Metabolic reprogramming induced by ketone bodies diminishes pancreatic cancer cachexia.
Level 5 - mechanism / opinion, no new human data
Preclinical cell line and animal research without human participants.
PubMed 25228990 · doi:10.1186/2049-3002-2-18
What was done
Researchers investigated the effects of ketone bodies and a ketogenic diet on tumor metabolism and cancer-induced cachexia. In vitro experiments using multiple pancreatic cancer cell lines assessed glycolytic flux, glutamine uptake, ATP content, apoptosis, and c-Myc regulation and promoter binding. In vivo effects on tumor growth, muscle loss, and body weight were tested using mouse orthotopic xenograft models fed a ketogenic diet.
What was found
No quantitative numbers, effect sizes, or p-values were reported in the abstract. Directionally, ketone body treatment decreased glycolytic flux, glutamine uptake, ATP levels, and cell survival while inducing apoptosis in pancreatic cancer cell lines. It also reduced c-Myc levels and its recruitment to glycolytic gene promoters. In cell models and mouse orthotopic xenografts, ketone bodies and a ketogenic diet diminished cachexia, slowed tumor growth, and inhibited muscle and body weight loss.
Why it matters
This work identifies a metabolic mechanism through which ketone bodies may downregulate c-Myc and glycolytic pathways, suggesting ketogenic dietary strategies could potentially counter pancreatic cancer cachexia.
Limits
The study is restricted to in vitro cell lines and mouse xenografts; no human clinical data were collected. The abstract omits sample sizes, quantitative measurements, specific dietary macronutrient compositions, and statistical uncertainty. Rodent models of cachexia and metabolism often do not directly translate to human disease.
Cited by
- supports Ketone ester supplementation elevating both beta-hydroxybutyrate and acetoacetate prevents muscle wasting in experimental models of cachexia.