Ketogenic Diet & Cancer: Interpreting the Research for You

We recently covered the science and clinical research behind using keto to treat pediatric epilepsy. Recently, scientists, doctors, and dietitians have assessed how the ketogenic diet can be utilized to manage symptoms of cancer.

Below we report the findings of their preliminary research. While it’s a stretch to say that keto cures cancer, in some cases, it might be a useful complement to conventional cancer treatments.

The Basic Facts of Cancer

Before delving into the clinical research between carbohydrate restriction and cancer, let us review the basic facts about cancer. Cancer is a broad disease group of diseases characterized by uncontrolled cell growth. These cells grow unchecked and start to inhibit the function of healthy cells. Over time, this may eventually take a toll on the human body and lead to life-threatening symptoms.

Cancer can start in most parts of the body where there is cell growth. Cancer cells typically form a lump called a neoplasm. People commonly call neoplasms “tumors.”

Scientists refer to tumors that do not spread to other parts of the body as “benign tumors.” These are not cancerous. Tumors that do spread to other parts of the body are cancerous and called “malignant tumors.”

Some general facts about cancer

There are over 100 documented forms of cancer with the five most common worldwide being lung, breast, colorectal, prostate, and stomach. [1] In 2012, over 14 million new cases of cancer were diagnosed worldwide (excluding some forms of skin cancer). [2] It inflicted about 8.2 million human deaths, or about 14.6% of human deaths, worldwide in 2012. [2]

Sugar & Cancer: The Warburg Effect

Cancer is a complex disease with many different underlying causes and contributing factors. One of the first observations about the disease was that cancer cells produce energy at a high rate through a process called glycolysis.

This process, which occurs in the cytosol of cells, uses glucose and is relatively inefficient. Typically, normal human cells produce the bulk of their energy through a process called oxidative phosphorylation. This involves glycolysis along with two processes that occur in the mitochondria (i.e. the cell’s powerhouse) called the citric acid cycle and electron transport chain.

These findings were largely made through experiments by German scientists Otto Warburg in the 1920s. He observed that tumor cells would convert high amounts of glucose into energy and a byproduct of glycolysis called lactic acid.

Thus, researchers refer to cancer cells’ high carbohydrate consumption as the Warburg Effect. [3] Otto Warburg did overextend his observations a bit far. He hypothesized that cancer cells eating glucose rapidly were the cause of cancer. However, modern-day scientists now believe that the real basis of cancer is due to mutations in oncogenes and tumor suppressor genes. [4]

Nonetheless, cancer cell’s high consumption of glucose is one of its defining biochemical features. According to a recent paper, the Warburg Effect “is an established hallmark of cancer.” [3] Studies in molecular models show that high levels of glucose are associated with higher cancer growth while depriving cancer cells of glucose leads to apoptosis.

Epidemiological studies show that high blood glucose, known as hyperglycemia, is strongly associated with increased risk of cancer. [5, 6]

Given this relationship between glucose and cancer cells, can a carbohydrate-restricted diet such as the ketogenic diet help manage cancer? Below, we document the early-stage research on using ketogenic diet along with conventional treatments to improve the quality of life in cancer patients.

A Collection of Case Studies: Starting with the Evidence

Showing a collection of case studies for cancer

The first study looking at the ketogenic diet and cancer was published in 1995 in the Journal of the American College of Nutrition. In it, researchers recruited two young female patients at the University Hospitals of Cleveland. Both had Glioblastoma Multiforme (GBM), a form of cancer that starts in the brain and rapidly spreads throughout the body.

GBM is the most aggressive cancer of the brain and is difficult to treat by using the conventional therapy of radiation and chemotherapy through the drug temozolomide. The median survival of people with GMB with intensive, standard treatment is an average of 15 months. [7] Both patients in this case study also had advanced stage brain tumors called “astrocytomas” that were unresponsive to conventional treatments such as chemotherapy.

As an intervention, the researchers asked the patients to consume a ketogenic diet for eight weeks that consisted of 60% medium chain triglycerides (MCTs). MCTs are saturated fats of medium length typically found in coconut oil.

In both patients, levels of blood glucose decreased to low/normal levels and ketones increased by 20 to 30 times within seven days of starting the ketogenic diet. [8] Results from scans indicated that there was a 21.8% decrease in glucose uptake at the tumor sites in both subjects. [8] Lower glucose is a strong indicator that a tumor is shrinking in size.

