Logo
    Search

    #30 - Thomas Seyfried, Ph.D.: Controversial discussion—cancer as a mitochondrial metabolic disease?

    enNovember 26, 2018

    Podcast Summary

    • Professor Tom Seifried's expert insights on metabolic therapies for chronic diseases, including cancer.Metabolic therapies play a significant role in cancer treatment, but their effectiveness should be balanced with other treatment options like immunotherapy and chemotherapy. Understanding key concepts is vital for a comprehensive understanding.

      Professor Tom Seifried is an expert in the field of metabolic therapies for chronic diseases such as epilepsy, neurodegenerative lipid storage diseases, and cancer. He has extensive research and publication experience in this area, including his book "Cancer as a Metabolic Disease." The discussion also touches on the Warburg effect, which is the belief that cancer is primarily a metabolic disease originating from mitochondrial or metabolic cell machinery damage. However, it's important to note that not everyone shares this view, including Peter Attia. While Attia supports the use of metabolic therapies in cancer treatment, he also recognizes the value of immunotherapy and chemotherapy. Understanding concepts such as respiration, oxidative phosphorylation, fermentation, and substrate level phosphorylation is crucial to comprehending the discussion.

    • A Multi-faceted Approach to Understanding and Treating CancerExploring alternative perspectives and research avenues is crucial to making progress in understanding and treating cancer.

      Cancer is a complex disease that requires a multi-faceted approach. Peter Attia believes that targeting cancer from multiple angles is essential, rather than focusing on just one aspect. He clarifies that biopsies do not increase the risk of metastatic cancer, disputing a claim made earlier. They also discuss glioblastoma multiforme, a particularly aggressive form of brain cancer that has historically had a low survival rate. However, there is growing interest in studying metabolic therapies for this type of cancer. While these alternative approaches may not have gained mainstream acceptance yet, there are researchers, like Tom, who have been working on them for decades and are starting to see their potential applications. This conversation highlights the need to explore various perspectives and research avenues to make progress in understanding and treating cancer.

    • From Tumor Research to Ketogenic Diets: A Journey of Perseverance and DiscoveryThomas Seyfried's journey emphasizes the significance of persistence and open-mindedness, as even a rejected grant proposal can lead to valuable opportunities and groundbreaking discoveries.

      Thomas Seyfried's initial interest in ganglioside changes in tumors ultimately led him to explore comparative studies of glycolipids in human and mouse brain tumors. He then delved into researching the therapeutic potential of ketogenic diets for epilepsy. Although his grant proposal on ketogenic diets was rejected, Seyfried later discovered that there was indeed significant interest in this area of study. This realization came after one of his PhD students attended a meeting on ketogenic diets for epilepsy and shared the positive response it received. This highlights the importance of perseverance and remaining open to new opportunities, even in the face of initial rejection or skepticism.

    • The dual impact of a drug on brain tumors and body weight sparked further exploration into the role of calorie restriction in tumor reduction.Calorie restriction, not the drug alone, plays a crucial role in shrinking tumors, emphasizing the necessity to understand a drug's mechanisms and consider calorie restriction for therapeutic benefits.

      The initial discovery of a drug's effect on brain tumors led to further investigation into the role of calorie restriction in tumor reduction. While studying gangliosides, Thomas Seyfried and his team discovered that the drug meant to reduce ganglioside synthesis also resulted in both tumor and body weight reduction in mice. This finding caught the attention of a drug company, leading to funding for further research. Through experiments comparing mice fed ad libidum and those with restricted calorie intake, it was determined that calorie restriction, rather than the drug itself, played a significant role in tumor shrinkage. This prompted Seyfried and his team to explore the potential of calorie restriction in other conditions like epilepsy. The conversation highlights the importance of understanding the mechanisms behind a drug's effects and considering the role of calorie restriction for therapeutic benefits.

    • Vagus Nerve Stimulation for Weight Loss and Seizure ControlStimulating the vagus nerve can reduce appetite, aid in weight loss, and potentially help manage seizures. Calorie restriction and ketogenic diets can also produce ketones that have anti-seizure benefits. Practice calorie restriction in a healthy manner to avoid starvation.

      Stimulating the vagus nerve can suppress appetite and promote weight loss. Thomas Seyfried mentions a vagal nerve stimulator that was implanted in epileptic patients, which effectively reduced their appetite and helped manage seizures. This device cost around $16,000 and showed promising results. Additionally, the conversation touches upon the connection between calorie restriction, ketogenic diets, and seizure control. It is revealed that both calorie restriction and a ketogenic diet can lead to the production of ketones, which have anti-seizure benefits. The level of ketosis achieved through calorie restriction can be similar to that achieved through therapeutic fasting in humans. However, it is important to practice calorie restriction in a healthy manner to avoid entering a state of starvation.

    • The body's ability to adapt to fasting or starvationWhile our bodies can adapt to periods of fasting, starvation can have severe consequences on our muscles and electrolyte balance. Yet, our species has evolved to endure food scarcity, ensuring our survival today.

      Our bodies have the ability to adapt to periods of fasting or starvation. While the duration can vary depending on factors such as body weight, age, and overall health, it is possible for individuals in good shape to go a long time without eating. This was observed in cases such as the prisoners in MACE prison who fasted as a protest. However, it is crucial to note that starvation can have devastating effects on the body, causing muscle loss and electrolyte imbalances. The diaphragm, in particular, is the last muscle to be affected, leading to the drowning of the individual in their own bodily fluids. Despite this, our species has evolved to withstand periods of food scarcity, and our ability to survive today is a testament to this adaptation.

    • The Impact of Nutritional State on Vitamin and Mineral AccessOur bodies need more nutrients when we are fed, but many foods today lack essential nutrients, leading to a state similar to starvation. Calorie restriction and stable glucose levels are important for managing epilepsy, and prolonged fasting can result in lasting changes to eating habits and weight.

      Our nutritional state plays a crucial role in our ability to access minerals and vitamins. Research indicates that our need for these nutrients tends to increase when our bodies are in a fed state. However, in today's society, many foods are depleted of these essential nutrients, leading some people to be in a state similar to starvation despite consuming food with little nutritional value. As a result, the body stores excess fat instead of efficiently using sugar for energy. Furthermore, calorie restriction has been found to be a key mechanism in the effectiveness of the ketogenic diet in managing epilepsy. While the effects may not be immediately visible, maintaining stable glucose levels is crucial in preventing breakthrough seizures. Additionally, some individuals who undergo prolonged fasting experience a lasting change in their eating habits and weight, suggesting a potential physiological shift rather than a behavioral one.

    • The Power of Ketogenic Diets in Managing Epilepsy and CancerLowering blood sugar and elevating ketones through ketogenic diets can have significant benefits in managing epilepsy and cancer, potentially leading to more effective treatments.

