View the Show Notes Page for This Episode  Become a Member to Receive Exclusive Content  Sign Up to Receive Peter’s Weekly Newsletter In this “Ask Me Anything” (AMA) episode, Peter dives deep into the critical topic of metabolic disease. He first sheds light on how poor metabolic health drives up the risk of developing other chronic diseases such as cardiovascular disease, cancer, neurodegenerative disease, and overall mortality. He explores the array of metrics and tests used to assess metabolic health, underscoring his preferred methodologies utilized with patients. Finally, Peter provides an overview of the factors one can manipulate in order to improve metabolic health. 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 #51 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here. We discuss:  Importance of metabolic health and a primer on metabolic disease [1:30]; How poor metabolic health increases one’s risk for other chronic diseases [6:00]; How useful is body weight and BMI for estimating metabolic health? [9:45]; Overview of various tests and metrics used to understand metabolic health [12:15]; Traditional biomarkers and how Peter’s point of view may differ from the guidelines [15:00]; Lactate: insights into metabolic health through fasting and resting lactate levels [17:00]; Zone 2 output: an important functional test of metabolic health [20:00]; Cardiopulmonary exercise testing (CPET) [25:45]; Visceral adipose tissue (VAT): what is VAT and how does it impact health? [27:00]; Oral glucose tolerance test (OGTT): how it works and why it is such an important metric for assessing metabolic health [32:15]; The utility of a continuous glucose monitor (CGM) [40:45]; Liver function and NAFLD [42:15]; Sleep as an intervention [46:00]; Exercise as an intervention [53:15]; Diet and nutrition [59:00]; How reducing stress can improve metabolic health [1:05:15]; and More.  Connect With Peter on Twitter, Instagram, Facebook and YouTube

#271 - AMA #51: Understanding and improving your metabolic health

View the Show Notes Page for This Episode  Become a Member to Receive Exclusive Content  Sign Up to Receive Peter’s Weekly Newsletter Andrew Huberman, Professor of Neurobiology at Stanford University and host of the Huberman Lab podcast joins us in a special journal club episode. Peter and Andrew each present a recent paper that sparked their interests, delving into the findings, dissecting their significance, discussing potential confounders and limitations, and exploring remaining questions. Importantly, they share their methodologies for comprehending research studies, providing valuable insights for listeners to navigate this process independently. Peter presents an epidemiological study reevaluating a noteworthy metformin result that intrigued the anti-aging community, leading to discussions on metformin&#39;s geroprotective potential (or lack thereof) and the current lack of aging biomarkers. Andrew introduces a paper examining how our beliefs about the medications we take influence their biological effects, distinguishing the &quot;belief effect&quot; from a placebo effect and highlighting its exciting implications for the future. We discuss:  The motivation behind this journal club conversation [2:45]; Why Peter chose a paper on metformin, how metformin works, and why it generated excitement as a longevity-enhancing agent [9:00]; Defining insulin resistance and its underlying causes [16:15]; Metformin as a first-line treatment for type 2 diabetes, and Peter’s evolving interest in metformin as a geroprotective drug [22:00]; Defining the term “geroprotection” [24:45]; The 2014 study that got the anti-aging community interested in metformin [26:00]; Peter presents the 2022 paper that repeats the analytical approach from the 2014 Bannister study [33:15]; Greater mortality in the metformin group: how results differed between the 2022 paper and the 2014 paper [40:00]; Understanding statistical significance, statistical power, sample size, and why epidemiology uses enormous cohorts [51:45]; Interpreting the hazard ratios from the 2022 metformin study, and the notable takeaways from the study [56:45]; Drugs that may extend lifespan, why Peter stopped taking metformin, and a discussion of caloric restriction [1:08:45]; Current thoughts on the use of metformin for longevity [1:21:00]; Could there be any longevity benefit to short periods of caloric restriction? [1:22:45]; Peter and Andrew’s process for reading scientific papers [1:26:45]; The biological effects of belief, and how “belief effects” differ from placebo effects [1:32:30]; The neurobiology of nicotine: a precursor conversation before delving into the paper Andrew chose [1:39:45]; Andrew presents a paper that demonstrates the impact of belief [1:45:30]; Analyzing the fascinating results of the Perl paper [1:54:30]; Exciting implications of the findings about “belief” reported by Perl and colleagues [2:03:15]; and More.  Connect With Peter on Twitter, Instagram, Face

