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    #14 - Robert Lustig, M.D., M.S.L.: fructose, processed food, NAFLD, and changing the food system

    Excess fat in the body can be cleared out through oxidation and export, but an increase in de novo lipogenesis and high triglyceride levels can lead to fatty liver and inflammation. Insulin resistance, chronic stress, and the release of cortisol and neuropeptide y also play a role.

    enSeptember 10, 2018

    About this Episode

    In this episode, Rob Lustig — a researcher, an expert in fructose metabolism, and a former pediatric endocrinologist — discusses what’s wrong with the current food environment, and what we can do to reduce our chances of becoming part of the obesity, diabetes, metabolic syndrome, and nonalcoholic fatty liver disease (NAFLD) epidemics. Rob recently earned a Master of Studies in Law because he believes that educating people about sugar from a scientific standpoint is only half the equation: the other half involves changing policy, which he explains in this episode.

    We discuss:

    • What’s the difference between glucose and fructose? [7:00];
    • Do we have biomarkers that can give us some indication of average exposure to fructose over a given period of time? [14:20];
    • What’s the difference between ALT and AST? [18:45];
    • Inflammation, endothelial function, and uric acid [21:30];
    • Is there something that fructose does better than glucose? [23:45];
    • For children that undergo a remarkable shift from metabolic health to metabolic derangement, is there a concern that these kids suffer an epigenetic hit that makes it harder for them later in life? [26:15];
    • How many times do you have to introduce a savory food vs a sugary food to an infant before they will accept it? [29:30];
    • How are alcohol and fructose similar in how they affect the brain? [33:51];
    • Advice for parents and kids for creating a sustainable environment that's going to prevent them from running into metabolic problems [40:30];
    • Why do some populations have a higher risk for NAFLD? [45:42];
    • What causes NAFLD? [48:45];
    • Is insulin resistance the result of NAFLD or is NAFLD the result of insulin resistance? [56:00];
    • HRV, cortisol, and norepinephrine [1:00:30];
    • What are the actual mechanisms that links metabolic syndrome, insulin resistance, fatty liver, and type 2 diabetes? [1:03:00];
    • Is the food industry still saying that all calories contribute equally to adiposity and insulin resistance? [1:09:00];
    • What is the difference between soluble and insoluble fiber and why do you need both? [1:13:00];
    • How can we change the food system when 10 companies control almost 90 percent of the Calories we consume in the US? [1:15:00]; and
    • More.

    Learn more at www.PeterAttiaMD.com

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    🔑 Key Takeaways

    • Avoiding sugar alone is not sufficient for a healthy diet; consuming both soluble and insoluble fiber from real foods like vegetables is equally important.
    • Glucose is essential for bodily functioning and energy, while fructose is primarily a storage form of energy in plants and is metabolized differently by gut bacteria.
    • Fructose has negative effects on the body, including decreased protein functionality, potential inflammation, and overeating, while glucose suppresses hunger and is metabolized differently in the brain. The claim that all sugars and calories are the same is inaccurate. Researchers are working on biomarkers for measuring fructose's effects.
    • Lowering sugar intake can improve blood pressure and liver health by reducing serum uric acid and ALT levels. It is important to be mindful of sugar consumption for overall well-being.
    • High levels of uric acid and homocysteine can harm cardiovascular health by inhibiting nitric oxide synthesis. It is important to manage these levels to maintain optimal cardiovascular function.
    • While not yet proven in humans, there is a possibility that maternal hyperglycemia during pregnancy can lead to epigenetic changes in offspring, impacting their metabolism. Promoting healthy eating habits for our children is beneficial regardless.
    • Chronic overstimulation of neurons can lead to cell death, addiction, and a decrease in the ability to experience joy. Understanding this impact is crucial for promoting overall well-being.
    • Addiction can be caused by a variety of substances and behaviors that stimulate dopamine in the brain, and addressing addiction may require different approaches depending on the specific substance or behavior involved.
    • Avoiding processed foods and focusing on a low sugar, high fiber diet of real, unprocessed foods is the key to maintaining a healthy lifestyle.
    • Educating ourselves and our children about the impact of food on our bodies can help us make healthier choices and prevent health issues in the long run.
    • Fructose consumption plays a significant role in the development of NAFLD and related health issues, highlighting the importance of addressing dietary factors in preventing and managing these conditions.
    • Excess fat in the body can be cleared out through oxidation and export, but an increase in de novo lipogenesis and high triglyceride levels can lead to fatty liver and inflammation. Insulin resistance, chronic stress, and the release of cortisol and neuropeptide y also play a role.
    • Chronic stress and overstimulation of the sympathetic nervous system can lead to the accumulation of harmful visceral fat, which is linked to various health issues. Excessive sugar consumption is a major contributor to these negative health outcomes.
    • Lowering blood insulin levels is crucial in addressing diabetes and chronic metabolic diseases, as it can help reduce weight gain, decrease the risk of heart attacks, and potentially prevent the development of cancer. Physicians need to prioritize addressing hyperinsulinemia alongside diabetes.
    • Not all calories are fully absorbed by the body, and consuming fiber is crucial for maintaining a healthy gut and digestive health.
    • The food industry's current practice of adding soluble fiber to processed foods is ineffective. Real food with both soluble and insoluble fiber is crucial for health, but changing the industry requires collaboration and addressing challenges.
    • Eliminating food subsidies and implementing regulations on unhealthy food marketing to children are important steps towards promoting healthier food choices and addressing the issue of distorted market prices.