      The key to managing epilepsy and cancer lies in lowering blood sugar and elevating ketones, which can be achieved through ketogenic diets. While the exact mechanism behind this is still under investigation, it is clear that calorie restriction and the Warburg effect play significant roles. Calorie restriction shrinks tumors by lowering blood sugar, and the Warburg effect refers to cancer cells continuing to produce lactic acid even in the presence of oxygen. By understanding these processes, we can potentially develop more effective treatments for cancer and epilepsy. It is fascinating to think that if Otto Warburg had known about ketogenic diets, he may have made groundbreaking discoveries in cancer research much earlier.

    • The Difference in Energy Production: Normal Cells vs. Cancer CellsCancer cells have a defective respiratory system, leading to the production of large amounts of lactic acid, as observed by Otto Warburg, greatly influencing the field of biochemistry.

      There is a significant difference in energy production between normal cells and cancer cells. Normal cells, when supplied with oxygen and not in excessive demand for ATP, can efficiently produce energy through cellular respiration in the mitochondria, generating over 30 units of ATP. However, cancer cells, even in the presence of abundant oxygen, continue to produce large amounts of lactic acid, indicating a defective respiratory system. This observation, made by Otto Warburg in the 20th century, led to further research and the formulation of the theory that the organelle responsible for energy production in cancer cells is faulty. Despite some controversy, Warburg's work had a profound impact on the field of biochemistry and his findings were widely reproduced by other scientists.

    • The role of mitochondria in cancer cell energy production and the importance of studying their respiration.Cancer cells have defects in their mitochondria, leading to reliance on fermentation for energy. Studying their respiration is important for understanding different types of cancer cells.

      All cancer cells have some form of defect in the number, structure, or function of their mitochondria, which affects their ability to generate energy through normal respiration. This defect leads to the Warburg effect, where cancer cells rely on fermentation for energy production. The focus on aerobic glycolysis in cancer research is a secondary problem, as the real issue lies in the impairment of respiration. It is important to note that studying cancer cells in culture can lead to misleading assumptions and artificial results, as they are no longer connected to the tissues and are growing in an unnatural environment. Quantifying aerobic respiration can be done by measuring the amount of oxygen consumed and lactic acid produced. Overall, understanding the diverse defects in mitochondrial respiration is crucial in comprehending the complexity of different types of cancer cells.

    • The Role of Organelle Structure and Mitochondrial Health in Cancer DevelopmentCancer is primarily caused by damage to the respiratory system and mitochondria in cells, emphasizing the importance of maintaining healthy mitochondria and avoiding risk factors to prevent cancer.

      The structure of organelles in biological cells determines their function. Abnormal structure leads to abnormal function. While some may refer to these abnormalities as mutations, Thomas Seyfried prefers to call them defects. Surprisingly, when studying cancers in mice, Seyfried's team found that the entire genome of the tumors had no genetic abnormalities or mutations that would impact function. This challenges the common understanding that cancers are caused by mutations that disrupt normal cell signaling. Instead, Seyfried argues that the primary cause of cancer is damage to the respiratory system of cells. Maintaining healthy mitochondria, which are responsible for respiration, is crucial in preventing cancer. This emphasizes the importance of avoiding risk factors like viral infections, radiation exposure, and carcinogenic exposure to protect mitochondrial health. Despite the Warburg effect, which was initially dismissed in the field, damage to respiration and mitochondria is consistently evident in cancer cells under microscopic examination.

    • The Role of Mitochondrial Dysfunction in Cancer DevelopmentUnderstanding and targeting mitochondrial dysfunction is crucial in the treatment of cancer, as research shows that both direct viral infection and genetic defects can disrupt mitochondrial function, leading to abnormal cell growth.

      Mitochondrial dysfunction plays a significant role in the development of cancer. Traditional biochemical analysis has shifted towards molecular biology analysis, leading to the belief that genetic defects and mutations cause cancer. However, it was not considered that viruses could also affect the mitochondria and disrupt respiration. Research shows that both direct viral infection and the integration of viruses into the nuclear genome can disrupt mitochondrial function. All cancers studied so far have shown to ferment, indicating abnormal mitochondrial function. Additionally, plants also exhibit dysmorphic cell growth following Warburg's metabolic profile, but they do not metastasize due to the absence of an immune system. This conversation emphasizes the importance of understanding and targeting mitochondrial dysfunction in cancer treatment.

    • Unique Energy and Building Block Acquisition in Cancer CellsCancer cells have a distinctive method of obtaining energy and building blocks through substrate level phosphorylation and organic substrates. Understanding these mechanisms is essential for developing effective cancer treatments.

      Cancer cells have a unique way of obtaining both energy and building blocks for growth. While regular cells primarily rely on oxidative phosphorylation for energy production, cancer cells utilize substrate level phosphorylation (SLP) in the mitochondria to generate ATP. SLP involves the transfer of phosphate groups from organic substrates to ADP, resulting in the restoration of ATP levels. This process allows cancer cells to compensate for the damaged respiration observed in Warburg's theory. Additionally, cancer cells obtain the necessary building blocks through glucose, glutamine, and the pentose pathway. Understanding the mechanisms of energy production and building block acquisition in cancer cells is crucial for developing effective therapeutic strategies.

    • Shifting Energy Production in Cancer CellsCancer cells rely on substrate level phosphorylation (SLP) for energy generation, lacking oxidative phosphorylation (oxfoss). This phenomenon is not widely understood in mainstream cancer research, but Thomas Seyfried predicts it will gain recognition.

      There is a shift in energy production from oxidative phosphorylation (oxfoss) to substrate level phosphorylation (SLP) in cancer cells. Unlike normal cells, cancer cells lack oxfoss and rely heavily on SLP for energy generation. This shift is supported by the findings of Katska's experiments on aquatic animals, where lactic acid and succinic acid (a stimulant for oxfoss) were found to be dumped into the bloodstream during periods of oxygen deprivation. The conversation also highlights the limited understanding of this phenomenon within the majority view of cancer research, which focuses more on gene expression rather than direct measurement of oxygen consumption and gas production. Thomas Seyfried believes that it is only a matter of time before this minority view gains wider recognition.

    • Unraveling the complexities of ATP production in cancer cellsMeasuring ATP levels and analyzing lactate production and mitochondrial defects can provide insights into ATP generation in cancer cells, aiding in the development of effective treatments.

      ATP production and oxygen consumption in cancer cells can be a complex and nuanced process. While measuring ATP levels can indicate whether a cell is alive or dead, it is challenging to determine the exact origin of ATP production within the mitochondria. The production of lactate and the presence of certain enzymes, such as pyruvate kinase, can provide clues about ATP generation. Additionally, structural defects in the mitochondria can impact ATP production, even in cells with normal mitochondrial genomes. Understanding these complexities is crucial in studying cancer cells and developing effective treatments. Further research is needed to unravel the mechanisms of ATP production in cancer cells and explore potential therapeutic avenues.

