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    #05 - Dom D’Agostino, Ph.D.: ketosis, n=1, exogenous ketones, HBOT, seizures, and cancer

    enJuly 16, 2018

    Podcast Summary

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

      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-ExperimentationSelf-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.

      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 OxygenAtomic 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.

      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 CellsHyperbaric oxygen therapy has shown promise in destroying cancer cells through the explosion of their mitochondria, offering new possibilities for cancer treatment.

      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 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.

      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 MechanismsKetones 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.

      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 cancerMetabolism and genetics are both important factors in cancer development and treatment.

      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 TherapyIncorporating 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.

      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 ExposureHigh 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.

      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)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.

      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 TreatmentsRigorous 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.

      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 fastingThe 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.

      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 UtilizationKetones 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.

      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.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.

      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 KetonesKetones 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.

      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 AdaptationAs 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.

      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 MCTsConsuming 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.

      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 DietsConsuming 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.

      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 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.

      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 LevelsConsuming ketones can lower insulin levels and measuring ketones can be done through urine strips or blood tests for accurate results.

      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 offer some quantitative information on ketosis but can be affected by hydration levels. NASA's NEEMO mission will provide more comprehensive metabolic measurements.

      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 PatternsReplicating certain stressful conditions like being underwater can mimic fasting and promote fat burning, thus offering potential benefits for weight loss and metabolic changes.

      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 RateLowering 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.

      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 KetonesWhen 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.

      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 SaltsThe 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.

      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-FriendlyCollaboration 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.

      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 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.

      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' PerformanceAthletes 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.

      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 CancersThe ketogenic diet and metabolic stress show promise in targeting cancer hallmarks and impeding tumor growth, offering hope for patients with limited treatment options.

      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 StressBy 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.

      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 TreatmentsUnderstanding 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.

      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.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.

      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 TherapiesConsuming 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.

      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 TherapiesCertain 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.

      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 ResilienceFasting 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.

      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 HealthBeta-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.

      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 HealthDom D'Agostino's dedication to researching and sharing knowledge on ketogenic nutrition has made a significant impact on individuals seeking therapeutic and preventive benefits.

      Dom D’Agostino is a valuable resource for anyone interested in ketogenic nutrition and metabolic health. He maintains a website, ketomutrition.org, 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 GuidanceDom D'Agostino is admired for his contributions, but it is crucial to remember the significance of seeking professional medical advice for individualized 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.

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    Ted Schaeffer is an internationally recognized urologist specializing in prostate cancer and a returning guest on The Drive. In this episode, Ted provides insights into the role testosterone plays, or doesn't play, in the initiation and progression of prostate cancer. He unpacks the findings and limitations of the recent TRAVERSE trial, exploring the complex relationship between testosterone and prostate cancer. Ted delves into the molecular nature of prostate cancer, explaining the androgen receptor saturation theory and the potential impact of testosterone on cancer growth. He also discusses the use of the Decipher test to predict cancer aggressiveness and guide targeted treatment. Furthermore, Ted shares how he counsels patients regarding testosterone replacement therapy (TRT), including its safe administration in patients with low-grade prostate cancer. Additionally, he highlights advancements in prostate cancer therapies and biomarkers that help develop precise treatment strategies while minimizing the need for broad androgen deprivation therapy.

    We discuss:

    • Background on the TRAVERSE trial: insights into exogenous testosterone and prostate cancer risk [3:00];
    • The androgen receptor saturation theory: how different organs respond to varying levels of testosterone [10:30];
    • The relationship between testosterone levels and prostate cancer aggressiveness: how aggressive prostate tumors have lower androgen receptor activity and rely on different growth mechanisms [16:15];
    • Using the Decipher score to assess prostate cancer aggressiveness and guide personalized treatment strategies [23:45];
    • Considerations for testosterone replacement therapy: how Ted counsels patients, how TRT can be safely administered in patients with low-grade prostate cancer, and more [31:15];
    • Advancements in prostate cancer therapies and PSA as a biomarker for precise treatment decisions, minimizing the need for broad androgen deprivation therapy [38:30]; and
    • More.