#270 ‒ Journal club with Andrew Huberman: metformin as a geroprotective drug, the power of belief, and how to read scientific papers

View the Show Notes Page for This Episode  Become a Member to Receive Exclusive Content  Sign Up to Receive Peter’s Weekly Newsletter This special episode is a rebroadcast of AMA #30, now made available to everyone, in which Peter and Bob Kaplan dive deep into all things related to studying studies to help one sift through the noise to find the signal. They define various types of studies, how a study progresses from idea to execution, and how to identify study strengths and limitations. They explain how clinical trials work, as well as biases and common pitfalls to watch out for. They dig into key factors that contribute to the rigor (or lack thereof) of an experiment, and they discuss how to measure effect size, differentiate relative risk from absolute risk, and what it really means when a study is statistically significant. Finally, Peter lays out his personal process when reading through scientific papers. We discuss:  The ever-changing landscape of scientific literature [2:30]; The process for a study to progress from idea to design to execution [5:00]; Various types of studies and how they differ [8:00]; The different phases of clinical trials [19:45]; Observational studies and the potential for bias [27:00]; Experimental studies: randomization, blinding, and other factors that make or break a study [44:30]; Power, p-values, and statistical significance [56:45]; Measuring effect size: relative risk vs. absolute risk, hazard ratios, and “number needed to treat” [1:08:15]; How to interpret confidence intervals [1:18:00]; Why a study might be stopped before its completion [1:24:00]; Why only a fraction of studies are ever published and how to combat publication bias [1:32:00]; Frequency of training for Olympic weightlifting [1:22:15]; How post-activation potentiation (and the opposite) can improve power training and speed training [1:24:30]; The Strongman competition: more breadth of movement, strength, and stamina [1:32:00]; Why certain journals are more respected than others [1:41:00]; Peter’s process when reading a scientific paper [1:44:15]; and More.  Connect With Peter on Twitter, Instagram, Facebook and YouTube

#269 - Good vs. bad science: how to read and understand scientific studies

View the Show Notes Page for This Episode  Become a Member to Receive Exclusive Content  Sign Up to Receive Peter’s Weekly Newsletter Wendy Chung is a board-certified clinical and molecular geneticist with more than 25 years of experience in human genetic disease research. In this episode, Wendy delves deep into the world of genetics by first exploring the historical landscape of genetics prior to decoding the human genome, contrasting it with what we know today thanks to whole genome and exome sequencing. She provides an overview of genetic testing by differentiating between various genetic tests such as direct-to-consumer, clinical, whole genome sequencing, and more. Additionally, Wendy unravels the genetic underpinnings of conditions such as PKU, breast cancer, obesity, autism, and cardiovascular disease. Finally, Wendy goes in depth on the current state and exciting potential of gene therapy while also contemplating the economic implications and ethical nature of gene editing. We discuss:  Wendy’s interest in genetics and work as a physician-scientist [2:45]; The genetics of phenylketonuria (PKU), a rare inherited disorder [5:15]; The evolution of genetic research: from DNA structure to whole genome sequencing [18:30]; Insights and surprises that came out of the Human Genome Project [28:30]; Overview of various types of genetic tests: direct-to-consumer, clinical, whole genome sequencing, and more [34:00]; Whole genome sequencing [39:30]; Germline mutations and the implications for older parents [45:15]; Whole exome sequencing and the importance of read depth [50:30]; Genetic testing for breast cancer [54:00]; What information does direct-to-consumer testing provide (from companies like 23andMe and Ancestry.com)? [1:01:30]; The GUARDIAN study and newborn genetic screening [1:06:30]; Treating genetic disease with gene therapy [1:18:00]; How gene therapy works, and the tragic story of Jesse Gelsinger [1:22:00]; Use cases for gene therapy, gene addition vs. gene editing, CRISPR, and more [1:28:00]; Two distinct gene editing strategies for addressing Tay-Sachs and fragile X syndrome [1:37:00]; Exploring obesity as a polygenic disease: heritability, epigenetics, and more [1:41:15]; The genetics of autism [1:48:45]; The genetics of cardiovascular disease [2:01:45]; The financial costs and economic considerations of gene therapy [2:06:15]; The ethics of gene editing [2:12:00]; The future of clinical genetics [2:21:00]; and More.  Connect With Peter on Twitter, Instagram, Facebook and YouTube

