Cancer is defined as uncontrolled cellular growth and can arise and spread to any part of the body. After multiple cells grow unrestrictedly, they can form lumps of cells that create tumors. The most common types of tumors are breast, lung, and prostate cancer. All cancers, however, result in alterations in metabolism.
It has been estimated that in 2020, 1.8 million people will be diagnosed with cancer, and about half of them will die from their disease. It has been a long-standing and accepted notion that cancer cells have an increased affinity for using glucose as a fuel source and rely heavily on the inefficient energy process known as anaerobic glycolysis in order to proliferate and survive.
Alterations in metabolism during cancer
In the 1900s, Noble laureate Otto Warburg was the first to discover the observed alteration in glucose metabolism within cancer cells. Dubbed as the Warburg effect, he noted this increased rate of fuel, or glucose, going to the mitochondria of cancer cells. This could be the reason for the rapid growth and proliferation seen within cancer cells. He also observed that when glucose supply is limited or restricted to the tumor cells; the normal unrestricted growth normally seen in cancer cells is halted.
The impact of cancer on the body can be devastating, especially in regard to alterations in metabolism which can lead to severe weight loss from an inefficient use of energy. This is most commonly seen in the discerned change in metabolism as mentioned above, using anaerobic glycolysis. Under normal conditions, the human body uses aerobic glycolysis, which is, put simply, the process of creating energy (ATP) from glucose (a sugar) in the presence of oxygen. Aerobic glycolysis results in changing one mole of glucose into 36 moles of ATP. In comparison for anaerobic glycolysis, one mole of glucose produces 2 moles of ATP. You can see, it is a very inept process of creating energy.
Where diet fits into the treatment plan
As promising as certain new treatments seem, there is still much to do to make an impactful change in cancer survivorship. Cancer is quite complex and can be described as a tree – where each branch is a different way to target its growth and hinder it. Diet can be one of those branches and can be a very effective tool to use to leverage cancer treatment and increase one’s chances of survivorship and increased quality of life, even throughout vigorous cancer treatments. There is a plethora of [mis]information out there on which diet one should consider to ameliorate cancer treatment. From veganism to the alkaline diet, to Gerson therapy, it’s hard to know what diet is best for cancer.
How about the keto diet?
Despite it being around for over one hundred years, the ketogenic (keto) diet has only recently gained a lot of traction in the world of oncology and research. The diet is classified as having a high proportion of calories coming from fat with a low number of calories coming from carbohydrates in order to mimic a state of fasting. During a fasted state when there is a low energy supply coming in, the body switches its metabolism from using glucose as its primary fuel source to adipocytes (fat cells) to create ketone bodies, which can be used as an alternative fuel source. Having high amounts of ketones and low amounts of blood glucose indicates a metabolic state of ketosis, which is the main aim of following this diet.
There are different types of ways that one could get into ketosis, thus there are variations of the ketogenic diet. The diet can be defined by a ratio, from 4:1 down to 1:1 to indicate the number of grams of fats eaten to the number of grams of carbohydrates and proteins combined. There is another type of ketogenic diet that utilizes the glycemic index of foods to determine what one eats in one day (Low Glycemic Index Treatment). There is also the Medium Chain Triglyceride (MCT) oil diet, which allows for a little more carbs to be eaten as MCT oil does not require breakdown for absorption and goes straight to the portal vein to create ketone bodies. 1
When determining if you should or what type of ketogenic diet to follow during treatment, there are many things to consider. Everyone’s individual metabolisms of fats and glucose differ, especially with cancer, as some cancer diagnoses have an increased reliance on and utilize a large amount of glucose to survive. This includes lung cancer, gastric cancer, esophageal cancer, and bone marrow transplant patients. With these cancers, weight loss is more rapid and more common and typically leads to muscle wasting, which can be dangerous and does not lead to better outcomes. There are other existing co-morbidities such as cardiovascular disease, altered liver function, altered kidney function, low physical function, and low social support, which are not conducive for following the diet. Additionally, some glucocorticoids, or steroids, that are used with treatment can lead to hyperglycemia (high blood sugars) and may benefit from a higher ratio of a ketogenic diet (i.e., 3:1) in order to ensure ketosis is achieved and maintained. Not to mention, if one is experiencing treatment-related side effects, a higher ratio of fats eaten may not be feasible depending on what is going on.
