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    #314 ‒ Rethinking nutrition science: the evolving landscape of obesity treatment, GLP-1 agonists, protein, and the need for higher research standards | David Allison, Ph.D.

    enAugust 19, 2024
    What challenges exist in translating nutrition research into practical outcomes?
    How have historical public health efforts failed to address obesity?
    What are GLP1 agonists used for in obesity treatment?
    What factors influence the complexities of obesity beyond caloric intake?
    Why is improving research quality important in nutrition science?

    Podcast Summary

    • Nutrition and ObesityDespite the complexity of nutrition research and historical trust issues with public health efforts, ongoing research is crucial to better understand the intricacies of nutrition's impact on body composition and address obesity effectively.

      While the relationship between nutrition and obesity seems straightforward, the complexity of nutrition research and the influence of various food factors beyond caloric intake make translating knowledge into practical outcomes challenging. The discussion also touched on the historical failures of public health efforts and policies in addressing obesity due to a trust problem with nutrition science. The emergence of GLP1 agonists for treating obesity was explored, along with the social and psychological implications of their use. Additionally, the adequacy of current protein intake recommendations and research gaps were discussed. Overall, the conversation highlighted the evolving landscape of nutrition science and the importance of ongoing research to better understand the intricacies of nutrition and its impact on body composition.

    • Obesity progressDespite advancements in obesity research, practical solutions have been limited. A new approach focusing on community interventions and social policies may yield better results.

      While our understanding of obesity and related fields like nutrition science and agriculture have advanced significantly over the past century, the actual impact on reducing obesity rates and improving public health has been limited. The speaker argues that we have not yet made the "orbit jumps" in knowledge that would lead to practical solutions. He uses the analogy of aviation safety improving over time despite initial setbacks, suggesting that our current state of knowledge about obesity is similar to the early days of aviation. However, he also acknowledges that clinical management, including pharmaceuticals and surgery, will play an increasingly important role in obesity management. The speaker expresses a nuanced view, acknowledging that public health efforts have been largely unsuccessful thus far but expressing a belief that there is still potential for progress if approached differently. He also criticizes the historical focus on biochemistry, molecular genetics, and pharmaceuticals, suggesting that investment in other areas like community interventions and social policies could yield better results. The speaker also mentions the limitations of recent Cochrane collaborations on public health initiatives around obesity, suggesting that they highlight the need for a new approach.

    • Obesity research shiftIn the late 80s and early 90s, obesity research shifted from academic and interdisciplinary to a more public health-focused approach due to perceived increase in obesity rates, leading to a mix of effective and ineffective research.

      The obesity research landscape in the late 80s and early 90s saw a shift from academic, interdisciplinary research to a more public health-focused approach. The National Health and Nutrition Examination Survey (NHANES) data revealed a perceived increase in obesity rates, leading to a sense of crisis and panic. Kelly Brownell, a behavioral psychologist, was a prominent figure in this transition, moving from focusing on individual treatment to advocating for environmental interventions. However, this shift also brought an influx of uninformed ideas and approaches, leading to a period of less effective research. The old guard of obesity researchers, who had a deep understanding of the physiology and complexities of obesity, were a part of this movement but also distinct from it, with some continuing rigorous research while others pursued funding opportunities.

    • Public health initiatives limitationsDespite good intentions, public health initiatives have limited evidence of preventing obesity in children and adolescents. A multifaceted approach that combines various interventions is crucial for effective obesity prevention.

      Community interventions and public health initiatives, while well-intentioned, have not shown compelling evidence of preventing obesity in children or adolescents through systematic reviews and meta-analyses. These interventions may have had some impact on reversing obesity rates, but the evidence is not as strong as for clinical treatments, which can include behavioral, community, family, policy, and pharmaceutical or surgical interventions. It's crucial to acknowledge the limitations of current public health initiatives and consider a multifaceted approach that incorporates various interventions within existing paradigms. We should not abandon public health solutions altogether but instead strive for subparadigm shifts that acknowledge their limitations and explore new possibilities.

    • Obesity assumptions and solutionsNudge techniques alone may not be enough to address obesity due to people's ability to adjust for reduced calories and shaky data supporting their effectiveness. We need to explore innovative solutions within the public health paradigm and fund non-clinical, non-pharmaceutical, non-surgery approaches.

      Our understanding of obesity and its solutions may be limited by our assumptions, lack of consideration of compensation, questionable data, and unwillingness to learn from past failures. Daniel Kahneman, a Nobel Prize-winning economist, emphasized the importance of acknowledging these factors when addressing obesity. He pointed out that nudge techniques, while useful, may not be enough due to people's ability to adjust for reduced calories. Additionally, the data supporting the effectiveness of nudge interventions may be shaky due to publication bias. Furthermore, we need to be open to trying radically different approaches within the public health paradigm instead of repeating ineffective strategies. As for resource allocation, there is a need for more funding for non-pharmaceutical, non-clinical, non-surgery approaches, but clinical treatments may yield more immediate results. The obesity epidemic is complex and likely influenced by multiple factors, including the food supply and intergenerational effects. It's crucial to acknowledge these factors and explore innovative solutions.

