Abstract
Cancer cells express an abnormal metabolism characterized by increased glucose consumption due to genetic mutations and mitochondrial dysfunction. Previous studies indicate that unlike healthy tissues, cancer cells are unable to effectively utilize ketone bodies for energy. Furthermore, ketones inhibit the proliferation and viability of cultured tumor cells. As the Warburg effect is especially prominent in metastatic cells, we hypothesized that dietary ketone supplementation would inhibit metastatic cancer progression in vivo. Proliferation and viability were measured in the highly metastatic VM-M3 cells cultured in the presence and absence of β-hydroxybutyrate (βHB). Adult male inbred VM mice were implanted subcutaneously with firefly-luciferase tagged syngeneic VM-M3 cells. Mice were fed a standard diet supplemented with either 1,3-butanediol (BD) or a ketone ester (KE), which are metabolized to the ketone bodies β-hydroxybutyrate (βHB) and acetoacetate (AcAC). Tumor growth was monitored by in vivo bioluminescent imaging. Survival time, tumor growth rate, blood glucose, blood βHB, and body weight were measured throughout the survival study. Ketone supplementation decreased proliferation and viability of the VM-M3 cells grown in vitro, even in the presence of high glucose. Dietary ketone supplementation with BD and KE prolonged survival in VM-M3 mice with systemic metastatic cancer by 51% and 69%, respectively (p<0.05). ketone="" administration="" elicited="" anti-cancer="" effects="" in="" vitro="" and="" vivo="" independent="" of="" glucose="" levels="" or="" calorie="" restriction="" the="" use="" supplemental="" precursors="" as="" a="" cancer="" treatment="" should="" be="" further="" investigated="" animal="" models="" to="" determine="" potential="" for="" future="" clinical="" p="">
Alex's notes: Interesting for sure. I am not well versed in the ketone literature, but what I found interesting was that the effects of supplementation were preserved in a high glucose environment. The reason this sticks out to me is that many individuals (myself included) cannot be on a ketogenic diet, be it for athletic performance in a high-glycotic sport or simple dietary adherence. There is an easy solution to this, and its name is medium-chained triglycerides. These fats are abundant in coconut oil (67%) and also easy to buy at your local supplement shop, and they are preferentially metabolized into ketone bodies within the liver.
