Share this post

🔑 Key Takeaways

  1. Dominic Dagostino discusses the differences between ketone esters and salts, the role of MCT and caprylic acid, and provides recommended dosage of ketones. The podcast also emphasizes seeking appropriate medical guidance for metabolic therapies for cancer.
  2. Self-experimentation and curiosity-driven exploration can lead to valuable discoveries, even in complex fields. Embracing unconventional approaches and combining personal experimentation with limited data can uncover new knowledge.
  3. Atomic force microscopy combined with hyperbaric oxygen can help researchers study the behavior of cancer cells at the microscopic level, providing valuable insights for targeted treatment strategies.
  4. Hyperbaric oxygen therapy has shown promise in destroying cancer cells through the explosion of their mitochondria, offering new possibilities for cancer treatment.
  5. Cancer cells rely on elevated levels of reactive oxygen species for growth, but therapies targeting oxidative stress, like hyperbaric oxygen and the ketogenic diet, could counteract cancer cell growth by pushing cells beyond their antioxidant potential and triggering cell death.
  6. Ketones can be a powerful anti-seizure strategy and may have potential in cancer treatment by thriving in low glucose environments and inhibiting the growth of cancer cells.
  7. Metabolism and genetics are both important factors in cancer development and treatment.
  8. Incorporating therapeutic ketosis strategies, such as using ketone esters, could make hyperbaric oxygen therapy safer and more effective for treating various conditions, including wounds. Adhering to dive tables is important to avoid seizures, but certain circumstances may increase the risk for divers.
  9. High levels of oxygen can cause seizures and oxidative stress, but these can be quickly stopped by removing or switching the oxygen source. The effects of oxygen toxicity on seizures vary based on genetics and other factors.
  10. HBOT has shown promising results in various areas such as wound healing, radiation necrosis treatment, decompression sickness management, and diabetic wound care. Further research is necessary to fully comprehend its advantages.
  11. Rigorous research is crucial for understanding and treating traumatic brain injuries, including exploring therapies like hyperbaric oxygen and metabolic-based approaches using ketones, while emphasizing the importance of proper research and guidance.
  12. The body can regulate glucose levels and adapt to prolonged fasting by releasing stored glycogen, breaking down muscle and triglycerides, and maintaining low insulin levels without experiencing hypoglycemia.
  13. Ketones can provide a significant amount of energy to the brain, challenging the conventional belief that glucose is the primary fuel source. Manipulating metabolism can help shift towards using fats and ketones as fuel.
  14. Understanding and tapping into the benefits of ketones requires significant physiological changes, such as following a strict ketogenic diet, to harness their potential for improved performance and health.
  15. Ketones produced during periods of fasting or carbohydrate restriction can be used as an alternative fuel source by the body, potentially benefiting neurological conditions and ATP production.
  16. As research progresses, scientists are realizing the complexity of cancer metabolism and the challenges in targeting specific pathways. Constant adaptation and learning are crucial in staying ahead in this rapidly evolving field.
  17. Consuming MCTs can boost ketone levels, especially pure C8 MCTs. It's important to choose MCTs in triglyceride form for safety, and powdered MCTs can be a convenient option for increasing ketone levels effectively.
  18. Consuming MCTs and reducing carbohydrates in the diet can potentially improve digestive health, aid in colonoscopy preparation, and have anti-seizure properties, but more research is needed to understand their full benefits.
  19. Exogenous ketones have the potential to benefit individuals with Angelman Syndrome and seizure disorders, but their use should be approached with caution due to the risk of lowering blood glucose levels.
  20. Consuming ketones can lower insulin levels and measuring ketones can be done through urine strips or blood tests for accurate results.
  21. Urine ketone strips offer some quantitative information on ketosis but can be affected by hydration levels. NASA's NEEMO mission will provide more comprehensive metabolic measurements.
  22. Replicating certain stressful conditions like being underwater can mimic fasting and promote fat burning, thus offering potential benefits for weight loss and metabolic changes.
  23. Lowering glucose levels while increasing ketones can boost metabolic rate, challenging the belief that fasting lowers metabolism. Calorie deficits may affect hormones, and disrupted circadian rhythms can impact body functioning.
  24. When choosing between ketone salts and ketone esters, consider taste, tolerability, and bioavailability. Ketone salts have better bioavailability, while ketone esters have a stronger taste and potency.
  25. The predominant d form of beta hydroxybutyrate in the body is different from the racemic ketone salts being sold, which can have negative side effects. The human ketone ester is a safer alternative.
  26. Collaboration between experts in the field of chemistry and research is essential in finding innovative solutions to improve the usability of therapeutic substances like ketone esters.
  27. The ratio of beta hydroxybutyrate to acetylacetate is crucial for anti-seizure effects, while racemic salts and esters pose no known health risks. The debate continues on the physiological benefits of ketone salts vs. ketone esters.
  28. Athletes who are fat adapted clear ketones more effectively and produce less lactate during intense exercise due to upregulated ketone transport facilitated by monocarboxylic acid transporters (MCTs), potentially influencing their ability to tolerate anaerobic activity.
  29. The ketogenic diet and metabolic stress show promise in targeting cancer hallmarks and impeding tumor growth, offering hope for patients with limited treatment options.
  30. By implementing press and pulse protocols, such as a calorie-restricted ketogenic diet and intermittent fasting, one can effectively limit fuel to cancer cells and suppress insulin levels, ultimately slowing down cancer growth.
  31. Understanding and targeting the metabolic physiology of cancer patients can enhance the effectiveness of traditional cancer treatments, offering more treatment options and potentially improving the chances of successful recovery.
  32. Hyperoxygenating tumors and inducing oxidative stress can be an effective treatment for tumors by triggering apoptosis and necrosis, contradicting the belief that antioxidants are always beneficial.
  33. Consuming low levels of antioxidants is generally harmless, but saturating the body with antioxidants may hinder the effectiveness of cancer treatments. Alternative protocols, like the pulse protocol, show promise in improving cancer treatment outcomes.
  34. Certain compounds can inhibit tumor cell growth and increase susceptibility to other therapies, when combined with a ketogenic diet and fasting, offering hope for alternative cancer treatments with minimal side effects.
  35. Fasting and achieving a ketogenic state can have significant impacts on the body's metabolism and resilience, highlighting the potential benefits and risks associated with extreme physiologic conditions. Further research is needed to fully understand these effects.
  36. Beta-hydroxybutyrate, produced during ketosis, has the ability to silence gene mutations and restore normal functioning in certain genetic diseases, highlighting the potential of alternative fuels and nutrition for improved health.
  37. Dom D'Agostino's dedication to researching and sharing knowledge on ketogenic nutrition has made a significant impact on individuals seeking therapeutic and preventive benefits.
  38. Dom D'Agostino is admired for his contributions, but it is crucial to remember the significance of seeking professional medical advice for individualized guidance.

