April 6, 2023
By Angie N Choi, EdD, Author of Whole New Me: Healing From Cancer in Body, Mind, and Spirit
The metabolic approach to cancer worked
The metabolic approach to cancer worked for me. I was diagnosed with ovarian cancer and went into remission by utilizing a metabolic approach that included a therapeutic ketogenic diet to limit glucose and anti-parasitic medication to restrict glutamine. Glucose and glutamine are the fuels that allow cancer cells to produce energy and by drastically limiting them, tumors shrink and cancer cells become metabolically stressed and die.1
I discovered I had cancer through a fluke MRI scan for back pain. Images revealed a large tumor, the size of a cantaloupe, on my left ovary. I decided to do standard treatment, a total hysterectomy with salpingo-oopherectomy (surgical removal of fallopian tubes and ovaries), to remove the tumor, but during the debulking process, spillage occurred, so my oncologist recommended 6 rounds of chemotherapy. I opted out of chemotherapy and chose a metabolic approach to cancer instead. I was concerned about my quality of life during and after standard treatment as well as secondary cancers related to chemotherapy.2-4 The metabolic approach, based upon Dr. Thomas Seyfried’s research on cancer as a metabolic disease,5 provided the scientific basis to make evidence-based, informed decisions to pursue non-toxic therapies for cancer treatment. For those who want to delve further into the research, I recommend Dr. Seyfried’s book Cancer as a metabolic disease: On the origin, management and prevention of cancer.
The ketogenic diet starves cancer cells
A ketogenic diet is a high fat, moderate protein, and low carbohydrate diet that produces ketone bodies instead of glucose as fuel for the body. When we stop eating carbohydrates whether through a carbohydrate-restrictive diet or fasting, our bodies burn their glucose stores in the liver in the form of glycogen and metabolically switch over to using ketones for fuel.6 This change in diet effectively starves cancer cells of glucose, their primary fuel source. Humans have evolved to be able to survive on ketones when food is scarce as our early ancestors experienced when they could not obtain food. The body and the brain are able to utilize ketones for energy. Cancer cells however are unable to fuel their rapid growth without glucose, though they can adapt to use glutamine. This metabolic inflexibility in cancer cells allows us to exploit this weakness by adopting a ketogenic diet.7
What is the Glucose Ketone Index for cancer?
Ketogenic diets have become popular for weight loss, but as a dietary treatment for cancer, more rigorous, therapeutic levels close to a 2.0 glucose/ketone index (GKI) are required. For cancer, the glucose ketone index (GKI) is a good measure for therapeutic levels of blood glucose and ketones.8 There are two measurements to take to determine the GKI: blood glucose and blood ketones. Ideally, for cancer, we want to have lower glucose and higher ketone levels to yield a low GKI. In order to calculate the GKI, blood glucose levels (mg/dL) are divided by 18, and the total is then further divided by ketone levels (mmol/L).
GKI = (blood glucose ÷ 18) ÷ blood ketones.
For example, if blood glucose is 96 and blood ketones are 1.5, the GKI would be 3.5.
Ex. GKI = (96 ÷ 18) ÷ 1.5 = 3.5.
Blood glucose and blood ketone levels may be measured with a two-in one-meter that reads both glucose and ketone levels. The brand I used was the Keto Mojo Glucose & Ketone Testing Kit, which I found to be more accurate than other brands I tried. Another highly recommended brand is the Precision Xtra Blood Glucose & Ketone Monitoring System. Either one will work well for reliable measurements. A two-in-one monitor will be more economical than buying both a glucometer and a ketone monitor. Glucose and ketone testing strips also need to be purchased separately.
My therapeutic ketogenic diet for cancer
In order to keep an optimal GKI between 2-3, my macronutrient ratio in calories was 70:20:10 for fats, protein, and carbohydrates respectively at each meal. For example, if I had a meal of 500 calories, 350 calories (70%) were fat, 100 (20%) were protein, and 50 (10%) were carbohydrates. The major portion of each meal was unsaturated fats such as avocados, olives, butter, macadamia nut butter, and olive, avocado and coconut oils. For protein, I ate foods with higher fat content such as eggs, salmon, mackerel, sardines, and lamb. I could only have a few grams of carbohydrates each meal in the form of cucumbers, salad greens, and cruciferous vegetables. All of these food sources were organic, pasture-raised, and wild-caught to minimize exposure to grains in feed, GMOs, pesticides, antibiotics, and hormones. Additionally, even though I was on a ketogenic diet, I still needed to limit my overall calorie intake. The positive effects of calorie restriction on tumor growth have been well documented and when combined with a therapeutic ketogenic diet, anti-tumor effects were even greater.9,10 In short, a therapeutic ketogenic diet is effective for managing cancer, but when combined with calorie restriction, the anti-cancer effects increase.