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    The Peter Attia Drive
    enJuly 22, 2024

    #309 ‒ AI in medicine: its potential to revolutionize disease prediction, diagnosis, and outcomes, causes for concern in medicine and beyond, and more | Isaac Kohane, M.D., Ph.D.

    #309 ‒ AI in medicine: its potential to revolutionize disease prediction, diagnosis, and outcomes, causes for concern in medicine and beyond, and more | Isaac Kohane, M.D., Ph.D.

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    Isaac "Zak" Kohane, a pioneering physician-scientist and chair of the Department of Biomedical Informatics at Harvard Medical School, has authored numerous papers and influential books on artificial intelligence (AI), including The AI Revolution in Medicine: GPT-4 and Beyond. In this episode, Zak explores the evolution of AI, from its early iterations to the current third generation, illuminating how it is transforming medicine today and unlocking astonishing possibilities for the future. He shares insights from his unconventional journey and early interactions with GPT-4, highlighting significant AI advancements in image-based medical specialties, early disease diagnosis, and the potential for autonomous robotic surgery. He also delves into the ethical concerns and regulatory challenges of AI, its potential to augment clinicians, and the broader implications of AI achieving human-like creativity and expertise.

    We discuss:

    • Zak’s unconventional journey to becoming a pioneering physician-scientist, and his early interactions with GPT-4 [2:15];
    • The evolution of AI from the earliest versions to today’s neural networks, and the shifting definitions of intelligence over time [8:00];
    • How vast data sets, advanced neural networks, and powerful GPU technology have driven AI from its early limitations to achieving remarkable successes in medicine and other fields [19:00];
    • An AI breakthrough in medicine: the ability to accurately recognize retinopathy [29:00];
    • Third generation AI: how improvements in natural language processing significantly advanced AI capabilities [32:00];
    • AI concerns and regulation: misuse by individuals, military applications, displacement of jobs, and potential existential concerns [37:30];
    • How AI is enhancing image-based medical specialties like radiology [49:15];
    • The use of AI by patients and doctors [55:45];
    • The potential for AI to augment clinicians and address physician shortages [1:02:45];
    • The potential for AI to revolutionize early diagnosis and prediction of diseases: Alzheimer’s disease, CVD, autism, and more [1:08:00];
    • The future of AI in healthcare: integration of patient data, improved diagnostics, and the challenges of data accessibility and regulatory compliance [1:17:00];
    • The future of autonomous robotic surgery [1:25:00];
    • AI and the future of mental health care [1:31:30];
    • How AI may transform and disrupt the medical industry: new business models and potential resistance from established medical institutions [1:34:45];
    • Potential positive and negative impacts of AI outside of medicine over the next decade [1:38:30];
    • The implications of AI achieving a level of creativity and expertise comparable to exceptional human talents [1:42:00];
    • Digital immortality and legacy: the potential to emulate an individual's personality and responses and the ethical questions surrounding it [1:45:45];
    • Parting thoughts [1:50:15]; and
    • More.

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    The Peter Attia Drive
    enJuly 15, 2024

    Zone 2 training: impact on longevity and mitochondrial function, how to dose frequency and duration, and more | Iñigo San-Millán, Ph.D. (#201 rebroadcast)

    Zone 2 training: impact on longevity and mitochondrial function, how to dose frequency and duration, and more | Iñigo San-Millán, Ph.D. (#201 rebroadcast)

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    Iñigo San-Millán is an internationally renowned applied physiologist and a previous guest on The Drive. His research and clinical work focuses on exercise-related metabolism, metabolic health, diabetes, cancer metabolism, nutrition, sports performance, and critical care. In this episode, Iñigo describes how his work with Tour de France winner Tadej Pogačar has provided insights into the amazing potential of elite athletes from a performance and metabolic perspective. He speaks specifically about lactate levels, fat oxidation, how carbohydrates in food can affect our lactate and how equal lactate outputs between an athlete and a metabolically unhealthy individual can mean different things. Next, he discusses how Zone 2 training boosts mitochondrial function and impacts longevity. He explains the different metrics for assessing one’s Zone 2 threshold and describes the optimal dose, frequency, duration, and type of exercise for Zone 2. Additionally, he offers his thoughts on how to incorporate high intensity training (Zone 5) to optimize health, as well as the potential of metformin and NAD to boost mitochondrial health. Finally, he discusses insights he’s gathered from studying the mitochondria of long COVID patients in the ICU.