📝 Podcast Summary

Expert insights on ketosis and exogenous ketones: a comprehensive resource for understanding their effects and applications.

Dominic Dagostino is an expert on ketosis and its various forms. He provides valuable insights on the use of exogenous ketones and their effects on the body. While the discussion can be highly technical at times, it is still understandable for those with a background in biochemistry. The podcast covers a range of topics, including the differences between ketone esters and salts, the role of MCT and caprylic acid, and the recommended dosage of ketones. Towards the end, there is a fascinating conversation about metabolic therapies for cancer, highlighting the importance of seeking appropriate medical guidance. Overall, the podcast serves as a comprehensive resource for anyone interested in understanding ketosis and its potential applications.

Unconventional Approaches and Curiosity: Unlocking Valuable Insights through Self-Experimentation

Self-experimentation and deep immersion in a subject can lead to valuable insights and discoveries. Dom D'Agostino's interest in diving physiology and extreme environments led him to study the brain and physiology's response to hyperbaric pressure and gas solubility. His background in neuroscience and physiology allowed him to develop new technologies, such as hyperbaric atomic force microscopy, to further investigate these areas. This highlights the importance of exploring unconventional approaches and embracing curiosity in order to expand our understanding of complex topics. By combining limited data with personal experimentation, we can uncover knowledge that may not be readily available or widely accepted yet.

