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    #279 - AMA #53: Metabolic health & pharmacologic interventions: SGLT-2 inhibitors, metformin, GLP-1 agonists, and the impact of statins

    enNovember 13, 2023

    Podcast Summary

    • Understanding Metabolic Health and Pharmacological OptionsImproving metabolic health is crucial in preventing and managing interconnected diseases. Lifestyle changes and medications such as SGLT2 inhibitors can play a significant role in achieving optimal metabolic health.

      Metabolic disease is interconnected with other types of diseases like cardiovascular disease, neurodegenerative disease, and cancer. It is crucial to improve metabolic health to prevent and manage these conditions. Lifestyle changes play a significant role in improving metabolic health. However, there are also pharmacological options available. SGLT2 inhibitors, Metformin, and GLP1 are some medications that can be used to improve metabolic health. SGLT2 inhibitors specifically target Sodium Glucose Co transporter Protein 2 (SGLT2) in the kidneys, helping to regulate glucose levels. Understanding the basics of these medications and their development can be complex, but visual aids can be helpful. Maintaining good metabolic health and exploring pharmacological options can provide potential benefits for overall well-being.

    • Kidney's Role in Glucose Regulation and Potential Solutions for High Blood Glucose Levels in Type 2 DiabetesThe kidney plays a crucial role in selectively retaining necessary substances but can also prevent reabsorption of filtered glucose, making it a potential target for managing high blood glucose levels in type 2 diabetes.

      The kidney's primary role is not to eliminate bad things from the body, but rather to understand what is good and retain it. As plasma passes through the kidney, it selectively pulls back into circulation the necessary substances like glucose, sodium, potassium, and chloride. However, there is an interesting opportunity here regarding glucose. Although the kidney's main task is not to regulate glucose concentration, it does have the ability to prevent the reabsorption of filtered glucose. By blocking a protein called SGLT 2, more glucose can be excreted in the urine, making it an attractive solution for high blood glucose levels in individuals with type 2 diabetes. This approach is focused on lowering glucose levels and can be used alongside other strategies such as increasing insulin sensitivity or managing insulin itself. Additionally, some drugs are developed based on naturally occurring substances, like fluorescein found in apples, which initially demonstrated glucosuria and became an important diagnostic tool for diabetes in the past.

    • The Relationship Between Natural Compounds and Drug DevelopmentNature serves as a valuable resource for pharmacologists, providing a foundation for drug development. Natural compounds like fluorescein and drugs derived from them, such as SGLT 2 inhibitors, offer effective treatments for diabetes.

      There is a similarity between naturally occurring compounds and the drugs derived from them. For example, fluorescein, a naturally occurring substance, has a similar structure to SGLT 2 inhibitors, which are used to treat diabetes. These inhibitors have different versions with varying potency and dosing. Furthermore, it is worth noting that some widely used drugs like statins and metformin are also derived from natural sources. This suggests that nature has provided a foundation for pharmacologists in drug development. Additionally, in the discussion of SGLT 2 inhibitors, it is mentioned that a higher dose leads to a greater reduction in hemoglobin A1c, indicating their effectiveness in managing diabetes.

    • SGLT 2 inhibitors: Beyond Blood Sugar RegulationSGLT 2 inhibitors have shown potential in reducing risks for heart failure patients, improving cardiovascular outcomes, and possibly reducing blood pressure.

      SGLT 2 inhibitors, such as Metformin and Conegaflozin, show promising benefits beyond just regulating blood sugar levels. While Metformin is commonly used for early intervention in type 2 diabetes, SGLT 2 inhibitors have shown greater potential in the scientific community. These inhibitors have been found to decrease the risk of hospitalization and death for heart failure patients, as well as improve cardiovascular outcomes for patients with reduced ejection fraction and preserved EF. Additionally, there may be a correlation between the use of SGLT 2 inhibitors and a reduction in blood pressure, possibly due to the impact on sodium excretion. Although the complex names of these drugs may be confusing, pharmaceutical companies deliberately choose catchy trade names to ensure brand association and prolonged sales.

