Glucose Ketone Index (GKI) and L-Glutamine Metabolism for Cancer Management

Press-Pulse Insights from Dr. Thomas Seyfried
Written by Keith Bishop, CN, B.Sc. Pharmacy, Author

Updated December 2024

This paper discusses the Glucose Ketone Index (GKI) a tool developed by Dr. Thomas Seyfried and his team at Boston College, and L-Glutamine restriction as a strategy for managing cancer growth.[1] The GKI It is the ratio of blood glucose to ketone bodies. The higher the ratio the higher the glucose and lower the ketone bodies. The lower the ratio the lower the glucose and higher the ketone bodies.

GKI and Cancer

There is a very strong association between elevated blood glucose, oxidative stress, inflammation and the higher risk of cancer.[2] Ketone bodies (the body using fat for energy) and ketogenic diets appear to be powerful agents in treating human cancers. Ketone bodies often enhance the effectiveness of chemotherapy treatments.[3]

Dr. Seyfried's research in the realm of cancer treatment has shown increasingly impressive therapeutic outcomes with lower GKI ratios¹ (lower blood glucose and higher ketone bodies). He claims that a GKI of less than 1.0 is prime therapy for patients with cancer¹. The GKI is one number that helps you determine your degree of ketosis.

Optimal GKI for Cancer Management

According to Dr. Seyfried, the optimal GKI range for cancer treatment and prevention is between 0.7-2.0, preferably around 1.0. This range is the most effective in preventing cancer cell growth⁵. At this range cancer cells have difficulty using glucose for energy while normal cells can easily adapt to ketone bodies for energy.

The KetoMojo fingerstick monitor is a convenient method of monitoring GKI. My clients typically measure GKI fasting, before meals and 2 hours after meals. 

GKI Numbers

Restricting L-Glutamine in Cancer Treatment

L-glutamine (glutamine) is an amino acid from protein. Most proteins have glutamine or amino acid precursors to glutamine. Our body requires glutamine to grow, repair, survive and multiply. Many cancer cells also use glutamine to grow, survive, and multiply — so much so that they can become dependent on it.[4] In fact, glutamine is believed to be such an important part of tumor progression that many researchers are studying restricting it as a potential cancer treatment.[5] It’s believed that normal body cells can adapt to lower levels of glutamine better than cancer cells. Restricting dietary glutamine is difficult and unhealthy so researchers are developing compounds to reduce the amount of glutamine the body can use or make from other amino acids.

DON (6-diazo-5-oxo-L-norleucine) is a prescription antagonist that blocks glutamine metabolism.[6] In theory, this compound and derivative could be used across a wide spectrum of cancer types. The challenge is finding a practitioner that is knowledgeable in prescribing and adjusting dosages based on patient response and side effects. Remember, normal cells must have glutamine so we can’t block it 100%.

Press – Pulse

The press-pulse therapeutic strategy for cancer management is illustrated with calorie restricted ketogenic diets (KD-R) of reduced glucose and increased ketones used together with drugs and procedures that create both chronic (press) and intermittent acute stress (pulse) on tumor cell energy metabolism, while protecting and enhancing the energy metabolism of normal cells.

I do several of the following Press-Pulse therapies to lower my familial risk of prostate cancer.

The Press

The press is putting stress on cancer cells all the time.

1. Intermittent Fasting
   Fasting lowers blood glucose and glutamine while increasing ketone bodies. I find most of my clients require 14+ hours of fasting from proteins and carbohydrates to get into a GKI of 1-3. Click here to learn more about Timed Eating for Cancer.