    We discuss:

    • The amazing potential of cyclist Tadej Pogačar [2:00];
    • Metrics for assessing athletic performance in cyclists and how that impacts race strategy [7:30];
    • The impact of performance-enhancing drugs and the potential for transparency into athletes’ data during competition [16:15];
    • Tadej Pogačar’s race strategy and mindset at the Tour de France [23:15];
    • Defining Zone 2, fat oxidation, and how they are measured [26:00];
    • Using fat and carbohydrate utilization to calculate the mitochondrial function and metabolic flexibility [35:00];
    • Lactate levels and fat oxidation as it relates to Zone 2 exercise [39:15];
    • How moderately active individuals should train to improve metabolic function and maximize mitochondrial performance [51:00];
    • Bioenergetics of the cell and what is different in elite athletes [56:30];
    • How the level of carbohydrate in the diet and ketogenic diets affects fuel utilization and power output during exercise [1:07:45];
    • Glutamine as a source for making glycogen—insights from studying the altered metabolism of ICU patients [1:14:15];
    • How exercise mobilizes glucose transporters—an important factor in diabetic patients [1:20:15];
    • Metrics for finding Zone 2 threshold—lactate, heart rate, and more [1:24:00];
    • Optimal Zone 2 training: dose, frequency, duration, and type of exercise [1:40:30];
    • How to incorporate high intensity training (Zone 5) to increase VO2 max and optimize fitness [1:50:30];
    • Compounding benefits of Zone 2 exercise and how we can improve metabolic health into old age [2:01:00];
    • The effects of metformin, NAD, and supplements on mitochondrial function [2:04:30];
    • The role of lactate and exercise in cancer [2:12:45];
    • How assessing metabolic parameters in long COVID patients provides insights into this disease [2:18:30];
    • The advantages of using cellular surrogates of metabolism instead of VO2 max for prescribing exercise [2:25:00];
    • Metabolomics reveals how cellular metabolism is altered in sedentary individuals [2:33:00];
    • Cellular changes in the metabolism of people with diabetes and metabolic syndrome [2:38:30]; and
    • More.

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    The Peter Attia Drive
    enJuly 08, 2024

    #308 - AMA #61: Sun exposure, sunscreen, and skin health: relationship between sun exposure and skin cancer, vitamin D production, and photoaging, how to choose a sunscreen, and more

    #308 - AMA #61: Sun exposure, sunscreen, and skin health: relationship between sun exposure and skin cancer, vitamin D production, and photoaging, how to choose a sunscreen, and more

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    In this “Ask Me Anything” (AMA) episode, Peter delves into two topics that have generated a lot of questions over the years: skin cancer and sunscreen. He begins by exploring the basics of UV radiation, discussing its effects on vitamin D conversion, photoaging, and its role in skin cancer. He examines various skin types, discussing their implications for sun exposure and vitamin D levels, as well as how to determine where you fall on the skin type scale. He then delves into the various types of skin cancer, with a particular emphasis on melanoma, exploring its complex relationship with UV exposure and other contributing risk factors. Additionally, he covers tanning beds, the importance of early skin cancer detection through regular skin checks, and the often confusing topic of sunscreen. He explains how sunscreen affects UV radiation and skin cancer risk, what SPF levels to choose, the differences between organic and mineral sunscreens, and what to consider when selecting the best sunscreen for your needs.

    If you’re not a subscriber and are listening on a podcast player, you’ll only be able to hear a preview of the AMA. If you’re a subscriber, you can now listen to this full episode on your private RSS feed or our website at the AMA #61 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here.