    • The role of glucose and glutamine in cancer growth and the potential benefits of therapeutic fasting and restricted ketogenic diets.Therapeutic fasting and restricted ketogenic diets can help lower blood sugar levels and create a direct competition between normal and tumor cells for glucose, potentially impacting cancer growth.

      Glucose and glutamine are the primary fuels that drive cancer growth. While it is not possible to completely eliminate glucose from the body, therapeutic fasting and restricted ketogenic diets can significantly lower blood sugar levels. These dietary interventions make normal cells glucose hungry, forcing them to transition to ketones for energy. In contrast, tumor cells that are mitochondrial defective cannot utilize ketones and depend on glucose for survival. This creates a direct competition between normal and tumor cells for glucose. Clinically, a ketogenic or calorie-restricted diet may initially cause physiological insulin resistance, but in the long run, calorie restriction increases insulin sensitivity in the body.

    • Measuring Insulin Resistance and Potential Prediabetic ConditionsAwareness of glucose and ketone levels is crucial during insulin resistance tests, as excessive insulin production and potential prediabetic conditions can arise even in individuals with normal fasting blood glucose levels. Communication and transparency with loved ones is important in emergencies.

      Insulin resistance can be measured by the steady state plasma glucose (SSPG) level, with higher levels indicating higher insulin resistance. This test is typically performed on individuals following a standard diet, and not on those who follow a ketogenic diet. However, injecting glucose and insulin into someone on a ketogenic diet can lead to excessive insulin production. Additionally, the test results showed that even individuals with normal fasting blood glucose levels can exhibit high SSPG levels, indicating potential prediabetic conditions. It is important for individuals to be aware of their glucose and ketone levels during such tests, as administering too much insulin can lead to dangerously low blood glucose levels. Communication and transparency with loved ones is also essential in case of emergencies.

    • Balancing Blood Sugar and Cancer TreatmentFinding the right balance between lowering blood sugar levels without harming overall health is crucial in utilizing insulin effectively in cancer treatment.

      The goal of cancer treatment is to starve the tumor cells without harming the rest of the body. While some individuals may experience insulin sensitivity and glucose disposal on a ketogenic diet, this may not be the case for everyone. Many patients on a ketogenic diet fail glucose tolerance tests and appear to have diabetes-like symptoms. However, if these patients are primed with a few days of consuming carbohydrates prior to the test, their insulin sensitivity improves. The challenge lies in finding the balance between lowering blood sugar levels to starve tumor cells and avoiding harm to the individual's overall health. Insulin can be protumorgenic, but with low glucose levels and careful management, it can be used effectively without stimulating tumor growth.

    • Targeting Glutamine in Cancer TreatmentStrategically targeting glutamine, a crucial nonessential amino acid, can selectively kill tumor cells while maintaining normal physiological systems with the help of drugs like Don 6.

      Strategically targeting glutamine is crucial in cancer treatment. Glutamine, although a nonessential amino acid, plays a massive role in various physiological systems such as the gut, immune system, and urea cycle. While there is no dietary strategy to effectively reduce glutamine, drugs like Don 6 can be used to block glutamine and selectively kill tumor cells. However, it is essential to have knowledgeable experts administering these drugs, as the immune system may be compromised if not done correctly. The press-pulse concept is developed to maximize the effectiveness of treatment, where glucose is pressed hard with diets and drugs, and then glutamine is pulsed. By restoring the immune system and gut function, the normal physiological systems can be maintained while targeting cancer cells.

    • The Role of Mitochondria in Cancer Cells: Energy Source and Structural ChangesThe compromised structure and function of mitochondria in cancer cells play a crucial role in the disease, highlighting the importance of understanding and targeting these energy sources for effective management strategies.

      The energy source of cancer cells is a crucial aspect to consider in managing the disease. Thomas Seyfried emphasizes the compromised structure and function of mitochondria in tumor cells, which is supported by extensive literature. He points out that without energy, nothing grows, and the evidence strongly indicates that the mitochondria in cancer cells are defective. Peter Attia raises the question of the functional flexibility of mitochondria, suggesting that even with structural changes, there may still be optimal function. However, Seyfried argues that mitochondria are highly adaptable but have certain critical genes that control cell survival. The malfunction of these genes prevents cancer cells from undergoing normal apoptosis. Overall, understanding the energy source and structural changes in cancer cells is crucial in developing strategies to manage the disease.

    • The role of fermentation in cancer cellsCancer cells are able to revert back to fermentation, enabling their survival and tumor formation, while normal cells cannot sustain fermentation for long periods.

      Cancer cells have a unique ability to upregulate fermentation pathways, allowing them to survive and multiply under low-oxygen conditions. Before oxygen existed on Earth, all cells operated through fermentation, but with the introduction of oxygen, most cells switched to oxidative phosphorylation as their primary energy source. However, cancer cells can revert back to fermentation, which normal cells cannot do for long periods. This adaptation is what allows cancer cells to thrive and form tumors. Skeletal muscle cells, although capable of temporary fermentation, cannot sustain it permanently without dying. This is why tumors rarely form in muscle cells. The difference in adaptability to fermentation between different cell types plays a crucial role in cancer development and the probability of tumor formation in various tissues.

    • Neurons, Heart Cells, and Cancer SusceptibilityBrain neurons and heart cells do not become tumor cells because of their lack of metabolic flexibility, while glial cells and microglia are more prone to brain tumors. Other cell types like colon and breast cells are susceptible to cancer due to their metabolic inflexibility.

      Brain neurons rarely become tumor cells because they are not capable of doing so. Instead, brain cells die, leading to neurodegeneration. Tumors in the brain are usually found in glial cells and microglia. It is important to distinguish between these cell types and neurons when discussing brain cancer. Additionally, it is counterintuitive that cardiac myocytes, the cells in the heart, also do not form cancer despite their ability to buffer lactate. This is because disruptions in oxidative phosphorylation, which occur in cancer cells, are catastrophic for brain and heart cells. The hypothesis suggests that the lack of metabolic flexibility in other cells, such as those found in the colon or breast, contributes to their susceptibility to cancer.

    • The Role of Oncogenes in Cancer MetabolismOncogenes play a crucial role in the metabolic changes of cancer cells, leading to a shift towards fermentation metabolism and the accumulation of mutations in the nuclear genome.

      Oncogenes play a crucial role in the metabolic changes observed in cancer cells. When the respiratory system of a cell is damaged, oncogenes upregulate fermentation pathways, leading to a shift towards a fermentation metabolism. This change requires additional fermentable fuels such as glucose and glutamine to compensate for the loss of energy from oxidative phosphorylation. Consequently, the genetic behavior of the cell begins to change, and mutations and defects accumulate in the nuclear genome. The damaged respiratory system also generates reactive oxygen species, which are mutagenic and carcinogenic. Additionally, high levels of lactic acid can be seen in patients with a high tumor burden, often stemming from the tumor cells themselves or due to multiple end organ ischemia caused by defective white blood cells.