Insights into Cancer Cell Behavior Using Atomic Force Microscopy and Hyperbaric Oxygen

Atomic force microscopy, combined with hyperbaric oxygen, can provide valuable insights into the behavior of cancer cells. Atomic force microscopy, which uses a sharp tip probe to detect changes in the sample's topography, has the ability to image living cells with high resolution. By placing this technology inside a hyperbaric chamber, researchers can observe the effects of hyperbaric oxygen on cancer cells at the microscopic level. It was observed that cancer cells produce excessive superoxide anion, a precursor to oxygen free radicals, and hyperbaric oxygen greatly accelerates this production. The use of atomic force microscopy allows for the measurement of membrane lipid peroxidation, providing a physical correlate of this phenomenon. This technology has the potential to further our understanding of cancer cell behavior and develop targeted treatment strategies.

Exploring the Potential of Hyperbaric Oxygen Therapy in Targeting Cancer Cells

Hyperbaric oxygen conditions can lead to the destruction of cancer cells. The experiment conducted by Dom D'Agostino showed that when cancer cells were exposed to almost five times atmospheric pressure of oxygen, their mitochondria exploded and the cells started to die. This observation was surprising because cancer cells are typically considered to be resilient. Further research is needed to fully understand the effects of hyperbaric oxygen on cancer cells, but this discovery opens up potential new avenues for cancer treatment. It is also important to note that the generation of free radicals and oxidative stress from the cells can affect neighboring cells within a cellular network. Overall, this conversation highlights the potential of hyperbaric oxygen therapy in targeting cancer cells.

The role of reactive oxygen species in cancer cell growth and potential therapeutic approaches.

Cancer cells have elevated levels of reactive oxygen species (ROS) that they use for growth, proliferation, metastasis, and invasiveness. While ROS are typically seen as damaging, they also serve as powerful signaling molecules for cancer cells. It is important to note that cancer cells have an antioxidant capacity, but their defective mitochondria lead to excessive production of ROS. The discovery was made when observing cancer cells under different conditions, including the presence of ketones. Interestingly, the cancer cells did not grow as rapidly in the presence of ketones. This finding suggests that therapies targeting oxidative stress, such as hyperbaric oxygen and chemotherapeutic drugs, as well as the ketogenic diet, could be used to counteract cancer cell growth by pushing cells beyond their antioxidant potential and triggering apoptosis.

The Potential of Ketones in Cellular and Molecular Mechanisms

Ketones have shown to be incredibly effective in cellular and molecular mechanisms. Dom D'Agostino discovered that ketones were a highly underutilized anti-seizure strategy and became motivated to integrate nutrition into his research projects. Through his studies, he found that normal healthy neurons thrived in a low glucose environment when ketones were present, while cancer cells were unable to survive. This discovery led him to further explore the relationship between ketones and cancer, even though it was not initially funded. The Warburg effect, which is insufficient mitochondrial oxidative phosphorylation, plays a crucial role in the development of cancer. Understanding this process and the effects of ketones can provide new insights into cancer treatment approaches.

The overlooked role of metabolism in understanding cancer

The Warburg effect, which describes how cancer cells generate energy through glycolysis and lactate production even in the presence of normal oxygen, was largely ignored in the study of cancer for several generations. This was primarily because scientists focused on understanding the genetic pathways associated with carcinogenesis rather than the metabolic processes. However, there has been a shift in recent years, with the recognition that metabolites and metabolism play a crucial role in cancer development. Metabolism produces various signaling molecules and epigenetic drivers, leading to the emergence of cancer metabolism conferences and the involvement of renowned scientists in the field. This highlights the importance of considering both genetics and metabolism in understanding and treating cancer.

Oxygen Toxicity Seizures and the Role of Ketone Esters in Hyperbaric Oxygen Therapy

There are two significant problems discussed: oxygen toxicity seizures in navy seal divers and the role of ketone esters in hyperbaric oxygen therapy. Oxygen toxicity seizures are a limitation for navy seal divers, and they also pose a risk in hyperbaric chambers. The use of ketone esters has shown an increase in resistance to oxygen toxicity by up to 600%. This suggests that incorporating therapeutic ketosis strategies could make hyperbaric oxygen therapy safer and more effective for treating various conditions, including wounds. Additionally, the conversation highlights the importance of adhering to dive tables to avoid seizures, but certain circumstances may require divers to go deeper, increasing their risk. Overall, understanding and addressing these challenges can significantly benefit the safety and health of divers and patients undergoing hyperbaric oxygen therapy.

