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    #125 - John Arnold: The most prolific philanthropist you may not have heard of

    enAugust 24, 2020

    Podcast Summary

    • Billionaire Entrepreneur Turned PhilanthropistJohn Arnold, a billionaire entrepreneur, transformed his career into philanthropy, focusing on criminal justice reform, health policy, and K-12 education, viewing it as a powerful tool to tackle complex problems, spending $400 million annually on grants, aiming to use their entire fortune to solve these issues in their lifetime.

      John Arnold, a billionaire entrepreneur, transformed his successful natural gas trading career into a full-time philanthropist. His Arnold Ventures foundation, co-chaired with his wife Laura, focuses on addressing the toughest social issues, such as criminal justice reform, health policy, and K-12 education. Arnold differentiates philanthropy from charity and government spending, viewing it as a powerful tool to tackle complex problems. The foundation currently spends approximately $400 million annually on grants. Arnold's goal is to use their entire fortune to solve these issues in their lifetime. Despite his background in natural gas trading, listeners can find the episode interesting, even if they're not interested in that subject, as it offers insights into Arnold's unique perspective on philanthropy and problem-solving.

    • The Chan Zuckerberg Initiative's approach to solving complex problemsThe Chan Zuckerberg Initiative, led by John and Laura Zuckerberg, focuses on areas where the left and right agree, despite criticism from both sides. They aim to give away most of their philanthropic intent during their lifetimes, making their approach to giving atypical.

      The approach to solving complex problems requires flexibility and an understanding that different issues call for different solutions. The Chan Zuckerberg Initiative, led by John and Laura Zuckerberg, has managed to make an impact by focusing on areas where the left and right are coming together, despite sometimes being criticized by both sides. John grew up in Dallas and started his entrepreneurial journey at a young age, from mowing lawns to selling baseball cards, eventually leading him to co-found Facebook and later, the Chan Zuckerberg Initiative. The foundation deploys about $400 million per year from assets worth over $2 billion, with a goal to give away the majority of their philanthropic intent during their lifetimes. This approach to philanthropy is not typical, as many view serious giving as a later-in-life endeavor.

    • Entrepreneurial start in baseball card market through geographic arbitrageIdentifying price differences and exploiting them through arbitrage can lead to success, even during teenage years, and pave the way for future careers in competitive industries

      The speaker started his entrepreneurial journey in the baseball card market during his teenage years by identifying price differences in different regions and exploiting them through geographic arbitrage. He was able to drive around young due to a family situation and built a network of buyers and sellers across the country. Arbitrage, as explained, is taking advantage of price differences with little to no risk. The speaker's success led him to pursue a career in finance, specifically on Wall Street, after graduating from college in just three years. He was drawn to the excitement and competition of the financial industry, despite growing up with parents in the field. This early experience in arbitrage laid the foundation for his future success in finance.

    • From lower-tier school to Enron, determination leads to opportunitiesDetermination and quick learning can lead to unexpected opportunities, even if initial setbacks occur. Stay focused on career goals and take advantage of arising chances.

      Determination and perseverance can lead to opportunities in unexpected places, even when facing initial setbacks. The speaker shares his experience of being unable to secure a job in investment banking despite attending a lower-tier school. However, he landed a job at Enron in 1995, which was on the cusp of transforming into an investment bank in the energy industry. Initially, he started as an assistant in the oil trading group, but his eagerness and quick learning abilities were soon recognized. This experience highlights the importance of staying focused on career goals and taking advantage of opportunities that may arise, even if they don't initially align with the desired path. Additionally, the corporate trend towards asset light business models played a role in Enron's transformation and the speaker's career progression.

    • Starting in the right job can shape your careerQuick learning abilities and adaptability are valuable skills in the job market, especially during industry changes. Starting in a small, undervalued division can lead to significant career growth.

      Finding the right fit in your first job can significantly impact your career trajectory. The speaker shares his experience of starting in commodities trading at Enron, which turned out to be the perfect match for his skill set despite being an accident. He explains that Enron had a small oil trading group, which was seen as the red-headed stepchild, while natural gas was the core business. The speaker's quick learning abilities and adaptability helped him rise through the ranks, especially during the industry's deregulation and price volatility in the late 1990s. He started as an assistant trader and, through hard work and dedication, became a valuable asset to the company. The environment at Enron during that time also facilitated career growth, as other companies sought to replicate its success by hiring its employees.

    • Rapid career growth from young age in fast-paced industry comes with health risksRising quickly in a demanding industry can lead to unhealthy habits and stress, impacting personal life and health. Prioritize self-care and balance.