   The combination of fasting or fasting-mimicking diets with radiotherapy or chemotherapeutic agents has demonstrated enhanced anticancer efficacy.[26] 

2. Low Glycemic Impact Foods
   During the eating time of 6-8 hours consuming foods with a low glycemic impact such as discussed in Cancer Food Tactics. I recommend using the Fitindex weight scale and smart phone app to make sure a person is maintaining muscle and bone while losing or maintaining appropriate amounts of body fat. I often recommend my clients use the Kancer Keto diet. Click ere to get your FREE Kancer Keto Guide. And use the following supplements 

Cancer cells often adapt to one therapy. Research is focusing on cutting off cellular energy by limiting glucose and L-Glutamine metabolism via several mechanisms.[7]

Supplements that can lower cancer cell glucose metabolism include:

• Berberine[8]
• Cannabidiol (CBD) [9]
• Curcumin[10]
• Quercetin[11]
• EGCG[12]
• Resveratrol[13]
• Beta Glucan[14]
• Silymarin[15]
• Vitamin D3[16]
• Zinc[17]

Drugs that can lower glucose metabolism and use include:

• Fenbendazole[18]
• Ivermectin[19]
• Diabetes prescription drugs including metformin[20]

Herbs that can lower L-glutamine metabolism and use include:

• EGCG (epigallocatechin gallate) from green tea via glutamate dehydrogenase[21]
• Quercetin via glutamate dehydrogenase[22]
• Curcumin via blocking attachment of glutamine to cancer cells[23]
• Berberine by blocking transport of glutamine into cancer cells[24]
• Resveratrol via glutamine absorption[25]

Download the Prevail Over Cancer Tactics Guide to learn my favorite supplement and repurposed medication sources. 

The Pulse

The Pulse putting severe stress on the cancer cells for short periods of time. Examples include:

• Exercise and activity after eating
• Medical Hyperthermia
  or
  Infrared Sauna or IR Heating pad over the tumor site
• Chemotherapy
• Radiation
• Repurposed drugs

Conclusion

The GKI, as proposed by Dr. Seyfried, presents a promising approach to cancer management. By maintaining a GKI of less than 1.0, it may be possible to inhibit cancer cell growth. However, more research is needed to fully understand and optimize this approach.

I often use the supplements and repurposed medications in the downloadable Prevail Over Cancer Tactics Guide.

Notice

This information is based on research that is intended for educational purposes and should not be taken as medical advice. Always consult with your healthcare provider before making changes to your health regimen. Supplement statements have not been evaluated by the Food and Drug Administration. These supplements are not intended to diagnose, treat, cure, or prevent any disease.

Reference Sources Include

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[18] Dogra N, Kumar A, Mukhopadhyay T. Fenbendazole acts as a moderate microtubule destabilizing agent and causes cancer cell death by modulating multiple cellular pathways. Sci Rep. 2018;8(1):11926. Published 2018 Aug 9. doi:10.1038/s41598-018-30158-6 https://www.nature.com/articles/s41598-018-30158-6 

[19] Feng Y, Wang J, Cai B, Bai X, Zhu Y. Ivermectin accelerates autophagic death of glioma cells by inhibiting glycolysis through blocking GLUT4 mediated JAK/STAT signaling pathway activation. Environ Toxicol. 2022;37(4):754-764. doi:10.1002/tox.23440 https://onlinelibrary.wiley.com/doi/abs/10.1002/tox.23440 

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[21] Sbirkov Y, Vergov B, Dzharov V, Schenk T, Petrie K, Sarafian V. Targeting Glutaminolysis Shows Efficacy in Both Prednisolone-Sensitive and in Metabolically Rewired Prednisolone-Resistant B-Cell Childhood Acute Lymphoblastic Leukaemia Cells. Int J Mol Sci. 2023;24(4):3378. Published 2023 Feb 8. doi:10.3390/ijms24043378 https://www.mdpi.com/1422-0067/24/4/3378 

[22] Marsico M, Santarsiero A, Pappalardo I, et al. Mitochondria-Mediated Apoptosis of HCC Cells Triggered by Knockdown of Glutamate Dehydrogenase 1: Perspective for Its Inhibition through Quercetin and Permethylated Anigopreissin A. Biomedicines. 2021;9(11):1664. Published 2021 Nov 11. doi:10.3390/biomedicines9111664 https://www.mdpi.com/2227-9059/9/11/1664 

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