Abstract
In their natural state within the body, normal cells use cellular respiration as their main source of ATP and energy. Carbohydrate deprived cells easily depend on the resulting ketone bodies for an alternative energy source. This natural evolutionary adaptation to starvation allows for survival of normal cells during times of fasting or famine. Cancer cells in contrast are defective in this respect, lacking the ability to utilize ketone bodies for energy and depend heavily on glycolysis for survival. The pancreas senses increased carbohydrate intake resulting in increased insulin secretion. Normal growth throughout the body depends on insulin, which by itself is also a potent growth factor which binds to cell membrane insulin receptors and stimulates mitosis via signal transduction and DNA synthesis, resulting in less apoptosis or tumor cell death. Consequentially, carbohydrate restriction will increase tumor cell destruction. We are conducting a pilot study to examine the safety and tolerability of the ketogenic diet KD in patients with advanced cancer within the Veteran Affairs Pittsburgh Healthcare System (VAPHS) oncology patient population.
Highlights
In 1956 postulated that cancer is caused by an irreversible damage to cellular respiration, which in turn drives cells to depend on glycolysis as their major source of energy even in oxygen rich conditions
Cancer cells, through the accumulation of mutations and gene rearrangements lost the flexibility to adapt to stress
The ketogenic diet has been in use for decades in the treatment of refractory epilepsy for which it appears to be safe as well as very effective
Summary
A 3-day trial of the diet under detailed individualized guidance of the dietician will occur. Patients who already had baseline scans within 30 days prior to starting the diet did not need a scan. It is best to screen the tumors before diet initiation. The three-day diet trial might significantly influence the PET/CT data. Seyfried et al found in their preliminary trial in the Dominican Republic that the restricted ketogenic diet could change tumor pathology over the short term. If after the trial the patient reports good compliance, a screening PET/CT scan will be obtained as a baseline to document that the tumors are F-18 FluoroDeoxy-Glucose (FDG) avid and serum ketones drawn to show that the body has entered a state of ketosis Serum ketone measurements would need to be obtained before diet initiation, if possible. Refined starches and food with high sugar or starch content will be highly discouraged and food portions will be measured daily in accordance with the dietician’s weekly advice
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