    📝 Podcast Summary

    Experts Discuss Nuanced Aspects of Sugar, Fiber, and Balanced Diets

    Discussions between experts like Peter Attia and Dr. Rob Lustig are crucial for understanding complex topics beyond the headlines. They delve into the nuanced aspects of issues like the effects of sugar on addiction and depression, as well as the importance of fiber in a balanced diet. Dr. Lustig emphasizes that avoiding sugar alone is not enough and highlights the significance of consuming both soluble and insoluble fiber, mainly found in real foods like vegetables. Practical advice on parenting and maintaining a healthy balance for children is also provided. This episode offers insights into topics such as fructose, liver function testing, uric acid, metabolic syndrome, and heart rate variability, providing a comprehensive understanding of these subjects.

    The Differences Between Glucose and Fructose

    There are significant differences between glucose and fructose, two types of carbohydrates. Glucose is essential for proper bodily functioning and is the main source of energy for all cells. Even if you don't consume glucose directly, your body can produce it through a process called gluconeogenesis. On the other hand, fructose is not a crucial nutrient for animal life and is primarily a storage form of energy in plants. When consumed, fructose is metabolized more efficiently by gut bacteria than by our own bodies. Furthermore, glucose and fructose have different biochemical properties, with fructose being more prone to causing the Amadori rearrangement, a process associated with aging. Understanding these distinctions is important when considering the effects of sugar and processed foods on our health.

    The Differences Between Fructose and Glucose

    Fructose and glucose have significant differences in their effects on the body. Fructose causes a browning reaction in the body's proteins at a much faster rate than glucose, leading to decreased functionality and potential inflammation. Additionally, fructose does not suppress the hunger hormone ghrelin like glucose does, which can result in overeating. In terms of brain metabolism, glucose is primarily metabolized in areas related to sensory-motor function, while fructose specifically activates the brain's reward center, similar to addictive substances like cocaine. The food industry's claim that all sugars and calories are the same is inaccurate and misleading. While measuring fructose consumption is challenging, researchers are working on finding long-term biomarkers for its effects.

    Effects of Excessive Sugar Consumption on Health

    Excessive sugar consumption leads to an increase in serum uric acid and ALT levels, which can have detrimental effects on our health. Consuming high amounts of fructose, found in sugary beverages and processed foods, puts us at higher risk for conditions like gout and elevated blood pressure. Uric acid inhibits an enzyme responsible for relaxing blood vessels, leading to increased blood pressure and an elevated risk of stroke. Lowering sugar intake can help decrease serum uric acid levels and subsequently improve blood pressure. Additionally, ALT levels indicate the amount of liver fat, and its increase suggests fatty liver disease. By reducing sugar consumption, ALT levels can decrease, promoting better liver health. It is crucial to be mindful of sugar intake and maintain levels within healthy limits.