    • The Role of Monocarboxillic Acid Transporters in Cancer MetabolismUnderstanding the complex microenvironment of tumors and the role of Monocarboxillic Acid Transporters is crucial for effective cancer treatment strategies and avoiding harmful interventions.

      The microenvironment of tumors is complex and contributes to the fermentation behavior of cancer cells. Lactic acid and hydrogen ions accumulate, creating an acidic mess. Monocarboxillic acid transporters (MCTs) play a role in both bringing in ketones and removing lactate, protecting the cell from harm. Ketogenic diets upregulate MCTs, increasing the intake of ketone bodies. Targeting blood vessels, as in anti-angiogenic therapies, has proven ineffective because cancer cells can ferment without them. Drugs like Avastin, which target blood vessels, may actually promote invasive behavior in brain cancer. Understanding the biology of cancer is crucial for effective treatment strategies and avoiding harmful interventions.

    • The Hidden Reality of Tumor Treatment with AvastinAvastin may give a false sense of improvement by spreading tumor cells throughout the brain instead of clustering them, potentially making the treatment less effective in the long run.

      Tumor cells, when treated with Avastin, spread throughout the brain instead of being clustered in one area. This phenomenon is not visible in radiographic images, making it seem like the treatment is effective. However, the overall survival rate remains unchanged or even lower. This false sense of improvement is due to the behavior of macrophage cells, which can fuse with neoplastic cells and make them more aggressive and invasive. Fusion involves the fusion of genetic and cytoplasmic material, and is prompted by the immune system's response to persistent wounds. The immune cells release growth factors and cytokines to facilitate wound healing, but inadvertently promote the growth of neoplastic cells. This fusion behavior and the resulting invasive nature of cancer cells are characteristics of macrophages. Ultimately, understanding this process is important in developing effective treatments for metastatic cancers.

    • Macrophages' inability to recognize and eliminate cancer cellsCancer cells disguise themselves and stimulate growth, hindering macrophages from effectively clearing them and leading to the spread of cancer.

      Macrophages, which are responsible for wound healing and clearing cellular debris, do not effectively kill cancer cells because they do not recognize them as foreign invaders. Cancer cells can mimic the appearance of normal epithelial cells, making it difficult for macrophages to identify and eliminate them. Additionally, the molecules produced by cancer cells to put out the "fire" of inflammation actually stimulate the growth of the abnormal cells. This can lead to the formation of metastatic lesions, where cancer cells spread from the original site to other parts of the body. The process of metastasis varies from person to person, and it is not solely dependent on the number of mutations present in the cancer cells.

    • The Unexpected Behavior of Cancer Cells and the Role of Needle BiopsiesNeedle biopsies, commonly used for tumor diagnosis, may potentially create a more aggressive environment around the tumor, increasing the risk of metastasis, but this phenomenon is not universally observed.

      Cancer cells can exhibit highly invasive and metastatic behavior without showing the expected mutations or abnormalities. This challenges the traditional understanding of how cancer spreads. In the case of two women with similar breast cancers, one may experience metastasis while the other remains disease-free, even though their primary tumors appear similar. Needle biopsies, commonly used for diagnosing tumors, can potentially create a more aggressive environment in the tumor's surroundings, increasing the risk of further spread. This phenomenon, known as inflammatory onco-taxis, has been observed in breast, colon, liver, and brain cancers. It is essential to understand that while needle biopsies can increase the risk of metastasis in some cases, the evidence is not universal.

    • Risks and Considerations of Needle Biopsies Following ResectionNeedle biopsies following resection carry a potential risk of metastatic cancer. While there is existing knowledge on tumor spread, the benefits of gaining curative information should be weighed against the risks involved.

      There is a potential risk of metastatic cancer when performing a needle biopsy following a resection. While this experiment has not been conducted, there is existing knowledge about needle biopsies facilitating tumor spread. However, it is important to distinguish this phenomenon from needle track seeding, as tract-related cancer cells can be dealt with separately. The risk of developing secondary glioblastoma after removing a low grade tumor is comparable to the risk associated with needle biopsies. To determine the control for this observation, a group of patients who do not undergo surgery would need to be included, but such experiments are not currently conducted. The philosophy mentioned is to shrink the tumor before debulking it, ultimately improving the probability of a successful cure. Thus, the question arises as to why anyone would want to put a patient at risk unless the information gained from the needle biopsy leads to a curative procedure.

    • The limitations and flaws of current cancer diagnosis and treatment approachesTo make progress in combating cancer, it is crucial to acknowledge the limitations of current methods and explore alternative approaches that address the complex nature of the disease.

      There are significant flaws in the current approach to diagnosing and treating cancer. Despite advancements in gene screening and biopsy procedures, there is a lack of understanding around the biological processes at play in different types of cancers. This has led to overlooked aspects of cancer, such as extracranial metastasis in glioblastoma cases, which research has shown to be more common than initially recognized. Furthermore, there is a concerning number of daily cancer-related deaths, indicating that current treatments may not effectively address the true nature of the disease. To make substantial progress in combating cancer, it is crucial to acknowledge the limitations of existing methods and explore alternative approaches that address the complex nature of cancer at its core.

    • Rethinking Cancer: A New Approach to Reduce Mortality RatesBy understanding the true nature of cancer and approaching it strategically, we have the potential to reduce the death rate by over 50% within a decade. Embracing necessary changes is crucial.

      There is a fundamental misunderstanding of the biology of cancer, leading to ineffective treatments and a high death rate. Thomas Seyfried argues that by understanding the true nature of the disease and strategically approaching it, we have the potential to reduce the death rate by more than 50% within 10 years. Currently, unnecessary procedures and tests are being conducted, such as needle biopsy tumor cells for genetic profiling, which do not contribute to understanding the disease. While there may be debates on the statistics and population demographics, the fact remains that more people are dying from cancer each year. To address this, it is crucial to focus on managing the disease based on its biology rather than outdated approaches. A bold reduction in mortality is possible if we embrace the necessary changes.

    • Integrating metabolic therapy with standard of care for breast cancer patients in Turkey holds promise for improved outcomes.Combining metabolic therapy, stress management techniques, and standard treatments like chemotherapy may enhance treatment effectiveness and improve the emotional well-being of breast cancer patients.

      Conducting an experiment to integrate metabolic therapy with standard of care for breast cancer patients may yield promising results. The goal is to combine metabolic therapy, which involves reducing blood sugar, elevating ketones, and targeting energy metabolism, with the standard treatments like chemotherapy. This approach is being done in Turkey, where the lowest dose of chemotherapy that complies with the law is employed. The metabolic therapy alone group would follow the press pulse concept, which begins with lowering blood sugar and achieving therapeutic ketosis through a ketogenic diet. Additionally, stress management techniques, such as music therapy and yoga therapy, are incorporated to address emotional stress. Further research and individualized approaches are necessary since response to therapy can vary among patients.

