Normally, sugar, fats and proteins flow in strictly regulated ratios in healthy body cells. However, tumor cells upset this balance. “In contrast to normal cells, the tumor cells show an extremely increased uptake of blood sugar,” explains biochemist Barbara Kofler, who University Clinic for Pediatrics and Adolescent Medicine at the University Hospital of Salzburg, in conversation with science.ORF.at. “Normal cells need blood sugar to convert it into energy, whereas tumor cells need it to grow.”
Tumor cells starve
Kofler’s research team therefore set itself the goal of removing the sugar from the system and thus making it more difficult for the tumor cells to grow. “We already know that these cells have little or no ability to metabolize the breakdown products of fats,” says the biochemist. The team therefore investigated in mice how a ketogenic diet affected the growth of tumor cells.
With this special form of nutrition, the carbohydrate intake is reduced to such an extent that the body begins to lack the energy it needs Glucose, but primarily or exclusively from fat. Healthy body cells cope well with this, but the tumor cells starve and get significantly less energy.
Multiple fronts in the fight against tumors
Despite the lack of sugar, growth and cellular respiration in the tumor cells do not stagnate completely. “We know that the cells can still continue to work, albeit to a lesser extent,” says Kofler. In addition to the ketogenic diet, the team added a second facet to the therapy.
The diabetes medication Metformin can block certain components of cellular respiration, which was very useful for the researchers in their experiments. The team compared the effects of different combinations of low-dose chemotherapy, ketogenic diet and metformin in mice that had previously been transplanted with human cancer cells.
A combination of all three components led to the best results. “It is important to emphasize that we would neither offer the ketogenic diet nor metformin as individual therapies against cancer, but only as complementary measures,” said Kofler.
Combination increases survival rate
It was shown that with triple therapy, more mice survived over a longer period of time. At the end of the experiment, 65 or 100 percent of the animals (depending on the type of tumor cell) were still alive, while 0 or 10 percent survived with chemotherapy alone. The dual combination of a ketogenic diet and chemotherapy also had an effect, but improved the therapy to a much lesser extent. The mice treated with it had a survival rate of 40 to 50 percent.
In the mouse experiment, the Salzburg team worked with human cells Neuroblastoma, which are the second most common solid tumors in children. “We have also carried out tests in the area of skin and breast cancer and other research teams are also investigating similar methods,” explains the biochemist. In around three quarters of all studies to date, the combined therapy was able to inhibit the growth of cancer cells.
However, it is currently unclear whether the method actually has an effect on all types of cancer. “There have also been a few studies in which the therapy actually promoted the growth of certain types of cancer,” says Kofler. It is therefore probably necessary to adapt the therapy individually to the respective type of cancer and, in some cases, to the needs of the patients. “So the treatment could also be part of the personalized medicine “says Kofler.
From animal models to clinical applications
“Of course, mice and humans cannot be directly compared,” explains the biochemist. However, she still sees the results of the investigation as “groundbreaking” progress. If you consider that the survival of patients with neuroblastoma has only been increased by a few percentage points over the past ten years, despite many international studies, the results from the mouse experiment are quite promising.
Kofler’s team is currently continuing to work with laboratory animals to clarify the underlying mechanisms in more detail. The aim of the researchers is to also apply the findings in the clinical area. This also requires comprehensive tests on people. If the results are also confirmed in the clinic, then the duration and dose of chemotherapy and thus the occurrence of side effects could be significantly reduced.
Medical assistance advisable
In any case, the biochemist clearly advises against self-experimentation and unsupervised use of metformin. A ketogenic diet should also be accompanied by medical and dietary advice. What patients with cancer can do themselves is to avoid foods that are particularly high in sugar: “Reducing sugar and carbohydrates is always a good idea.”