Understanding the Impact of Oxygen Levels on Brain Function and Hyperbaric Oxygen Exposure

High levels of oxygen can lead to seizures and oxidative stress, particularly in extreme environments such as underwater or hyperbaric chambers. Navy divers and recreational divers are at risk of experiencing these seizures, which can be underreported. However, the seizures quickly cease once the oxygen source is removed or switched to breathing hyperbaric air. The seizures occur due to the imbalance between excitatory and inhibitory neurotransmitters in the brain. Furthermore, the exposure to high-pressure oxygen can have adaptive effects, such as enhancing antioxidant defenses and promoting cellular protection. However, the individual response to oxygen toxicity seizures varies based on genetics and other factors like sleep deprivation, diet, and illness. Overall, the conversation highlights the importance of understanding the impact of oxygen levels on brain function and the potential benefits and risks associated with hyperbaric oxygen exposure.

The Potential Benefits and Applications of Hyperbaric Oxygen Therapy (HBOT)

Hyperbaric oxygen therapy (HBOT) has multiple approved applications and potential benefits. HBOT has shown effectiveness in enhancing wound healing, treating radiation necrosis in cancer patients, managing decompression sickness in divers, and addressing diabetic wounds. It is also being explored as a treatment for noise-induced hearing loss and traumatic brain injury. While some applications may seem counterintuitive, such as the susceptibility of newborns to high levels of oxygen, HBOT has exhibited remarkable responses in certain cases, including the regeneration of brain cells in severely hypoxic brain injuries. However, it is important to note that while there are anecdotal reports, further research is needed to better understand and validate the range of benefits of HBOT.

The Need for Studying Traumatic Brain Injuries and Their Treatments

There is a need for rigorous and empirical studies on traumatic brain injuries (TBIs) and their treatments. Both athletes and soldiers are highly affected by TBIs, yet there seems to be a resistance when it comes to studying this issue. The conversation highlights the complexity of finding the right treatment methods, such as hyperbaric oxygen therapy, which can have both positive and negative effects. It is emphasized that such therapies should be studied thoroughly and not pursued without proper research and guidance. Additionally, the conversation touches on the potential benefits of implementing a metabolic-based therapy, specifically through the use of ketones, in order to improve brain energy metabolism and reduce neuroinflammation.

Glucose levels decrease and are maintained during prolonged fasting

During a prolonged fasting period, the levels of glucose in the subjects' bodies decreased significantly and remained low throughout the experiment. This suggests that the liver still had glycogen stores and was continuously releasing glucose into the bloodstream. The subjects maintained glucose levels through homeostatic mechanisms and the breakdown of muscle and triglyceride glycerol. Interestingly, insulin levels also became very low by day 7 and remained low. Moreover, the subjects did not experience any symptoms of hypoglycemia, even when injected with high doses of insulin that would be fatal for someone not in a fasted state. These findings highlight the body's ability to adapt and maintain glucose levels even during an extended fasting period.

The Role of Ketones in Brain Energy Utilization

The brain can use both glucose and ketones as sources of energy, with ketones becoming the predominant fuel after prolonged fasting. The discussion highlights how ketones can play a crucial role in providing energy to the brain, accounting for approximately 60% of its energy during a fasted state. This challenges the traditional belief that glucose is the exclusive and predominant fuel for the brain. The conversation also reveals the potential of manipulating metabolic physiology to shift towards utilizing fats and ketones as fuel sources. While the specifics of unpublished research are not shared, it is suggested that further experimentation in animals has shown the potential for glucose levels to be lowered even more, emphasizing the adaptability and flexibility of the brain's energy utilization.

The potential of ketones in revolutionizing metabolic physiology and enhancing performance and health.

The discovery of the unique properties of ketones has revolutionized our understanding of metabolic physiology. Ketones, such as lactate, have been found to be a great fuel source for the brain and can even replace glucose as the primary energy source. Moreover, ketones have signaling properties that go beyond their role in metabolism, including epigenetic effects and inflammation suppression. However, in order to tap into the benefits of ketones, significant physiological changes are required, such as following a strict ketogenic diet that involves restricting carbohydrates and protein. The conversation highlights the importance of exploring both endogenous and exogenous pathways to harness the potential of ketones for improved performance and health.