Keto for reducing tumor growth
There are several preclinical studies and a handful of clinical studies that support the use of a ketogenic diet to halt tumor growth and change the tumor microenvironment to make it less favorable for cancer to grow.
As stated above, most malignant cells thrive off glucose consumption to continue their aberrant growth. With the ketogenic diet, there is a distinct decrease in glucose coming in from the diet, thus reducing the amount of glucose available to the tumor cells. In cancer, there is a dysregulation of hormones called insulin-like-growth factor 1, or IGF-1 and 2, which can lead to the overgrowth of tumor cells to engender hyperproliferation. With the lower glucose coming from carbohydrates, there is less insulin signaling and therefore less IGF-1 that gets created, thus less growth. It has also been shown that ketone bodies such as beta-hydroxybutyrate (BHB) have an inverse relationship with IGF-1, meaning, as BHB levels increase, IGF-1 decreases.
Preclinical studies have shown that the diet can act as a sensitizing agent during chemotherapy and radiation, making cancer treatments more effective in killing the malignant cells and sparing normal cells. This change is mediated by less vascularization, or blood flow, and increased autophagy (The body’s way of getting rid of damaged cells) triggered by cellular stress brought on by the metabolic switch and could potentiate oxidative stress. Tumor suppressor gene p53 is one of the most commonly mutated genes seen in cancer, especially glioblastoma. This gene helps to regulate blood vessel growth or angiogenesis, apoptosis or programmed cell death, and cellular metabolism, including gluconeogenesis, or the making of new glucose from byproducts of metabolism. This gene is specifically sensitive to glucose deprivation. Mutated p53 genes in cancer cells are another way the ketogenic diet could regulate cancer growth and halt it.
It is important to note that most of the compelling evidence reported comes from animal studies and case series/reports in humans, or phase 1 tolerability/feasibility clinical trials. There have been very few randomized controlled trials in humans, which are considered the gold standard of research. The strongest evidence to date to support the ketogenic diet and cancer is with glioblastoma, a brain tumor. A highly vascular disease, the decrease in glucose coming in through diet and nutrition can help in a variety of ways as shown above.
Keto for reducing cancer cachexia and preserving lean body mass
One of the main side effects seen with cancer treatment that coincides with the ketogenic diet is weight loss. Weight loss happens when following a ketogenic diet due to the mobilization of glycogen stores. Glycogen is a branched molecule made up of glucose, which is stored in the liver and muscles that we access in times of fasting. Each gram of glycogen has at least 3 grams of water bonded to it. Thus, when implementing the diet, most people lose a significant amount of water weight. And, there is the potential to continue to lose weight, especially when paired with cancer-directed treatment. Cancer cachexia is most commonly defined as a metabolic abnormality that leads to muscle wasting and weight loss and can increase one’s morbidity and mortality significantly.
Although there are only a few studies out there that specifically look at body composition, not just weight loss and the ketogenic diet during cancer treatment, those that are available are very promising. The KETOCOMP study used bioelectric impedance to demonstrate the opposite of what most would assume would happen to rectal, head and neck, and breast cancer patients while following a ketogenic diet during radiation therapy. These patients showed an increase in body weight, fat-free mass, and skeletal muscle mass while undergoing radiation therapy. Another study explains how ketone bodies are protein sparing by attenuating a nitrogen balance, reducing proteolysis, and promoting more skeletal protein anabolism rather than catabolism to prevent cachexia. In an in vitro study using pancreatic cancer cells, there were significant decreases in proteins that are associated with cancer-related cachexia when they were exposed to ketone bodies such as beta-hydroxybutyrate.
