An Introduction: A Ketogenic Diet for Cancer
Caveman Doctor often discusses ketogenic diets in his posts and podcasts (whatever a podcast is). However, he frequently gets questions regarding a ketogenic diet as well as those asking for a simple description. Therefore, he set out to explain a ketogenic diet and cancer in less than 1,000 words.
A Ketogenic Diet for Cancer: In Fewer than 1,000 Words:
A ketogenic diet is one in which carbohydrates, and to a lesser extent, protein are restricted in the diet and replaced with fat. This treatment has been effective for seizure control in epileptic children for over a century1 and more recently for the treatment of obesity-related disorders.2 It may also provide a benefit in cancer subtypes with outcomes closely related to obesity and metabolic risk factors, such as breast cancer.3 It generally implements a ratio of 4:1 fat to protein and carbohydrates. However, many people will reach significant ketosis when their carbohydrates are limited to less than 50g per day, and others at around 20-30g.
What are Ketones?
Ketones are energy sources produced by our liver that can freely cross our blood brain barrier to provide a source of energy for our neurons (brain cells). These ketones replace glucose when it is not available, such as during fasting, during the winter months in traditional societies, and all the time in modern hunter-gatherer societies like the Inuit Eskimos or Maasai tribesmen, who consume very little carbohydrate sources.4 Frankly, many readers of this blog likely have a significant amount of ketones floating around in their blood some mornings, and the low-carb followers even more often.
How Can a Ketogenic Diet Help Cancer Treatment?
Much like most things in cancer, including chemotherapy, biologic agents, and even radiation therapy, we do not quite know exactly how a ketogenic diet works. However, there are several potential mechanisms:
- First and foremost a ketogenic diet may work simply through decreasing available glucose to tumor cells. Many decades ago, Otto Warburg stated that a hallmark of cancer was the uptake of glucose by cancer cells.5 Cancer cells rely on glucose for energy; therefore any method of limiting this may help to “starve” cancer cells. Recent data from several universities, including Johns Hopkins have shown that in brain tumors, the higher a patient’s blood glucose level, the lower their survival.6,7
- Other data has shown that this occurs due to deficient and defective mitochondria. Since mitochondria can create energy from proteins and fats, this deficiency leaves cancer cells reliant on glycolysis, or the breakdown of sugar, for energy. Interestingly, our cells use this process as well, especially when oxygen is not available. This is what occurs in muscle cells during sprinting or lifting heavy weights. Lactic acid is released, resulting in a burning sensation within the muscles. Cancer cells, on the other hand, appear to use glycolysis for energy regardless of whether oxygen is present or not. This process is very inefficient for energy production, and mitochondria can create around 20 times more ATP than the process of glycolysis. A ketogenic diet allows the body to rely on the mitochondria for energy. Lastly, mitochondria are the organelles within our cells that can recycle old parts or kill cells that appear to be malfunctioning, or in other words mitochondria are used to kill cells in our body that may turn malignant. Upregulating the mitochondria may serve as a way to increase our body’s housekeeping processes that can eliminate potential cancerous cells. Also, while our normal cells can use ketones for energy, data shows that cancer cells are unable to effectively derive energy from ketones.8
- Due to their faulty mitochondria, cancer cells also rely on glucose to fix free radical damage.9-13 Much like our normal cells, cancer cells are constantly experiencing bombardment with free radicals, and maybe even more so than our cells. Since their mitochondria do not function properly, they rely on even more uptake of glucose, which is used to counter free radical damage. Limiting this glucose will inhibit their cell damage repair.
- Cancer cells require more than just fuel to survive, much like our normal cells, they use signaling hormones that tell them to grow and survive. Cancer cells have receptors on them, like the insulin growth factor receptor (IGF-1R). Insulin growth factor (IGF) can bind to this, as can insulin, which is secreted in our bloodstream in response to carbohydrate consumption. Insulin then activates several pathways that increase cancer growth and survival. A recent study in advanced cancer patients confirmed the ability of a ketogenic diet to significantly decrease the insulin pathway in tumor cells.14 Another pathway that has received much attention is the AMP-K pathway. When upregulated, it inhibits several pathways that are activated by insulin. Studies in humans have shown that the diabetes drug Metformin can activate AMP-K, as can intense exercise and carbohydrate restriction.15 In fact, there are now trials supplying breast cancer patients with metformin as part of their treatment. Therefore, minimizing the pathways that lead to cancer growth and activating those that limit it is another potential mechanism by which a ketogenic diet works.
- Finally, several of the pathways listed above can decrease chemotherapy and radiation sensitivity of cancer cells, or in other words, make cells more resistant to these treatments. There are the same pathways that can be induced by intermittent fasting, to turn on autophagy. Activation of the insulin receptor and several pathways downstream within cancer cells allows them to more readily fix damage from chemotherapy and radiation. However, keep in mind that radiation therapy works mostly by interacting with the water molecules in and around cancer cells to create free radicals that attack the cancer cells, causing DNA damage. Restricting glucose through a ketogenic diet may take advantage of this inability to counter damage from free radicals, making radiation more effective. A study in mice has shown that radiation therapy efficacy is significantly increased in the face of a ketogenic diet when treating brain tumors.16
- Last but not least, some people have hypothesized that ketones themselves may fight cancer. This is more speculative with little data, but reports on many societies, most notably those in Africa17 and the Inuit Eskimos reveal few cases of cancer. Dr. Urquhart served as the district surgeon of the far north, and in 7 years with all the x-rays and surgical equipment of his day, has published that he never say a single case of cancer, and this was in people of all ages.18
In the next decade, the power of diet, exercise, and specifically ketogenic diets in the prevention and treatment of cancer may take a front seat within the field of oncology. A ketogenic diet is just one of many nutritional and lifestyle interventions that may prove valuable in the fight against cancer. Further studies must assess this potential.
P.S. I went over by about 45 words.
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