    We discuss:

    • The impact of UV radiation on the skin [2:00];
    • Understanding solar UV: from the electromagnetic spectrum to skin health [3:45];
    • The role of sunlight in vitamin D production [8:30];
    • Factors contributing to vitamin D deficiency: insufficient UV exposure, magnesium levels, and more [9:45];
    • Sun exposure needs for different skin types, and the limitations of current studies in defining vitamin D deficiency [12:45];
    • The acute and long-term effects of excessive UV exposure: sunburn, photoaging, and the increased risk of skin cancer [15:30];
    • Types of skin cancer and associations with UV exposure [17:45];
    • The complex relationship between melanoma and UV exposure [22:15];
    • Why UV exposure alone doesn’t necessarily explain the risk for melanoma [25:15];
    • Other risk factors for melanoma [29:15];
    • Tanning beds and skin cancer risk [34:45];
    • Balancing sun exposure: benefits and risks [38:15];
    • Tattoos and sun exposure [40:30];
    • The importance of regular skin checks, dermatologists, and emerging technologies showing promise for early detection of cancer [41:45];
    • Self-skin checks: what to look for [46:30];
    • Prevalence of skin cancer and the importance of early detection [49:30];
    • Summary of the major risk factors for melanoma [54:15];
    • The role of sunscreen in reducing skin cancer risk [55:45];
    • How sunscreen works, the differences between chemical and mineral sunscreens, an explanation of SPF, and more [58:30];
    • How to determine the appropriate sunscreen SPF to use based on the UV index [1:04:45];
    • Choosing the right sunscreen for your individual needs [1:07:00];
    • The impact of water and perspiration on sunscreen effectiveness [1:12:00];
    • Chemical vs. mineral sunscreens: safety concerns and recommendations [1:14:00];
    • Concerns about hormone effects from chemical sunscreens [1:19:15];
    • Sunscreen summary: skin types, key considerations, recommended brands, and more [1:23:15]; and
    • More.

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    The Peter Attia Drive
    enJuly 01, 2024

    #307 ‒ Exercise for aging people: where to begin, and how to minimize risk while maximizing potential | Peter Attia, M.D.

    #307 ‒ Exercise for aging people: where to begin, and how to minimize risk while maximizing potential | Peter Attia, M.D.

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    In this special episode, Peter addresses the common questions about starting or returning to an exercise routine over the age of 50. Individuals in this age group have frequently reached out with questions about whether it's too late to start exercising and often express concern over a lack of prior training, a fear of injury, or uncertainty about where to begin. Peter delves into the importance of fitness for older adults, examining all four pillars of exercise, and provides practical advice on how to start exercising safely, minimize injury risk, and maximize potential benefits. Although this conversation focuses on people in the “older” age category, it also applies to anyone of any age who is deconditioned and looking to ease into regular exercise.

    We discuss:

    • Key points about starting exercise as an older adult [2:45];
    • Why it’s never too late to begin exercising and incorporating the four pillars of exercise [5:45];
    • The gradual, then sharp, decline in muscle mass and activity level that occur with age [10:00];
    • The decline of VO2 max that occurs with age [15:30];
    • Starting a training program: exercise variability, movement quality, realistic goals, and more [18:30];
    • Improving aerobic capacity: the malleability of the system, the importance of consistency, and setting long-term fitness goals [25:15];
    • Starting cardio training: base building, starting with low volume, and zone 2 training [30:45];
    • The critical role of VO2 max in longevity [36:45];
    • How to introduce VO2 max training to older or deconditioned individuals [46:15];
    • Options for performing zone 2 and VO2 max training [53:45];
    • The ability to make gains in strength and muscle mass as we age [57:00];
    • How to implement strength training for older individuals [1:01:00];
    • Advice for avoiding injury when strength training [1:07:30];
    • Risk of falls: the devastating consequences and the factors that increase fall risk [1:12:15];
    • Mitigating fall risk: the importance of foot and lower leg strength, ankle mobility, and balance [1:19:45];
    • Improving bone mineral density through resistance training [1:24:30];
    • The importance of protein in stimulating muscle protein synthesis, especially in older adults [1:31:00];
    • Parting advice from Peter [1:34:00]; and
    • More.

