KETO FOR CANCER
THE RATIONALE FOR USING KETOGENIC DIETS AS AN ADJUNCTIVE (ADD-ON) CANCER TREATMENT
Ketogenic diets (KD) are very low-carbohydrate, adequate protein, high-fat diets that cause the body to use fat as a primary fuel. There are many different ways to do the diet but each type of KD has the common goals of 1) lowering blood glucose (i.e., blood sugar), 2) lowering insulin and insulin-like growth factor 1 (IGF-1) levels (the chemicals in our bodies that let our cells use blood sugar for energy) and 3) raising ketone bodies (i.e., biochemicals our livers produce from fat that our cells can use for energy in place of blood sugar). By altering the levels of these three substances in the blood, KDs can potentially suppress growth in many types of tumors.
Ketogenic diets have been used for almost 100 years to treat epilepsy. Thus, there is a long history demonstrating that ketogenic diets are safe and feasible. However, they are therapeutic diets that must be followed by professional monitoring. And although, there is a strong and growing body of research that suggests that KDs can suppress tumor growth, especially alongside conventional treatment like chemotherapy and radiation, there is no evidence that KDs can be used in place of standard of care.
How It Potentially Works
The tumor-suppressive effect of KDs is thought to occur through one or more of the following mechanisms:
Scientists have known for almost 90 years that most solid cancers use blood sugar (glucose) as their primary source of energy (Vander Heiden 2009). The German scientist Otto Warburg discovered that tumor cells consume glucose at a much higher rate than normal healthy cells. This has come to be known as the Warburg effect (Poff 2017). The KD decreases available glucose to tumor cells. This in itself might have a therapeutic effect. One of the first human studies to examine a ketogenic diet in the context of cancer (Fine 2012) showed through PET scans that even mild ketosis (~1.5 BHB mml/dl) over the span of a month can significantly reduce glucose uptake (20%) in tumors of advanced cancer patients. Longer and more in-depth studies need to look at whether this decrease in glucose uptake translates into tumor regression. But smaller studies suggest that this relationship between between glucose levels and tumor progression (McGirt 2008; Derr 2009) is may be causal.
The KD increases circulating ketone bodies. In a state of ketosis, ketone bodies are used by almost all normal cells but may not be abled to be used effectively by most cancer cells. A body in ketosis is more metabolically flexible because it is using both glucose and ketone bodies for energy production. While all normal cells can use either glucose or ketones for energy, the Warburg effect present in most cancers shows that cancer cells invariably have defective mitochondria that make them less effective in using the alternative fuel in ketone bodies (Maurer 2011). Another way that ketosis might help is that a body in ketosis is making higher demands of mitochondria for energy production. This makes mitochondria work harder and so may serve to increase the effect of mitochondria's role as the body's housekeeper as it recycles old cellular parts or kills damaged cells. Perhaps potential cancerous cells are more likely to be disposed of in a ketotic environment (Champ and Klement 2014).
Because cancer cells rely on glucose to repair free radical damage, limiting glucose might also limit this reparative ability (Spitz 2000; Seyfried 2014). This suggests that the KD can be especially effective as an adjunctive (add-on) treatment alongside conventional therapies like chemotherapy and radiation. In other words, the KD appears to work best as a way to enhance other cancer treatments.
The KD decreases circulating insulin and IGF-1, both of which are implicated in tumor progression. Insulin and IGF-1 activate several metabolic pathways that are known to promote cancer growth and survival. Lower insulin should lead to an inhibition of these pathways.
The KD appears to increase the sensitivity and susceptibility of cancer cells to chemotherapy and radiation. To quote Colin E. Champ, a radiation oncologist and researcher: "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." See Abdelwahab 2012 and Allen 2013 as examples.
The KD appears to help the body’s immune system fight tumors. Researchers at Harvard University have published a series of papers describing how cancer hides from immune cells (Husain 2013). The natural byproduct of tumors consuming an extremely high amount of glucose is lactate. The high levels of lactate in the tumor environment serve to hide the tumor from the body’s immune system. A KD lowers glucose metabolism and thus lowers the amount of lactate being produced by the tumor. This in turn allows for the immune cells to “see” the tumor better.
Lastly, some researchers speculate that ketones themselves might have some anti-cancer effect that is yet unknown. This hypothesis is currently being studied. In a recent study, researchers showed that ketone supplementation can reduce cancer growth even in the presence of high glucose (Poff et al 2014). This suggests that the ketones have an independent anticancer effect.
How to Determine if Keto is Right for You
This is a very personal and complex question that relates to one's diagnosis, stage in treatment, family culture, and more. The diet is proven to be safe and effective for a number of neurological conditions but it is a big change for those accustomed to a high-carbohydrate, standard American diet. It's definitely possible to achieve a wonderful quality of life, that will only be enhanced by the diet's benefits to the body and brain, but if it incurs too much stress in the home it may not be the right fit for the family. A ketogenic diet approach has the highest potential of success for those cases in favorable home environments facing active disease in the form of solid tumors, especially during the time of radiation and chemotherapy. For many others, including those in survivorship and fighting blood cancers, a low-carbohydrate and higher fat approach is a significant and helpful change that does not require a strict ketogenic approach.
The best way to determine if the ketogenic diet is right for your child is to 1) read our full introductory guide, downloadable below; 2) read our research review, accessible below; 3) consult a ketogenic nutritionist, listed below; and discuss with your oncology team.
Our friends at The Charlie Foundation explain the process of ketosis.
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