Ketosis and the Potential Benefits of Ketones

The body can produce ketones, specifically beta hydroxybutyrate and acetoacetate, as an alternative fuel source during periods of fasting or carbohydrate restriction. This process, called ketosis, occurs when the body's stored glycogen is depleted and fat is mobilized for energy. The liver plays a crucial role in producing and releasing ketones, which can be utilized by the brain and peripheral tissues. Ketones have been shown to have potential neuroprotective and anti-convulsive effects, making them beneficial for certain neurological conditions. Furthermore, the Krebs cycle, which is responsible for ATP production, can be influenced by the presence of ketones in different cells and pathways. Understanding ketone metabolism may have implications for various areas, including cancer research.

The Complexities of Cancer Metabolism: A Constant Need for Adaptation

The rate at which new information is being discovered in the field of cancer metabolism is exceeding the rate at which researchers can fully understand and assimilate it. Both Peter Attia and Dom D’Agostino express their surprise at the complexity and nuances of metabolic pathways that they previously thought were simple and well-understood. They discuss the importance of aspartate and glutamine in cancer metabolism, as well as the challenges in targeting these pathways for treatment due to potential toxicity. They also highlight the beneficial role of medium chain triglycerides (MCTs) in enhancing ketone levels and supporting the ketogenic diet. This conversation emphasizes the constant need for researchers to adapt and continue learning in order to stay ahead in their field.

Increasing Ketone Levels with MCTs

MCTs (medium-chain triglycerides) can significantly increase ketone levels in the body. Consuming 2 to 3 tablespoons of MCT on a high carb diet can elevate blood ketone levels to approximately 0.5 to 1 millimolar. Pure C8 (Caprylic acid) MCTs have a more pronounced effect compared to a mix of C10 (Capric acid) and other MCTs. However, it is important to purchase MCTs in the triglyceride form rather than as pure acid, as the latter can be harmful when ingested. Powdered MCTs, such as the Quest MCT formula, can be a convenient and effective way to increase ketone levels. Incorporating MCTs with meals and spreading their consumption throughout the day can enhance tolerability and effectiveness.

The Potential Health Benefits of MCTs and Low Carb Diets

Consuming MCT (medium-chain triglycerides) can have positive effects on digestive health and potentially aid in colonoscopy preparation. MCTs have the ability to cross the blood-brain barrier and be utilized as fuel by the brain, making them a functional fat with potential anti-seizure properties. While the exact mechanism of how MCTs work is still being studied, research suggests that they may play a significant role in the benefits of a ketogenic diet, alongside ketones. Additionally, reducing carbohydrates in the diet, particularly through low glycemic index foods, can also have positive effects on certain types of seizures. Further research is needed to understand the potential anti-seizure benefits of exogenous ketone supplementation in individuals on a high-carbohydrate diet.

Potential of exogenous ketones as therapy for Angelman Syndrome and seizure disorders, with positive effects reported but caution needed due to potential blood glucose level decrease.

Exogenous ketones have shown potential as a therapy for Angelman Syndrome and various seizure disorders. In some cases, they have been used as an alternative to the ketogenic diet. The feedback from individuals using exogenous ketones has indicated positive effects, which is supported by animal models. However, it is important to consider that exogenous ketones can lower blood glucose levels, even to dangerously low levels. Researchers are still trying to understand why ketones lower glucose levels and why aggressive exercise can lead to a decrease in ketones and an increase in glucose. Possible explanations include a ketone-induced release of insulin, which affects glucose disposal. Further research is needed to fully understand the mechanisms involved.

Ketones and Insulin Levels

Consuming ketones can decrease baseline levels of insulin over time. Researchers have found that the addition of ketones to rat chow resulted in a significant decrease in insulin levels. This effect was also observed in the speaker's personal experimentation, where consuming exogenous ketones led to insulin levels below the reference range. Additionally, when compared to consuming protein or carbohydrates, ketones only caused a small increase in insulin levels. It is important to note that measuring ketones can be done through urine strips or blood tests, with both methods providing accurate results. While urine ketone strips can indicate if someone is in ketosis or not, blood tests offer a more precise measurement of beta hydroxybutyrate levels.

The role of urine ketone strips in measuring ketosis and their limitations, coupled with the impact of hydration status on results.

Urine ketone strips can be a useful tool for individuals to measure their state of ketosis. While they may not be highly accurate, they do provide some quantitative information through color changes on the strip that can be measured using a device. However, it is important to consider factors such as hydration status, as it can affect the results. The conversation also highlights the experiences of maintaining ketosis in extreme environments, such as a hyperbaric habitat on the ocean floor, where dehydration and lower blood glucose levels were observed. The upcoming NASA NEEMO mission will provide more comprehensive metabolic measurements, including glucose and ketones, on an all-female crew.