Metabolic activity in cancer
Metabolism refers to the process of converting energy from food into cellular energy, a series of biochemical processes that results in the production of adenosine triphosphate or ATP, energy-carrying molecules.11 When food is initially eaten, it is in large macromolecules that must be broken down into simple compounds through enzymatic actions.12 Proteins are broken down into amino acids, carbohydrates into glucose, and fats into fatty acids and glycerol. Oxygen is required to produce energy from eating food, and this process is called aerobic (with oxygen) respiration. There are three main steps involved in aerobic respiration.13
- Glycolysis
- Tricarboxylic acid (TCA) cycle, also known as the Krebs cycle or Citric acid cycle
- Electron transport chain
Glycolysis, the first phase, is the process where glucose is converted into pyruvate, the end product of glycolysis. Then, the next steps for pyruvate depend upon whether cells have 1) mitochondria and 2) sufficient oxygen or not. Mitochondria are organelles in cells that generate the majority of the chemical energy needed for biochemical reactions. If cells have mitochondria and sufficient oxygen is present, then the citric acid cycle is initiated followed by the electron transport chain process which can yield up to 32 ATP. This process is called oxidative phosphorylation. However, if cells do not have mitochondria (like bacteria) or enough oxygen is not present, then, pyruvate converts to lactate molecules which is referred to as anaerobic (without oxygen) glycolysis.
Tumor cells have a special feature in relation to glycolysis where they take the path of anaerobic glycolysis even though they have mitochondria and sufficient oxygen is present. This means the pyruvate created during glycolysis converts to lactate – instead of following the pathway of aerobic respiration ― and only yields 2 ATP per glucose molecule. This is a highly inefficient route that cancer cells take. Why would cancer cells that require enormous amounts of energy for their rapid growth take this paradoxically inefficient pathway given that they have mitochondria and enough oxygen is present? It is because they have damaged mitochondria and cannot properly use oxygen to produce energy (to “breathe” or respirate), thereby requiring a primitive, fermentation (anaerobic) process instead.14
In the 1920s, Dr. Otto Warburg, a German physiologist, physician, and Nobel laureate (1931), observed that cancer cells, unlike healthy cells, fermented glucose (an anaerobic process) at abnormally high rates even when sufficient oxygen was present.15 This observation of cancer cells’ abnormal behavior was eponymously called the Warburg effect. Electron microscopy, unavailable during Warburg’s time, has since revealed that almost all cancer cells have damaged mitochondria.16
What are metabolic therapies for cancer and how effective are they?
There are several metabolic therapies for cancer that are promising.
- Calorie Reduction Diet
- Ketogenic Diet
- Extremely Low Carbohydrate Diet
- Glutamine Inhibition (Antiparasitic medications)
- Fasting (water fasting, short-term fasting, intermittent fasting)
- Hyperbaric Oxygen Therapy
Dietary metabolic therapies
The foundations of these therapies are primarily dietary ones that involve either restricted caloric intake or low glucose consumption as in ketogenic diets. Early studies noted the positive effects of caloric reduction on tumors in mice.19,20 Other researchers found that the positive effects on tumor cells were due to caloric content independent of dietary content.21 The caloric count of the food was more significant than the nutritional content or specified diet for fighting tumor growth.22 In comparisons between caloric restriction and a ketogenic diet for brain cancer, results indicated a synergistic effect between the two metabolic treatments. For example, when mice were fed a ketogenic diet but could eat as much as they liked, tumors did not shrink; however, if they ate a reduced-calorie ketogenic diet that lowered body weight, tumors reduced significantly.23,24 As always though with cancer, individuals may present with diverse physical, mental, and environmental terrain, and many may have undergone standard treatments like surgery, chemotherapy, or radiation, so the impact of dietary therapies must be considered individually. Moreover, some dietary therapies may be better for some individuals given their conditions. Working with certified nutritionists or naturopathic doctors (NDs) who specialize in the metabolic approach is highly recommended while also keeping your conventional oncologists or doctors informed.
Glutamine inhibition
Besides glucose, glutamine, an amino acid derived from protein, also feeds some types of cancer cells. Glutamine is the most abundant amino acid circulating in the body so there is no specific diet that can completely eliminate glutamine,25 but studies have indicated that glutamine antagonists are effective for various types of cancer.26 The glutamine suppressor 6-diazo-5-oxo-L-norleucine (DON) in combination with a ketogenic diet was found to be effective in killing tumor cells and reversing disease symptoms in brain tumors in mice.27 Despite its effectiveness as a glutamine antagonist, DON produces toxicity and side effects which has prevented it from reaching clinical trials.28 It is also difficult to obtain, expensive, and must be delivered intravenously.