    • Factors influencing obesityAccepting some level of dissatisfaction or the use of pharmaceuticals might be necessary for maintaining a lean body composition due to the complex influence of various factors like food availability, affordability, environmental factors, cultural norms, and potential intergenerational effects. Improving research quality and standards is crucial for accurate and reliable answers.

      The complex issue of obesity is influenced by various factors, including the availability and affordability of highly palatable foods, environmental factors like temperature and cultural norms, as well as potential intergenerational effects. The search for a single "right way" to eat may be a misguided pursuit, and we may need to accept that maintaining a lean body composition might require acceptance of some level of dissatisfaction or the use of pharmaceuticals. Additionally, it's crucial to increase the quality and standards of research in the field to ensure accurate and reliable answers. The issue of lousy evidence being spent on in nutrition research is a significant problem, and it's essential to hold the field to higher standards.

    • Nutrition research reliabilityDespite concerns over reproducibility and public trust, the pharmaceutical industry's stricter regulations and oversight produce more reliable nutrition research than academia, but biased study questions can still impact results.

      There are concerns about the reliability and reproducibility of research in the field of nutrition science, particularly in nutritional epidemiology. The Pew Charitable Trusts have found that the public trusts nutrition experts and clinicians less than they trust other forms of science, due in part to the confusion and noise created by nutrition research. Reproducibility and replicability are major issues, with studies often producing incorrect or irreproducible results. The criteria for selecting studies to examine include their size, interestingness, and potential for paradigm-shifting findings. The pharmaceutical industry, which is subject to stricter regulations and oversight, tends to produce more reliable research than academia. The industry hires Clinical Research Organizations to conduct studies and have independent analysts review the data. However, the question asked in a study can introduce bias, determining how the study is designed to find a particular answer. The non-industry funded research varies greatly in quality, with some types producing non-verifiable results more frequently than others. Better data and assessment are needed to address these issues and improve the reliability and trustworthiness of nutrition research.

    • Diabetes drugs and weight lossNew diabetes drugs, semagluetide and tricepatide, show potential in managing diabetes and aiding weight loss. GLP1's role in obesity and ethical considerations are topics of discussion.

      The latest drugs for type 2 diabetes, semagluetide and tricepatide, have shown promising results not only in managing diabetes but also in helping patients lose weight. This discovery came about by observing the positive effects on diabetes patients and led to further research on non-diabetic obese individuals. The drugs' effectiveness and apparent safety have sparked significant interest, leading to discussions on various aspects such as the role of GLP1 in obesity, potential impact on stigma, and ethical considerations around motivation and moral judgment. Despite some challenges like safety concerns, cost, and availability, the future looks promising as more production sites come online and regulations around compounding pharmacies are clarified. Overall, this development marks an exciting advancement in the field of obesity treatment.

    • Weight loss recommendationsIndividual medical needs and personal motivations should be considered when making weight loss recommendations, acknowledging potential risks and benefits specific to the population.

      When it comes to treating individuals seeking weight loss, it's essential to consider both their medical needs and personal motivations. Society may make moral judgments, but these distinctions don't necessarily dictate the same recommendations. The cost-benefit analysis should be based on the specific patient population, acknowledging that the risks and benefits are studied in that population. While it's understandable for individuals to desire to improve their appearance or quality of life, the lack of clear long-term data on the risks of weight loss drugs for those not at medical risk complicates the decision-making process. Ultimately, it's a complex issue requiring careful consideration of individual circumstances, potential risks, and personal values.

    • Sports and ethical dilemmas of drug useThe use of performance-enhancing drugs in sports raises ethical dilemmas concerning individual freedom and societal regulations, requiring thoughtful and informed discussions to find a balanced solution.

      While there is a consensus on the informational and moral aspects of honest communication regarding the use of certain drugs, the decision on whether to use them for individuals outside of the studied populations or for cosmetic purposes raises ethical dilemmas. These dilemmas revolve around the balance between individual freedom of choice and societal regulations, particularly in the context of sports where weight management plays a significant role. The sporting world introduces an additional party with its own set of interests, which may lead to differing perspectives on what should be considered performance-enhancing drugs and how to regulate their use. Ultimately, it's essential to consider the values and principles underlying the regulations and engage in a thoughtful and informed discussion to find a balanced solution.

    • Optimal protein intakeThe optimal amount and minimum and maximum thresholds for protein intake are not clear-cut, and more rigorous and larger studies are needed to definitively answer these questions.