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    The Peter Attia Drive
    enJune 24, 2024

    #306 - AMA #60: preventing cognitive decline, nutrition myths, lowering blood glucose, apoB, and blood pressure, and more

    #306 - AMA #60: preventing cognitive decline, nutrition myths, lowering blood glucose, apoB, and blood pressure, and more

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    In this “Ask Me Anything” (AMA) episode, Peter provides insights on a broad range of important topics. He delves into the prevention of cognitive decline, the link between cardiovascular disease and Alzheimer's disease, and methods to lower blood glucose, insulin, and apoB. He also addresses nutrition-related queries, exploring the impact of dietary habits on weight loss and longevity, how a person can identify the best diet for themselves, and common nutrition myths. Additional discussions include optimal blood pressure, daily step goals, the benefits of standing versus sitting desks, and much more.

    If you’re not a subscriber and are listening on a podcast player, you’ll only be able to hear a preview of the AMA. If you’re a subscriber, you can now listen to this full episode on your private RSS feed or our website at the AMA #60 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here.

    We discuss:

    • Overview of topics and episode format [1:40];
    • Preventing cognitive decline [5:00];
    • How to lower blood glucose and insulin [13:30];
    • The relationship between lipids, CVD, and Alzheimer’s disease, and whether statins can increase the risk of neurodegenerative disorders and AD [23:15];
    • Reducing apoB levels through exercise and diet [31:45];
    • Pharmacological options for lowering apoB [38:00];
    • How nutrition impacts longevity via metabolic health, muscle mass, BMD and more [40:15];
    • How can someone determine the best diet for themselves? [43:45];
    • Nutrition myth: All weight loss is good [46:45];
    • Nutrition myth: Metabolic rates are dramatically different among individuals based on genetics [49:00];
    • Nutrition myth: Losing weight after a brief period of overeating is impossible [53:45];
    • Nutrition myth: GLP-1 agonists are a replacement for a healthy lifestyle [57:45];
    • Nutrition myth: There is a single best diet for weight loss [1:03:00];
    • Nutrition oversimplification: All calories are created equal [1:05:45];
    • Daily step goals [1:06:45];
    • The benefits of standing versus sitting throughout the day [1:10:45];
    • How to identify the most impactful and easiest-to-implement ways to improve your health [1:12:30];
    • The critical importance of emotional health [1:14:30];
    • Why supplements should be considered as supportive aids rather than primary solutions in one’s strategy to improve longevity [1:18:00];
    • Strategies for reducing high blood pressure [1:20:45];
    • Peter’s biggest frustrations with "mainstream health advice" [1:28:00];
    • Peter’s chaotic, yet cherished, morning routine [1:31:00]; and
    • More.

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    The Peter Attia Drive
    enJune 17, 2024

    #305 ‒ Heart rate variability: how to measure, interpret, and utilize HRV for training and health optimization | Joel Jamieson

    #305 ‒ Heart rate variability: how to measure, interpret, and utilize HRV for training and health optimization | Joel Jamieson

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    Joel Jamieson is a conditioning expert who developed Morpheus to give people a smarter way to build their conditioning regimen and improve their recovery. In this episode, Joel dives deep into the world of heart rate variability (HRV), explaining its scientific foundation, how it measures the balance between the sympathetic and parasympathetic nervous systems, the various methods of measurement, and how it can guide healthier lifestyle choices and improved training performance. He explores the nuances of HRV calculation, the impact of aging on HRV, and the roles of genetics, exercise, and other lifestyle factors in this process. He also covers Morpheus, the innovative training tool that won Peter over after his initial skepticism, highlighting its practicality and effectiveness in guiding training and optimizing fitness outcomes.

