The Ketogenic Diet  

Questions about Ketogenic Diets?

Call Us 780-757-8378

Ketosis: In-Depth

Ketogenic diets are an extremely cost effective intervention that has potential in a large range of Cancers.

Ketogenic diets are composed of high-fat, moderate protein and low-carbohydrate components. 

Ketosis is a state where the body obtains its energy from ketone bodies, as opposed to glucose. 

Fat-derived ketone bodies are produced by the liver when dietary and storage forms of glucose are depleted.

Technical section: In the liver, fatty acids are converted into acetyl-CoA (acetyl-coa is made through mitochondrial beta-oxidation from fatty acyl-Coa which is transported into the mitochondria by Carnitine)

Acetyl-CoA can enter the Krebs cycle to generate energy or can be converted into the ketone bodies acetoacetate, beta-hydroxybutyrate and acetone. Beta-hydroxybutyrate is the major circulating ketone. 

In brain, heart or muscle, ketone bodies produced in the liver are used as an energy source via conversion of the ketone bodies into acetyl-CoA which then enters the Krebs cycle.

Diet types

Long Chain Triglyceride (LCT) diet - using standard oils and fats to make ketones.

Medium Chain Triglyceride (MCT) diet

The use of Medicum Chain Triglycerides ("MCTs" from coconut oil, especially liquid coconut oil) do not require Carnitine for entry into the mitochondria and produce ketones more efficiently and rapidly.

Technical Section: MCTs are hydrolyzed into free fatty acids in the intestine and rapidly absorbed. They are quickly transported to the liver (by albumin). MCT are thought to be more ketogenic, producing higher ketone yields per kilocalorie of dietary energy in comparison with Long Chain Fatty Acids. Following hepatic uptake, they easily cross the mitochondrial membrane and are converted into Acetyl-Coa (beta-oxidation) and then enter the citric acid cycle or are converted into ketone bodies. 

Main MCTs are:  MCTs are caprylic and capric acid and, to a lesser extent, caproic acid and lauric acid. 

LCTs have to be incorporated into transporters called chylomicrons and are taken via the thoracic duct (lymphatic system) into the blood circulation. Also LCTs need carnitine as a carrier to enter the mitochondria and then undergo beta-oxidation to make Acetyl-Coa. A complicated and cumbersome process compared to MCTs. 

Metabolic Treatment of Cancer

One hallmark of nearly all cancer cells is characterized by a metabolic shift from respiration towards
glycolysis (usually only anerobic in normal cells but aerobic in cancer cells).

In the majority of normal cells pyruvate generated from glucose (via glycolysis) is shuttled to the Krebs Cycle (oxidative phosphorylation). Cancer cells, on the other hand, use pyruvate mostly in the lactic acid fermentation pathway. 

Elevated glucose levels and uptake rates have been consistently associated with poor prognosis in cancer patients. 

The Ketogenic diet reduces glucose availability to tumour cells while providing ketone bodies as an alternative fuel to normal cells. 

This allows for the selective starvation of tumour cells, which, in contrast with normal cells, are unable to adapt to ketone metabolism.  
 

Furthermore, lower circulating levels of glucose will also lower insulin and IGF-1 levels, thereby decreasing the activation of the PI3K/Akt/mTOR pathway. 

At our clinic we exploit various agents that help to "choke off" this same pathway. In particular, we work with IV Alpha Lipoic Acid, CoQ10, Solomon's Seal and Oral Garcinia "Hydroxycitrate" to take advantage of these pathways. 

Hyperbaric oxygen synergizes with ketosis, as it encourages oxygen dependant oxidative phosphorylation (pyruvate going down the vertical pathway pictured above).

In fact, this particular approach to cancer is called "the Metabolic approach" to Cancer therapy. Our clinic focuses on this approach as it can yield superior results in our experience compared to other alternative cancer treatments. 

Questions about Alternative treatments?

Call Us 780-757-8378

Human Data

Some of the preclinical studies have shown the effect of ketogenic diet to reduce tumor growth and improve survival in animal models of malignant glioma, prostate cancer, colon cancer, and gastric cancer⁵.

Human data on Ketosis and Cancer is severely lacking. However, many trials are currently underway. 

