A ketogenic diet may have potentially serious side effects when used for cancer treatment, although incorporating a specific medication may effectively reverse those side effects, according to a recent study.
Potential Side Effects of the Ketogenic Diet for Cancer Treatment
The principle behind using the ketogenic diet for cancer treatment is that it switches the body’s energy source to ketones from glucose. This metabolic shift aims to deprive cancer cells of their fuel, as they can’t utilize ketones and would have limited access to glucose. However, the actual effects and safety of the ketogenic diet for cancer treatment are still being studied.
A study published in Cell Metabolism in June found that improper implementation of the ketogenic diet during cancer treatment could lead to an earlier onset of cachexia, a wasting syndrome associated with cancer.
The researchers divided mice with cancer into two groups and fed them either a ketogenic diet (high in fat, moderate in protein, and low in carbohydrates) or a standard diet.
The results showed that the ketogenic diet slowed tumor growth compared to a standard diet, demonstrating its anti-cancer effects. In addition to the commonly known mechanism of cancer cell starvation, the researchers provided another explanation: The consumption of fats in the ketogenic diet results in their oxidation, producing lipid peroxides. The accumulation of this substance results in a type of programmed cell death, known as ferroptosis, in cancer cells dependent on iron.
However, the ketogenic diet also has exhibited some severe side effects.
Compared to a standard diet, the ketogenic diet accelerated the onset of cancer cachexia in these mice. The animals experienced a significant reduction in body weight (more than 15 percent) and systemic wasting, and had a shorter lifespan than the cancer-afflicted mice on a standard diet. The median overall survival rate of mice on the ketogenic diet was only 10 days, while it was 14 days for the mice on a standard diet.
Míriam Ferrer, a postdoctoral researcher at Cold Spring Harbor Laboratory, said in a statement that the “first and most striking finding” of the study was that mice fed a ketogenic diet exhibited slower tumor growth and smaller tumors but also experienced an earlier onset of cachexia.
Additionally, while the mice with cancer that were on a ketogenic diet showed a significant increase in ketones in their bodies as compared with those on a standard diet, the magnitude of the increase was much lower as compared with healthy mice following the same diet. This indicates that the tumor inhibited the ketogenic effect, hindering the body’s utilization of ketones.
“Given that our research focuses on cachexia, we wondered whether the potential anti-tumor effects of a ketogenic diet might be overshadowed by the strain it puts on the body,” the study’s lead author Dr. Tobias Janowitz, an assistant professor at Cold Spring Harbor Laboratory and a member of the Northwell Health Cancer Institute, said in the statement.
Understanding Cancer Cachexia: The Wasting Syndrome Associated With Cancer
People’s fear of cancer stems not only from the terror of the tumor itself, but also from the apprehension of enduring the distressing effects of cancer cachexia.
The term “cachexia” originates from the Greek words “kakos” and “hexis,” which mean “bad condition.”
Cancer cachexia—also called wasting syndrome—is a complex metabolic syndrome characterized by loss of skeletal muscle and, in some cases, wasting of adipose tissue. This condition can’t be reversed by simply increasing calorie and protein intake. Unfortunately, the exact mechanisms underlying cancer cachexia aren’t yet fully understood.
“The relationship of cancer leading to cachexia can be thought of as a continued process, like a wound that does not heal,” Dr. Janowitz told The Epoch Times in an interview.
There are multiple factors associated with cancer cachexia. For example, cancer patients may experience appetite loss because of dysgeusia (a taste disorder) and nausea. Tumors and other cells can also release specific substances that induce anorexia. Furthermore, hormonal changes can contribute to a decline in anabolic processes and an increase in catabolic metabolism, ultimately resulting in an imbalance between energy intake and expenditure.
Cancer cachexia can cause various physical and psychological discomforts, including dry mouth, vomiting, diarrhea, inflammation, pain, energy loss, sleep disturbances, fatigue, and anxiety. It can also impact cancer treatment, resulting in reduced anti-tumor efficacy, increased chemotherapy toxicity, and a higher risk of complications from cancer surgery.
Most cancer patients experience cachexia, with up to 80 percent of cases occurring in the advanced stages of the disease. Compared to late-stage cancer patients without cachexia, those with it may experience a 30 percent reduction in survival rate.
Regrettably, there are currently no effective methods to fully reverse cachexia.
Improved Survival With Corticosteroid Medications
However, researchers have identified a potential solution to sustain the ketogenic diet’s anti-cancer effects while preventing the onset of cachexia.
“Healthy mice also lose weight on keto, but their metabolism adapts, and they plateau. Mice with cancer can’t adapt,” Dr. Janowitz said.
This is because of their inability to produce sufficient amounts of corticosterone, a hormone similar to cortisol in humans. Corticosterone is a steroid hormone that plays a role in regulating metabolism during times of stress and helps modulate the effects of ketones.
A substance called NADPH is required for the production of corticosterone. However, in a ketogenic diet, NADPH is heavily used by the body to detoxify lipid peroxides, resulting in a deficiency of this building block.
“The depletion of the building blocks is a side effect of the biochemical processing of the lipids that are part of the ketogenic diet,” Dr. Janowitz said.
The weight of the mice with cancer continued to decline, as they lacked the necessary hormone to regulate metabolism.
Therefore, researchers used a medication called dexamethasone in conjunction with the ketogenic diet, resulting in positive outcomes. The overall survival of the mice with cancer increased from 10 days to 33 days, more than tripling the initial duration.
Dexamethasone administration also extended the survival of the mice with cancer that were on a standard diet, increasing it from 14 days to 19 days. However, their magnitude of improvement was significantly lower than that observed in the mice with cancer that received both the ketogenic diet and dexamethasone.
“But with the steroid, [the mice with cancer] did much better. They lived longer than with any other treatment we tried,” Ms. Ferrer said.
Dexamethasone is a type of corticosteroid commonly used as a supportive treatment for cancer patients undergoing standard therapy. By administering dexamethasone, the body receives supplemental hormones essential for metabolic adaptation.
Meanwhile, the ketogenic diet continued to induce ferroptosis in cancer cells, significantly improving the survival of the mice with cancer.
Additionally, dexamethasone didn’t impact the tumor size and weight of the mice with cancer on the ketogenic diet. In contrast, the mice with cancer on a standard diet combined with dexamethasone experienced a twofold increase in tumor growth at the end of their lifespan.
Future Challenges and Prospects
Researchers are continuing to conduct more preclinical studies. However, Dr. Janowitz believes that it’s “too early to say” when human clinical trials can start.
He said that the upcoming research will face a major question: Why do patients with cachexia experience loss of appetite following weight loss?
“Our study emphasizes the importance of considering the overall effects of an intervention on the entire body rather than solely focusing on tumor growth,” Dr. Janowitz said.