    We discuss:

    • Heart rate variability (HRV): evolution, science, and practical applications of HRV in athletic training [4:00];
    • Methods of measuring HRV: EKG, wrist-based sensors, and more [11:30];
    • How HRV is calculated from the data [22:30];
    • The role of the autonomic nervous system (ANS) in regulating HRV [25:45];
    • The decline in HRV with age, and the mitigating effects of fitness and other lifestyle factors [33:30];
    • The role of genetics in HRV, the modifiability of HRV, and a comparison of VO2 max and HRV as predictors of mortality [37:00];
    • How aging affects HRV and sympathetic drive, and the importance of spontaneous movement and exercise in maintaining the body's adaptability [43:30];
    • How Morpheus measures HRV using RMSSD and normalizes it to a 100-point scale for easier interpretation [49:45];
    • The Morpheus system: development, integration with various metrics, and personalized daily training recommendations to optimize fitness and recovery [51:30];
    • The benefits of morning HRV readings for assessing daily readiness compared to overnight HRV measurements [1:03:00];
    • Why Morpheus recommends using a chest strap rather than an arm band [1:10:00];
    • The impact of consistent exercise, stress, alcohol, and other lifestyle factors on HRV [1:11:15];
    • Optimizing zone 2 training with Morpheus [1:18:15];
    • Using heart rate recovery (HRR) as an indicator of athletic conditioning and the balance between aerobic and anaerobic systems [1:22:45];
    • The importance of tracking HRV trends over time rather than focusing on data from a given day [1:29:00];
    • Effect of GLP-1 agonists on heart rate and HRV [1:34:45];
    • Where HRV belongs in the hierarchy of health metrics [1:42:00];
    • Parting thoughts [1:46:30]; and
    • More.

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    The Peter Attia Drive
    enJune 10, 2024

    #304 – NEW: Introducing quarterly podcast summaries - Peter shares his biggest takeaways on muscle protein synthesis, VO2 max, toe strength, gut health, and more

    #304 – NEW: Introducing quarterly podcast summaries - Peter shares his biggest takeaways on muscle protein synthesis, VO2 max, toe strength, gut health, and more

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    In this quarterly podcast summary (QPS) episode, Peter introduces a new format aimed at summarizing his biggest takeaways from the last three months of guest interviews on the podcast. Peter shares key insights from each episode, covering diverse topics such as protein and muscle building with Luc van Loon, toe strength with Courtney Conley, VO2 max with Olav Aleksander Bu, liquid biopsies for cancer with Alex Aravanis, gut health and probiotics with Colleen Cutcliffe, and road safety with Mark Rosekind. Additionally, Peter shares any personal behavioral adjustments or modifications to his patient care practices that have arisen from these engaging discussions.

    If you’re not a subscriber and are listening on a podcast player, you’ll only be able to hear a preview of the AMA. If you’re a subscriber, you can now listen to this full episode on your private RSS feed or our website at the episode #304 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here.

    We discuss:

    • How Peter keeps track of his takeaways from each podcast episode [5:15];
    • Luc van Loon episode: fat utilization, muscle protein synthesis, dietary protein, aging and inactivity, and more [8:45];
    • Behavioral changes that have come about from the conversation with Luc van Loon [23:45];
    • Courtney Conley episode: importance of toe strength and the impact of dedicated foot training [26:45];
    • Olav Aleksander Bu episode: the importance of VO2 max for lifespan, and the practicalities of measuring and improving VO2 max [36:45];
    • Behavioral changes that have come about from the conversation with Olav [56:00];
    • Alex Aravanis episode: liquid biopsies for cancer detection [1:01:30];
    • Colleen Cutcliffe episode: the importance of gut bacteria balance, and the potential therapeutic uses of probiotics, particularly Akkermansia [1:16:45];
    • Mark Rosekind: the significant issue of road fatalities and injuries, their causes, and practical safety measures to reduce risks [1:27:00]; and
    • More.

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    The Peter Attia Drive
    enJune 03, 2024

    #303 - A breakthrough in Alzheimer’s disease: the promising potential of klotho for brain health, cognitive decline, and as a therapeutic tool for Alzheimer's disease | Dena Dubal, M.D., Ph.D.