There is some preliminary data on Melanoma and Lung cancer from a 16 week feasibility trial in advanced cancer patients. At 16 weeks, three patients had stable disease and one had reduced disease symptoms¹³. Three of the patients had metastatic melanoma and one had stage iv lung cancer.

In a case report two female pediatric patients with advanced stage malignant Astrocytoma tumors. Ketosis was maintained by consuming a 60% medium chain triglyceride oil-based diet. One patient exhibited significant clinical improvements in mood and new skill development during the study. She continued the ketogenic diet for an additional twelve months, remaining free of disease progression².

In a different case report, a patient with glioblastoma multiforme (GBM) had an incomplete surgical resection. Prior to initiation of the standard therapy (temozolomide) the patient conducted water-only therapeutic fasting and a ketogenic diet that delivered about 600 kcal/day. The patient also received the restricted ketogenic diet concomitantly during the standard treatment period. After two months treatment, no discernable brain tumor tissue was detected using either PET or MRI imaging. The authors noted that rapid regression of GBM is rare in older patients following incomplete surgical resection and standard therapy alone, therefore the response observed in this case could result in part from the action of the calorie restricted ketogenic diet³.

A 2011 Pilot trial demonstrated some evidence of improved aspects of quality of life and blood parameters in some patients with advanced metastatic tumors undergoing a ketogenic diet⁴.

A 2014 study looked at ketogenic diet in 20 patients with recurrent glioblastoma. Three patients discontinued the diet for poor tolerability. One patient achieved a minor response and two patients had stable disease after 6 weeks and stabilization lasted for 11, 12 and 13 weeks in these patients. There was a trend for longer progression free survival in the group who had stable ketosis compared to the other patients⁷. 

A 2010 trial looked at 10 patients with advanced cancers where progressive disease occured after at least two conventional anticancer treatments. Carbohydrates were reduced to 5% of the macronutrient intake. Four patients demonstrated continued progressive disease. Six patients responded: 5 had stable disease and one had partial remission. All responding patients exhibited high levels of ketosis, whereas the mildest ketosis was observed only in patients with continued progressive disease. Responders were: 1 breast, 2 lung and 2 colorectal cancer¹⁶. This trial is somewhat limited as the time on the diet was 26-28 days.

Two patients were discussed in a 2015 case report with glioblastoma multiforme. Both did not respond to a ketogenic diet which indicates that it is difficult to understand or anticipate which patients will respond to ketosis¹⁴.

Eight patients continued diet with the salvage treatment consisting of ACNU/teniposide in 1 patient and bevacizumab alone (in 4 patients) or in combination with irinotecan (in three patients). Median progression free survival from bevacizumab was 20.1 weeks versus 16.1 weeks in a similar cohort treated only with bevacizumab⁷. 

MSCT

Metabolically supported chemotherapy "MSCT" is the administration of chemotherapy following insulin induced hypoglycemia plus a ketogenic diet, and the addition of Hyperthermia and Hyperbaric Oxygen.

In a 2019 study, 44 lung cancer patients with distant metastasis received MSCT. HBOT and Hyperthermia was given the same day or the next day sequentially after chemotherapy. Hyperbaric chambers were set to 1.5 ATA pressures.

In the MSCT study the overall response rate was 61.4%. Mean overall survival and progression-free survival was 42.9 months and 41.0 months respectively¹⁹. 

In a 2017 case report, a 29-year-old female with stage IV triple-negative breast cancer received MSCT. Triple Negative tumors are often more aggressive and have a poorer prognosis than more common receptor positive types.  An October 2016, PET-CT scan revealed a large primary tumor in her left breast, multiple pectoral and axillary lymph nodes, multiple widespread liver metastases, and an upper left abdominal lesion. 

After a six-month treatment period using MSCT her follow-up whole body PET-CT scan in February 2017 showed a complete therapeutic response with no evidence of abnormal FDG uptake²⁰. 

In a 2020 study, 25 patients with stage IV pancreatic cancer received MSCT with either gemcitabine-based or FOLFIRINOX. Ketogenic diet, hyperthermia, and Hyperbaric Oxygen were of course part of the MSCT regimen.