      Taking on significant responsibility at a young age in a fast-paced industry can lead to rapid career growth. However, the intense stress and long hours can negatively impact one's health and personal life. The speaker, a former head natural gas trader at Enron, experienced this firsthand, rising quickly through the ranks but also dealing with high levels of stress that led to unhealthy habits. The trading industry can be addictive, with the rush of successful trades providing a dopamine surge similar to gambling or alcohol. The speaker acknowledges that he saw this addiction in some traders, but for him, it was more of an intellectual exercise. The experience was formative, shaping his understanding of handling stress and leading him to eventually prioritize his health and personal life over his career.

    • Emotional detachment and confidence in tradingBeing emotionally detached and confident are essential traits for successful trading. Detachment helps minimize emotional biases, while confidence allows for bold decisions. Balance is key to avoid excessive risk-taking.

      Successful trading requires emotional detachment and confidence. John, a renowned natural gas trader, shares that he was born with the ability to detach from emotions, which is a valuable trading superpower. He also emphasizes the importance of confidence, acknowledging that a certain level of arrogance is necessary to make trades but avoiding excessive arrogance that can lead to career-ending risks. These traits served him well not only in his trading career but also in his philanthropy work. Despite Enron's eventual bankruptcy, the trading group was making significant profits, which some believed could support the struggling divisions. However, hindsight reveals that some of Enron's business ventures were questionable, and the company's culture of never admitting failure contributed to the downfall. Overall, emotional detachment and confidence are crucial for traders, but they must also be balanced to avoid excessive risk-taking.

    • The importance of trust in business relationshipsThe loss of creditor and investor trust can lead to a company's downfall, impacting employees and future business endeavors.

      The loss of faith from creditors and Wall Street can lead to a company's downfall, as seen in the case of Enron. The financial business, which Enron had transformed into, relied heavily on the trust of creditors and investors. When that trust was broken, Enron was unable to secure funding and ultimately went bankrupt. For those employed by the company, this meant losing their jobs and having to make difficult decisions about their future. Despite his success and profitability within Enron, the interviewee realized he didn't want to continue with the company when it lost credibility. He went on to start his own hedge fund, but faced challenges due to the negative association with Enron. The quick downfall of Enron serves as a reminder of the importance of maintaining trust and faith in business relationships.

    • Profitable risk intermediation during market inefficiencyUnderstanding risk and return, and the potential synergy of bundling these aspects, can lead to profitable opportunities during market inefficiencies.

      During times of market inefficiency, there are opportunities for profitable risk intermediation. The Enron scandal led to a mass exit of players from the energy merchant business, resulting in an inefficient market willing to pay high rates for risk management. This created a lucrative environment for arbitrage trades with low risk and high returns. The speaker, an energy trader, was able to capitalize on this situation, making significant profits in the first few years through a combination of market making and speculative trading. The importance of understanding risk and return, and the potential synergy of bundling these two aspects of a business, were key to his success. While the speculative side of energy trading often grabs headlines, the speaker's experience demonstrates the value of providing market liquidity and managing risk during times of market inefficiency.

    • First year success in natural gas market leads to philanthropic considerationsA trader's early success in a volatile market led him to feel financially secure and explore philanthropy, but increased competition forced him to keep his business narrow to maintain profits.

      During his first year in the natural gas market, the trader experienced remarkable success due to high demand and low supply, leading to significant price spikes during a cold winter. He made substantial profits from these trades, which allowed him to feel financially secure and consider his future in philanthropy. However, this success attracted attention from other hedge funds, leading to increased competition and new entrants in the market. The trader deliberately kept the focus of his business narrow to maintain its success. Despite recognizing the limited social value of trading, he had begun to explore K-12 education philanthropy earlier in his career and continued to increase his involvement in it as his hedge fund grew.

    • Staying focused on a niche can lead to successSpecializing in a specific area and maintaining expertise can lead to better investment returns, even with a smaller asset base.

      Focusing on a specific niche and maintaining expertise in that area can lead to success, even if it limits the size of the business. As an example, a hedge fund that specialized in natural gas and power trading in North America, despite having only $6 billion in assets under management (AUM), was able to become the best in the field by staying focused and not trying to expand into other areas. The fund's founder, who was also the largest investor, made investment decisions based on what he believed was a good investment for his own money, and if others wanted to join, that was welcome. In 2005, the fund's natural gas trader, Brian Hunter, made significant profits due to Hurricane Katrina causing damage to offshore and onshore natural gas production and processing facilities, leading to a significant increase in natural gas prices. However, in 2006, Hunter kept his bullish bet on natural gas despite the market becoming oversupplied and bearish. This trade, known as the Amaranth trade, resulted in significant losses for the fund, but the overall strategy of focusing on expertise and not trying to manage too much assets paid off in the long run.

