Frontiers in Science: Simple test could help track metabolic health in cancer and chronic disease
Researchers writing inFrontiers in Sciencepropose using simple tests to track metabolic health in non-communicable diseases, which cause three in four deaths worldwide
The paper makes the case for using the glucose ketone index (GKI)—the ratio of glucose and ketones in blood taken from a finger prick. The proposed test could indicate metabolic state, assess long-term nutritional adherence, and support the monitoring of strategies aimed at improving mitochondrial function, which is linked to many noncommunicable diseases (NCDs)
The commonest chronic NCDs—including cancer, cardiovascular diseases, type 2 diabetes, obesity, and neurodegeneration—are forecast to rise substantially worldwide by 2050 and overtake infectious diseases for health burden
The authors argue that the GKI could help track whether diet, fasting, or exercise interventions shift the body toward nutritional ketosis—a metabolic state marked by lower glucose and higher ketone availability, which may be linked to lower NCD risk or improved management. However, the authors note that disease-specific target ranges must still be validated in future clinical studies
Lead author Prof Thomas Seyfried, from Boston College, USA, said: “Within the next few decades, NCDs could account for up to 75% of all disability-adjusted life-years, contributing to a substantial decline in life expectancy. These conditions are not the result of genetic fate but are largely shaped by lifestyle factors. This GKI-based metabolic roadmap outlines a proposed clinical pathway that could support the prevention and management of cancer and chronic disease.”
The authors say that ketogenic approaches should be considered as management strategies for chronic disease under specific circumstances rather than cures, and that any approach should be taken under clinical supervision
The glucose ketone index
The GKI was originally developed as a point-of-care blood biomarker for assessing diet adherence in cancer therapy. It measures the ratio of blood glucose to β-hydroxybutyrate—a ketone body that the authors link to more efficient mitochondrial ATP production, the process cells use to generate usable energy
Emerging evidence suggests that many chronic diseases are linked to, or significantly influenced by, mitochondrial dysfunction—defined as the inability to efficiently regulate ATP production in response to energy demand
The authors say that measuring β-hydroxybutyrate alongside glucose may give a clearer picture of metabolic state than glucose or body weight alone. Lower GKI values suggest lower glucose and higher ketone availability—metabolic conditions associated with more efficient mitochondrial metabolism—while higher values suggest higher glucose and lower ketone availability, which might be associated with impaired mitochondrial performance
The GKI could therefore give doctors a quantitative readout of metabolic state and help them guide and monitor shifts in metabolism that may reduce systemic inflammation, high blood glucose, high blood insulin, and reactive oxygen species production—metabolic and inflammatory processes implicated in many chronic diseases. The finger-prick test could then track metabolic responses to interventions in real time, while future studies test how these values relate to disease risk or progression
Lead author Dr Derek Lee, also from Boston College, said: “Mitochondrial dysfunction is linked to many chronic illnesses and cancers, with poor nutrition and reduced physical activity remaining among the most significant—and preventable—risk factors. When combined with evidence-based nutrition and exercise, the GKI could offer a framework for monitoring mitochondrial health across diverse patient groups and disease contexts. If validated in larger studies, this could inform efforts to address the wide health burden of NCDs.”
Targeting preventable risk factors
The largest global disease burden is expected to shift from infectious diseases to NCDs over the coming decades. The paper highlights the scientific evidence showing that lack of physical activity and poor nutrition are major preventable drivers of the chronic disease epidemic in developed nations
The paper advances a case that nutritional ketosis, as assessed by the GKI, could offer a broadly applicable strategy for decreasing both chronic high blood glucose and insulin while, at the same time, increasing the body’s own production of β-hydroxybutyrate—a shift that might enhance the efficiency of mitochondrial energy production, support metabolic balance, and potentially reduce disease risk or progression
The authors call for studies to standardize reporting of glucose, ketone, and GKI values, ideally weekly or daily, whenever ketosis is assessed clinically. They say previous studies often report ketone or GKI values too infrequently, making comparison difficult
They also say future studies should report other blood biomarkers alongside the GKI, including triglycerides, inflammatory markers, and insulin, to clarify whether a low GKI correlates with broader metabolic changes
More clinical data are also needed to identify the right GKI ranges, adherence levels, and effective time spent in each range for different diseases—as well as how diet adherence can be supported across diverse socioeconomic and cultural contexts
Co-author Dr Isabella Cooper from the University of Westminster, UK said: “NCDs cause an unacceptably high, rapidly rising toll on global health across nearly all age groups. Introducing quantitative GKI testing could provide a clear, cohesive readout that goes beyond weight loss, and one that supports and tracks sustained behaviour change to help assess disease risk and treatment response
“To move this forward we urgently need larger, standardized clinical studies to test how well GKI values can predict health outcomes across different diseases, and to define disease-specific target ranges.”
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The article is part of the Frontiers in Science multimedia article hub ‘Glucose ketone index and metabolic health’. The hub features a policy outlook, and a version of the article for kids, from other eminent experts: Corinne Bush and Amy Smith (American Nutrition Association, USA)
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