Median overall survival and median progression-free survival of these pancreatic cancer patients was 15.8 months and 12.9 months versus 11.1 months and 6.8 months in a different study where FOLFIRINOX and gemcitabine group were used in isolation therefore MSCT clearly provides a survival advantage²¹. 

In a 2009 study, 22 lung cancer patients with multiple pulmonary metastases intravenously received paclitaxel and carboplatin and Hyperthermia was also administered weekly during the carboplatin in all patients. 16 of 22 patients received hyperbaric oxygen therapy immediately after weekly chemotherapy.

The median time to progression of disease in all patients was 8 months and in 16 patients with HBO was 9 months indicating a benefit from the inclusion of HBO²². We personally believe this preliminary study would have seen enhanced benefit if additional metabolic therapies that Hyperbaric treatment synergizes with were included as in later studies²².

PKD

Paleolithic ketogenic diet (PKD) has been used by one group in Hungary in the treatment of several chronic diseases in more than 5000 patients for the last decade.  In the PKD the source of the fats and proteins is of the utmost importance.

The PKD is an animal fat-meat based diet with a fat:protein ratio of approximately 2:1 (in grams). Red and fatty meats are the predominant foods in the patient’s diet, with regular consumption of organ meat from cattle and pork as well. Protein levels are often 60-80 grams daily. 

In practical terms this means that the PKD excludes all artificial sweeteners, food additives, dairy products, cereal grains, plant oils (including coconut oil and olive oil), nuts, nightshades, legumes and dietary supplements; i.e. all foods that were not routinely available before the advent of agriculture 10,000 years ago. Removal of plant oils and dairy are definitely deviations from common ketogenic diets.

In essence a PKD diet is much closer to a carnivore ketogenic diet. It is thought that the removal of plant sources helps in the normalization of intestinal permeability, which the group claims is a critical factor in the mechanism of action of the PKD in cancer.  The utility of this may help in autoimmunity:  the group has published case reports in Type Diabetes and Crohn's.

38-Month Long Progression-Free and Symptom-Free Survival of a Patient With Recurrent Glioblastoma Multiforme: A Case Report of the Paleolithic Ketogenic Diet (PKD) Used As a Stand-Alone Treatment¹⁸: 

In a 2019 case report describing a patient with glioblastoma multiforme (GBM). Glioblastoma is the most aggressive form of brain tumor in adults with a prognosis of a median survival of 15 months after standard therapy. The patient had initially been treated with standard care including surgery, radiation and chemotherapy (temozolomide). Despite standard treatment, the patient experienced a recurrence of the glioblastoma seven months later.

Subsequently, the patient refused further radiation and chemotherapy and opted to use the paleolithic ketogenic diet (PKD) as a stand-alone treatment. Following the adoption of the PKD, progression of the disease has been completely halted.

During the follow-up of 38 months seven consecutive MRI scans were performed 3-6 months apart. Each of them showed stable sizes of the tumor and the associated cyst 

At the time of writing, the patient has remained in remission for 38 months (more than three years). 

The group strongly insists that the normalization of intestinal permeability from the PKD is key to its success as normalizing intestinal permeability is key to controlling inflammation. The group felt that this particular patient's inflammation was exacerbated from periods of coffee consumption. 

Paleolithic ketogenic diet (PKD) as a stand-alone therapy in cancer: Case studies²³

In this 2019 publication, two case studies were looked at in detail that followed the PKD diet. The first patient was already described above, however the second patient a 46 year old female who was initially diagnosed with invasive ductal Breast cancer in 2013 experienced a recurrence in 2018 despite hormonal therapy (liver and hip metastases). 

Using the PKD diet alone for 5 months she experienced regression in the the size and metabolic activity of the metastases. 

The report also briefly describes a 43 year old female breast cancer patient stable on PKD for a total of 69 months with no chemotherapy, surgery or radiation used. 

The authors also describe a 3 year old female with a brain tumor, stable for 59 months on PKD using only surgery.  

Treatment of Rectal Cancer with the Paleolithic Ketogenic Diet: A 24-months Follow-up²⁴

This case report describes a rectal cancer patient that initially received 6 weeks of radiation therapy and then used the PKD diet as a stand-alone therapy for 22.5 months. The patient declined concurrent chemotherapy. As with many PKD patients from these authors, the patient was not taking any medicines or dietary supplements while on the diet.

