Background

Metabolic therapy using ketogenic diets (KD) is emerging as an alternative or complementary approach to the current standard of care for brain cancer management. The KD targets tumor energy metabolism by lowering blood glucose and elevating blood ketones (β-hydroxybutyrate). Brain tumor cells, unlike normal brain cells, cannot use ketone bodies effectively for energy when glucose becomes limiting. Although plasma levels of glucose and ketone bodies have been used separately to predict the therapeutic success of metabolic therapy, daily glucose levels can fluctuate widely in brain cancer patients. This can create difficulty in linking changes in blood glucose and ketones to efficacy of metabolic therapy.

Methods

The ‘ Glucose Ketone Index’ (GKI) was created to track the zone of metabolic management for brain tumor management that tracks the ratio of blood glucose to ketones as a single value.

A mathematical tool called the Glucose Ketone Index Calculator (GKIC) was developed that can calculate the GKI and monitor changes in this GKI parameter on a daily basis. The GKIC generates a single value that can assess the relationship of the glucose, the major fermentable tumor to ketone bodies, the non-fermentable fuel.

Results

The GKIC was used to estimate the GKI for humans and mice with brain tumors that were treated with either calorie restriction or ketogenic diets from five previously published reports. The results showed a clear relationship between the GKI and therapeutic efficacy using ketogenic diets and calorie restriction. Therapeutic efficacy of the KD or calorie restriction is greater with lower GKI values than with higher values. The results suggest that GKI levels that approach 1.0 are therapeutic for managing brain tumor growth.

Conclusions

As brain tumor cells are dependent on glucose for survival and cannot effectively use ketone bodies as an alternative fuel, the authors assert that a zone of metabolic management can be achieved under conditions of low glucose and elevated ketones.

The zone of metabolic management is likely entered with GKI values between 1 and 2 for humans. Optimal management is predicted for values approaching 1.0, and blood glucose and ketone values should be measured 2– 3 hours postprandial, twice a day if possible. This will allow individuals to connect their dietary intake to changes in their GKI. Therefore, the GKIC was developed to more reliably and simply predict therapeutic management for brain cancer patients under these dietary states than could measurements of either blood glucose or ketones alone.

 

The authors also suggest that the GKIC could have utility not only for managing brain cancer and possibly other cancers dependent on glucose and aerobic fermentation for survival, but also for managing other diseases or conditions where the ratio of glucose to ketone bodies could be therapeutic. Such diseases and conditions include Alzheimer’ s disease, Parkinson’ s disease, traumatic brain injury, chronic inflammatory disease, and epilepsy. They caution that further studies will be needed to determine the utility of the GKIC for predicting therapeutic success in
the metabolic management of disease.

Citation

Meidenbauer et al., (2015). The glucose ketone index calculator: a simple tool to monitor therapeutic efficacy for metabolic management of brain cancer. Nutrition & Metabolism 12:12