    • Revolutionizing Cancer Treatment Through Metabolic Ketosis and Targeted TherapiesMetabolic ketosis and targeted treatments offer hope in cancer management by reducing stress, marginalizing tumor cells, inducing cell death, and providing potent anti-inflammatory effects.

      Metabolic ketosis, combined with strategic management techniques, can have a significant impact on cancer treatment. Thomas Seyfried emphasizes the importance of informing patients that their disease is not terminal and that reducing stress can enhance the effectiveness of medicine. By achieving metabolic ketosis, various options become available, such as insulin therapy and hyperbaric oxygen, which primarily affects tumor cells without harming normal cells. Targeting glutamine with pulse drug treatments further weakens the tumor cells' antioxidant capacity, making them more susceptible to hypobaric therapy. It is crucial to reach a significant reduction in glucose levels and lower glutamine availability. Cancer cells, which are dependent on glucose, cannot utilize ketones efficiently due to defective mitochondria. Providing normal cells with an alternative fuel source marginalizes tumor cells over time. Hyperbaric oxygen therapy, administered at approximately 2.5 atmospheres for 90 minutes daily, aims to replace radiation therapy by inducing oxidative stress and cell death in the tumor cells. Therapeutic ketosis also proves to be a potent anti-inflammatory therapy. Overall, this conversation highlights the potential of metabolic ketosis and targeted treatments in cancer management.

    • A Metabolic Approach to Cancer Treatment: Targeting Tumor Microenvironment for Increased Vulnerability and Reduced InflammationBy focusing on the tumor's dependence on specific fuels and reconfiguring its microenvironment, metabolic therapy shows potential in reducing inflammation, making surgery easier, and increasing the chances of treating and eliminating cancer.

      A metabolic approach to cancer treatment shows promise in reducing the death rate and potentially curing certain types of cancer. By targeting the tumor's microenvironment and reconfiguring it to make it less inflamed, proapoptotic, and anti-angiogenic, the tumor becomes more vulnerable and damaged. Surgery would take place at a midpoint where the tumor is visibly shriveled and less inflamed, making it easier for the surgeon to remove without extensive collateral damage. This metabolic approach focuses on the tumor's dependence on specific fuels and aims to disrupt those fuels without harming the rest of the body. One potential drug, Don, which targets glutamine metabolism, has shown promise in clinical trials. By shifting the focus from genetic mutations to metabolic therapy, the potential for treating and eliminating cancer is increased.

    • Targeting Cancer Cells with Metabolic TherapyMetabolic therapy, such as the use of a ketogenic diet, has the potential to effectively treat cancer by targeting the main fuels of cancer cells. This can lead to extended lifespan and improved quality of life for patients.

      Current cancer therapies are not effectively targeting the metabolic nature of cancer. Traditional treatments like radiation and chemotherapy may actually worsen the condition and decrease overall survival. Metabolic therapy, specifically through the use of a ketogenic diet, has shown promising results in terms of extending lifespan and improving quality of life for cancer patients. By targeting the two prime fuels for cancer cells, glucose and glutamine, metabolic therapy offers the potential for a cure rather than just another treatment option. Implementing metabolic therapies as a standard of care could significantly reduce death rates and dramatically improve overall survival for cancer patients.

    • Metabolic therapy in cancer management: Extending survival and improving quality of lifeAdopting a therapeutic ketogenic diet potentially eliminates the toxic effects of standard cancer treatments and offers better outcomes for patients, particularly in the case of aggressive brain tumors like GBM.

      Implementing a metabolic therapy program for managing cancer could potentially extend overall survival and improve quality of life. While it may be challenging to determine if a person is truly cured, being disease-free for 10 years can serve as a good indication. Standard cancer treatments may not only have negative effects on long-term survival but also lead to other diseases. Therefore, adopting a therapeutic ketogenic diet could eliminate the toxic effects of conventional treatments and potentially offer better outcomes. In the case of aggressive brain tumors like GBM, a combination of debulking surgery and metabolic therapy could be a viable strategy to consider, even though complete disease eradication may not be achieved. It is important to weigh the metabolic risks of radiation, corticosteroids, and surgery and prioritize the least metabolically harmful options.

    • Rethinking radiation in glioblastoma treatmentEliminating radiation and incorporating metabolic therapy may significantly improve survival rates for glioblastoma patients, as seen in the case of a patient who experienced tumor regression and no tumor growth.

      Eliminating radiation from the treatment plan may significantly increase survival rates for patients with glioblastoma (GBM). Thomas Seyfried suggests that metabolic therapy combined with surgery and delayed radiation can lead to better outcomes. He highlights the case of a young patient who rejected radiation and chemotherapy, opting for metabolic therapy instead. Contrary to medical predictions, the patient not only survived but also experienced tumor regression and eventually had no tumor left. Seyfried emphasizes the importance of publishing these findings and generating interest for clinical trials. By reevaluating the role of radiation in GBM treatment, there is a potential to double or triple the amount of survival for patients.

    • Importance of Unbiased Experimentation in Cancer ResearchUnbiased experimentation is crucial in cancer research to examine the role of structural deficits in mitochondria and fermentation in tumor cells, and to explore metabolic therapy as a potential solution for eliminating cancer cells. Researchers should consider all evidence and avoid dismissing alternative facts.

      There is a need for unbiased experimentation to test hypotheses in the field of cancer research. The discussion highlights the importance of conducting dream experiments under ideal conditions with no resource constraints to examine the role of structural deficits in mitochondria and the production of lactate and fermentation in tumor cells. By depriving tumor cells of fermentable fuels, such as glucose and glutamine, and implementing metabolic therapy, it is possible to eliminate cancer cells. However, there is disagreement among researchers, demonstrating the necessity for convincing data and open-mindedness. This conversation emphasizes the significance of considering all available evidence and avoiding the dismissal of alternative facts when exploring complex scientific topics.

    • Ignoring Evidence: A Hindrance to Scientific ProgressCollaboration and a willingness to explore new experiments are crucial in addressing the crisis of disregarding conflicting evidence, ultimately leading to improved patient outcomes.

      There is a worrying trend in the scientific community of ignoring evidence that doesn't align with preconceived notions or mainstream beliefs. Just like the Catholic Church refused to accept that the Earth was not the center of the solar system, researchers in the cancer field are disregarding massive evidence that shows structural and functional issues with mitochondria. This crisis of ignoring conflicting evidence hinders progress and stalls the development of effective treatments. To overcome this, collaboration and the generation of new experiments are necessary. By understanding the biology of diseases and basing strategies on that understanding, we can improve overall survival rates and quality of life for patients.

