The effect of a dietary ketone ester on doxorubicin-induced heart failure

Anti-cancer drugs have greatly increased cancer-survival rates over the last few decades. However, some of these drugs, such as doxorubicin, can cause serious side effects in the heart. On average, 1 in 20 patients treated with doxorubicin will develop heart failure and currently there is no effective preventative therapy. The heart needs fuels such as sugar and fat to generate energy for contraction and the use of these fuels becomes perturbed in the doxorubicin-treated hearts. Ketones are an effective fuel source for energy generation but they are usually not available in high enough amounts in the body, unless during prolonged starvation or high-fat low-carbohydrate diet. However, such dietary manipulations are unpalatable, cause serious side effects and therefore long-term compliance is poor. Recently, a novel ketone ester supplement developed by University of Oxford researchers has become available. Consumption of this supplement can increase ketone levels without the need of any dietary interference. In this study, we hypothesise that ketone ester supplements can serve as an alternative fuel to mitigate doxorubicin-induced heart failure. We propose to supplement doxorubicin-treated rats with ketone ester and assess the usage of fuels as well as energy generation in the hearts using advanced imaging techniques.  

This project may lead to a novel prophylactic treatment for patients undergoing doxorubicin chemotherapy to prevent cardiotoxic side-effects. 

This award allows the formation of a new collaboration between Dr Kerstin Timm (non-clinical researcher) and Dr Cher-Rin Chong (clinical researcher) , both from Department of Physiology, Anatomy and Genetics.

Image title: CINE MR images of hearts in maximum systole and diastole from a rat fed with ketone diet compared to one fed with western diet.