    • Market dynamics and supply considerations impact commodity pricesUnderstanding market dynamics, considering alternative scenarios, and being aware of information handicap can help traders make informed decisions despite disadvantages.

      The market dynamics and supply considerations can significantly impact commodity prices beyond the initial bet on weather or climate events. In the discussed example, a trader's large position on a macro hedge fund during the early hurricane season led to a significant price collapse when no hurricane hit. However, it's essential to consider the second-order bet - the market's ability to bear the supply shock. The trader who profited from the situation had carefully considered the potential outcomes and sized his position accordingly. The real lesson here is the importance of understanding the market's dynamics, considering alternative scenarios, and being aware of the information handicap when trading against larger players. The trader's obsession with knowing everything and having better analysis helped him overcome this disadvantage and make informed decisions.

    • Ideal commodity for trading: Natural Gas in North AmericaDue to its closed system, deregulation, and seasonality, natural gas in North America provided a favorable environment for fundamental trading, enabling Centaurus to build a strong research team and achieve above-average returns.

      The natural gas market in North America was an ideal product for trading due to its closed system, deregulation, and seasonality. The closed system allowed for better prediction of future flows, while deregulation forced transparency and a Chinese wall between transportation and trading. Seasonality introduced a forcing mechanism for prices to return to fair value twice a year. These factors enabled Centaurus to build a strong fundamental research department and achieve above-average returns. The ease of tracking natural gas molecules compared to oil was another advantage, as oil's complex physical business made it harder for outsiders to follow. Overall, the unique characteristics of the natural gas market made it an attractive commodity for fundamental trading.

    • Recognizing changing market conditions and shifting prioritiesSuccessful individuals must be adaptable and willing to shift priorities when necessary to maintain success and find fulfillment in new pursuits.

      Successful individuals, whether in business or research, often need to dedicate their full focus to their endeavors to achieve great success. However, as time passes and opportunities change, it may become necessary to shift priorities and allocate time and resources to new pursuits. The interviewee, a successful hedge fund manager, shares his personal experience of dedicating over a decade to natural gas trading before realizing the market conditions had changed and it was time to shift his focus to philanthropy full-time. This transition was a difficult decision, as his identity and success were closely tied to his career as a trader. However, by recognizing the changing market conditions and the opportunity to make a significant impact through philanthropy, he was able to make the shift and find fulfillment in his new pursuits.

    • From Trading to Philanthropy: Emotional Resilience and Expertise are KeyTransitioning to a new life path requires emotional strength and quick expertise acquisition. Fear of dissatisfaction is common, but gaining knowledge and making a meaningful impact can lead to fulfillment.

      Making a significant life change, like transitioning from a successful trading career to full-time philanthropy, requires emotional resilience, confidence, and the ability to quickly become an expert in new areas. The speaker shares his personal experience of grappling with the fear of not finding satisfaction in the new endeavor and the importance of gaining expertise to make a meaningful impact. He also discusses the challenges of scaling successful educational interventions and the ongoing quest to find effective solutions in the K-12 education system.

    • From traditional public schools to a system of schoolsGovernment should regulate instead of providing services, enabling innovation, quality control, and proper regulation for all kids.

      Education is a fundamental issue for the long-term health and viability of a country, and the traditional public school system lacks the necessary attributes for robust evolution and improvement. The school system should become a system of schools, with the natural role for government being the regulator instead of the service provider. This shift, as seen in New Orleans after Katrina, allows for innovation, quality control through parental choice, and proper regulation to ensure all kids are served. Philanthropy plays a crucial role in this sector, accounting for approximately 1% of the economy, and its funds should be used effectively to drive positive change.

    • Maximizing Impact Through Strategic PhilanthropyEffective philanthropy involves deep analysis, expertise, and a focus on systems change to complement government services and address root causes of social issues, despite the complexities and challenges.

      Effective philanthropy goes beyond just writing checks to charities. It requires deep analysis, expertise, and a focus on systems change to maximize impact. The role of philanthropy is not to replace government services but to complement them by addressing the root causes of social issues. However, this type of giving is complex and challenging, even for large foundations, as it requires significant resources and research capabilities. The process of identifying effective programs and making informed decisions can be time-consuming and frustrating, as the evidence base for what works is often unclear or contested. Despite these challenges, strategic philanthropy offers the potential for significant, scalable impact.

