Researchers at the Cold Spring Harbor Laboratory (CSHL), have discovered that apart from shrinking pancreatic and colorectal tumors, keto-dieting also accelerates a lethal wasting condition called cachexia in mice models with cancer. However, pairing a steroid treatment with the diet may solve this problem.
The keto diet is one of the most popular weight-loss strategies worldwide. Its premise is simple—high-fat, low-carb meals that cause the body to go into a metabolic state known as ketosis. Due to the lack of glucose, the body resorts to burning fat in need of energy, leading to weight loss.
According to scientists, this trick could also help fight various cancers by starving tumors of the glucose they require to grow. However, there is a catch. Reporting in Cell Metabolism, scientists have shown that in mice with pancreatic and colorectal cancer a keto diet speeds up a disease known as cachexia, causing the animals to experience extreme weight loss, fatigue and immune suppression.
“Cachexia results from a wound that doesn’t heal. It’s very common in patients with progressive cancer. They become so weak they can no longer handle anti-cancer treatment. Everyday tasks become Herculean labors,” said Tobias Janowitz, MD, PhD, assistant professor at CSHL and co-author of the study in a press statement.
The study shows that the condition was accelerated in mice due to toxic lipid byproducts of the diet, that help kill the cancer cells by inducing a process called ferroptosis but simultaneously deplete the body of an essential hormone called corticosterone. To make up for this loss, Janowitz and the team had the idea to pair the keto-diet with corticosteroids.
“Healthy mice also lose weight on keto, but their metabolism adapts and they plateau,” Janowitz explained. “Mice with cancer can’t adapt, because they can’t make enough of a hormone called corticosterone that helps regulate keto’s effects. They don’t stop losing weight.”
According to the researchers, combining the corticosteroid treatment with a keto diet prevented cachexia in mice with cancer. Their tumors shrank in size and the mice were shown to have a longer lifespan compared to those on keto-diets who didn´t receive the corticosteroid treatment.
“Cancer is a whole-body disease. It reprograms normal biological processes to help it grow. Because of this reprogramming, mice can’t use the nutrients from a keto diet, and waste away. But with the steroid, they did much better. They lived longer than with any other treatment we tried,” explained Miriam Ferrer, PhD, postdoctoral fellow at CSHL and lead author of the study.
The team is now working on refining the corticosteroid timing and dosage to be used in cancer treatments in combination with the keto-diet.
“We want to push back against cancer even harder, so it grows slower still. If we can broaden this effect, make the treatment more efficient, we can ultimately benefit patients and improve cancer therapeutics,” Janowitz concluded in a press statement.