    Managing Uric Acid and Homocysteine Levels for Cardiovascular Health

    High levels of uric acid and homocysteine in the body can have detrimental effects on cardiovascular health. These substances can inhibit nitric oxide synthesis, leading to vasoconstriction in coronary arteries and increased risk of metabolic syndrome. The empirical and interventional data now available confirm the plausibility argument and highlight the importance of managing uric acid and homocysteine levels. Additionally, the discussion suggests that fructose consumption in its natural state (as in fruits) may have an advantage over glucose in quickly replenishing liver glycogen stores. However, this advantage is largely insignificant, as real food can effectively restore glycogen levels within a day. Overall, understanding the impact of these substances and their role in metabolic health is crucial for maintaining optimal cardiovascular function.

    The Potential Link between Maternal Hyperglycemia and Offspring's Metabolic Dysfunction

    There may be a link between maternal hyperglycemia during pregnancy and epigenetic changes in offspring that can lead to metabolic dysfunction later in life. While this has been observed in animal studies, it has not been conclusively proven in humans. However, if it is true, it could explain the increasing prevalence of metabolic syndrome and related conditions. As parents, we should consider the food environment our children are exposed to and make efforts to promote healthy eating habits. Even if the link between epigenetics and metabolism is eventually proven untrue, there is no downside to encouraging our children to eat well, aside from the effort it requires.

    The Impact of Overstimulation on Neurons

    Chronic overstimulation of neurons can lead to cell death and a decrease in the ability to experience joy. Neurons are designed to be excited but not constantly bludgeoned with neurotransmitters. When neurons are continuously overstimulated, they down regulate their receptors to protect themselves, reducing the risk of cell death. However, this down regulation also leads to tolerance, where larger and larger hits are needed to achieve the same rush. Eventually, chronic stimulation causes neuronal cell death, resulting in addiction and permanent damage. It's important to note that not all drugs are stimulatory; there are also inhibitory drugs like benzodiazepines and psychedelics. Understanding the impact of overstimulation on neurons is crucial in order to prevent addiction and promote overall well-being.

    The Impact of Different Substances and Behaviors on Dopamine and Addiction

    Different substances, including drugs and certain behaviors, can stimulate dopamine in the brain and lead to addictive behaviors. Not all drugs have the same negative impact on neurons. For example, psychedelics do not cause receptor down-regulation or withdrawal symptoms. Ethanol, on the other hand, not only acts as a gaba agonist but also produces acetaldehyde through metabolism, leading to the creation of reactive oxygen species that can harm neurons. Similarities between ethanol and fructose exist in both the liver and the brain, as they both stimulate the reward center through different mechanisms. Additionally, addictive behaviors such as gambling or using social media can also trigger dopamine response and induce tolerance. It is important to recognize that addiction can encompass a wide range of substances and behaviors, and addressing them may require different approaches.

    The Hidden Dangers of Processed Foods

    Processed foods are the main problem when it comes to sugar consumption. The added sugars that we are aware of, such as those found in sodas and candies, only make up about half of the added sugars consumed by children. The other half comes from foods where sugar is hidden, like bread and pasta sauce. This is because sugar is added to these products to act as a preservative and keep the water content high. It's important to focus on consuming a low sugar, high fiber diet, which is known as real food. The goal is not to fixate on specific target numbers, but rather to prioritize whole, unprocessed foods in order to maintain a healthy lifestyle.

    The importance of a real food diet and understanding the difference between processed and real food.

    A diet consisting of real food is essential for maintaining good health. Processed foods, such as grocery store bread, should be avoided as they lack nutrients and can have negative effects on our bodies. Parents need to understand the difference between real food and processed food, and teach their children to make healthy food choices. Although it may require more time and money, investing in real food is worth it for our well-being. Furthermore, certain ethnic groups, such as Latinos, may have a genetic predisposition to conditions like non-alcoholic fatty liver disease (NAFLD). Therefore, it is especially important for those at higher risk to eliminate excessive sugar consumption from their diet. By educating people about the impact of food on our biochemistry and behavior, we can make healthier choices and prevent health issues.

    Understanding the Link Between NAFLD, Diabetes, and Fructose Consumption

    Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes are both on the rise among children and adults, suggesting an environmental insult rather than solely genetics. The speaker, Robert Lustig, had initially misunderstood his patients' claims of not consuming alcohol, only to later discover that they had NAFLD. He explains that the production of liver fat can occur through dietary fat or de novo lipogenesis, the process of turning sugar into fat. Despite previous beliefs that de novo lipogenesis was a minor pathway, it is now known to be a major pathway, contributing significantly to liver fat. This reveals the importance of addressing fructose consumption as a driving factor behind NAFLD and its related health issues.