    • Overcoming Resistance to Alternative Cancer TherapiesChallenging the status quo and exploring new approaches is crucial for advancing alternative cancer therapies and potentially improving outcomes for patients.

      There is a significant roadblock preventing the advancement of alternative cancer therapies. Thomas Seyfried's proposal of metabolic therapy as an alternative to the standard of care is met with resistance and inflexibility from the medical community. Despite having data and case studies that show promise, there is a reluctance to deviate from the established treatment protocols. This is hindering progress and potentially preventing better outcomes for cancer patients. There is a need to challenge the notion that the standard of care should always be followed without question, as it may impede the exploration of potentially more effective therapies. To make a real difference, there is a call for a change in mindset and the willingness to try new approaches, even if they go against convention.

    • A Potential Alternative Approach to Cancer Treatment: Immediate Surgery and Metabolic TherapyAdvocating for specialized treatment clinics that offer comprehensive care and showcasing positive results and testimonies can promote the success of the alternative approach to cancer treatment.

      There is a potential alternative approach to cancer treatment that combines immediate surgery with metabolic therapy. Peter Attia suggests that delaying radiation and corticosteroid therapy until necessary may increase the chances of success. However, finding advocates who support this thinking is crucial. Thomas Seyfried acknowledges the need for bold individuals to set up specialized treatment clinics where patients can receive comprehensive care in one place. Peter Attia emphasizes the importance of promoting this approach from a position of pull, rather than push, by showcasing the positive results and testimonies of those who have benefited from it. Despite differing opinions on whether cancer is primarily a genetic or metabolic disease, both agree that cancer is a complex condition that requires a multifaceted strategy.

    • Embracing a Multidisciplinary Approach for Cancer TreatmentBy incorporating various oncology specialties and supporting research efforts, we can explore every possible therapy for cancer and improve the chances of accessing effective treatments through clinical trials.

      There is potential value in using metabolic therapies for cancer treatment regardless of whether cancer is primarily caused by genetics or metabolic dysfunction. Rather than engaging in unnecessary debates about the exact nature of cancer, the focus should be on incorporating various oncology specialties, including medical oncology, radiation oncology, surgical oncology, immuno-oncology, and metabolic oncology. By embracing a multidisciplinary approach, we can explore every possible therapy for cancer, including novel and innovative treatments. It is important for patients and their loved ones to support research efforts and promote funding for metabolic therapy programs, either through foundations or universities. This support can contribute to the development of effective therapies and improve the chances of accessing these treatments through clinical trials. Furthermore, creating public awareness and advocating for increased risk tolerance in clinical trials for high-stakes cancers like glioblastoma can lead to advancements in cancer treatment.

    • Differing Views on Risks in Disease TreatmentsBalancing risks and benefits is vital in medical decision-making, as different perspectives exist on the level of risk that should be accepted when trying new treatments for diseases.

      There is a difference in opinion regarding the risks involved in trying new treatments for a disease. Thomas Seyfried believes that taking risks to find potential solutions is worth it because it cannot harm anyone and could potentially have positive outcomes. However, Peter Attia disagrees, stating that the outcome of the disease is uniformly bad and there is a risk of potentially doing worse. He believes that acknowledging the risks involved when discussing treatment options is crucial for maintaining credibility. Both agree that there will always be risks involved in medical procedures, but they differ in their perspectives on the level of risk that should be accepted. Ultimately, the conversation highlights the importance of carefully weighing risks and benefits in medical decision-making.

    Recent Episodes from The Peter Attia Drive

    #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.

    View the Show Notes Page for This Episode

    Become a Member to Receive Exclusive Content

    Sign Up to Receive Peter’s Weekly Newsletter

    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.

    Connect With Peter on TwitterInstagramFacebook and YouTube

    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

    View the Show Notes Page for This Episode

    Become a Member to Receive Exclusive Content

    Sign Up to Receive Peter’s Weekly Newsletter

    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.

    Connect With Peter on TwitterInstagramFacebook and YouTube

    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

    View the Show Notes Page for This Episode

    Become a Member to Receive Exclusive Content

    Sign Up to Receive Peter’s Weekly Newsletter

    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.

    Connect With Peter on TwitterInstagramFacebook and YouTube

    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

    View the Show Notes Page for This Episode

    Become a Member to Receive Exclusive Content

    Sign Up to Receive Peter’s Weekly Newsletter

    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.

    Connect With Peter on TwitterInstagramFacebook and YouTube

    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.

    View the Show Notes Page for This Episode

    Become a Member to Receive Exclusive Content

    Sign Up to Receive Peter’s Weekly Newsletter

    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.

    Connect With Peter on TwitterInstagramFacebook and YouTube

    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.

    View the Show Notes Page for This Episode

    Become a Member to Receive Exclusive Content

    Sign Up to Receive Peter’s Weekly Newsletter

    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.

    Connect With Peter on TwitterInstagramFacebook and YouTube

    The Peter Attia Drive
    enMay 20, 2024

    #301 - AMA #59: Inflammation: its impact on aging and disease risk, and how to identify, prevent, and reduce it

    #301 - AMA #59: Inflammation: its impact on aging and disease risk, and how to identify, prevent, and reduce it

    View the Show Notes Page for This Episode

    Become a Member to Receive Exclusive Content

    Sign Up to Receive Peter’s Weekly Newsletter

    In this “Ask Me Anything” (AMA) episode, Peter delves into the often misunderstood concept of inflammation. He first defines inflammation and differentiates between acute inflammation and chronic inflammation, the latter of which is linked to aging and a plethora of age-related diseases. Peter breaks down the intricate relationship between chronic inflammation, obesity, and metabolic health, and highlights the signs that might suggest someone may be suffering from chronic inflammation. From there, the conversation centers on actionable advice and practical steps one can take to manage and minimize chronic inflammation. He explores how diet plays a crucial role, including the potential benefits of elimination diets, and he examines the impact of lifestyle factors such as exercise, sleep, and stress management. Additionally, he discusses the relevance of food inflammatory tests and concludes by examining the potential benefits and drawbacks of drugs and supplements in managing inflammation.

    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 #59 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here.

