Ketogenic Diet May Mitigate Low Platelet Counts From Chemotherapy, Suggests Mouse Study

A ketogenic diet may mitigate reduced blood platelet counts as a result of chemotherapy, according to a new study published in Science Translational Medicine.

Side effects of cancer treatment

Chemotherapy is an important part of cancer treatment, with chemotherapy drugs aiming to kill fast-growing and cancerous tumor cells. However, these drugs can also affect the healthy cells in our body – for example, in bone marrow, the spongy tissue inside our bones that produce blood cells.

This can cause potentially dangerous side effects, such as reducing a patient’s blood platelets – cells that help our blood clot after injuries – resulting in a condition called chemotherapy-induced thrombocytopenia (CIT). CIT increases the risk of bleeding and often requires chemotherapy to be reduced or even completely stopped, as although an estimated 1 in 10 patients receiving chemotherapy develop CIT, there are currently no approved treatments for the condition.

In the current study, researchers aimed to investigate whether they could tackle CIT through dietary changes. “We found metabolites like glucose alter platelet properties,” explained Dr. Yunlong Yang, deputy head of the Department of Cell and Genetic Medicine at Fudan University and senior author of the study. “This work led us to further investigate whether other metabolites such as ketone bodies affect platelets.”

The study focused on ketogenic diets, which are extremely low in carbohydrates and high in fat. These diets boost a process called ketogenesis, in which the liver produces ketone bodies to use as an energy source. The therapeutic potential of ketogenic diets has also been investigated for conditions such as epilepsy and diabetes.

Ketones for chemotherapy

In their study, the researchers first focused on mouse models to study the effect of ketogenic diets on platelet counts. Over a 21-day period, mice were given either ketogenic diets – in which fat made up 90% of their calories – or a control diet. By the end of the study period, the ketogenic-fed mice had lost body weight and had raised levels of ketones in their blood and significantly elevated platelet counts, while their red and white blood cells were unaffected.

The researchers then investigated whether a ketogenic diet would have a similar effect in mice with CIT. Mouse models of pancreatic and lung cancer were treated with chemotherapy drugs and fed either a ketogenic or control diet. After two weeks, mice fed the control diet developed CIT, whereas mice on the ketogenic diet were resistant to CIT, maintaining platelet counts at levels similar to healthy mice.

Nevertheless, the effects of ketogenic diets on CIT still need to be explored in a way more relevant to patients. Due to a lack of large randomized controlled trials, the researchers conducted a small retrospective study of 28 cancer patients who underwent treatment involving chemotherapy.

Of these patients, 11 reported a “ketogenic lifestyle” (which the authors describe as “low carbohydrate, moderate protein and high fat”), and 17 reported a “conventional dietary lifestyle”. Platelet counts were found to be significantly higher in the ketogenic lifestyle group compared to the conventional diet group, and while two patients in the conventional diet group developed CIT, none developed CIT in the ketogenic lifestyle group.

Importantly, Yunlong Yang expands on the limitations of this study and its findings: “These clinical data are preliminary, and the cohort size was limited. It requires further validation. Of note, the ketogenic lifestyle is not a strict ketogenic diet as we used in volunteers or mouse models.”

More in-depth studies needed

The authors make it important to note the preliminary nature of this data, stating, “the therapeutic potential of the ketogenic diet on CIT requires validation in large-scale prospective clinical trials”.

“Although [there is a] lack of long-term clinical observation results, various clinical case reports showed the safety of the ketogenic diet in patients with cancer. In general, this diet is well-tolerated in cancer patients. However, it requires strong commitment and cooperation from both the patient and his/her family to maintain ketosis for the long term,” Yunlong Yang adds.

Next, the researchers plan to work with clinicians and recruit cancer patients for further clinical studies to determine treatment regimens and assess the safety of using diet to treat CIT.

Reference: Xie S, Jiang C, Wu M, et al. Dietary ketone body–escalated histone acetylation in megakaryocytes alleviates chemotherapy-induced thrombocytopenia. Science Translational Medicine. 2022;14(673):eabn9061. doi: 10.1126/scitranslmed.abn9061

Dr. Yunlong Yang was speaking to Sarah Whelan, Science Writer for Technology Networks.