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Transcript: Dominic D’Agostino on Starving Cancer at TEDxTampaBay

Dominic D’Agostino

This is the transcript of Dominic D’Agostino, assistant professor at the University of South Florida, TEDx Talk: Starving Cancer at TEDxTampaBay.

Listen to the MP3 Audio here: Starving cancer by Dominic D’Agostino at TEDxTampaBay

TRANSCRIPT: 

Navy SEAL divers are the best at what they do. But they have a problem that limits their ability to do their mission.

Our research focused on solving the problem and it led to an unexpected path of discovery for neurological diseases and cancer. The problem results from the specialized equipment that the Navy SEAL divers use, including the oxygen rebreather. The advantage of the rebreather is that there are no bubbles, so it’s very quiet and helps the SEAL evade detection from the enemy.

The disadvantage of the oxygen rebreather is that the high levels of oxygen and the pressure from the undersea environment causes a potential for a seizure. These seizures occur with little or no warning and there is no effective mitigation strategy to prevent them.

So the question we ask is: Why do the seizures occur and how can we prevent them? To answer this question required funding from the Office of Naval Research to develop a microscope that was installed inside a hyperbaric chamber, or a high-pressure chamber. This chamber could simulate the underwater environment and the pressure of the underwater environment. Using this technology we demonstrated that neurons in the brain, when subjected to high pressure and high oxygen, are overstimulated. The overstimulation of the brain from the high oxygen and pressure causes a decrease in brain energy metabolism.

When this happens, it causes the potential for a seizure. These oxygen seizures occur with little or no warning and there is no effective way to prevent them. These drug resistant seizures are similar to epilepsy patients that have drug resistant seizures, and in the case of patients they can use a special diet to prevent these seizures.

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One example of the patient who used diet is Mike Dancer. Mike used a variety of antiseizure medication, and the medication caused severe side effects and was not able to control his seizures. So, due to the severe side effects Mike stopped all the antiseizure medication and when he did, he saw an increase in his seizure frequency. At about this time Mike discovered there was a dietary intervention, that he could use to control his seizures. And when he did, he found a sharp decrease in his seizure frequency. I’m happy to say that Mike has been on the diet for 5 years now, and he’s been managing his epilepsy for 5 years without medication.

So what is the ketogenic diet? Compared to a normal diet, the ketogenic diet is very low in carbohydrates and it’s very high in fat. People have used the diet for years to help them regulate their body weight, reduce their body weight, and control or reduce their blood glucose levels.

But most importantly, the ketogenic diet is proven to control seizures, when drugs fail. No organization has done more to educate the public about therapeutic potential of the ketogenic diet than The Charlie Foundation started by Hollywood producer Jim Abrahams. Jim’s son Charlie was stricken with seizures. They were so severe and no amount of drugs could help him. So Jim looked into alternative approaches to manage his son’s seizures. And with his research he discovered that the ketogenic diet was being used at Johns Hopkins Hospital, so it was a treatment that was used specifically for pediatric epilepsy.

So Jim took Charlie to Johns Hopkins Hospital and they worked pretty closely with a dietician there, and within a short amount of time Charlie’s seizures were under control. And Charlie was actually cured of his epilepsy at Johns Hopkins Hospital with the use of the ketogenic diet. So Charlie is actually off the diet completely today, and he remains seizure-free.

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The ketogenic diet is effective for a variety of neurological disorders, including Glucose Transporter Type 1 Deficiency Syndrome. Children with this disorder lack the ability to transport glucose into the brain. So their brains are literally starved of glucose and this causes a potential for seizures.

So it’s known that, you know, the brain can use glucose as the primary fuel, but it can readily adapt to using ketones for energy. So in this way the brain is like a hybrid engine, right? So it uses glucose as the primary fuel but during periods of limited glucose availability the brain can readily adapt to using this alternative fuel source.

So we are exploiting the neuroprotective effects of ketones by developing ketone supplements for the Navy SEAL divers for oxygen seizures. So the advantage of the ketone supplement is that you can circumvent the need for the dietary restriction that’s required to elevate and sustain blood levels of ketones. There are many therapeutic applications of ketones because nearly all healthy cells in a body can use ketones for fuel as an alternative energy source.

Surprisingly, cancer cells lack the ability to transition from using glucose for fuel to using ketones. So, in a way, cancer cells are like damaged hybrid engines. They use large amounts of glucose much more than healthy cells, and they lack this ability to transition over to an alternative fuel source.

So we can say that ‘sugar addiction’ is really the Achilles heel of cancer cells. This observation inspired me in the lab, and I asked a question, I wondered, why very little attention was being given to nutrition to exploit this weakness of cancer cells. So, it turns out that the sugar addiction was actually observed over 80 years ago by Otto Warburg. So, Otto Warburg did experiments, he won a Nobel prize for these experiments, demonstrating that cancer cells are damaged in their metabolism and the damage in their metabolism results in high amounts of sugar uptake.

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More recently, Thomas Seyfried from Boston College has been a pioneer, really, in validating Warburg’s hypothesis and proving that cancer is a metabolic disease. In Tom’s experiments, he demonstrated that there is a specific, metabolic defect of cancer cells as glucose dependency, and that we can target that with a variety of non-toxic alternative approaches.

Oncologists target this weakness in cancer cells, which is excess glucose consumption, with something called a FGD-PET Scan. The PET Scan actually shows the excess consumption of glucose in cancer cells relative to the healthy tissues surrounding it. So this allows for the imaging of excess glucose consumption that oncologists use. But this information really isn’t used to exploit the cancer for a treatment modality. The excess glucose consumption of cancer cells allows them to thrive and proliferate in a low oxygen environment.

Another interesting observation that we made in the lab is that high pressures of oxygen are actually damaging to cancer cells. We’ve demonstrated that when high levels of oxygen are given to cancer cells that they overproduce oxygen free radicals, and these are damaging to the cell membrane. At high magnification we can observe bumps on the surface of the membrane that are indicative of membrane damage.

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