    • SGLT 2 inhibitors offer potential benefits beyond diabetes treatment, particularly in heart failure patients.SGLT 2 inhibitors may have positive outcomes for heart failure patients, even without diabetes, and there is growing interest in their potential cardioprotective effects.

      SGLT 2 inhibitors, often used to treat type 2 diabetes, have shown positive outcomes in patients with heart failure, even if they do not have diabetes. The reduction in blood pressure may be one potential reason for this, but there may be other factors at play as well. Additionally, there is growing interest in the potential cardioprotective effects of SGLT 2 inhibitors. Many individuals who are not diabetic are curious about these benefits, similar to the interest in Metformin for its potential protective properties. By becoming a premium member, you can access the complete AMA episode, as well as enjoy exclusive member benefits like comprehensive show notes, monthly AMA episodes, premium newsletters, a private podcast feed, and more. Remember, the information provided in this podcast is for general informational purposes only, and it is essential to consult with healthcare professionals for personalized advice and treatment.

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    In this “Ask Me Anything” (AMA) episode, Peter provides insights on a broad range of important topics. He delves into the prevention of cognitive decline, the link between cardiovascular disease and Alzheimer's disease, and methods to lower blood glucose, insulin, and apoB. He also addresses nutrition-related queries, exploring the impact of dietary habits on weight loss and longevity, how a person can identify the best diet for themselves, and common nutrition myths. Additional discussions include optimal blood pressure, daily step goals, the benefits of standing versus sitting desks, and much more.

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    View the Show Notes Page for This Episode

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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.

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    The Peter Attia Drive
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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.

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    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.

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    The Peter Attia Drive
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    #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];
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    • 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];
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    The Peter Attia Drive
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    #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:

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    • Resveratrol [32:45];
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    • Blood flow restriction (BFR) training [44:00];
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    • 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.

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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.

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    Is Ozempic a Weight Loss Miracle?

    Is Ozempic a Weight Loss Miracle?

    Unless you’ve been living off-grid for the last few months, chances are you’ve heard of Ozempic (or semaglutide)– the newest FDA approved miracle injection for weight loss. Social media has ignited feeds across the world with weight loss transformation posts from semaglutide injections- and 812 million views on TikTok to be exact.

    Tailored to diabetes, this drug works by stimulating insulin secretion and therefore lowering fasting and postprandial glucose levels in four mechanisms. During the Ozempic drug trials, it was noted that weight loss was such a consistent and dramatic side effect that the FDA approved semaglutide for weight loss under the brand name Wegovy in 2021.

    In this episode, I discuss:

    • The four mechanisms of Ozempic
      •  Changes in insulin sensitivity
      • Increased energy expenditure by encouraging stored fat to turn into energy.
      • Slows gastric emptying
      • The impact on appetite.
    • And what current research is finding. (Hint: It might not be a long-term weight loss miracle!)

    To sum it up, weight loss medications like Ozempic cannot have substantial results without compromise (i.e. losing lean muscle mass). Most importantly, NONE of the weight loss medications are fixing the root cause of the problem. The purpose of this podcast is to help you make an informed decision about your options for weight loss. If you are considering semaglutide injections for weight loss, talk to your doctor about the pros and cons!

    Love it? Hate it? We’d love to hear your feedback!

     

    References used for this episode:  

    1.    https://pubmed.ncbi.nlm.nih.gov/30122305/

    O'Neil PM, Birkenfeld AL, McGowan B, et al. Efficacy and safety of semaglutide compared with liraglutide and placebo for weight loss in patients with obesity: a randomised, double-blind, placebo and active controlled, dose-ranging, phase 2 trial. Lancet. 2018;392(10148):637-649. doi:10.1016/S0140-6736(18)31773-2

    2.   https://pubmed.ncbi.nlm.nih.gov/33755728/ 

    Rubino D, Abrahamsson N, Davies M, et al. Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical Trial. JAMA. 2021;325(14):1414-1425. doi:10.1001/jama.2021.322

    3.   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6769337/ 

    Sargeant JA, Henson J, King JA, Yates T, Khunti K, Davies MJ. A Review of the Effects of Glucagon-Like Peptide-1 Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors on Lean Body Mass in Humans. Endocrinol Metab (Seoul). 2019 Sep;34(3):247-262. doi: 10.3803/EnM.2019.34.3.247. PMID: 31565876; PMCID: PMC6769337.