Keto on Quality of life
There are a number of studies that show when cancer patients follow a ketogenic diet, they experience an increase in their quality of life. In one study with advanced cancer patients who were on chemotherapy, three-quarters of the patients who completed the study reported better sleep quality and better emotionality. Another study showed 80 breast cancer patients reporting a better physical activity and global quality of life score after 6 weeks of following a ketogenic diet. In a randomized controlled trial comparing the ketogenic diet and the American Cancer Society diet in women with ovarian/endometrial cancer showed that those women who followed the ketogenic diet improved their physical function, had better energy levels, and fewer food cravings for unhealthy foods (such as fast and processed foods), implying an increase in their quality of life. Anecdotally in my own practice, I have seen patients get through their cancer treatments better compared to those who do not follow a ketogenic diet. This is characterized by better energy, maintaining their fitness and physical activity as well as less symptomology.
The right kind of Ketogenic Diet for cancer
The ketogenic diet has been popularized by mass media in the last few years, and the information that gets disseminated is neither accurate nor healthy. The Atkins Diet, a low carb, but high protein and high-fat diet, has been rebranded as being “keto.” Contrary to popular belief, this type of ketogenic diet is not supported by research to be considered an effective adjunct to cancer treatment. This is mainly because high protein intake leads to a large amount of circulating amino acids after breakdown. Amino acids can easily enter the tricarboxylic acid (TCA) cycle and be used during gluconeogenesis to make more glucose. Additionally, another trend that has arisen from social media is “dirty” or “lazy” keto. This is when people replace one highly processed food, for another lower-carb processed food. For example, low-carb chips, bacon, hot dogs, deli meats, cheese, pork rinds, and fast foods are staples of this kind of keto diet. The whole mindset behind dirty or lazy keto is “if it fits within your macros, you can eat it.” This diet is full of foods that are very high in saturated (and trans) fats, nitrates, high amounts of omega-6 fatty acids, and preservatives. This way of keto is not conducive to health, and in fact, could be harmful to one’s health.
When it comes to keto for cancer, it is really important to have a well-planned diet to avoid nutrient deficiencies and to optimize one’s well-being to get the maximum health benefit. This includes getting the majority of your fats from plants or omega-3 fatty acids, include a plethora of non-starchy vegetables, and have adequate amounts of lean proteins. Omega-3 fatty acids can reduce inflammation (especially cerebral edema), they are heart-healthy and cardio-protective and can help protect against and help mitigate symptoms arising from neurodegeneration and cognitive decline. The best sources of omega-3 fatty acids are cold-water fatty fish (like salmon, mackerel, and sardines), olives and olive oil, avocado and avocado oil, nuts, and seeds such as walnuts, chia/flax/hemp seeds, and fortified products like eggs. Having a variety of low carbohydrate, non-starchy vegetables like greens, cucumbers, asparagus, mushrooms, cauliflower, celery, and eggplant, provides essential vitamins and minerals as well as phytonutrients known to be cancer fighters. Because the diet lacks major food groups, it is essential to work with a Registered Dietitian or trained health professional that is well versed and trained in the ketogenic diet (or ketogenic metabolic therapy) to prevent nutrient deficiencies such as fiber, folate, selenium, zinc, calcium, Vitamin D, B vitamins and probiotics.
The bottom line
There are many potential benefits that one can reap from following a well-planned and well-executed ketogenic diet in the context of cancer. It can help reduce inflammation, reduce the amount of circulating blood glucose going to tumor cells, reduce building blocks for growth such as IGF-1, decrease the amount of blood flow going to tumors, and increase one’s quality of life. However, as with any type of adjunctive cancer treatment, it is imperative to talk to your oncology team before starting this diet by yourself.
Written by: LJ Amaral MS, RD, CSO; Reviewed by Dr. Dominic D`Agostino
L.J. Amaral, M.S., R.D., CSO, is a registered dietitian who is board certified in oncology nutrition. Amaral attended the University of Connecticut where she obtained a Bachelor of Science in Nutritional Science and went on to get her Master of Science in Clinical Nutrition and Dietetics from NYU while subsequently completing her internship to become a registered dietitian at Memorial Sloan Kettering Cancer Center in Manhattan. She is currently located in the outpatient cancer center at Cedars-Sinai in Los Angeles, CA as a clinical and research Dietitian, and is researching the efficacy of the Ketogenic Diet as a therapy for CNS malignancies. Amaral specializes in cancer nutrition during treatment, for survivorship, for cancer prevention, specifically, in therapeutic Ketogenic diets and oncology nutrition research.