The Impact of Saturated Environment on Testosterone Levels and Sleep Patterns

Dom D'Agostino's experience in a saturated environment for 10 days led to a 25% decrease in his testosterone levels. Additionally, his sleep patterns were significantly affected, with less time spent in deep sleep and REM sleep. However, being in water and experiencing hypothermia seemed to enhance his body's ability to burn fat, as his ketone levels increased and glucose levels decreased. This effect was more pronounced during longer periods of underwater activity compared to nitrox dives. The combination of temperature and duration of exposure appeared to play a significant role in these metabolic changes. It suggests that replicating certain stressful conditions, such as being underwater, may have potential benefits in terms of mimicking fasting and promoting fat burning.

The Impact of Glucose Levels and Ketones on Metabolic Rate

Dom D'Agostino's experience during the NASA NEEMO mission showed that even with high calorie consumption, his metabolic rate remained high due to low glucose levels and high ketone levels. This contradicts the expectation that fasting for a week would lower metabolic rate. It suggests that anything that lowers glucose levels while increasing ketones can have a positive impact on metabolic rate. Dom also mentioned that being in a calorie deficit during the mission may have decreased his testosterone and increased his cortisol levels. Additionally, the disrupted circadian rhythm due to being away from natural light could have affected his body's functioning. The discussion also touched on the first exogenous ketone to be manufactured, which was 13 butane dial, and the difference between a salt and an ester form of beta hydroxybutyrate.

Understanding Different Forms of Ketones

There are different forms of ketones available, including ketone salts and ketone esters. Ketone salts are formed through an ionic bond between the ketone molecule and various cations like sodium, potassium, calcium, and magnesium. One advantage of magnesium BHB is its bioavailability, but the GI tolerability may be limited. On the other hand, ketone esters are formed through a covalent bond and can be created using different compounds like 13 butane dial or glycerol. These esters tend to have a stronger taste compared to ketone salts, as their potency increases. Overall, both ketone salts and ketone esters have their own benefits and it's important to consider taste, tolerability, and bioavailability when choosing between them.

Enantiomers of Ketones and Concerns with Racemic Ketone Salts

There is a distinction between the enantiomers of ketones, specifically the d and l forms of beta hydroxybutyrate (BHP). The d form is the predominant form of BHP in the body during nutritional or starvation ketosis. However, many ketone salts being sold are racemic, meaning they contain equal amounts of both the d and l forms. This raises concerns as the wrong enantiomer can have negative side effects, as seen with infamous cases like FENFEN and FELITIMID. The human ketone ester, on the other hand, is completely d and mirrors physiological levels. Elevating acetylacetate along with beta hydroxybutyrate seems to have an anti-seizure effect, although the exact mechanism is not fully understood.

Overcoming the Taste Challenge: Making Ketone Esters More User-Friendly

Ketone esters have shown remarkable positive effects on biomarkers, but their taste is a major challenge. As a result, they may be more suitable as a medical food or a parenteral IV therapy capsule. Dom D'Agostino, an expert in the field, reached out to researchers and chemists, including Patrick Arnold, to find a way to synthesize the esters in a consumable form. Patrick Arnold played a significant role in perfecting the organic chemistry process, synthesizing the esters into a pure diester compound. This collaboration highlights the importance of teamwork and expertise in developing innovative solutions to make therapeutic substances more user-friendly.

The impact of exogenous ketones and their effect on seizures and health concerns.

The use of exogenous ketones in the form of pure beta hydroxybutyrate is not beneficial for anti-seizure effects. It has been found that delivering exogenous ketones in a beta hydroxybutyrate to acetylacetate ratio of 1 to 1 has remarkable anti-seizure effects. Acetylacetate is necessary for these effects. However, there is no data suggesting that racemic salts or esters that produce both d and l forms of beta hydroxybutyrate are a health concern. Companies selling racemic salts have not reported any negative consequences. There may be some intellectual property in the formulation of ketone salts, but the debate remains on whether ketone salts or ketone esters have more physiological benefits. The l form of beta hydroxybutyrate tends to have stronger anti-inflammatory effects. The racemic beta hydroxybutyrate has also been observed to lower glucose levels, especially with 13 butane dial.

