#120 - AMA with Dom D'Agostino, Ph.D., Part II of II: Ketosis for cancer and chronic disease, hyperbaric oxygen therapy, and the effect of ketosis on female health
In this AMA, Dom D'Agostino, an Associate Professor at the University of South Florida, discusses ketosis's impact on chronic diseases like cancer, Alzheimer's, and Parkinson's, hyperbaric oxygen therapy, and ketosis for female health and performance.
Deep Dive Analysis
7 Topic Outline
Introduction to Dom D'Agostino and Episode Focus
Updates on Press-Pulse Metabolic Cancer Therapy
Synergistic Effects of Ketogenic Diet and Hyperbaric Oxygen
Role of High-Dose Vitamin C in Cancer Treatment
Targeting Glutamine Metabolism in Cancer Therapy
Mitochondrial Function and Dysfunction in Cancer Cells
Benefits of Ketosis During Cancer Interventions
6 Key Concepts
Press-Pulse Metabolic Therapy
A strategy to compromise tumor growth and proliferation by using therapeutic ketosis and other modalities (like hyperbaric oxygen therapy or specific drugs) to weaken the tumor, making it more vulnerable to further treatments. This approach aims to create metabolic stress on cancer cells while protecting healthy cells.
Therapeutic Ketosis in Cancer
A metabolic state that suppresses insulin signaling, lowers glucose availability to tumors, elevates ketone bodies (which most cancer cells cannot readily use as fuel), and impairs the tumor's endogenous antioxidant pathways. This creates a scenario where cancer cells are metabolically disadvantaged.
Glucose Ketone Index (GKI)
A ratio of glucose to ketones (in millimolar concentrations) used to assess the metabolic state for cancer therapy. A lower index, ideally in the one to two range or below one, indicates a state that slows tumor growth and makes it more vulnerable to other therapies.
Pro-oxidant Effect of IV Vitamin C
High-dose intravenous vitamin C, particularly its oxidized form (dihydroascorbic acid), can act as a glucose antagonist and dramatically increase reactive oxygen species (ROS) in cancer cells. This effect is amplified by high levels of free iron in tumors, which drives the Fenton reaction and can lead to cancer cell death.
Glutamine Addiction in Cancer
Tumor cells often exhibit a dependency on glutamine (glutaminolysis) for anabolic processes and some ATP generation, which fuels their rapid proliferation. This makes targeting glutamine metabolism with inhibitors a potential therapeutic strategy, especially when combined with other metabolic interventions.
Mitochondrial Aberrations in Cancer
While cancer cells consume oxygen, their mitochondria are often dysregulated or transformed in ways that enhance biosynthetic processes and overproduce reactive oxygen species in response to elevated oxygen levels. This occurs due to defects in the electron transport chain and the presence of free iron, rather than the mitochondria functioning perfectly normally for ATP production via oxidative phosphorylation.
5 Questions Answered
Press-pulse therapy aims to compromise tumor growth by using therapeutic ketosis to suppress insulin and glucose, elevate ketones, and impair tumor antioxidant pathways, thereby making the tumor vulnerable to other treatments like hyperbaric oxygen therapy or specific metabolic drugs.
HBOT can synergize with a ketogenic diet by providing an oxidative challenge that cancer cells, already metabolically compromised by ketosis, cannot defend against. This leads to increased reactive oxygen species and cell death, especially when tumors are oxygenated.
Yes, high-dose intravenous vitamin C acts as a pro-oxidant and a glucose antagonist, increasing reactive oxygen species in cancer cells and driving the Fenton reaction due to high free iron, which can dramatically kill cancer cells while sparing healthy ones.
Cancer cell mitochondria are not perfectly normal; they are aberrant or dysregulated to enhance biosynthetic processes and can overproduce reactive oxygen species, especially in response to elevated oxygen levels, due to defects in the electron transport chain and free iron.
Yes, being in a state of ketosis is absolutely beneficial during these interventions, as it metabolically compromises cancer cells, making them more susceptible to the oxidative stress induced by radiation or hyperbaric oxygen.
20 Actionable Insights
1. Maintain Ketosis During Interventions
Maintain a state of ketosis while undergoing radiation or hyperbaric oxygen interventions, as there is an absolute benefit to doing so.