During the first five month of the PKD diet the patient exhibited excellent adherence which was paralleled by improving laboratory parameters including decreasing tumor marker levels and decreasing tumor size.

CEA levels steadily declined from 7.2 at onset to their lowest at 1.2 seven months later. 

From the seventh month on, his adherence level was fluctuating with periods of worse adherence paralleled with negative changes in laboratory parameters. His food diary indicated the consumption of alcoholic drinks with variable frequency, an increased coffee intake, as well as occasional consumption of tomato and oilseeds which was mirrored by a slow increase in the CEA. 

22 months after diagnosis, although MRI showed that there was no increase in the size of the tumor, the patient reported an alteration in bowel habits and that the bloody stool had returned and rectal surgery was performed, 24 months after initial diagnosis.

The case of the patient exemplifies that deviations from the diet, even those not affecting ketosis and blood glucose level, may induce negative changes such as elevation of blood pressure, tumor marker and inflammatory marker levels as well as negative changes on imaging and ultimately disease progression. The authors put forward that this is the most evolutionary adapted diet in humans and as such it may have the largest potential for boosting regeneration.

Complete Cessation of Recurrent Cervical Intraepithelial Neoplasia (CIN) by the Paleolithic Ketogenic Diet: A Case Report²⁵

The authors present a 2018 case report where recurrent cervical intraepithelial neoplasia (CIN), a premalignant condition of cervical cancer was successfully treated with the paleolithic ketogenic diet.

The patient had a history of high grade CIN in 2011, which was successfully treated with cervical conization (excision) and curettage. In October 2015 she was found to have a recurrence of high grade CIN (HSIL: High Grade Squamous Intraepithelial Lesion) which is, if left untreated, patients are at high risk for developing cervical cancer.

The patient then commenced the PKD and her repeat Pap (Papanicolaou) smear three months later was found to have reverted to normal. The patient has remained on the paleolithic ketogenic diet for 26 months, her repeat smears have stayed normal, and "she is free of symptoms and side effects." 

Halted progression of soft palate cancer in a patient treated with the paleolithic ketogenic diet alone: A 20-months follow-up¹⁷:

A 2016 case report described a tumor of the soft palate where the patient denied conventional treatment options. Instead, the patient started a ketogenic diet which resulted in a halted progression of the tumor as evidenced by imaging. At time of writing, the patient is on the diet for 20 months, without symptoms or side effects. A myoepithelial tumor of the soft palate is associated with rapid progression and poor outcome¹⁷.

Treatment of high-grade brain tumor using the paleolithic ketogenic diet (PKD): Three cases²⁵

The authors describe three cases, one of which we've already reviewed in detail above.

The two other cases, a 57 and 37 year old with an Anaplastic Oligodendroglioma (AO) and Glioblastoma. The AO patient did not commence standard treatments whereas the Glioblastoma patient did do surgery and concurrent radiotherapy, HBOT and unspecified "supplements". 

The AO patient was alive after 25 months on the PKD diet. The Glioblastoma patient seemed to progress after initiation of other therapies but was stable after 2 months of PKD.   

The AO patient did experience progression after 9 months which was preceded with a gradual increase in food intake, and reintroduction of coffee and alcohol. 

Metabolic Therapies

A few therapies we work with are synergistic with the Ketogenic diet.

ALA (Alpha Lipoic Acid) and HCA (hydroxycitric acid) synergize with ketosis¹⁰. 

Ketogenic diets are often employed simulatanously with these strategies. 

The Mitochondrial Rescue protocol also adds B1, Acetyl-L-Carnitine, Niacinamide and Metformin⁹. 

Intense Aerobic Activity can also be helpful⁹.

These therapies are in our opinion the strongest available Alternative Cancer Therapies.

Although not all patients respond, for those that do, the results can be dramatic. 

There is also preliminary data that ketosis can improve radiation therapy¹². A 2016 paper discussing ketosis used at the same time as radiation also confirmed no negative impact of ketosis in 6 patients on radiation¹⁵. 

hyperbaric oxygen

A few therapies we work with are synergistic with Hyperbaric Oxygen, we call these "metabolic therapies" or "the metabolic approach."

