials about how Keto affects other cancer treatments:
Ketogenic diet reduces toxicity and improves QoL in people receiving chemotherapy.[36] Since that paper was published, 15 randomized clinical trials currently recruiting patients (as of 11/19/23) are in progress to assess the adjunctive role of Ketogenic Diet in cancer care.

What randomized trials are now in progress to assess benefits and risks of Ketogenic Diet in cancer care?
One of the most compelling, underway at the University of Calgary in Edmonton, Canada, is based on preclinical data showing that low carbohydrate eating inhibits glycolysis, and moderately intensive exercise temporarily improves blood flow to the tumor and increasing oxygen levels within the tumor, the operative theory is the combination of the two will reduce result in lower tumor burden, reduced chemotherapy side-effects, and improved quality of life.[37] The other randomized trials focus solely on addition of ketogenic diet to standard of care, in varying definitions of what is ketogenic, and recruiting people with a wide range of cancers undergoing varying treatments. In the table below, to find a study of interest, note the NCT (Trial ID) number from the first column, navigate your browser to clinicaltrials.gov, and search using that NCT number.

Future updates
This narrative is current as of 11/29/23, and will be updated periodically.

Substitutions for low-quality or processed foods often recommended on a ketogenic diet – Maximizing both nutritional value and health benefits.

Low-Quality FoodHigh-Quality SubstituteBenefits
Processed Meats (e.g., salami, sausages, bacon)Grass-Fed or Organic MeatLower in additives, higher in Omega-3 fatty acids, and more ethically sourced.
Farm-Raised FishWild-Caught FishHigher in Omega-3s, lower in contaminants, more sustainably produced.
Vegetable Oils (e.g., soybean, corn oil)Extra Virgin Olive Oil or Avocado OilRich in monounsaturated fats and antioxidants; better for heart health.
MargarineGrass-Fed Butter or GheeNatural, contains healthy fats, and free from trans fats and chemical additives.
Artificial Sweeteners (e.g., aspartame)Stevia or ErythritolNatural, no impact on blood sugar levels, and no known health risks.
DairyOrganic, Full-Fat DairyFree from antibiotics and hormones, higher in Omega-3s and vitamins.
Fast Food Keto OptionsHome-Cooked Keto MealsControl over ingredients, no added sugars or unhealthy fats.
Keto Snack Bars (with additives)Nuts, Seeds, or Homemade Keto BarsWhole food ingredients, no artificial additives, and better nutrient profile.
Store-Bought Salad DressingsHomemade Dressings with Olive OilAvoid sugar and unhealthy fats, plus the benefits of wholesome ingredients.
Processed CheeseArtisanal or Aged CheeseHigher quality, less processed, and richer flavor profiles.
Pork RindsKale ChipsControl over the quality of oil and seasoning, potentially lower in unhealthy fats.

Personalizing and monitoring a ketogenic diet: 

Success with Keto involves considering factors like age, physical activity level, health status, and specific health goals.

  • Assessment of Individual Needs: Before starting a ketogenic diet, a thorough assessment of individual dietary preferences, nutritional requirements, and health goals is necessary. Adapting the diet to meet individual calories and protein needs can be efficiently organized with the Carb Manager phone app.
  • Macronutrient Ratios: The standard ketogenic diet typically consists of about 70-75% fat, 20-25% protein, and 5-10% carbohydrates. However, these ratios can be adjusted based on personal goals and responses. For instance, athletes or individuals undergoing cancer treatment will require more protein. A weight gain calculator is an essential tool for ensuring caloric adequacy.
  • Monitoring Ketone Levels: Monitoring blood ketone levels is crucial for ensuring the diet’s effectiveness. Nutritional ketosis is generally achieved when blood ketone levels are between 0.5 to 3.0 mmol/L. Maintaining these levels can be monitored through blood ketone meters. The Abbott Laboratories Precision Xtra can measure both glucose and ketones.
  • Regular Health Check-ups: Regular consultations with healthcare professionals are vital, especially for individuals with pre-existing conditions like diabetes or heart disease. Blood tests and health check-ups can help monitor the diet’s impact on overall health.
  • Adjustments Based on Feedback: The diet should be regularly adjusted based on individual feedback and health outcomes. For instance, if a person experiences fatigue, weight loss or nutrient deficiencies, dietary adjustments may be required.

Current in-progress clinical trials of Ketogenic Diet in cancer care:

To find a study, copy and paste the NCT number below into https://clinicaltrials.gov.   