2. Target Low Glucose Ketone Index
Aim to achieve a Glucose Ketone Index (GKI) of one to two, or ideally below one (glucose level over ketone level in millimolar concentrations), as this slows tumor growth and proliferation, making tumors more vulnerable to therapies like hyperbaric oxygen.
3. Utilize Therapeutic Ketosis for Cancer
Implement therapeutic ketosis to suppress insulin signaling, lower glucose availability to tumors, and elevate ketone bodies, which cancer cells struggle to use as fuel, thereby impairing their antioxidant defenses.
4. Combine Ketosis and Hyperbaric Oxygen
Suppress glycolysis by reducing glucose and inhibiting insulin, then apply hyperbaric oxygen therapy to create an oxidative challenge that can potentially kill cancer cells.
5. Ketogenic Diet & HBOT Protocol
For metastatic cancer, consider a modified ketogenic diet combined with hyperbaric oxygen therapy delivered at 2.5 atmospheres of oxygen for 60 minutes, three times a week, as this showed decreased tumor burden and extended lifespan in an animal model.
6. Potent Pro-Oxidant Cancer Therapy
Consider combining hyperbaric oxygen therapy, radiation, and intravenous vitamin C, or just hyperbaric oxygen and IV vitamin C, as a potent pro-oxidant therapy to target cancer cells.
7. IV Vitamin C as Glucose Antagonist
Administer intravenous vitamin C to achieve millimolar concentrations in the blood, as it acts as a glucose antagonist by using glucose transporters and dramatically increases reactive oxygen species in cancer cells due to their high free iron content.
8. Combine Fasting with IV Vitamin C
For aggressive KRAS-mutated tumors, consider a combination of fasting with intravenous vitamin C, as a mouse study showed remarkable effects with this non-toxic approach.
9. Fasting, Ketogenic Diet, Immune Therapy
For difficult-to-treat cancers like metastatic thymoma, consider a protocol involving water fasting, ketogenic diet, periodic water fasting, and immune-based therapies, which has shown significant tumor burden reduction in a case study.
10. Oxygenate Tumors Before Radiation
To increase the efficacy of radiation therapy, oxygenate the tumor prior to radiation, as the damage is directly proportional to oxygenation due to increased reactive oxygen species generation.
11. HBOT During Targeted Radiation
Dramatically sensitize tumors to targeted radiation therapy by undergoing hyperbaric oxygen therapy concurrently with the radiation.
12. HBOT Before/After Radiation
Undergo hyperbaric oxygen therapy before or after radiation therapy, as this can lead to a residual elevation of reactive oxygen species in the tumor for hours, potentially enhancing treatment.
13. Target Glutamine in Cancer
Consider targeting glutamine with inhibitors like DON as a cancer strategy, but be mindful of its toxicity and the need for developing less toxic molecules that reduce glutamine levels or act as antagonists.
14. Ketogenic Diet Reduces DON Toxicity
When considering glutamine inhibitors like DON for cancer therapy, combining them with a ketogenic diet may help reduce toxicity, as observed in mouse studies.
15. Explore Metabolic Cancer Drugs
Investigate metabolic drugs such as 2-deoxyglucose, 3-bromopyruvate, DCA, metformin, high-dose vitamin C, and SGLT2 inhibitors, as these can inhibit glycolysis and other pathways relevant to cancer.
16. Consult Healthcare Professionals
Do not use this podcast as medical advice; always seek assistance from healthcare professionals for any medical conditions.
17. Utilize VMM3 Cancer Model
Cancer researchers are encouraged to utilize the VMM3 model for studying metastatic cancer and cancer cachexia, as it is considered a highly effective and deadly animal model.
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3 Key Quotes
If you can cure cancer in this model system, then you've cured cancer.
Tom Seyfried (quoted by Bob Kaplan)
I'm so into the pro-oxidant effect of vitamin C and down to the redox pathways that I don't even think about as an antioxidant anymore.
Dom D'Agostino
The efficacy of radiation therapy is proportional to the PO2 of the tumor.
Dom D'Agostino
1 Protocols
Ketogenic Diet with Hyperbaric Oxygen Therapy for Metastatic Cancer (VMM3 Model)
Dom D'Agostino (describing Dr. Angela Poff's work)- Follow a modified ketogenic diet.
- Receive hyperbaric oxygen therapy at 2.5 atmospheres of oxygen.
- Each HBOT session lasts 60 minutes.
- Administer HBOT three times a week.