The Glucose-Ketone Index Approach to Cancer Therapy – Some Early Insights

The Glucose-Ketone Index Approach to Cancer Therapy - Some Early Insights

Introduction

This recent article appeared in March 2015. Thomas Seyfried and colleagues came up with a way to monitor the therapeutic efficacy for managing brain cancer by introducing the glucose ketone index.

This tool measures the ratio of blood glucose to ketones (BOHB) and it’s helpful because it outputs a single number that would tell if a patient is predominantly burning ketones or glucose. It would assess whether the patient is successful into implementing a ketogenic dietary approach (or a fasting approach) to managing different pathological conditions.

GKI – The Glucose Ketone Index

As they discuss it [1]:

The Glucose Ketone Index (GKI) was created to track the zone of metabolic management for brain tumor management. The GKI is a biomarker that refers to the molar ratio of circulating glucose over β-OHB, which is the major circulating ketone body. A mathematical tool called the Glucose Ketone Index Calculator was developed that can calculate the GKI and monitor changes in this parameter on a daily basis. The GKIC generates a single value that can assess the relationship of the major fermentable tumor fuel (glucose) to the non-fermentable fuel (ketone bodies).

The formula is quite comprehensive and it can be used with different unit systems and devices:

The Glucose-Ketone Index Approach to Cancer Therapy - Some Early Insights - 2

Simply put:

GKI = Glucose/Ketones

The graphics above show you how you can switch between mg/dL and mM (millimolar).

So, far they’ve used the calculator to estimate the GKI for mice and humans with brain tumors “that were treated with either calorie restriction or ketogenic diets from five previously published reports.”[1]

They noticed that the optimal results in terms of the efficacy of the treatment would be when GKI was around 1, or lower. I suspect that lower than 1 would be even better. This would simply mean that more ketones (as serum concentration) are in circulation compared to glucose.

1. In the first study they analyzed, there were:

2 pediatric patients:

– one with anaplastic astrocytoma (malignant brain tumor)
– one with cerebellar astrocytoma

“Both individuals were placed on a ketogenic diet for eight weeks. During the 8-week treatment period, GKI dropped from about 27.5 to about 0.7–1.1 in the patients.”[1]

Both patients responded well to the treatment as FDG uptake (fluorodeoxyglucose) at the tumor site decrease by ~20%.

2. The second study is another human study:

– 65 year old woman suffering from glioblastoma multiforme (aggressive brain tumor)

She was put on a low-calorie ketogenic diet (600 kcals a day) for 8 weeks. She also followed standard chemo and radio therapy. Her GKI went from 37.5 to 1.4 during the first 3 weeks of the intervention.

“No discernible brain tumor tissue was detected with MRI in the patient at the end of eight weeks of the calorie restricted ketogenic diet. It is also important to mention that the patient was free of symptoms while she adhered to the KD.”[1]

Sadly, the tumor recurred 10 weeks after her getting off the ketogenic diet. I would suspect that if the patient adhered for a much longer time on the strict ketogenic diet with a very well formulated approach that focused on nutrient richness and also caloric restriction, the recurrence may not have happened.

3. The third study followed mice that were implanted astrocytomas:

“Mice were implanted with tumors and fed one of four diets for 13 days:

1) standard diet fed unrestricted,
2) calorie restricted standard diet,
3) ketogenic diet fed unrestricted, or
4) calorie restricted ketogenic diet.”[1]

Mice on diets 1 and 3 (unrestricted standard and unrestricted ketogenic) had rapid tumor growth and GKIs of 15.2 and 11.4.

Mice on diet 2 experienced significant decrease in the volume of their tumors and had a GKI of 3.7.

Mice on diet 4 experienced significant decrease in the volume of their tumors and also a GKI of 4.4.

The promising results of 2 and 4 are somewhat contrary to the standard dietary approach in cancer treatment where patients are recommended against caloric restriction.

4. The fourth study also followed mice with tumor implants

“Tumors were implanted and grown in the mice for three days prior to diet initiation. After three days, mice were maintained on one of three diets for 8 days:

1) standard diet fed unrestricted,
2) ketogenic diet fed unrestricted, or
3) calorie restricted ketogenic diet. “[1]

The only diet that reduced tumor weight was the calorie restricted diet (3). These mice also had a significant reduction in GKI, drawing an important conclusion with respect to the efficiency of a low-calorie approach to tumor treatment.

Mice on diets 1 and 2 had GKIs ranging from 9.6 to 70, while mice on diet 3 had GKIs ranging from 1.8 to 4.4

5. The last study where GKI was used by these researchers was also focused on tumor implanted mice:

“The mice were implanted with tumors, and three days later they were placed on either a standard diet fed unrestricted or a ketogenic diet fed unrestricted. Mice were also assigned to groups that either received or did not receive concomitant radiation therapy.”[1]

So, these were basically 4 groups:

– keto diet, fed unrestricted, no radiation
– keto diet, fed unrestricted, radiation
– standard diet, fed unrestricted, no radiation
– standard diet, fed unrestricted, radiation

Those on the keto-unrestricted-no-radiation, group 1, had a GKI of 6.4 and survived on average 28 days. Mice on the standard-unrestricted-no-radiation, group 3, had a GKI of 50 and survived on average 23 days. This would make the keto diet, even with unrestricted feeding, somewhat more advantageous than the standard diet, when no radiation therapy is implemented.

Mice on the keto-unrestricted-with-radiation, group 2, had a GKI of 5.7 and survived on average 200+ days. Mice on the standard-unrestricted-with-radiation, group 4, had a GKI of 32.3 and survived on average 41 days.

This is where we can actually see a major difference in terms of survival. Even unrestricted, keto+radiation seems to elicit far better results compared to the other interventions. What’s left to more observation is to see how these findings translate to human studies.

Conclusions

“Besides ketogenic diets, other dietary therapies, such as calorie restriction, low carbohydrate diets, and therapeutic fasting, can also lower blood glucose and elevate β-OHB levels and can have anti-tumor effects.”[1]

As we learn more about cell proliferation and as we progress with diagnosis technologies, we understand that cancer is an extremely complex and complicated health issue. To succeed in managing and, why not, curing it, we have to take a multi-perspective approach. While some ketogenic diets alone, seem to be effective in some variations of cancers, in others they fail as much as other single perspective approaches (radiation alone, chemo alone, diet alone, etc). A more efficient approach would combine each of these strategies tailored to the individual and their specific form of cancer.

From what I’ve investigated and also wrote in my book on periodic and intermittent fasting, low-calorie keto + chemo/radio + nutrient rich diet could be an approach. Fasting + chemo/radio could be another one. Intermittent Fasting + nutrient rich diet + low-carb could be another one. And more similar…And to these ones I mentioned, the Glucose Ketone Index (GKI) is a good tool for determining whether or not the metabolism focuses on fat oxidation rather than sugar burning.

Please share your thoughts and let’s help those in need…

Resources

Meidenbauer, J. J., Mukherjee, P., & Seyfried, T. N. (2015). The glucose ketone index calculator: a simple tool to monitor therapeutic efficacy for metabolic management of brain cancer. Nutrition & metabolism, 12(1), 12.

Photos: here

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