Veronique Chachay, The University of Queensland
The gold standard treatment for cancer in the last few decades has been a combination of surgery – to remove tumours – and chemotherapy and radiotherapy – to kill cancer cells. With the progress of personalised medicine, where identifying specific mutations in the tumour guides treatment selection, there has been increasing success in survival rates.
But there has been little improvement in reducing side effects on healthy cells caused by chemotherapy, which also limit the dosage that can be administered.
Over the last two decades, research in animals has shown restricting calories – with alternating periods of fasting and feeding – promotes protection mechanisms for healthy cells, while increasing white blood cells that kill cancer cells.
A 2008 study showed mice with neuroblastoma, a common childhood cancer, that had only water for two days before receiving a large dose of chemotherapy, experienced less or no side effects compared to mice fed normally. In another study, tumour cells were killed more efficiently in mice who weren’t fed than in those that were.
Since then, further animal studies and early trials in humans confirmed short-term fasting prior to, and after, chemotherapy treatment reduced side effects. It also protected healthy cells from the toxicity of the drug, while killing cancerous ones.
So does this mean we can use fasting to help with cancer treatment?
Glucose and cancer
Cancerous cells are known to rely on glucose, a type of sugar, for their energy metabolism, rapid growth, and resistance to chemotherapy.
That cancer cells thrive on glucose was first shown by German physiologist Otto Warburg in the 1950s. He also showed they were unable to use fatty acids as efficiently for energy, or at all. This idea of cancer being a disease reliant on rapid glucose metabolism, has reemerged recently.
Under total fasting conditions, where someone only has water, the body initially uses carbohydrate stores, called glycogen, to maintain blood glucose levels, and for cellular energy production. When these stores are depleted, protein from muscle is used to produce new glucose, and fat stores start to be used for energy production.
Body cells that would normally use glucose as their main energy source have the ability to gradually switch to a different fuel: a product of fat metabolism called ketone bodies. This is to spare muscle mass so it is not used too much to make new glucose.
Cancer cells are unable to use ketone bodies efficiently, because the mechanism that would convert ketone bodies to energy does not function well in cancer cells. So under low blood glucose conditions, cancer cells are in effect being starved, becoming more vulnerable to chemotherapy.
Healthy cells on the other hand, can use ketone bodies for energy. They are also protected from chemotherapy side effects because fasting stimulates the expression of genes that promote cellular clean-up and defence systems, called autophagy. This means larger doses of the drug can be administered to better kill cancer cells.
In a case report of ten patients, those who fasted between two and six days prior to, and between five hours and two and a half days after, chemotherapy reported greater tolerance to treatment and less fatigue and weakness. They also reported less gastrointestinal symptoms, such as vomiting and diarrhoea. Fasting didn’t impair the impact of treatment.
But fasting to aid cancer treatment is a difficult balancing act, because malnutrition is a significant problem for many with specific cancers such as head and neck, pancreatic, colon and lung cancers.
Malnutrition in cancer patients is estimated to be as high as 88% depending on the stage of the cancer. This is due to a number of factors, including appetite loss as the disease progresses, side effects of treatment, and cancer’s increased demands on metabolism.
Malnutrition and related weight loss are associated with lower survival rates. Further, the side effects of chemotherapy, which may include severe nausea, vomiting and diarrhoea increase the risk of malnutrition and related weight loss.
So practice guidelines recommend patients receive enough energy and protein to counter weight loss. For head and neck cancer patients, for instance, the aim is to have 1.2 to 1.4 grams of protein per kilogram of body weight per day, which is higher than what’s recommended for an average healthy adult male.
But clinical trials are underway that investigate various fasting protocols, including something called the fasting mimicking diet. This protocol addresses the difficulty of hunger discomfort experienced by patients who fast with water only.
The fasting mimicking diet is a seven-day fasting protocol tailored around chemotherapy treatment. It ensures the provision of micronutrients (vitamins and minerals), while significantly reducing the energy intake, in particular from carbohydrates (which become glucose once absorbed) and protein. Patients return to a normal diet after the seven days, thus limiting the impact on weight loss and malnutrition over time.
Less may be more when it comes to dealing with certain cancer cells. Suppressing the specific energy supply that uses an inborn protective mechanism in human physiology to prevent cancer development deserves close investigation.
[hr] Veronique Chachay, Research & Teaching Academic, The University of Queensland