Could a Low-Carb Diet be a Form of Cancer Therapy?

In 1920, German physiologist Otto Warburg discovered that the rate of glucose consumption and lactate production dramatically increased within tumor cells (Liberti & Locasale, 2016). Furthermore, Warburg also discovered that tumor cells favorably undergo aerobic glycolysis as the main pathway of producing ATP. This metabolic phenomenon within cancer cells is now recognized as the Warburg Effect and could be the answer to a new form of cancer therapy.

Glucose is the central macronutrient that can be formed into ATP. The metabolism of glucose is essential for supporting mammalian life. However, tumor cells metabolize glucose in a different fashion compared to other cells. As mentioned before, tumor cells dramatically increase their use of glucose and favorably undergo aerobic glycolysis – as opposed to performing oxidative phosphorylation. This phenomenon occurs even in the presence of oxygen and fully functioning mitochondria (Liberti & Locasale, 2016). Furthermore, tumor cells cannot metabolize fatty acids or amino acids due to mitochondrial and electron transport chain defects (Tan-Shalaby, 2017). Therefore, metabolism of glucose is the only way in which tumors can obtain energy and proliferate.

By understanding the way in which tumors use energy to proliferate, it becomes possible to create effective cancer therapies. One possible form of cancer therapy is the consumption of a low-carbohydrate diet. By reducing or even cutting out all forms of carbohydrates within the diet, it might be possible to starve and stop the growth of the tumor cells due to their dependence of aerobic glycolysis. While this makes sense in theory, clinical evidence has not supported the claim yet. As of 2016, there have only been 13 active clinical trials that have investigated the link between low-carbohydrate diets and cancer (Osher). However, pre-clinical trials have produced promising results. For example, treatment of glioblastoma was enhanced within mouse models when the mice were fed a ketogenic diet (Osher). In addition, mice that were fed a ketogenetic diet had prolonged survival and decreased tumor growth (Osher). As such, continued clinical research is necessary and beneficial as decreased consumption of carbohydrates could be a promising form of cancer therapy.

Figure 1. Schematic representation of the differences between oxidative phosphorylation, anaerobic

glycolysis, and aerobic glycolysis. Adapted from (Heiden, Cantley, & Thompson, 2009).

References:

Heiden, M. G. V., Cantley, L. C., & Thompson, C. B. (2009). Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation. Science, 324(5930), 1029–1033.

Liberti, M. V., & Locasale, J. W. (2016). The Warburg Effect: How Does it Benefit Cancer Cells? Trends in Biochemical Sciences, 41(3), 211–218.

Osher Center for Integrative Medicine. Low Carbohydrate Diet. Retrieved from https://osher.ucsf.edu/patient-care/integrative-medicine-resources/cancer-and-nutrition/faq/low-carbohydrate-diet.

Tan-Shalaby J. (2017). Ketogenic Diets and Cancer: Emerging Evidence. Federal practitioner : for the health care professionals of the VA, DoD, and PHS, 34(Suppl 1), 37S–42S.