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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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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.

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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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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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