    Body's methods for clearing out excess fat and the role of dietary fats and lipogenesis in fatty liver and inflammation.

    There are two ways for the body to clear out excess fat: oxidation and export. Oxidation refers to the process of breaking down fatty acids for energy, while export involves moving fat out of the liver through VLDL or phosphatidylcholine. The decrease in dietary fats is not the cause of fatty liver, but rather the increase in de novo lipogenesis, the creation of fat from non-fat sources. This leads to fatty liver and inflammation, making the mitochondria less functional and impairing fatty acid oxidation. The high triglyceride levels in patients who consume fructose indicate that more fat is coming in than being cleared out. Insulin resistance and NAFLD are interconnected, but the adipogenic hypothesis of metabolic syndrome, which links fat cells and liver dysfunction, is only one of the pathways. Another pathway involves the accumulation of visceral fat due to chronic stress and the release of cortisol and neuropeptide y.

    The Impact of Chronic Stress and Sympathetic Overstimulation on Visceral Fat Accumulation.

    Chronic overstimulation of the sympathetic nervous system, combined with chronic stress, leads to the accumulation of visceral fat. This visceral fat is distinct from subcutaneous fat and is more problematic for health. Additionally, the conversation highlights the role of cortisol and neuropeptide y in promoting lipogenesis and fat accumulation. This insight is supported by the correlation observed between low heart rate variability (indicating higher sympathetic tone) and higher glucose levels. The conversation also emphasizes the detrimental effects of liver dysfunction caused by cytokines released from visceral fat or due to primary hepatic dysfunction. Ultimately, the main culprit in promoting these negative health outcomes is excessive sugar consumption.

    The Impact of Hyperinsulinemia on Chronic Metabolic Diseases

    Hyperinsulinemia, or high levels of insulin in the body, is a significant factor in chronic metabolic diseases. Insulin's primary function is to store energy, but it also causes inflammation and cell division. This can lead to weight gain, increased risk of heart attacks, and even the development of cancer. Lowering blood glucose levels alone is not enough to address diabetes; lowering blood insulin levels is equally important. Currently, the food industry perpetuates the idea that all calories contribute equally to weight gain and insulin resistance, but this is not true. It is crucial for physicians to recognize the importance of hyperinsulinemia and address it as seriously as diabetes itself.

    The Impact of Fiber on Calorie Absorption and Gut Health

    Not all calories are the same, contrary to popular belief. The example of almonds shows that even though they may have 160 calories, only about 75% of those calories are actually absorbed by the body. The soluble and insoluble fiber in the almonds form a gel in the intestines, preventing early absorption. This means that the remaining calories pass into the colon where they can be metabolized by the gut bacteria. Consuming fiber is crucial because it provides food for the gut bacteria, preventing them from damaging the mucin layer in the intestine. Both soluble and insoluble fiber are necessary for forming this protective barrier. It is important to include sources of fiber in our diet to maintain a healthy gut and overall digestive health.

    The importance of functional fiber in promoting health and the need to transform the food industry's business model.

    The food industry's current approach of adding soluble fiber to processed foods is not effective in promoting health. The industry claims that these products are good because they contain extra fiber, but the truth is that they lack functional fiber. Real food, on the other hand, provides both soluble and insoluble fiber, which work together to improve health. However, the challenge lies in changing the food industry's business model, as they currently profit from selling sugary products. To bring about change, there are four potential approaches: educating the public to make better food choices, executive branch efforts (although currently limited), legislative changes (difficult due to industry influence), and lawsuits targeting the food industry. Overall, transforming the food system requires a collective effort from various stakeholders.

    The role of food subsidies in distorting the market and the need for regulatory measures to promote healthier food choices.

    Food subsidies play a significant role in distorting the market and making junk food cheaper than real food. Robert Lustig emphasizes that getting rid of these subsidies would allow the market to function properly. While the price of most foods wouldn't change, corn and sugar would become more expensive, as they are major sources of dietary sugar. Lustig suggests incorporating the issue of the metabolic cost of food into the Farm Bill, which governs agricultural policies, to strengthen the link between food, productivity, and healthcare costs. Additionally, he acknowledges the importance of awareness and regulation in curbing unhealthy food marketing to children, as voluntary measures by industry players have proven insufficient. Overall, addressing food subsidies and marketing practices are vital steps towards promoting healthier food choices.