    4.  https://pubmed.ncbi.nlm.nih.gov/35441470/ 

    Wilding JPH, Batterham RL, Davies M, et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension. Diabetes Obes Metab. 2022;24(8):1553-1564. doi:10.1111/dom.14725

     

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    Please review the Empowered Nutrition Podcast on Apple Podcasts or wherever you listen! Then, send me a screenshot of your positive review to podcast@empowerednutrition.health as a DM on Instagram (@empowerednutrition.health).Include a brief description of what you’re working on with your health and/or nutrition and I’ll send you a free custom meal plan!

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    139. JASON PHILLIPS: How to make success inevitable.

    139. JASON PHILLIPS: How to make success inevitable.

    This week’s badass guest is Jason Phillips.

    Jason is an impactful entrepreneur who has established immense reverence + authority in the health + fitness industry through his incredible knowledge in nutrition, fitness, as well as his experience in creating + up-leveling, health/fitness businesses into multi-million businesses. 

    Jason is the Founder + CEO of the Nutritional Coaching Institute, an institute that certifies health coaches + arms them with invaluable tools that help them to become leaders in the field + turn their business models into a 6-7 figure business.  

    Jason is largely contributing as one of the most profound thought leaders in the industry. 

    From coaching world-class athletes to contributing his high-level expertise to monster brands like GOOGLE to writing for major publications like Men’s Fitness & Entrepreneur Weekly, and writing his own books; he continues to lead from his heartbeat philosophy that is:  “Impact over everything.”


    In this inspiring conversation, Jason & I take you through:

    • What + why Jason leads himself + all aspects of his business with his core principle: “Impact over everything.”
    • Jason’s journey of battling anorexia + why he left his corporate $200k job in a flash moment, to pursue his passion for empowering others through the optimization of nutrition + fitness for increased performance, body composition + overall health. 
    • How to assess your biofeedback to know when to push + when to recovery.
    • Stress and its impact on your health + fitness goals that you may be unaware of.

    • Essential recovery to accelerate the progress that most people don’t recognize

    • Jason’s Self-Mastery formula that helps you create your ultimate business success

    • Cultivating a “why not me?” mindset to conquer fear + achieve your ultimate potential in life.

    This episode is so empowering + exudes what I call “the heart of an underdog + the mindset of a champion.” Jason’s journey is truly just that. He is living a LEGENDARY path. I'm proud to share his genius + amazing energy in this talk with you. 

    Enjoy!

    xRx

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    Gary Fettke - Why the Push for Veganism is so Strong: Ep26

    Gary Fettke - Why the Push for Veganism is so Strong: Ep26

    We caught up with Dr. Gary Fettke and his wife Belinda during the 2019 San Diego conference and I put the question a question to him asking where he planned to go from here now that he had been absolved of all the trumped up charges levelled at him by his governing body, AHPRA.  He promptly ignored me and started talking about the discovery his wife has made over the last few years about the influence the Seventh Day Adventist Church has hod on our current dietary guidelines.  Apparently he is pretty fired up about all that and very proud of the enormous amount of work his wife Belinda has put into uncovering this whole story.

    I did put the question to him again later and we have posted that response in an earlier podcast but we decided to post this response now too as it is very interesting.  You can find the earlier podcasts of his and of Belinda's at the links below.


    https://www.lowcarbusa.org/plant-based-diet-episode-10/
    https://www.lowcarbusa.org/gary-fettke-exoneration-episode-8/