The aberrant signaling that drives tumor angiogenesis creates immature and leaky blood vessels which are unable to adequately perfuse the entire tumor. This leads to the formation of hypoxic regions and upregulates HIF-1.  HIF-1 enhances the expression of over 60 genes, many involved in glycolysis and fermentation, angiogenesis, growth, and survival. 

Cancer metabolism is characterized by lactate fermentation in the presence of oxygen, a phenomenon known as the Warburg effect. 

Glucose dependency and lactate production, two key features of the Warburg effect, correlate strongly with aggressive capacity and invasive potential. 

The anti-cancer effects of the Ketogenic Diet are largely attributed to a reduction in the glycolytic substrates and insulin signaling which fuel cancer metabolism. 

The expression of ketone utilization enzymes is often reduced in malignant cancers compared to their normal tissue counterparts. 

The ketogenic diet, ketone supplementation, and Hyperbaric Oxygen Treatment target overlapping metabolic pathways which are especially prominent in metastatic cells. 

Poff and D’Agostino (2013) studied the VM-M3 mouse model of metastatic cancer to compare tumor progression and survival in mice fed a standard diet or Ketogenic diet with or without Hyperbaric Oxygen delivered atm 2.5 ATA for 90 min three times weekly. 

The ketogenic diet alone significantly decreased tumor growth, and increased mean survival time by 56.7% in mice with systemic metastatic cancer. Hyperbaric Oxygen alone did not influence cancer progression, combining the Ketogenic diet with Hyperbaric Oxygen elicited a significant decrease in tumor growth rate, with a 77.9% increase in mean survival time.²¹

Hyperbaric dives are often suggested 2x weekly alongside other metabolic treatments at 1.5 ATA.²⁶

Eating Ketogenic

The following discusses how to eat a ketogenic diet.

This was developed for both our Cancer and Neurological disease patients to follow.

Annotated from the Wahls Protocol¹¹.

It is a nutrient dense MCT ketogenic diet.

6 Basic Rules:

Three to Five Tablespoons Minimum of Added Coconut Oil Daily

Four to Nine Cups of Vegetables Daily

Fruit maximum once daily as berries (1 cup)

No grains, legumes or starches (including yam, sweet potato and potato)

Maximum twelve ounces of meat daily.

Limited starchy vegetables (eg. squash) to twice weekly

SAMPLE BREAKFAST:

1 tablespoon coconut oil

diced peppers, onion, cabbage

cubed 1/2 chicken breast

fry with salt and pepper to taste

SAMPLE SMOOTHIE

2/3 cup blueberries

1/2 cup coconut milk full fat

handful of spinach

1.5 cups water

1-2 tablespoons chia seeds

blend

SAMPLE DINNER/LUNCH

1 small chicken breast

2 cups diced broccoli 

10 asparagus shoots

steam or bake

top with 1tbsp coconut oil

Confirming Ketosis

We need to measure ketones either in your blood or urine.

We usually recommend patients purchase "Ketostix" at their local pharmacy.

A pack of 50 strips is usually no more than $10. 

Dipping the stick in  urine will result in various degrees of pink to indicate ketosis.

If the strip stays tan, then you are not in ketosis at that moment.

For cancer we try to make at least the minimum which is trace ketones or .5mmol/L (5mg/dL)

This is light pink on the ketostix. 

However, some sources recommend 3mmol/L as optimal for cancer (blood or urine) which is somewhere between small and moderate ketones^8,26

It usually takes 24-72 hours to clear all your stores of carbohydrates and begin making ketones consistently.

Side effects of increased fat intake can be digestive (diarrhea, bloating) as well as nausea as you adapt to taking in more fat.

The adaptation period can sometimes cause a what's been called "ketoflu" - mostly fatigue as your body adapts.

Intermittent fasting eg. 7pm to 7am and oral ketone supplementation is suggested by some sources to hit the desired 3mmol/L. Oral MCT "liquid coconut oil" is another strategy to increase ketone levels especially in cachexic patients to stabilize weight as this is an easy strategy to increase daily caloric load²⁶.

Questions about Ketogenic Diets?

Call Us 780-757-8378