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    • The impact of impaired driving: alcohol, cannabis, prescription drugs, and more [1:26:15];
    • Mitigating the effects of vehicle speed [1:38:15];
    • The promise and challenges of autonomous vehicles for road safety [1:44:15];
    • Automatic emergency braking (AEB): the effectiveness and challenges of implementing AEB as a standard feature in new vehicles [1:53:00];
    • Sleep deprivation: the impact of poor sleep, drowsiness, and disrupted circadian rhythm on driving [1:58:15];
    • Protecting pedestrians: strategies for reducing the risk of fatal accidents with pedestrians on foot or bicycle [2:02:30];
    • Empowering safe driving: essential resources and tips for parents and teenage drivers [2:14:00];
    • Promoting a culture of proactive safety: parting thoughts from Mark [2:19:15]; and
    • More.

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    The Peter Attia Drive
    enMarch 25, 2024

    #294 ‒ Peak athletic performance: How to measure it and how to train for it from the coach of the most elite athletes on earth | Olav Aleksander Bu

    #294 ‒ Peak athletic performance: How to measure it and how to train for it from the coach of the most elite athletes on earth | Olav Aleksander Bu

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    Olav Aleksander Bu is an internationally renowned sports scientist acclaimed for his coaching prowess with elite athletes spanning a diverse range of sports disciplines. In this episode, Olav delves deep into the intricacies of VO2 max and its profound impact on performance. They explore the relationship between VO2 max and ATP production, energy efficiency, and power, as well as the impact of low-intensity training on VO2 max. The conversation extends to Olav’s experiences pushing the boundaries with high-performance athletes and the data driven interventions he uses to improve performance. They also dissect the role of lactate threshold, discuss other important metrics to track, and explore the exciting possibility of utilizing a portable VO2 testing device as a practical alternative to traditional lab-based assessments.

    We discuss:

    • Olav’s background, expertise in exercise physiology, coaching experience, and interest in the extremes of human capability [4:15];
    • The processes of energy conversion within the human body and its implications for performance [9:30];
    • Improving movement efficiency, and the importance of mindfulness in training to optimize performance [20:00];
    • The relationship between VO2 max, power output, and endurance performance in different sporting contexts [34:45];
    • How VO2 max is measured in the lab, and why it’s a crucial predictor of both lifespan and quality of life [44:45];
    • Absolute vs relative VO2 max, the significance of functional threshold power in cycling, and the importance of longer duration tests for accurate assessments [54:00];
    • Portable VO2 testing devices as a practical alternative to lab-based tests [1:05:15];
    • The complexities of measuring ventilation and its impact on performance metrics like VO2 max and heart rate [1:15:45];
    • Training interventions to increase VO2 max, and factors that impact performance outcomes [1:23:30];
    • The respiratory exchange ratio (RER) and endurance sports, and how factors such as diet composition and exercise intensity influence RER values and performance [1:32:45];
    • Science-guided training for versatile athletes: maximizing VO2 max, power, torque, and cadence in cycling, and the importance of incorporating diverse stimuli to enhance performance [1:41:00];
    • Physiological limitations on VO2 max [2:02:15];
    • The different energy systems used during work, and other things to monitor like VCO2 and heart rate [2:06:00];
    • Lactate threshold and other metrics to guide your training [2:10:30];
    • Analysis of a lactate power curve: exploring lactate dynamics in endurance training and performance [2:23:15]; and
    • More.

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    The Peter Attia Drive
    enMarch 18, 2024

    #293 - AMA #57: High-intensity interval training: benefits, risks, protocols, and impact on longevity

    #293 - AMA #57: High-intensity interval training: benefits, risks, protocols, and impact on longevity

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    In this “Ask Me Anything” (AMA) episode, Peter delves into the topic of high-intensity interval training (HIIT), starting with addressing some common misunderstandings around this type of exercise and breaking down what HIIT truly entails. He examines the correlation between HIIT and VO2 max, a vital metric for overall health and longevity, and describes the beneficial impact of HIIT on longevity when incorporated properly. Additionally, he emphasizes the importance of building a wide base of cardiovascular fitness, reveals the optimal protocols for incorporating HIIT into a balanced routine, and discusses the risk of injury and other potential drawbacks of HIIT.