NCT Number: NCT05708716
Study Title: Diet and Cognitive Training in Hematologic Cancer Survivors
Sponsor: University of Alabama at Birmingham, with National Cancer Institute (NCI)
Locations: University of Alabama at Birmingham

NCT Number: NCT04631445
Study Title:
Study Evaluating the Ketogenic Diet in Patients With Metastatic Pancreatic Cancer
Sponsor: Translational Drug Development
Locations: Honor Health, Scottsdale, AZUSC/Norris Comprehensive Cancer Center, Los Angeles, CANuvance Health-Danbury Hospital, Danbury, CTNuvance Health, Norwalk, CTAtlantic Health System, Morristown, NJTennessee Oncology, Nashville, TNSouth Texas Accelerated Research, San Antonio, TXBaylor Scott and White, Temple, TX

NCT Number: NCT05183204
Study Title: Paxalisib With a High Fat, Low Carb Diet and Metformin for Glioblastoma
Sponsor: Weill Medical College of Cornell University
Locations: Weill Cornell Medicine, New York, NY

NCT Number: NCT05708352
Study Title: Phase 2 Study of the Ketogenic Diet vs Standard Anti-cancer Diet Guidance for Patients With Glioblastoma in Combination With Standard-of-care Treatment
Sponsor: Cedars-Sinai Medical Center, with National Cancer Institute (NCI)
Locations: Cedars-Sinai Medical Center, Los Angeles, CAUniversity of California San FranciscoPacific Neuroscience / Saint John’s, Santa Monica, CADuke University, Durham, NCBaylor Scott & White Health, Temple, TX

NCT Number: NCT05428852
Study Title:
Keto-Brain: Investigating the Use of Ketogenic Diets in Brain Metastases
Sponsor: Ohio State University Comprehensive Cancer Center
Locations: Ohio State Comprehensive Cancer Center, Columbus, OH

NCT Number: NCT05564949
Study Title:
A Ketogenic Diet as a Complementary Treatment on Patients With High-grade Gliomas and Brain Metastases
Sponsor: Attikon Hospital
Locations: Attikon University General Hospital, Athens, Greece

Citations 

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https://www.clinicalnutritionjournal.com/article/S0261-5614(20)30339-3/fulltext

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https://www.pnas.org/doi/pdf/10.1073/pnas.78.11.7214

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https://www.science.org/doi/10.1126/science.123.3191.309

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https://www.pnas.org/doi/pdf/10.1073/pnas.0803341105

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https://journals.biologists.com/jcs/article-abstract/136/18/jcs260964/328449/ILT4-reprograms-glucose-metabolism-to-promote?redirectedFrom=fulltext

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https://www.jlr.org/article/S0022-2275(20)35173-7/pdf

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  4. Alsomali, M., Severe ketoacidosis in a lactating woman on a ketogenic diet. Intern Med J, 2021. 51(1): p. 144-145. 
  5. Borhan, M.K., et al., A Case of Severe Lactation Ketoacidosis in a Nondiabetic Mother on a Ketogenic Diet. JCEM Case Rep, 2023. 1(6): p. luad134. 
  6. Alkhayat, A., et al., Ketoacidosis associated with ketogenic diet in a non-diabetic lactating woman. BMJ Case Rep, 2020. 13(6). 
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  8. Mistry, S. and D.C. Eschler, Euglycemic Diabetic Ketoacidosis Caused by SGLT2 Inhibitors and a Ketogenic Diet: A Case Series and Review of Literature. AACE Clin Case Rep, 2021. 7(1): p. 17-19. 
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  10. Garay, P.S., G. Zuniga, and R. Lichtenberg, A Case of Euglycemic Diabetic Ketoacidosis Triggered by a Ketogenic Diet in a Patient With Type 2 Diabetes Using a Sodium-Glucose Cotransporter 2 Inhibitor.Clin Diabetes, 2020. 38(2): p. 204-207. 
  11. Fieger, E.I., et al., SUCCESSFUL REIMPLEMENTATION OF A VERY LOW CARBOHYDRATE KETOGENIC DIET AFTER SGLT2 INHIBITOR ASSOCIATED EUGLYCEMIC DIABETIC KETOACIDOSIS. AACE Clin Case Rep, 2020. 6(6): p. e330-e333. 
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https://mdpi-res.com/d_attachment/nutrients/nutrients-13-01388/article_deploy/nutrients-13-01388.pdf?version=1618973403

  1. Kirkham, A.A., et al., Rationale and design of the Diet Restriction and Exercise-induced Adaptations in Metastatic breast cancer (DREAM) study: a 2-arm, parallel-group, phase II, randomized control trial of a short-term, calorie-restricted, and ketogenic diet plus exercise during intravenous chemotherapy versus usual care. BMC Cancer, 2021. 21(1): p. 1093. https://www.ncbi.nlm.nih.gov/pubmed/34629067