    #303 - A breakthrough in Alzheimer’s disease: the promising potential of klotho for brain health, cognitive decline, and as a therapeutic tool for Alzheimer's disease | Dena Dubal, M.D., Ph.D.

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    Dena Dubal is a physician-scientist and professor of neurology at UCSF whose work focuses on mechanisms of longevity and brain resilience. In this episode, Dena delves into the intricacies of the longevity factor klotho: its formation and distribution in the body, the factors such as stress and exercise that impact its levels, and its profound impact on cognitive function and overall brain health. Dena shares insights from exciting research in animal models showing the potential of klotho in treating neurodegenerative diseases as well as its broader implications for organ health and disease prevention. She concludes with an optimistic outlook for future research in humans and the potential of klotho for the prevention and treatment of Alzheimer’s disease.

    Disclosure: Peter is an investor in Jocasta Neuroscience, a company working to develop klotho as a therapy for people with Alzheimer’s disease.

    We discuss:

    • Dena’s fascination with aging and how she came to study klotho [3:30];
    • Biological properties of klotho: production, regulation, decline with age, and factors influencing its levels [11:45];
    • Potential benefits of klotho on brain health [22:00];
    • The relationship between soluble klotho protein, platelet factors, and cognitive enhancement [33:45];
    • The role of platelet factor 4 (PF4) and it’s interaction with GluN2B in mediating cognitive enhancement [46:45];
    • Benefits of klotho observed in a mouse model of Parkinson’s disease [55:45];
    • Benefits of klotho observed in a mouse model of Alzheimer’s disease [1:03:00];
    • Promising results of klotho in primate models, and the importance of finding an appropriate therapeutic dose before moving to human trials [1:08:00];
    • Speculating why a single klotho injection has such long-lasting effects [1:25:30];
    • Potential cognitive benefits of klotho in humans, the impact of the KL-VS genetic variant on klotho levels, and the need for human trials to confirm these effects [1:27:45];
    • The interaction between the KL-VS genetic variant and APOE4 and how it impacts risk of Alzheimer’s disease [1:34:45];
    • The significance of klotho levels: studies linking lower levels to increased mortality and the broader implications for organ health and disease prevention [1:47:15];
    • Measuring klotho levels and determining an individual’s KL-VS status [1:52:15];
    • The promising potential of klotho for Alzheimer’s disease treatment, and the importance of philanthropy for funding research [1:58:00]; and
    • More.

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    The Peter Attia Drive
    enMay 27, 2024

    #302 - Confronting a metabolic epidemic: understanding liver health and how to prevent, diagnose, and manage liver disease | Julia Wattacheril, M.D., M.P.H.

    #302 - Confronting a metabolic epidemic: understanding liver health and how to prevent, diagnose, and manage liver disease | Julia Wattacheril, M.D., M.P.H.

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    Julia Wattacheril is a physician scientist and director of the Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD) program at Columbia University Irving Medical Center. In this episode, Julia delves deep into the complex world of liver health, beginning with a foundational overview of liver physiology. She provides an in-depth look at how alcohol impacts liver function, breaking down the metabolism of ethanol and its detrimental effects. Julia then shifts the focus to understanding liver function tests and optimal enzyme levels, providing a detailed explanation of AST and ALT and elucidating why fluctuations in these levels may or may not be concerning. She provides a primer on the four major stages of liver disease, discussing risk and emphasizing the importance of early diagnosis. Julia highlights the role of liver disease in increasing the risk of cancer and cardiovascular disease and covers in detail the various strategies for diagnosing, treating, and preventing the progression of liver disease.