The Role of Fat Adaptation and Monocarboxylic Acid Transporters in Athletes' Performance

Athletes who are fat adapted, meaning they have trained their bodies to efficiently utilize ketones for fuel, are able to dispose of and utilize ketones more effectively. When these athletes are given high doses of ketones, they quickly clear them from their systems due to upregulated ketone transport across membranes. This upregulation is facilitated by monocarboxylic acid transporters (MCT) which also transport lactate and pyruvate. The increased density of MCTs in the membranes of these athletes may explain why they produce less lactate during intense exercise. This finding suggests that the genetic differences observed in athletes' ability to tolerate anaerobic activity could be related to the efficiency of lactate clearance.

Alternative Approaches for Complex Cancers

When faced with a cancer diagnosis that has exhausted all standard therapies, alternative approaches may be considered. Specifically, in the case of glioblastoma (GBM) and metastatic breast cancer, the ketogenic diet and metabolic stress can potentially be beneficial. A PET scan can be useful in identifying high glycolytic tumors like GBM. The ketogenic diet targets the Warburg effect, which is a characteristic of cancer cells, and addresses various hallmarks of cancer such as enhanced proliferation, immune system evasion, and angiogenesis. By achieving a glucose ketone index, metabolic stress can be applied to cancer cells, impeding their growth and proliferation. While further research is needed, this approach offers hope for individuals facing limited treatment options for complex cancers.

Slowing Cancer Growth Through Metabolic Stress

There are effective ways to slow down cancer growth and proliferation by metabolically stressing cancer cells. One approach is through press protocols, which involve continuous methods like a calorie-restricted ketogenic diet, intermittent fasting, and low-dose metformin. The ideal glucose to ketone ratio for maintenance is 1 to 2, with glucose never being more than twice the ketone level. Achieving this ratio can be done through tools like supplemented ketogenic intermittent fasting and consuming exogenous ketones within a restricted time window. These methods limit fermentable fuels to cancer cells and suppress insulin levels. Additionally, pulse protocols can be used to target the Warburg effect and other cancer hallmarks by changing metabolic physiology. It is important to focus on achieving and maintaining a glucose ketone index of 1 to 2 or better.

The Role of Metabolic Oncology in Enhancing Cancer Treatments

There is a need for a new type of oncologist known as a metabolic oncologist. Currently, cancer treatment primarily focuses on chemotherapy, radiation, immune-based therapies, and surgery. However, by understanding and targeting the metabolic physiology of cancer patients, new modalities can be developed to enhance the effectiveness of these treatments. Research has shown that being in a state of nutritional ketosis can significantly improve the efficacy of radiation therapy in mouse models of glioblastoma. Hyperbaric oxygen therapy, when done at a specific frequency, can also reverse tumor hypoxia and increase tissue oxygenation, leading to better treatment outcomes. By combining these metabolic interventions with traditional cancer treatments, we can expand the options for patients and potentially improve their chances of successful recovery.

Inducing oxidative stress through hyperoxygenation and intravenous vitamin C as a potential treatment for tumors.

By hyperoxygenating a tumor through hyperbaric oxygen and intravenous vitamin C, one can induce a massive oxidative stress specifically to the tumor while relatively sparing healthy cells. This is because tumors thrive in a low oxygen environment and have damaged mitochondria. The hyperoxygenation causes the production of superoxide anions and hydroxyl radicals, leading to a significant oxidative stress on the tumor cells. This can trigger apoptosis and necrosis, ultimately destroying the tumor. Interestingly, this approach contradicts the common belief that antioxidants are always beneficial. In the case of cancer, using antioxidants may not be the best strategy. Instead, inducing oxidative stress can potentially be an effective treatment.

The Potential Impact of Antioxidants on Cancer Therapies

Antioxidants may potentially hinder the effectiveness of certain cancer therapies, such as chemotherapeutic drugs and radiation. While consuming low levels of antioxidants from sources like blueberries is generally fine, saturating the body with a cocktail of antioxidants should be avoided. Research in animal models and humans does not support the use of antioxidants in the context of cancer treatment. On the other hand, certain protocols like the pulse protocol can benefit cancer patients. One potential addition to the pulse protocol is a low dose of metformin, which can activate amp kinase and potentially decrease insulin and increase ketones. Other potential components of the pulse protocol include hyperbaric oxygen, IV vitamin C, and drugs like 2doxyglucose and dichloroacetate (DCA) that inhibit glycolytic pathways and make cancer cells more vulnerable to oxidative stress. These treatments are currently being studied in humans, and early data suggests potential efficacy and safety. DCA is also used to treat lactic acidosis.

