Controversial Discussion: Is Cancer a Mitochondrial Metabolic Disease? | Thomas Seyfried, Ph.D on The Drive with Dr. Peter Attia

Check out The Peter Attia Drive Episode Page & Show Notes

Key Takeaways

  • “We can reduce the death rate by 50% if you view the tumor as a metabolic problem rather than a genetic problem” – Thomas Seyfried
    • No clinics are treating cancer as a metabolic disease today
    • We can starve the disease of the 2 fermentable fuels (glucose and glutamine)
  • Normal cells can burn ketones to stay alive, cancer cells cannot
    • Using calorie-restricted ketogenic diets transition normal cells to ketones for fuel while also keeping them hungry for glucose, normal cells then compete with tumor cells for glucose
  • The ideal goal would be to figure out a way to starve cancer cells without starving or harming the normal cells
  • Thomas’s group published a paper demonstrating that a ketogenic diet (through calorie restriction and maintaining low blood sugar levels) is the key to controlling epileptic seizures
  •  “We only know that you don’t get cancer if your mitochondria remain healthy” – Thomas Seyfried

Intro

  • Thomas Seyfried (@tnseyfried) is a cancer researcher and professor of biology at Boston College
  • Host – Peter Attia (@peterattiamd)

About Thomas Seyfried

  • While at Yale, Thomas worked on lipid storage diseases and gangliosides
  • He was also interested in studying the ketogenic diet and its affect on epilepsy
    • Unfortunately his grant was denied
  • Thomas later worked with a drug company that created a drug to reduce gangliosides, while testing it on mice.  Thomas saw it reduced brain tumors.
    • The company gave Tom $200K to investigate
      • Thomas found that the drug didn’t make much of a difference, but restricting caloric intake did.

We Need To View Cancer As A Metabolic Problem

  • “We can reduce the death rate by 50-percent if you view the tumor as a metabolic problem rather than a genetic problem” Thomas Seyfried
    • “Gene mutations are all downstream, they’re red herrings”
      • “How many clinics in the country in the world are treating cancer as a metabolic disease using a strategy that will take away the two prime fermentable fuels for the disorder? And the answer is no one.”
  • “I think if you’re doing metabolic therapy, you should eliminate radiation right away”– Thomas Seyfried
    • Thomas believes that with metabolic therapy, you can 2-3x your chances of survival
      • Pablo Kelly, was diagnosed with terminal, inoperable, malignant brain tumor (GBM) and given 6-9 months to live
        • He refused chemotherapy and started the ketogenic diet–He’s still alive today 

Ketogenic Diets & Caloric-Restriction

  • Thomas’s group published a paper demonstrating that a ketogenic diet (through calorie restriction and maintaining low blood sugar levels) is the key to controlling epileptic seizures

Caloric restriction is healthy up until the point where your body starts breaking down muscle, then you go into starvation

  • “Our existence today is dependent on our ability to go long periods of time without eating”
  • With epilepsy, there is an immediate feedback loop: Increase in blood glucose àbreakthrough seizures  
    • Drink a glass of grape juice; get a seizure within minutes
  • Calorie-restricted ketogenic diets help manage epilepsy and cancer
    • We don’t know how this diet manages epilepsy, but we do know that caloric-restriction shrinks tumors by lowering blood sugar

Cancer & Mutations

  • Thomas’s group sequenced the entire genome of five different independently derived cancers from mice
    • All derived from different origins, and didn’t find a single genetic pathogenic abnormality in mitochondrial DNA
    • “We only know that you don’t get cancer if your mitochondria remain healthy”Thomas Seyfried
      • To prevent cancer, keep your mitochondria healthy avoid exposure to pollution, radiation, and carcinogens 
  • Mutations Can Be Important Too: Germline mutations in TP53 can cause Li-Fraumeni syndrome, an inherited disorder that leads to a higher risk of certain cancers
    • Inherited mutations in the BRCA1 and BRCA2 genes are associated with hereditary breast and ovarian cancer syndrome
      • Tumors associated with BRCA1, BRCA2, P53 mutations are fermenters
    • If the inherited mutation damages the respiratory system of the cell, the probability of cancer increases
    • Tom believes there are no living cancer cells that has normal respiration functions

How Cancer Cells Create Energy

  • Cancer cells can ferment both glucose and glutamine (the fuel)
    • Glutamine is fermented via mitochondrial substrate level phosphorylation (mSLP) in the TCA cycle (AKA Krebs cycle) of the mitochondria
      • mSLP is the production of ATP: Changing a phosphate group from an organic substrate into an ATP molecule
        • In  normal cells you make most of your ATP from oxidative phosphorylation (OXPHOS)
        • In cancer cells you make most of it from mSLP inside the same organelle (the mitochondria)
          • Substrate level phosphorylation in the mitochondria may be far greater than the amount of ATP produced in the cytoplasm of tumor cells

Mitochondria & Cell Health

  • Mitochondrial damage or defect can happen in a number of different ways–A carcinogen enters into the mitochondria and causes oxidative stress
  • Cardiolipin, the signature lipid in the mitochondrial inner membrane, is defective in all tumor cells  
  • Normal cells can burn ketones to stay alive, cancer cells cannot
    • Starve the tumor without harming healthy cells: Calorie-restricted and/or ketogenic diets can transition normal cells to use ketones for fuel while also keeping them hungry for glucose in normal cells then compete with tumor cells for glucose
  • Cellular immune cells are also glutamine dependent
    • If you kill too many tumor cells too quickly, you’ve got to have a cell system to remove the corpses–-You’ve got to have some immune cells, that’s what macrophages are for
    • This is why you need some carbs/glutamine
      • Otherwise, you can get infections and die from the indirect effects of these things

More On Cancer

  • In the US about 1,600 people die every day from cancer
    • In China, that number is about 1,800–More people now die from cancer in China than from heart disease
      • Thomas believes that in the next 10 years, death from cancer rates will drop by 50%
  • Thomas’s dream clinical 3-arm trial to test the hypothesis of reducing the death rates of cancer by 50% is to have metabolic therapy without standard of care: The goal is that this shrinks the tumor by removing inflammation and surgeons can then remove what is left
    • Control A: Standard of care ONLY
    • Control B: Standard of care + Metabolic Therapy (reducing blood sugar, elevating ketones and targeting the energy metabolism which we include things like metformin, HBOT)
    • Variable Group:
      • Either Metabolic Therapy ONLY
      • OR the Press-Pulse Concept:
        • First lower the patients’ blood sugar, put them in therapeutic ketosis (along with stress management techniques (yoga, meditation, adequate sleep)
        • Then place patients in hyperbaric oxygen which creates oxidative stress predominantly in the tumor cell and not in the normal cells 
        • Finally, “Pulse with drugs that target glutamine and together you’re removing the antioxidant capacity of the tumor, making it vulnerable to hyperbaric oxygen” – Thomas Seyfried
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Drive with Dr. Peter Attia : , , ,
Notes By Alex Wiec

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