One patient experienced significant improvements in clinical health and overall mood throughout the study. She then continued the ketogenic diet for another year, where her disease did not progress at all.

Due to these findings, the authors concluded, “While this diet does not replace conventional antineoplastic treatments, these preliminary results suggest a potential for clinical application which merits further research.” [8]

A 2010 case study published in Nutrition & Metabolism also suggests that the ketogenic diet may have potential to help certain individuals with cancer. For their evaluation, researchers chose a 65-year old woman with GBM.

This particular patient had a tumor in her right hemisphere that led to chronic headaches, frequent fatigue, and increasing memory loss. Doctors removed some of the tumor through an incomplete surgical resection. However, her symptoms persisted.

To control her tumor, the patient partook in a ketogenic diet for two months. She participated in a water fast followed by a restricted 4 to 1 ratio diet of fats to carbohydrates and protein. Overall, this diet contained a total of 600 calories per day.

She supplemented the diet with minerals and vitamins. The patient also participated in conventional therapies to treat the tumor but stopped taking her steroid medications.

After two months, the patient had no detectable brain tumor tissue. A blood analysis revealed that she had lower levels of blood glucose and increased levels of urinary ketones. She also had lost 20% of her body weight, which was a desirable outcome in this case.

The patient experienced no notable side effects due to her ketogenic diet. After suspending her diet and her therapy for 10 weeks, her tumor resurfaced. The doctors reinitiated chemotherapy. She eventually succumbed to her illness less than two years after the initial diagnosis.

Patients with GBM rarely experience a rapid tumor regression after surgical resection and conventional therapy. Thus, the researchers emphasized that the, “…response of the GBM in this patient after standard treatment alone would be unlikely, further suggesting a role for targeting energy metabolism as part of the management strategy.” [9]

In their conclusions, they stated that the favorable response could be attributed “in part” to the calorie-restricted ketogenic diet. [9] However, the researchers emphasized, “Further studies are needed to evaluate the efficacy of restricted ketogenic diets, administered alone or together with standard treatment, as a therapy for GBM and possibly other malignant brain tumors.” [9]

Key Takeaways: Case studies on patients with advanced cancer suggest that the ketogenic diet has the potential to slow down cancer growth when coupled with conventional treatments.

Digging Deeper with Pilot Randomized Trials

Researchers have not conducted formal, randomized clinical control trials on the ketogenic diet and cancer. Medical professionals and scientists regard these as the most rigorous method in assessing the efficacy of a clinical intervention, whether it is a prescription drug, diet, or other intervention.

However, researchers have conducted some pilot trials about the ketogenic diet’s relationship to cancer. Scientists define these as:

“…exploratory studies limited in size and scope that give insight into the actions, efficacy, and safety of a drug or device but cannot provide definitive support for specific mechanistic or therapeutic claims” [10]

This means that pilot studies are smaller in scale than a standard clinical trial. However, they yield important evidence and indicate which treatments should be assessed further. Typically, scientists perform pilot studies after case studies and animal studies yield promising results.

Scientists published the first pilot study on the relationship between the ketogenic diet and cancer in 2011. For their study, they recruited 16 patients (12 women and 4 men) with various cancers in advanced stages. They had an average age of 50.4 years (30-65 years). All of them had metastatic tumors, which means that they grew and spread throughout the body.

Researchers instructed the patients to follow a ketogenic diet for 3 months consisting of less than 70 grams of carbohydrates per day.

They asked the subjects to eat a protein/fat shake each day along with a diet rich in foods such as sunflower seeds, flaxseed, cold-water fish, high fiber vegetables, and organic red meat. Typically, dietitians regard these as healthy, low-carb foods.

Digging deeper with pilot randomized trials

Each meal contained no more than 20 grams of carbohydrates. The researchers monitored key blood parameters such as glucose and quality of life measures at the beginning of the study and then every two weeks until the study finished 3 months later.

Of the 16 patients, five stuck with keto for the full duration of the trial. Most of the patients who stopped did so for unrelated reasons, such as strong progression of cancer not associated with the ketogenic diet or death. Three patients had difficulty complying with the diet and stopped.

Tumors did not progress at all at all in the five patients that successfully completed the ketogenic trial. This is a positive outcome given the advanced stage of their cancer. Additionally, some of these patients experienced favorable changes in glucose, HDL: LDL ratio, triglycerides, and healthy levels of weight-loss. These findings further support the healthy impact a ketogenic diet may have on cancer. [11]

Two patients also had significantly lower levels of CRP, a key indicator of inflammation, while the other three had relatively little change. [11] This indicates that some patients who complete the diet may have more favorable responses than other patients may in regards to some parameters.