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

    We discuss:

    • Common questions about high-intensity interval training (HIIT) [1:30];
    • The origins of HIIT [3:15];
    • Defining HIIT training and differentiating it from sprint interval training (SIT) [5:45];
    • Why HIIT is often touted as a more efficient way to exercise [14:00];
    • Navigating the nuances of HIIT research: understanding limitations and the importance of a blended exercise routine [20:30];
    • The four pillars of exercise [24:15];
    • Using HIIT to improve VO2 max [26:00];
    • HIIT training for the untrained individual: impact on VO2 max and the interplay between exercise-induced adaptations and potential weight loss [33:00];
    • Sprint interval training (SIT) vs. HIIT: comparing the relative improvements in VO2 max and the impact of longer duration intervals [40:00];
    • Benefits and limitations of HIIT, drawbacks of overtraining with HIIT, and the importance of a diversified routine to increase total cardiorespiratory capacity [44:15];
    • HIIT protocols Peter recommends [58:45];
    • The risk of injury and other potential drawbacks of HIIT [1:02:15];
    • The importance of incorporating a balance of continuous moderate-intensity cardio and HIIT when aiming for longevity [1:04:00]; and
    • More.

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    The Peter Attia Drive
    enMarch 11, 2024

    #292 ‒ Rucking: benefits, gear, FAQs, and the journey from Special Forces to founding GORUCK | Jason McCarthy

    #292 ‒ Rucking: benefits, gear, FAQs, and the journey from Special Forces to founding GORUCK | Jason McCarthy

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    Jason McCarthy is a former US Special Forces member and the founder of GORUCK, a company specializing in rucking equipment. In this episode, Jason recounts his journey from military service to navigating the challenging transition back into civilian life and ultimately embracing the mission of introducing rucking to the masses. Delving into the significance of rucking in military training and its applicability to the wider population, he discusses the mental and physical benefits of rucking as a mode of training, provides practical tips for beginners, and answers frequently asked questions about packs, weights, footwear, and more.

    We discuss:

    • Jason’s upbringing and what inspired him to join the military [3:15];
    • Jason’s path to becoming a Green Beret, his calling to serve, and staying true to oneself [10:30];
    • About the Green Berets: their role in the military, unique abilities, missions, and more [20:00];
    • The mental and physical challenges of special forces training and selection [25:00];
    • Rucking challenges as a Green Beret [37:00];
    • How Jason trained in his off-time and stayed mentally prepared [46:30];
    • Jason’s difficult decision to leave the army, and the challenges many veterans face returning to civilian life [51:30];
    • Jason’s struggles after leaving the army: loss of identity, feelings of shame, and the how he overcame a period of despair [57:15];
    • The origin of GORUCK [1:10:30];
    • The GORUCK Challenge [1:24:30];
    • The company's evolution from event organizer to manufacturing specialist, spurred by the growing interest in rucking as a form of training [1:35:30];
    • FAQs about rucking: packs, weight, rucksack vs. weighted vest, chest straps, and more [1:38:45];
    • Commemorating Normandy: GORUCK's plans for the 80th anniversary of the Normandy landings [1:51:30];
    • Footwear for rucking, and how GORUCK got into the footwear business [1:57:30];
    • How to avoid the most common injuries from rucking, and the benefits of rucking for VO2 max, strength, and sleep quality [2:05:00];
    • Advice for using rucking as a mode of training, and the advantages of rucking over other forms of training [2:12:45]; and
    • More.

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    The Peter Attia Drive
    enMarch 04, 2024

    #291 ‒ The role of testosterone in males and females, performance-enhancing drugs, sustainable fat loss, supplements, and more | Derek, More Plates More Dates Pt.2

    #291 ‒ The role of testosterone in males and females, performance-enhancing drugs, sustainable fat loss, supplements, and more | Derek, More Plates More Dates Pt.2

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    Derek is a fitness educator, the entrepreneur behind More Plates More Dates, and an expert in exogenous molecules commonly used and misused by bodybuilders and athletes. In this episode, Derek returns to the podcast to explore the impact of exogenous molecules on male and female health. He covers testosterone, DHT, DHEA, progesterone, clomiphene (Clomid), hCG, and various peptides, alongside updates from the FDA affecting peptide use. Additionally, he addresses the recent hype around increasing muscle mass through myostatin inhibition via follistatin gene therapy and supplementation. Additionally, Derek discusses the various strategies that bodybuilders use for losing fat while preserving muscle, including insights on weight loss drugs.

