Cancer, Metabolic Syndrome

The glucose ketone index: a proposed quantitative biomarker to support cancer and chronic disease prevention and management 

Mitochondrial dysfunction is increasingly recognized as a common feature of many chronic diseases, including cancer, type 2 diabetes, cardiovascular disease, obesity, neurodegenerative disorders, and some psychiatric conditions. Impaired mitochondrial function reduces cellular energy production, increases oxidative stress and inflammation, and contributes to metabolic dysregulation.

In this review, the authors propose that ketogenic metabolic therapy may help restore mitochondrial function by lowering blood glucose while increasing circulating ketone bodies, particularly β-hydroxybutyrate (BHB). They further suggest that the glucose ketone index (GKI) – calculated by dividing blood glucose (mmol/L) by blood BHB (mmol/L) – may serve as a practical biomarker for monitoring metabolic health, nutritional ketosis, and adherence to ketogenic interventions. Although originally developed for brain cancer, the authors propose that the GKI may have broader applications across a range of chronic diseases.

The review summarizes evidence linking mitochondrial dysfunction to chronic disease pathogenesis and discusses how BHB may improve mitochondrial bioenergetics. Compared with glucose-derived pyruvate and fatty acids, BHB may support more efficient ATP production, reduce reactive oxygen species, suppress inflammatory signaling, promote mitochondrial maintenance, and enhance metabolic flexibility. The authors argue that monitoring both glucose and ketone levels through the GKI provides a more comprehensive assessment of metabolic status than either measurement alone.

Key Findings

• Mitochondrial dysfunction: Mitochondrial dysfunction is proposed as a common underlying mechanism linking cancer and numerous chronic diseases, contributing to impaired energy production, oxidative stress, inflammation, and metabolic dysfunction.
• Ketogenic metabolic therapy: By lowering glucose and increasing β-hydroxybutyrate (BHB), ketogenic metabolic therapy may improve mitochondrial ATP production, reduce oxidative stress, support mitochondrial maintenance, and restore metabolic homeostasis.
• Glucose ketone index (GKI): The GKI integrates blood glucose and BHB into a single biomarker that may better reflect metabolic status than either measurement alone.
• Proposed GKI targets: The authors suggest that a GKI near 10 may represent light nutritional ketosis, whereas values around 1–2 may be appropriate for therapeutic ketosis in cancer. These proposed targets remain hypothetical and require clinical validation.
• Clinical monitoring: The authors recommend reporting glucose, BHB, and GKI daily or weekly in studies of ketogenic metabolic therapy. They suggest measuring GKI approximately two hours after a meal, preferably in the evening.
• Clinical applications: The GKI may complement established clinical markers, including HbA1c, fasting insulin, triglycerides, C-reactive protein, and blood pressure, when monitoring metabolic health and response to therapy.
• Research limitations: Much of the supporting evidence comes from mechanistic studies, preclinical research, case reports, and small clinical studies. Disease-specific GKI targets have not yet been validated in large prospective trials.

Conclusion

The authors propose that mitochondrial dysfunction is a shared biological mechanism underlying cancer and many chronic diseases. Rather than serving only as a measure of nutritional ketosis, the GKI is presented as a practical biomarker for monitoring metabolic interventions designed to improve mitochondrial function. By lowering glucose and increasing β-hydroxybutyrate, ketogenic metabolic therapy may enhance mitochondrial ATP production, reduce oxidative stress and inflammation, and restore metabolic homeostasis. However, the authors emphasize that disease-specific GKI targets and broader clinical applications require further validation in larger prospective studies.