Antiparasitic medication
Antiparasitic medications, commonly used to treat worms, have similar therapeutic efficacy as DON and can be repurposed (used off-prescription) to treat cancer.29-31 Antiparasitic drugs like mebendezole are inexpensive and have a record of low toxicity in humans.32 Other studies have indicated that prolonged use of some antiparasitic medications like albendazole cause liver toxicity.33 The efficacy of antiparasitic medications is greater when combined with ketogenic dietary therapy as cancer cells undergo increased metabolic pressure.34 The combination of a ketogenic diet with glutamine inhibition creates a press-pulse effect that has greater efficacy than either alone.35 The ketogenic diet acts as a long-term pressure (press) and antiparasitic medication acts as an intermittent and concentrated stressor (pulse) to devastate tumor cells.
In my case, I used a therapeutic ketogenic diet along with the canine antiparasitic febendezole. Prior to working with an integrative doctor, I was unable to get mebendazole as it requires a prescription from a doctor. Most conventional physicians will not prescribe medications off label, but integrative doctors who understand the metabolic approach will be more supportive. It is also important to be under the care of medical doctor or naturopathic doctor who understands metabolic therapy for cancer when doing this approach. Initially, instead of mebendazole, I used febendezole which is typically used to deworm dogs. A prescription was not required to get it, but as with any drug, its toxicity, side effects, and long-term repercussions must be carefully considered. I found a material safety data sheet (MSDS) compiled by the company that produced the canine medication that indicated its chemical composition and toxicological information. I decided to take the risk and was on the medication for two months. The combination was effective and brought my cancer antigen levels way down to the lowest end of normal levels.
Fasting
Fasting is another metabolic therapy for cancer, but it can be difficult for people to do prolonged fasts especially if they are already in a weakened state. Calorie-restrictive diets are most effective soon after diagnosis when individuals have greater energy. Intermittent fasting (IF) is an alternative for those unable to undergo strict water fasts and shows promise for inhibiting tumor growth, though the relationship between long-term IF and harm from low calorie intake is not well studied.36 For patients undergoing chemotherapy, short-term fasting reduced treatment side effects, protected healthy cells from the toxicity of treatment, and demonstrated greater efficacy on cancer cells.37,38 In my case, after recovering from surgery, I combined intermittent fasting with the therapeutic ketogenic diet. I ate during a 6-hour window from 9:00 am to 3:00 pm (breakfast and lunch) and fasted until the next day. Approximately once a month, I also did a 1-3 day water fast. This combination put further metabolic pressure on cancer cells.
Hyperbaric oxygen therapy
Hyperbaric oxygen therapy (HBO) is another metabolic therapy that raises the amount of oxygen in tissues expressed in atmospheres (atmospheric pressure at sea level).39 Cancer cells thrive in hypoxic (low oxygen) environments by adapting their cellular metabolism. HBO saturates cells with oxygen to put metabolic stress on tumor cells. HBO exhibited anti-cancer effects (decrease in blood glucose, decrease in tumor growth rate and increase in mean survival time) in mice when combined with a ketogenic diet but not as a stand-alone treatment.40 Although there were concerns about HBO’s safety and a potential proliferative effect for tumors in early research, recent research indicated that HBO had a low risk of complications, did not increase growth in tumors, and reduced cancer growth for breast cancer, but not for cervical and bladder cancers.41
The commonality in these metabolic therapies for cancer management is that the combination of metabolic therapies is more effective than any alone. In fact, some therapies alone may not have much of an effect on tumor cells. I used a combination approach with a therapeutic ketogenic diet (with calorie reduction) and antiparasitic medication in a press pulse fashion. A therapeutic ketogenic diet, calorie reduction diet, or intermittent fasting could act as a long-term stressor (a press) on tumor cells and glutamine inhibition could act as an intermittent but concentrated stressor (a pulse) to devastate already weakened cancer cells.42 When I stopped taking the antiparasitic drugs, I continued the ketogenic diet and combined it with daily intermittent fasting, periodic short-term water fasting, and calorie reduction and the results were effective. My cancer antigens levels went down to extremely low levels and a CT-scan nine months later showed no evidence of disease. Metabolic therapy for cancer worked well for me, and others should be informed of these treatment options. Each person’s cancer can present differently, but what is common to all types of cancer is that they have damaged mitochondria. That is why a metabolic approach can be effective across many types of cancer.
References
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