    We discuss:

    • Defining inflammation (and the cultural impact of Napoleon Dynamite) [1:45];
    • Acute vs chronic inflammation [8:00];
    • The connection between chronic inflammation, aging, and age-related diseases [11:00];
    • The impact of inflammation on metabolic health [18:30];
    • Understanding and diagnosing chronic inflammation: blood tests and other approaches, and challenges with measurement [20:00];
    • Factors that contribute to low-level chronic inflammation [28:00];
    • Minimizing inflammation through diet [29:45];
    • The important role of fiber for gut health and inflammation [33:45];
    • A closer look at the impact of trans fats and saturated fats on overall health [34:45];
    • Why Peter prefers dietary fiber from food sources over supplements [38:30];
    • Debunking “superfoods”: emphasizing proven methods over marketing claims for reducing inflammation [39:00];
    • Is there any value in over-the-counter food inflammatory tests? [42:30];
    • Food elimination diets: how they work, symptoms and markers to watch, challenges and limitations [45:15];
    • Identifying dietary triggers for gut-related symptoms through low-FODMAP diets like the “carnivore diet” [51:15];
    • Dairy: the complex role of dairy on inflammation and individual responses [55:00];
    • Wheat: the complexities and conflicting evidence around wheat's inflammatory effects [57:45];
    • How exercise influences inflammation [1:02:00];
    • How sleep quality and duration impacts inflammation [1:07:00];
    • The potential impact of chronic psychological stressors on inflammation [1:13:00];
    • The impact of oral health on inflammation and overall well-being [1:15:00];
    • The role of medications in managing chronic inflammation [1:18:15];
    • Supplements: evaluating the efficacy of various anti-inflammatory supplements [1:22:15];
    • Parting thoughts and takeaways [1:27:00]; and
    • More.

    Connect With Peter on TwitterInstagramFacebook and YouTube

    The Peter Attia Drive
    enMay 13, 2024

    #300 - Special episode: Peter on exercise, fasting, nutrition, stem cells, geroprotective drugs, and more — promising interventions or just noise?

    #300 - Special episode: Peter on exercise, fasting, nutrition, stem cells, geroprotective drugs, and more — promising interventions or just noise?

    View the Show Notes Page for This Episode

    Become a Member to Receive Exclusive Content

    Sign Up to Receive Peter’s Weekly Newsletter

    In this special edition celebrating 300 episodes of The Drive, Peter discusses a variety of popular topics and health interventions and classifies them based on their level of evidence and relevance using the following categories: proven, promising, fuzzy, noise, and nonsense. Peter first delves into the topic of geroprotective molecules, covering rapamycin, metformin, NAD and its precursors, and resveratrol. Next, he explores the significance of metrics like VO2 max and muscle mass, as well as emerging concepts like blood flow restriction and stem cells. The conversation extends to nutrition, addressing questions surrounding long-term fasting, sugar consumption, sugar substitutes, and the contentious role of red meat in cancer. Peter not only provides his current stance on each topic—most of which have been covered in great detail in the previous 300 episodes—but also reflects on how his opinion may have evolved over the years.

    We discuss:

    • Defining the categories of “proven, promising, fuzzy, noise, and nonsense” [3:15];
    • Rapamycin [9:30];
    • Metformin [17:00];
    • NAD and its precursors [24:30];
    • Resveratrol [32:45];
    • The importance of VO2 max, muscle mass, and muscular strength for lifespan [38:15];
    • Blood flow restriction (BFR) training [44:00];
    • Using stem cells to treat osteoarthritis or injury [51:30];
    • Fasting as a tool for longevity (and why Peter stopped his fasting protocol) [55:45];
    • The energy balance theory [1:06:30];
    • The idea that sugar is poison [1:12:00];
    • The idea that sugar substitutes are dangerous [1:22:15];
    • The debate on red meat and cancer [1:28:45]; and
    • More.

    Connect With Peter on TwitterInstagramFacebook and YouTube

    Special episode with Dax Shepard: F1 and the 30th anniversary of Ayrton Senna’s death

    Special episode with Dax Shepard: F1 and the 30th anniversary of Ayrton Senna’s death

    View the Show Notes Page for This Episode

    Become a Member to Receive Exclusive Content

    Sign Up to Receive Peter’s Weekly Newsletter

    This is a special episode of The Drive with Peter’s friend and fellow car enthusiast Dax Shepard. In this podcast, which commemorates the 30th anniversary of the death of Brazilian Formula One legend Ayrton Senna, Dax sits down with Peter to better understand what made Senna so special and why Peter remains an enormous fan. This conversation focuses on Senna’s life, the circumstances of his death, and his lasting impact and legacy on the sport of F1.

    We discuss:

    • Peter’s interest in motorsports began as a child [2:30];
    • The drama and dangers of F1 [6:00];
    • What made Senna special [13:00];
    • What Senna meant to Brazilians [24:00];
    • The cause of the fatal crash [28:15];
    • Why Peter is obsessed with Senna [40:30];
    • Being the best versus having the best record [43:30];
    • Senna’s unique driving style and incredible intuition about automotive engineering [46:30];
    • Back to the day of the dreadful race [53:00];
    • What Peter believes caused the crash [1:02:45];
    • Views on dying young, in the prime of life [1:13:00];
    • Senna lives on in his foundation and in safety changes adopted by F1 [1:21:00];
    • Statistics aren’t enough for fandom, and why people like who they do [1:24:15];
    • The biggest difference between F1 today and F1 in the 80s [1:28:30];
    • Senna’s driving superpower [1:30:30];
    • The fastest drivers currently in F1 [1:38:30];
    • Current F1 obsessions [1:45:00];
    • How hard it is to do what the top F1 drivers do [1:50:15];
    • Dax’s love of motorcycles and his AMG E63 station wagon [1:52:15];
    • Awesome Senna mementos from Etsy [2:01:15];
    • What makes specialists interesting, and Max’s devotion to F1 [2:10:15];
    • What Senna might have done if he had not died that day [2:14:00];
    • Michael Schumacher and Max Verstappen are also top F1 drivers [2:17:30];
    • Interlagos in Sao Paulo Brazil is always an incredible experience [2:18:45]; and
    • More.

    Connect With Peter on TwitterInstagramFacebook and YouTube

    #299 ‒ Optimizing muscle protein synthesis: the crucial impact of protein quality and quantity, and the key role of resistance training | Luc van Loon, Ph.D.

    #299 ‒ Optimizing muscle protein synthesis: the crucial impact of protein quality and quantity, and the key role of resistance training | Luc van Loon, Ph.D.

    View the Show Notes Page for This Episode

    Become a Member to Receive Exclusive Content

    Sign Up to Receive Peter’s Weekly Newsletter

    Luc van Loon is an internationally renowned expert in skeletal muscle metabolism. In this episode, Luc starts with an exploration of the roles of insulin and triglycerides in endurance exercise, highlighting their impact on skeletal muscle metabolism, and he offers profound insights into the significance of protein in this context. He elucidates how different protein types and forms influence muscle protein synthesis rates, exploring the nuances of protein absorption, digestibility, amino acid quality, and their implications for performance and recovery. Delving deeper, he differentiates between animal and plant protein sources, unraveling the distinctive properties of various protein types, from the differences between whey and casein to the emerging trends in collagen protein supplementation. Moreover, Luc dissects the intricate connections among physical activity, lean muscle mass, muscle protein synthesis induced by resistance training, and dietary protein.