    We discuss:

    • Testosterone and DHT: mechanisms of action, regulation of muscle growth, and influence on male and female characteristics [2:15];
    • TRT in women: the complexities and potential risks associated with testosterone use in women [9:00];
    • DHEA supplementation: exploring the benefits and risks for women, and the differing effects on men vs. women [22:00];
    • The role of progesterone in both men and women, pros and cons of supplementation, the importance of tailored doses, and more [28:00];
    • Measuring levels of free testosterone [37:15];
    • The trend towards earlier interest in TRT, and the risks of underground sources of testosterone [42:00];
    • The complexities and considerations surrounding the use of Clomid, E-Clomid, and hCG in TRT [46:00];
    • Low testosterone: diagnosis, potential causes, treatment options, and other considerations [53:45];
    • Growth hormone-releasing peptides: rationale and implications of the recent FDA categorization as high-risk substances [1:03:45];
    • Follistatin gene therapy and myostatin inhibition for increasing muscle mass: the recent hype online, human and animal data, and the need for more research [1:14:45];
    • Simple tips for lowering calorie intake and losing fat [1:32:30];
    • Methods of sustainable fat loss with muscle preservation: insights gleaned from bodybuilders [1:40:00];
    • Could prolonged fasting impact testosterone levels? [1:55:30];
    • High-protein ice cream [1:57:00];
    • Exploring fat loss supplements and drugs: L-carnitine, yohimbine, and more [2:02:15];
    • Potential remedies for individuals experiencing metabolic dysfunction due to hypercortisolemia [2:12:30];
    • The cornerstones of body composition improvement remain nutrition and exercise, even in the presence of exogenous testosterone [2:19:15];
    • The importance of approaching health advice found online with a critical eye and a healthy dose of skepticism [2:23:30]; and
    • More.

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    The Peter Attia Drive
    enFebruary 26, 2024

    #290 ‒ Liquid biopsies for early cancer detection, the role of epigenetics in aging, and the future of aging research | Alex Aravanis, M.D., Ph.D.

    #290 ‒ Liquid biopsies for early cancer detection, the role of epigenetics in aging, and the future of aging research | Alex Aravanis, M.D., Ph.D.

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    Alex Aravanis is a leader in research and development of technologies and clinical tests utilizing the latest tools in DNA analysis and data science. In this episode, Alex delves into two interconnected topics: liquid biopsies and epigenetics. He begins by tracing the trajectory of genome sequencing and tumor sequencing, setting the stage for a detailed exploration of liquid biopsies as an early cancer detection method. The discussion encompasses key concepts such as cell-free DNA, DNA methylation, sensitivity, specificity, and the predictive values associated with liquid biopsies. Transitioning to epigenetics, Alex examines the intricate interplay of DNA methylation and aging biology and explores the possibility of using cellular reprogramming to reverse epigenetic changes that occur with aging.

    We discuss:

    • Alex’s background in applying engineering to problems in medicine [3:15];
    • A primer on human genetics, and the history and current landscape of DNA sequencing [11:00];
    • The advent and evolution of liquid biopsies for early detection of cancer [23:15];
    • The role of cell-free DNA in cancer detection: how incidental findings in non-invasive prenatal testing led to the development of liquid biopsies [40:15];
    • The development of a universal blood test for cancer detection and a discussion of specificity of tests [46:00];
    • Advancements in cell-free DNA analysis and development of a multi-cancer screening test at GRAIL [51:00];
    • DNA methylation explained [58:15];
    • Optimizing cancer detection with methylation analysis of cfDNA in small blood samples [1:02:45];
    • The importance of understanding sensitivity, specificity, positive predictive value, and negative predictive value in cancer screening [1:08:00];
    • The performance of the GRAIL Galleri test and its ability to detect various types and stages of cancer [1:21:00];
    • Do early cancer detection methods, like liquid biopsies, translate to improvement in overall survival? [1:27:45];
    • The role of epigenetics in aging [1:39:30];
    • How cell-free DNA methylation patterns can help identify a cancer’s tissue of origin [1:45:30];
    • Cellular and epigenetic reprogramming and other exciting work in the field of aging [1:52:30]; and
    • More.

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    The Peter Attia Drive
    enFebruary 19, 2024