      While we know that protein is essential for human health and that we need a certain amount, the optimal amount and the minimum and maximum thresholds are not clear-cut. The evidence supporting the idea of a minimum threshold for anabolic response, such as 20-30 grams in a single sitting, is based on small studies and needs further investigation. The quality and quantity of evidence on protein needs is significantly less compared to other areas like pharmaceuticals. We need to conduct more rigorous and larger studies to definitively answer these questions.

    • Protein upper limitsDespite concerns, there's no definitive proof of negative health effects from excessive protein intake through large-scale trials. Studies on specific populations may provide insights.

      The upper limits and potential negative health effects of consuming excessive protein are not yet definitively proven through large-scale, randomized control trials. While there are concerns about potential risks such as kidney damage, bone loss, and rabbit starvation, there is a lack of concrete evidence to support these claims. Some studies suggest that time-release protein or consuming protein with carbohydrates may enhance anabolic effects, but there is no compelling evidence to support this either. The appetite for clinical investigation into macronutrient questions, particularly in the context of nutrition science's focus on pharmacology for obesity and diabetes treatment, is not guaranteed to yield definitive answers in the coming decade. However, studies focusing on specific populations, such as older adults seeking to increase strength and muscle mass, may provide valuable insights into protein intake and upper limits.

    • Impact of protein intake on longevityThere's no solid evidence that higher protein intake reduces human lifespan, but more research is needed to determine the optimal protein intake for longevity and how it varies between species and life stages.

      While there is ongoing debate about the impact of protein intake on longevity, there is currently no compelling evidence to suggest that higher protein consumption leads to reduced lifespan in humans. The optimal protein intake may depend on species, individual circumstances, and stages of life. The Zone Diet, which advocates for balanced macronutrient consumption and up-regulating AMPK while minimizing MTOR activation, suggests that excessive protein may negatively affect longevity. However, the evidence is not definitive, and more research is needed to establish a definitive link between protein intake and longevity. Additionally, people should be cautious of sensational headlines in media and strive to read beyond them to gain a clear understanding of the underlying studies.

    • The Drive with Peter Attia benefitsThe Drive with Peter Attia's premium membership provides access to comprehensive podcast show notes, monthly AMA episodes, a dedicated newsletter, a private podcast feed, and a highlight reel podcast, offering in-depth information on longevity. Host discloses conflicts of interest and encourages professional advice.

      A premium membership to The Drive with Peter Attia offers numerous benefits for those interested in longevity. These benefits include comprehensive podcast show notes, monthly Ask Me Anything (AMA) episodes with detailed responses to subscriber questions, a dedicated team-compiled newsletter, access to a private podcast feed, and a highlight reel podcast called The Qualys. The premium membership is not a substitute for professional medical advice, but rather a resource for those seeking in-depth information on the topic. Additionally, the host, Peter Attia, discloses all conflicts of interest and encourages listeners to seek professional advice for any medical concerns.

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    • How Peter defines longevity [3:45];
    • Why healthspan is a crucial component of longevity [11:15];
    • The evolution of medicine from medicine 1.0 to 2.0, and the emergence of medicine 3.0 [15:30];
    • Overview of atherosclerotic diseases: the 3 pathways of ASCVD, preventative measures, and the impact of metabolic health [26:00];
    • Cancer: genetic and environmental factors, treatment options, and the importance of early and aggressive screening [33:15];
    • Neurodegenerative diseases: causes, prevention, and the role of genetics and metabolic health [39:30];
    • The spectrum of metabolic diseases [43:15];
    • Why it’s never too late to start thinking about longevity [44:15];
    • The 5 components of the longevity toolkit [46:30];
    • Peter’s framework for exercise—The Centenarian Decathlon [47:45];
    • Peter’s nutritional framework: energy balance, protein intake, and more [58:45];
    • Sleep: the vital role of sleep in longevity, and how to improve sleep habits [1:08:30];
    • Drugs and supplements: Peter’s framework for thinking about drugs and supplements as tools for enhancing longevity [1:13:30];
    • Why emotional health is a key component of longevity [1:17:00];
    • Advice for newcomers on where to start on their longevity journey [1:19:30]; and
    • More.

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    The Peter Attia Drive
    enJuly 29, 2024

    #310 - The relationship between testosterone and prostate cancer, testosterone replacement therapy, and tools for predicting cancer aggressiveness and guiding therapy | Ted Schaeffer, M.D., Ph.D.

    #310 - The relationship between testosterone and prostate cancer, testosterone replacement therapy, and tools for predicting cancer aggressiveness and guiding therapy | Ted Schaeffer, M.D., Ph.D.

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

    We discuss:

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

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    The Peter Attia Drive
    enJuly 22, 2024

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

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

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

    We discuss:

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

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    The Peter Attia Drive
    enJuly 15, 2024

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

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

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

    We discuss:

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

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    The Peter Attia Drive
    enJuly 08, 2024