    We discuss:

    • Luc’s background and insights about fuel selection during exercise [3:30];
    • Fuel utilization during endurance exercise [9:30];
    • Fat metabolism, intramuscular lipids, and the nutritional dynamics of endurance sports [17:15];
    • The optimal window for replenishing intramuscular fat stores and glycogen post-exercise [25:15];
    • Luc’s interest in protein metabolism and exploration of amino acids' dual role as building blocks and signaling molecules in driving muscle protein synthesis [32:15];
    • How protein metabolism differs between sedentary individuals and those engaged in predominantly strength training or endurance training [38:45];
    • The basics of how proteins are digested and absorbed, and how muscle protein synthesis is measured [50:30];
    • How factors like food texture, cooking methods, and protein composition impact muscle protein synthesis, and the importance of protein distribution throughout the day [59:45];
    • Differences in whey and casein proteins, and the ability of ingested protein to stimulate muscle protein synthesis [1:03:30];
    • Dietary protein distribution and quantity for the maximization of muscle protein synthesis [1:09:00];
    • Muscle loss with age and inactivity and the importance of resistance exercise to maintain type II muscle fibers [1:17:15];
    • Differences between whey and casein proteins, and the importance of both quantity and quality of protein sources [1:28:30];
    • Optimizing muscle protein synthesis: exercise, timing of protein intake, protein quality, and more [1:37:00];
    • How to preserve muscle while trying to lose weight [1:46:00];
    • Anabolic resistance and overcoming it with physical activity [1:55:45];
    • Importance of protein intake and physical activity in hospitalized patients [2:06:30];
    • Reviewing the efficacy of collagen supplements [2:13:30];
    • Plant-based diets: how to ensure a balance of amino acids, and other considerations [2:20:30];
    • Future research: understanding protein metabolism in the brain [2:23:45]; and
    • More.

    Connect With Peter on TwitterInstagramFacebook and YouTube

    Related Episodes

    #02 - Rhonda Patrick, Ph.D.: the performance and longevity paradox of IGF-1, ketogenic diets and genetics, the health benefits of sauna, NAD+, and more

    #02 - Rhonda Patrick, Ph.D.: the performance and longevity paradox of IGF-1, ketogenic diets and genetics, the health benefits of sauna, NAD+, and more

    Rhonda and I go on a Nerd Safari into the jungle of health, nutrition, fitness, performance, and longevity. We visit IGF-1 and whether there’s a tradeoff of having high or low levels. We discuss the PPARs (receptor proteins) and genetic polymorphisms. Does Rhonda think there’s any benefit in a NAD+ booster for health and longevity? Can saunas lower the risk of heart disease, dementia, and all-cause mortality? 

    Rhonda is a wealth of knowledge on so many topics and was the perfect companion to dig into so many fun topics in this episode. She puts a ton of thought into her research and it really shows in this conversation.

     

    We discuss:

    • What Rhonda believes differently today than she did a few years ago [5:40];
    • The paradox of GH/IGF-1 in performance and longevity [21:00];
    • The role of PPAR in fat metabolism and ketogenic diets [23:00];
    • The possible genetic explanations for why some patients don’t respond well to a ketogenic diet [31:00];
    • The health benefits of heat and cold exposure [1:12:30];
    • NAD+ [1:32:45];
    • And more.

    Learn more at www.PeterAttiaMD.com

    Connect with Peter on Facebook | Twitter | Instagram

    Episode 910: Thursday's Nugget - February 22, 2024

    Episode 910: Thursday's Nugget - February 22, 2024

    Faith in Prayer Persistence!
    In Colossians 4:2-3, the apostle Paul provides profound insight into the power and significance of faith in the life of a believer. He encourages the Colossian church, and by extension, all believers, to devote themselves to prayer with an attitude of thanksgiving. This simple instruction is packed with deep spiritual truths that can transform our understanding and practice of faith.

    UFYB 18: Massive Action

    UFYB 18: Massive Action

    This week, I want to teach you one of my favorite coaching tools for achieving tremendous results in any part of your life – taking massive action. Join me as I explain how this simple, yet powerful, tool can help you change your relationship with failure, eliminate doubt and fear, and allow you to get exactly what you want.

    Get full show notes and more information here: https://unfckyourbrain.com/18

    540: Cop Salary to $300 Million in Real Estate w/ Whitney Sewell

    540: Cop Salary to $300 Million in Real Estate w/ Whitney Sewell
    How do you build massive wealth while keeping your passions, family, faith, and bank account intact? Successful real estate investors will tell you the same thing: you need to automate and systematize to make time for it all, and they aren't kidding. Whitney Sewell was working as a cop when he got his start in real estate. Looking at his $35,000 salary, he realized that the long hours and tiresome, but enjoyable work, wouldn’t allow him financial freedom. Whitney wanted more time with his kids, his wife, and his beloved horses. So, he started attending every real estate conference he could go to, networking with anyone who owned any amount of real estate. He hired a performance coach, built a successful podcast, and flipped his limiting beliefs on their head, so he could tackle big deals. In only three years, Whitney built a real estate empire with over $300M assets under management. Part of his personal profits are donated to help adopted children and those who need adoptive parents. Whitney talks about how his faith and social goals have played a huge part in his real estate and how doing good must be the driving force behind wealth accumulation. In This Episode We Cover: Why it’s important to “overcommit” if you really want to succeed in real estate The “most dangerous book to reach on a beach” Why your network is your net worth and pushing yourself to connect with other like-minded investors Why wealth and faith don’t need to contradict each other Giving yourself the “thinking time” to spawn new, ingenious ideas Outsourcing and upgrading your business so you can make more while loving life And So Much More! Links from the Show BiggerPockets Youtube Channel BiggerPockets Pro Membership - Use discount code: podcast21 BiggerPockets Blogs BiggerPockets Forums BiggerPockets Webinars BiggerPockets Real Estate Podcast BiggerPockets Books by Brandon Turner The Official BiggerPockets Facebook group BiggerPockets Podcast 401: Follow these Steps to Get People to Know, Like, and Trust You with Jordan Harbinger BiggerPockets Podcast 227: From Single Family Houses to $130,000,000 in Multifamily with Joe Fairless Harley Davidson Straight Path Horses Website Click here to check the full show notes: https://www.biggerpockets.com/show540 Learn more about your ad choices. Visit megaphone.fm/adchoices

    Chris Joyce - Gusher

    Chris Joyce - Gusher

    Chris Joyce has seen it all. Literally. At 24 companies and counting, Chris has already explored more careers, businesses, and industries than most people could ever dream of.

    Chris personifies persistence. Not only does he exemplify this day in and day out, but his infectious "never give up" attitude has inspired countless entrepreneurs. Join us as we discuss what it takes to scale a business on this week's episode of The CEO Next Door.