    • Addressing root causes of criminal justice issuesThe founders of this philanthropy recognized the importance of addressing systemic issues in the criminal justice system and spent a year researching inefficiencies to identify where they could have the most impact.

      The founders of this philanthropy recognized the importance of addressing the root causes of issues within the criminal justice system, rather than just funding individual programs. They were particularly moved by the Innocence Project and its efforts to free wrongfully convicted individuals. However, they realized that saving one life at a time was not a sustainable solution. Instead, they decided to focus on systemic change and spent a year researching the inefficiencies in the system. They brought in experts to help identify where their foundation could have the most impact. This approach required patience, but they believed that investing wisely today would lead to greater impact in the future. The foundation's resources and lack of inherent power in the system presented unique challenges, but they believed that by identifying leverage points, they could steer the system towards improvement. Initially, they had two versions of the foundation, but currently, the entire organization operates as a C3.

    • Historical policies fueled mass incarceration and racial disparitiesUnderstanding the historical context of criminal justice policies is essential for addressing racial disparities and advocating for systemic change.

      The criminal justice system's issues, including racial disparities and difficulties in appealing convictions, stem from historical policies driven by bipartisan efforts to address violent crime in the late 20th century. These policies, such as increased policing, harsher sentences, and a war on drugs, contributed to mass incarceration. However, it's challenging to attribute the subsequent crime reduction solely to these policies. Factors like demographic trends, economic growth, and improved education and policing tactics also played a role. Globally, similar trends were observed, further emphasizing the complex nature of this issue. Ultimately, understanding the system's roots is crucial for advocating for meaningful policy changes.

    • Factors contributing to US high incarceration ratesThe US has high incarceration rates due to longer sentences, conviction rates, plea bargains, and systemic racism within law enforcement, resulting in disproportionate impact on minorities.

      The high incarceration rates in the US, which peaked in the 90s and have since decreased, can be attributed to various factors including longer sentences, conviction rates, and the plea bargain system. The system's inability to handle the volume of cases has led to incentives for pleading guilty, even for those who may be innocent. This issue is further complicated by systemic racism within law enforcement, leading to disproportionate arrests, convictions, and imprisonment of minorities. The challenge lies in addressing the culture where the system cannot handle everyone going to trial, and finding a solution without a massive infusion of resources. Philanthropy can play a role in criminal justice reform by addressing the issue of racism within law enforcement and its secondary effects on families and communities. The current mainstream discussion acknowledges the historical disproportionate impact on black men in prison, but also considers the broader implications for children and communities. The goal is to create a policing system that treats people equitably and justly, while also addressing the crime problem and the high cost to communities.

    • Addressing criminal justice issues needs a multi-faceted approachFocus on rehabilitation before release and invest in long-term solutions through philanthropy to reduce high recidivism rates

      Addressing the complex issues within the criminal justice system requires a multi-faceted approach. While policing reforms and reducing recidivism are crucial, they are just pieces of a larger puzzle. The problems within the system were created over long periods of time and require more than just new policies to be solved. Rehabilitation is a vital component of the criminal justice system, yet it is often overlooked or underfunded. The lack of rehabilitation programs can lead to high recidivism rates, making it essential to focus on this aspect before an individual's release. Additionally, the financial constraints faced by governments limit their ability to invest in long-term solutions, making philanthropy a valuable partner in funding experimental programs and reimagining prisons to better support rehabilitation.

    • Identifying long-term solutions in complex systemsThe Chan Zuckerberg Initiative looks for areas with clear flaws and potential solutions, even if political will is lacking, to create evidence-based ideas and communications for future implementation.

      Effective change in complex systems like criminal justice and health policy requires a long-term perspective and evidence-based solutions. The Chan Zuckerberg Initiative focuses on identifying areas with clear flaws and potential solutions, even if the political will to implement changes isn't present yet. In criminal justice, they aim for programs with positive ROI and societal benefits. In health policy, they zeroed in on drug pricing as an area for reform eight years ago, anticipating a future political window of opportunity. By preparing evidence-based ideas and communications, they can act swiftly when the opportunity arises.

    • The complexities of pharmaceutical industry and its impact on American healthcare costsDespite the NIH's investment in drug research, Americans pay high prices due to lack of price discounts. The federal government's lack of budget constraints exacerbates the issue, requiring a multifaceted approach and political will to address unsustainable costs.