    We discuss:

    • Julia’s training, the importance of liver health, and the challenges and innovations of hepatology [3:15];
    • The complex and crucial functionality of the liver, its four most essential functions, and more [8:45];
    • Liver injuries: historical and evolving understanding of causal factors, and the progression to liver diseases and cancer [13:15];
    • How the liver metabolizes nutrients and what happens in the presence of excess calories or alcohol [24:45];
    • Methods of diagnosing liver disease and how insights guide treatment and management strategies [33:30];
    • The poisonous nature of ethanol to the liver [40:30];
    • Varied responses to alcohol, damaging effects of alcohol beyond the liver, and the process of advising patients on their alcohol consumption [47:15];
    • Understanding liver enzymes AST and ALT—interpreting levels, lifestyle factors that affect them, and diagnostic approaches [58:30];
    • Interpreting liver function tests for fatty liver disease, and the challenges of diagnosing liver pathologies, particularly in children versus adults [1:13:15];
    • Comprehensive liver health assessments via imaging and various diagnostic tools to prevent overlooking potential liver pathologies [1:18:45];
    • Potential impact of recreational drugs, statins, and other medications on liver function test results [1:26:45];
    • Shifting nomenclature from NAFLD to MASLD to reflect accuracy in the underlying pathophysiology and understanding of liver diseases [1:30:30];
    • Pathophysiology of MASLD, the need for proactive screening, and the significance of liver fat percentage as an indicator of metabolic health [1:36:30];
    • The importance of screening for rare conditions alongside common metabolic diseases associated with fatty liver accumulation [1:42:45];
    • Practical strategies for managing MAFLD [1:45:30];
    • The impact of fructose consumption on liver health and the challenges of disentangling its effects from other factors like obesity and insulin resistance [1:52:45];
    • The potential of GLP-1 agonists for the treatment of MASLD [1:57:45];
    • How the four stages of liver disease have evolved [2:00:30];
    • Increased cancer and heart disease risk associated with early-stage MAFLD [2:05:15];
    • Emerging drugs and therapies for addressing fat accumulation and fibrosis related to MAFLD [2:12:15];
    • Peter’s major takeaways [2:18:45]; and
    • More.

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    The Peter Attia Drive
    enMay 20, 2024

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    • Moms and dads think — and react — differently to newborn baby smells.
    • Clock and Cycle factors control circadian rhythm and protect your eyes as you age. 
    • Oleic acid produced in the brain helps regulate memory, learning, and mood; promotes neurogenesis; and increases cell proliferation.


    EPISODE SPONSOR: The Eng3 NanoVi device helps repair oxidative stress damage and support the body’s natural repair mechanisms. https://eng3corp.com/DAVE/. Learn more: The Anti-Aging Science Behind the NanoVi Device – Rowena Gates & Hans Eng – #416.

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    Stories of Self-Experimentation

    Stories of Self-Experimentation
    What happens when the scientist... becomes the subject? We're examining the strange world of self-experimentation, from the history of martyr medics and kooky romantics, to the modern biologists dosing themselves with DIY COVID vaccines in the months after the pandemic began. Plus, is mixing vaccines the best way to fight coronavirus? Scientists capture an elusive element, number 99... and the physics behind why wombats poo in cubes! Like this podcast? Please help us by supporting the Naked Scientists

    Molecular Hydrogen: Helpful for Cataracts, Diabetic Retinopathy and Macular Degeneration?

    Molecular Hydrogen: Helpful for Cataracts, Diabetic Retinopathy and Macular Degeneration?

    Molecular Hydrogen is surging in popularity as a potential treatment for a wide range of conditions, including eye diseases. Is this fascination with molecular hydrogen merely another passing supplement trend? Is there a substantive basis for considering it as a therapeutic option? 

    Dr. Marc Grossman is a Holistic Optometrist and Acupuncturist. Check out  https://www.naturaleyecare.com/ to find the supplements described in this episode and a wealth of vision knowledge.


    138 | My New Favorite Lab Test…the Advanced Oxidative Stress Test (Part 2)

    138 |  My New Favorite Lab Test…the Advanced Oxidative Stress Test (Part 2)

    Part 2: Why knowing your total Glutahtione status and how much damage is happening to your cells and DNA is so critical to your health and success.

    Visit my LabShop store to self-order the same tests I use with my one-on-one coaching clients. 

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    Check out my online store for self-learning/DIY programs for thyroid, gut health and detox.
    You can use this form to reach out and request an Initial Consultation
    Visit my LabShop store to self-order the same tests I use with my one-on-one coaching clients.
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