Potential Therapeutic Approaches for Treating Cancer with Metabolic Stress and Alternative Therapies

There are potential therapeutic approaches that can be used to treat cancer by inducing metabolic stress on tumor cells. Dom D'Agostino explains that certain compounds, such as bromopyruvate and lonitamine, can inhibit the growth of tumor cells and increase their susceptibility to other modalities like hyperbaric oxygen therapy and IV vitamin C. The use of these therapies, when combined with a ketogenic diet and fasting, can create a gentle stress on the tumor cells, making them more vulnerable and less resistant to treatment. This comprehensive metabolic-based therapy aims to improve the overall metabolic biomarkers of patients while minimizing collateral damage and side effects commonly associated with traditional chemotherapy and radiation. Although still in the theoretical stage, there are physicians who are experimenting with these approaches, providing hope for alternative cancer treatments.

Exploring the Impacts of Fasting and Ketogenic State on Metabolism and Resilience

Fasting and achieving a ketogenic state can have significant impacts on the body's metabolism and resilience. Dom D’Agostino shares his experience of a 7-day fast, during which his ketone levels and glucose levels dropped dramatically. This motivated him to focus on researching metabolic therapies that utilize ketones as an alternative energy source. Peter Attia emphasizes the importance of conducting further research and experiments to understand the potential benefits and risks associated with such extreme physiologic conditions. Dom's physical performance during the fast, including deadlifting impressive weights, highlights the body's ability to adapt and remain resilient in a keto-adapted state. This understanding has implications not just for personal health and performance, but also for military applications where maintaining physical and cognitive resilience under austere conditions may be crucial.

The Power of a Ketogenic Diet on Gene Regulation and Health

The body's ability to adapt to a ketogenic diet can have profound effects on gene transcription and epigenetic regulation. Dom D’Agostino highlights the remarkable discovery that beta-hydroxybutyrate, a metabolite produced during ketosis, functions as a powerful endogenous signaling molecule and histone deacetylase inhibitor. Through these actions, it can silence gene mutations and restore normal functioning in certain genetic diseases, such as Kabuki Syndrome. This reveals the potential for alternative fuels and nutrition to have significant impacts on our health and biology. It also underscores the importance of maintaining mitochondrial health and bioenergetic efficiency, as they play a crucial role in preserving genome stability and suppressing tumor growth. These findings are just the tip of the iceberg in our understanding of metabolic processes and their influence on gene expression, highlighting the exciting potential for future research and discoveries.

Dom D'Agostino: A Leading Expert in Ketogenic Nutrition and Metabolic Health

Dom D’Agostino is a valuable resource for anyone interested in ketogenic nutrition and metabolic health. He maintains a website,, where he shares podcasts, nutrition consultants, and resources like the Charlie Foundation. Dom also conducts self-experiments, tests ketone supplements and foods, and collects data that he shares on his blog. He is also involved in organizing the Metabolic Health Summit, which aims to make nutritional ketosis accessible to a wider audience for therapeutic, preventive, and lifestyle purposes. Dom encourages sponsors and speakers to participate in the summit. Peter Attia expresses his gratitude to Dom for his generosity in sharing knowledge and mentions how Dom's work has positively impacted the life of a breast cancer patient on a ketogenic diet.

Dom D'Agostino's Appreciation and Importance of Medical Guidance

Dom D'Agostino is highly regarded and appreciated by many. Peter Attia expresses his admiration for Dom and refers to him as an amazing person and a treasure. In response, Dom expresses his gratitude for the platform provided by Peter and acknowledges the value it will bring to many individuals. Despite their professional relationship, Peter emphasizes the importance of seeking professional medical advice and clarifies that the podcast is for general informational purposes only, and does not constitute medical advice or establish a doctor-patient relationship. Peter also highlights his commitment to transparency by mentioning his conflicts of interest and providing a link for disclosures. Overall, the key takeaway is the appreciation for Dom's contribution and the importance of seeking proper medical guidance.