      The pharmaceutical industry's complexities and incentives create a challenging issue for policymakers, with numerous potential solutions. The United States, as a large consumer and subsidizer of pharmaceuticals, faces unsustainable costs. The NIH's investment in drug research should result in lower prices for Americans due to their contribution to R&D. However, the lack of price discounts for Americans remains a significant issue. The federal government's lack of budget constraints limits its ability to make difficult decisions, leading to increasing healthcare spending and potential future inflation. The complexity of the issue requires a multifaceted approach and significant political will to address.

    • Economic environment and pharmaceutical industry risksLow interest rates and high debt levels could lead to economic instability if inflation emerges, and the pharmaceutical industry's unique financial situation may result in questionable returns on investment, requiring attention before a crisis.

      The current economic environment, with low interest rates and high debt levels, could lead to significant issues if inflation were to emerge. The combination of rising interest rates and mounting debt could overwhelm the country's GDP, leading to negative consequences for households, businesses, and governments. Furthermore, the pharmaceutical industry's unique financial situation, where it doesn't have to compete for resources like other industries, results in questionable returns on investment. The speaker believes that change, whether it be economic or in the pharmaceutical industry, often comes gradually but can suddenly and dramatically impact the system. It's crucial to address these issues before a crisis occurs.

    • Persistence and long-term commitment in philanthropyDecades-long dedication to solving complex social issues can lead to significant impact despite slow progress

      Persistence and long-term commitment are crucial in philanthropy, even when progress seems slow or uncertain. The example of the advocate who worked for 20 years to change the military's "don't ask, don't tell" policy illustrates this idea. Similarly, philanthropists like the interviewee and Rick Doblin have dedicated decades to solving complex social issues. While the feedback loop in philanthropy is much longer than in trading, the potential impact can be significant. Climate change is a major issue where the downside risks are immense, making it an area where society should invest resources to mitigate the risks. The interviewee's philanthropic work often focuses on "orphaned" issues with limited attention and resources.

    • Bipartisan approach to climate changeEngage with individuals and organizations from all political sides to create lasting, sustainable climate change solutions. Focus on personal growth before joining family foundation or considering a role in philanthropy.

      Addressing climate change requires a bipartisan approach. The speaker emphasizes the importance of engaging with individuals and organizations from both sides of the political aisle to create lasting, sustainable solutions. This includes working with philanthropists, researchers, advocates, and politicians from the right, as well as the left. The speaker also discusses the impact of philanthropy on children, encouraging them to develop their own interests and experiences before potentially joining the family foundation. Additionally, the speaker stresses the importance of not allowing the perception of having a checkbook to define one's identity during the formative years. Instead, young adults should focus on building their own careers and relationships before considering a role in philanthropy.

    • Making a difference through intelligent givingSmall contributions, given intelligently, can create significant impact on communities and society as a whole.

      Making a difference in the world through charitable giving is not limited to those with large means. Even small contributions can create significant impact when given intelligently and with the understanding that the dollar is creating more total good than it would if spent elsewhere. The concept of local giving, defining one's community in various ways, can lead to more informed and effective giving. Giving a portion of income to charity, no matter the amount, can strengthen communities and improve society as a whole. It's remarkable how giving and philanthropy are deeply ingrained in American culture due to the country's wealth and security, enabling many to prioritize the needs of their communities. Ultimately, the importance of giving lies in the positive impact it has on individuals and communities, regardless of the amount or scale.

    • Private podcast feed for subscribers with discounts and benefitsSubscribers get access to short episodes, discounts, and additional benefits through a private podcast feed

      Peter A. Morgan, MD offers a private podcast feed for subscribers, providing access to short, five-minute episodes called Qualys, summarizing the best topics and tactics from previous shows. This is a convenient way for listeners to catch up on past episodes without having to listen to the entire backlog. Additionally, subscribers receive steep discounts on products endorsed by Dr. Morgan, as well as other benefits. Interested individuals can learn more and subscribe at peteratiamd.com/subscribe. Dr. Morgan can be found on various social media platforms, and users are encouraged to leave reviews on podcast players. The podcast is for general informational purposes only and does not constitute medical advice. Users should consult healthcare professionals for medical concerns. Dr. Morgan discloses conflicts of interest on his website.

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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.

    View the Show Notes Page for This Episode

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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

    #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

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    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.

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    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?

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    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.

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    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

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    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.

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    #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

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    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

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