Many patients experienced worsening cognitive function and symptoms such as pain and fatigue throughout the trial. However, the scientists attributed this primarily to the advanced stage of the disease.

Because of their findings, researchers concluded that “these pilot data suggest that a KD is suitable for even advanced cancer patients.” [11] They also noted that the ketogenic diet “has no severe side effects and might improve aspects of quality of life and blood parameters in some patients with advanced metastatic tumors.” [11]

It is important to emphasize, however, that the ketogenic diet had a variable response. Some patients were able to comply with it better than other patients were. Additionally, of those that completed the trial, some had changes that are more favorable in certain parameters such as CRP. This suggests that the ketogenic diet is not suitable for everyone.

Another study from 2014 suggests that the ketogenic diet is a safe, effective treatment to manage aggressive cancers when used with conventional therapies. For their retrospective study, researchers reviewed 53 patients with glioma, a tumor that starts in glial cells in the brain and spinal cord. These patients were treated with chemoradiotherapy and other standard treatments from August 2010 to August 2013. Six of these patients also consumed a ketogenic diet while on treatment.

The ketogenic diet subjects tolerated the diet and experienced no toxicity; one did experience mild fatigue. At the follow-up of 14 months, four of these six patients were alive. The mean blood glucose of patients eating standard diet was 122 mg/dl (scientists define diabetes as blood glucose greater than 125 mg/dl). [12]

In contrast, patients eating the ketogenic diet had an average blood glucose of 84 mg/dl. [12] These lower levels of blood glucose are associated with more restrained growth of tumors and better managements of cancer symptoms.

Due to these findings, the researchers stated, “Based on this retrospective study, a KD appears safe and well tolerated during the standard treatment of GBM.” [12] They also noted that the ketogenic diet reduces blood glucose even when used with steroids such as Dexamethasone that treat tumor swelling.

Oftentimes, a negative side effect of steroids is higher blood sugar. The researchers also noted, “Larger prospective trials to confirm this relationship are warranted.” [12]

Key Takeaways: Pilot trials in cancer patients indicate that the ketogenic is safe and effective in some patients when used with standard treatments. More research needs to be done to further assess the value of carbohydrate restriction in treating symptoms of cancer.

Putting the Research in Context

What does the available literature as a whole say about carbohydrate restriction and cancer? A meta-analysis by Schwartz et al looked at the literature on 32 glioma patients treated using the ketogenic diet as an alternative or complementary therapy.

All of these patients had measurable disease after going through conventional therapies. Their life expectancy was at least three months. Six of these patients were from the study above by Champ et al. Five were from case studies including the three from the studies by Nebeling et al. and Zucculo et al. discussed above.

Nineteen of these patients were from a randomized pilot study conducted in Germany by Rieger et al and two were case studies enrolled by the authors of the meta-analysis.

Researchers discovered that the ketogenic diet yielded no major side effects in patients. However, some patients did not personally like the diet and had difficulty sticking with it. The authors suggested that regular support from a dietitian or nutrition community (such as Ruled.me) could improve compliance.

They also noted that some patients were more responsive to the ketogenic diet than other patients were. The best response was in a 3-year-old girl who had complete remission five years of treatment with a ketogenic diet. Two other patients also experienced complete remission after the diet and the other two patients had disease progression after stopping keto. It is critical to emphasize that all of these patients used conventional treatments along with the diet.

The two patients the authors of the meta-analysis treated with the ketogenic diet had disease progression. They attributed this in part to the lack of regular contact these patients had with a dietitian. [13]

In the large pilot study by Rieger et al, they noted a “trend towards an increase in progression-free survival was reported in patients with stable ketosis.” [13] They noted that a dietitian did not support subjects and that steroid drugs may have increased levels of blood glucose. [13]

The authors of the study concluded that the ketogenic diet “is safe and without major side effects… treatment with KD may be effective in controlling the progression of some gliomas.” [13] They emphasized the importance of working extensively with a dietitian to adjust the patient’s diet as needed and measure ketones and glucose.

