The Ketogenic Diet  

Questions about Ketogenic Diets?

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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. 

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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.

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. 

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. 

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 ketones⁸.

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.

Questions about Ketogenic Diets?

Call Us 780-757-8378