October 7, 2023
By Angie N Choi, EdD, Author of Whole New Me: Healing From Cancer in Body, Mind, and Spirit
A promising approach in cancer treatment has emerged in recent years called metabolic cancer treatment. This innovative approach focuses on exploiting metabolic weaknesses that cancer cells exhibit. Metabolic cancer treatments focus on altering the metabolism of cancer cells to treat tumors. This innovative therapy aims to disrupt aberrant metabolic processes within cancer cells, providing a promising approach for treating malignancies. Metabolism in the human body refers to biochemical processes at the cellular level that convert food into energy, and metabolic cancer treatments obstruct and target processes that cancer cells use to produce energy. A metabolic approach deprives cancer cells of the nutrients and energy they need to survive, which creates the conditions for their demise. Metabolic cancer treatment aims to disrupt altered metabolic pathways present in cancer cells while not harming healthy normal cells. Unlike conventional treatments (chemotherapy and radiation), that broadly affect both cancerous and healthy cells, metabolic cancer treatments are more precise, targeted, and non-toxic.
The Role of Nutrition in Metabolism
Before continuing with metabolic cancer treatments though, a brief review of how the body produces energy from food may be helpful. When food is eaten, it is broken down and turned into energy for the body to use through a complex series of steps.1 First food is chewed and broken down into smaller pieces (boluses) with the help of enzymes in saliva. When partially digested food enters the stomach, digestive enzymes and stomach acid assist in further breaking down food. From there, this digested food, known as chyme, enters the small intestine where the majority of digestion and absorption of nutrients happens. The pancreas releases digestive enzymes and the liver discharges bile to further assimilate macronutrients (carbohydrates, proteins, and fats) into their molecular components (glucose from carbs, amino acids from proteins, and fatty acids from fats). Within the small intestine, these nutrients are then absorbed into the bloodstream where they are carried to various cells and tissues throughout the body.2 Food is no longer the salad, rice, and salmon consumed during lunch but now glucose, amino acids, and fatty acids. In order to produce energy from these nutrient molecules, a process called cellular respiration takes place in the cytoplasm (fluid substance that fills cells and is enclosed by the cell membrane) and mitochondria (power plants) in our cells. Cellular respiration is a series of enzymatic reactions that results in ATP (adenosine triphosphate) production, which is the energy available for cellular processes in the body.3
How Cancer Cells Differ from Healthy Cells in Metabolism
What is unique about cancer cells and energy production is that instead of continuing down efficient metabolic pathways of cellular respiration like healthy cells, cancerous cells choose a fermentation process to produce energy.4 The first stage of breaking down glucose into energy is called glycolysis where a molecule of glucose is broken down into two molecules of pyruvate. From there, the metabolic process continues to the second (citric acid or Krebs cycle) and third (electron transport chain) steps of cellular respiration. These three steps of cellular respiration produce ATP (energy)in an efficient manner.
In cancer cells, metabolism at the first stage of glycolysis behaves differently where pyruvate (the end product of glycolysis) is turned into lactate through a process called lactic acid fermentation.5 This conversion from pyruvate to lactate typically occurs in low oxygen (anaerobic) environments, however, cancer cells produce lactate through fermentation even in the presence of abundant oxygen. This process, called aerobic glycolysis, was first noticed by Otto Warburg, a German biochemist in the 1920s.4
Lactic acid fermentation is an inefficient way to produce energy compared to cellular respiration pathways so why do cancer cells behave in this abnormal manner when they require enormous amounts of energy to fuel their growth? Why do cancer cells choose such an inefficient way to create energy when they demand much more energy than healthy cells? It is because they have damaged mitochondria and cannot continue the metabolic steps (2nd and 3rd steps) in cellular respiration that occur within the mitochondria. Although cancer cells use inefficient pathways to produce energy, they are still able to generate enormous amounts of energy for their growth by increasing the rate of glycolysis (greater amounts of pyruvate to lactate). If cancer cells could use an energy-efficient route they would but they can’t. It is as if cancer cells say,” we can’t work smarter (waste less energy), so we’ll work faster and harder”.
Ketogenic Diet as Metabolic Cancer Treatment
Metabolic cancer treatments focus on cutting off cancer cells’ main fuel, glucose (carbohydrates), primarily through therapeutic ketogenic diets, calorie-reduction diets, fasting-mimicking diets, and fasting or some combination of any or all.4,6,7 I wrote an article sharing my success story with a therapeutic ketogenic diet for those who want more information. When carbohydrates are restricted in the diet, the body burns glucose stores in the liver (glycogen) and switches over to using ketones instead of glucose for energy. The same metabolic shift occurs when fasting because there is no food intake at all. Healthy cells are flexible and able to make this metabolic shift to utilize ketones for energy, but cancer cells cannot, thus exposing a significant vulnerability to exploit. When cancer cells are unable to produce enough energy to sustain their rapid growth, they become sensitive to death signals (apoptosis), the blood network (vasculature) that provides nutrients breaks down, proliferation (metastasis) stops, and tumors shrink. Fasting, though effective, may not be appropriate for all cancer patients long-term, but a therapeutic ketogenic diet would provide sufficient nutrients to strengthen the body while essentially putting cancer cells under great stress by depriving nutrients. Additionally, this non-toxic diet does not come with severe side effects that the standard of care (surgery, radiation, and chemotherapy) often comes with, particularly in advanced stages of cancer.
Glutamine, Cancer’s Compensatory Fuel
Although cancer cells’ preferred fuel source is glucose, they can also use glutamine, an amino acid (derived from protein) as a secondary, compensatory fuel that can be converted into energy through fermentation.4 This is another reason why a ketogenic diet is an appropriate strategy in the management of cancer. A therapeutic ketogenic diet is high in fat, moderate in protein, and low in carbohydrates. On this diet, cancer cells are being deprived of glucose and only getting moderate amounts of glutamine, a simultaneous combination that would limit cancer cells’ energy production.8 Combining low-calorie ketogenic diets with drugs that limit glutamine also has produced a synergistic effect in tumor reduction in mouse studies.9
Other Metabolic Cancer Treatments
Besides diet, some research in animal studies has indicated that hyperbaric oxygen therapy (HBOT) may also be another non-dietary metabolic treatment for cancer, and perhaps more effective in combination with dietary strategies.10,11 See my article on metabolic therapies for more information on HBOT. Other promising developments in metabolic cancer treatment include medications like metformin used to treat type 2 diabetes. Metformin can disrupt the proliferative signaling that leads to cancer progression, promote cellular death that cancer cells evade, and modulate immune cells in the tumor microenvironment for increased immunity against cancer.12-14 Targeted therapies that focus on specific metabolic pathways also have potential for cancer treatment. For example, researchers are exploring drugs that inhibit glycolysis and the enzyme glutaminase involved in amino acid metabolism.15,16
The future of metabolic cancer treatment is promising and backed by scientific studies supporting the premise that cancer is a metabolic disease.4 Metabolic cancer treatment that is non-toxic, protective of healthy cells, and harmful to cancer cells is gaining greater momentum. The metabolic inflexibility of cancer cells allows researchers to exploit this vulnerability. While significant progress has been made, there is much work to be done before metabolic treatments are offered in clinical settings. Until metabolic treatments become standard clinical practice, cancer patients should be informed of these complementary approaches.
References
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