They also suggested that a keto-friendly community such as Ruled.me might be useful service in ensuring that people stick with the diet. Additionally, they commented on the need for more rigorous research, stating “further studies are needed to determine factors that influence the effectiveness of KD, whether as a monotherapy or as adjunctive or supplemental therapy in treating glioma patients.” [13]

Back to the Biochemistry: How Does Keto Combat Cancer?

The preliminary evidence behind using the ketogenic diet to treat cancer as a complementary treatment to conventional therapies is promising. Let’s recap how scientific theory explains the findings. According to dietitian Heidi H. Pfeifer at the MGH Center for Dietary Therapy, the ketogenic diet may be effective because of the following two reasons.

First, the macronutrient composition of the diet deprives cancer cells of energy. Cancer cells rely on glucose for energy and they cannot function without it. By its nature, the ketogenic diet is very low in carbohydrates (typically 20 to 50 grams/day). This provides minimal energy to cancer cells. Furthermore, cancer cells cannot use the ketones produced when the body breaks down fat for energy.

Second, the ketogenic diet suppresses insulin like growth factor (IGF-1). This molecule is associated with the formation and progression of cancerous cells. It is “upregulated” when you increase more carbohydrates. This means that the body produces more of it when you eat carbs.

Because the ketogenic diet is much lower in carbohydrates, scientists suspect that this suppresses IGF-1 production. This ultimately slows the formation of cancerous cells.

Where Should the Research Go From Here?

Where does the research on keto and cancer go?

Case studies and pilot randomized controlled studies in human subjects show that carbohydrate restriction has the potential to delay cancer growth when used with conventional treatments (such as chemotherapy).

Other studies show an association between hyperglycemia and increased activity of cancer. The next step is for researchers to use larger study samples to show what impact the ketogenic diet has on cancer especially in advanced stage cancer patients.

If you or a loved one is suffering from cancer, we strongly urge you to talk with an oncologist, dietitian, and your primary care doctor before utilizing the ketogenic diet a part of your treatment plan.

They know your individual case best and can determine if it is a suitable plan for you or a loved one. Also, remember that the ketogenic diet is not a substitute for conventional therapies such as chemotherapy and drugs.

Sources

  1. World Cancer Report 2014. World Health Organization. 2014. pp. Chapter 1.1. ISBN 9283204298.
  2. Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray, F. GLOBOCAN 2012 v1.1, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2014. Available from: http://globocan.iarc.fr, accessed on 16/01/2015.
  3. Klement, Rainer J., and Ulrike Kämmerer. “Is there a role for carbohydrate restriction in the treatment and prevention of cancer?.” Nutrition & metabolism 8.1 (2011): 1.
  4. Bertram, John S. “The molecular biology of cancer.” Molecular aspects of medicine 21.6 (2000): 167-223.
  5. Goodwin, Pamela J., et al. “Fasting insulin and outcome in early-stage breast cancer: results of a prospective cohort study.” Journal of Clinical Oncology 20.1 (2002): 42-51.
  6. Weiser, Mary Ann, et al. “Relation between the duration of remission and hyperglycemia during induction chemotherapy for acute lymphocytic leukemia with a hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone/methotrexate–cytarabine regimen.” Cancer100.6 (2004): 1179-1185.
  7. Stewart, B. W. K. P., and Christopher P. Wild. “World cancer report 2014.” World (2015).
  8. Nebeling, Linda C., et al. “Effects of a ketogenic diet on tumor metabolism and nutritional status in pediatric oncology patients: two case reports.” Journal of the American College of Nutrition 14.2 (1995): 202-208.
  9. Zuccoli, Giulio, et al. “Metabolic management of glioblastoma multiforme using standard therapy together with a restricted ketogenic diet: Case Report.” Nutrition & metabolism 7.1 (2010): 1.
  10. Loscalzo, Joseph. “Pilot Trials in Clinical Research Of What Value Are They?.” Circulation 119.13 (2009): 1694-1696.
  11. Schmidt, Melanie, et al. “Effects of a ketogenic diet on the quality of life in 16 patients with advanced cancer: A pilot trial.” Nutrition & metabolism 8.1 (2011): 1.
  12. Champ, Colin E., et al. “Targeting metabolism with a ketogenic diet during the treatment of glioblastoma multiforme.” Journal of neuro-oncology 117.1 (2014): 125-131.
  13. Schwartz, Kenneth, et al. “Treatment of glioma patients with ketogenic diets: report of two cases treated with an IRB-approved energy-restricted ketogenic diet protocol and review of the literature.” Cancer Metab 3.3.10 (2015): 1186.