#268 ‒ Genetics: testing, therapy, editing, association with disease risk, autism, and more | Wendy Chung, M.D., Ph.D.

View the Show Notes Page for This Episode  Become a Member to Receive Exclusive Content  Sign Up to Receive Peter’s Weekly Newsletter Keith Flaherty is the director of clinical research at the Massachusetts General Hospital Cancer Center and a previous guest on The Drive. In this episode, Keith first delves into the statistics on cancer's prevalence as we age, underscoring the significance of finding effective treatments and early detection methodologies. He touches on the history of cancer therapeutics and illuminates the notable enhancements in cancer therapy within the last decade that are setting the stage for a promising future. He goes into detail on the potential of immunotherapy and therapies that can combat cancer’s evasive tactics while explaining some of the existing challenges around specificity, cost, and scalability. Additionally, Keith highlights the significant leap in early detection methodologies, namely liquid biopsies, which have the potential not only to determine if a cancer is present in an early stage, but also identify the possible tissue of origin. We discuss:  Keith’s interest and expertise in cancer [3:15]; Cancer deaths by decade of life, and how cancer compares to other top causes of death [7:00]; The relationship between hormones and cancer [12:00]; The link between obesity and cancer [18:45]; Current state of treatments for metastatic cancer and reasons for the lack of progress over the decades [22:30]; The interplay between the immune system and cancer cells [32:00]; Different ways cancer can suppress the immune response, and how immunotherapy can combat cancer’s evasive tactics [39:30]; Elimination of a substantial portion of cancers through immune cell engineering faces challenges of specificity, cost, and scalability [52:15]; Why TIL therapy isn’t always effective, and the necessity for multimodal therapy to address various aspects of the cancer microenvironment [1:01:00]; Potential developments in cancer therapy over the next five years: T-cell activation, metabolic interventions, targeting tumor microenvironments, and more [1:06:30]; The challenge of treating metastatic cancer underscores the importance of early detection to improve survivability [1:19:15]; Liquid biopsies for early detection of cancer and determining the possible tissue of origin [1:24:45]; Commercially available cancer screening tests [1:33:45]; How to address the disparity in cancer care, and the exciting pace of progress for cancer detection and treatment [1:40:15]; and More.  Connect With Peter on Twitter, Instagram, Facebook and YouTube

#267 ‒ The latest in cancer therapeutics, diagnostics, and early detection | Keith Flaherty, M.D.

View the Show Notes Page for This Episode  Become a Member to Receive Exclusive Content  Sign Up to Receive Peter’s Weekly Newsletter In this "Ask Me Anything" (AMA) episode, Peter delves into the realm of genetics, unraveling its connection to disease and emphasizing the value of understanding one's genetic risks. He elucidates essential background knowledge on genetics before delving into the myriad reasons why individuals might consider genetic testing. Peter differentiates scenarios where genetic testing provides genuine insights from those where it may not be as useful. From there, Peter explores a comprehensive comparison of commercial direct-to-consumer genetic tests, providing insights on interpreting results and identifying the standout options for gaining insights into personal health. 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 #50 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here. We discuss:  Defining the term “genetics” and why it’s important [2:15]; What is DNA, and how does it impact our biology and traits? [5:45]; How are genetics passed down from parent to child? [8:45]; How much do genes vary across individuals? [13:00]; Which traits are determined by genetics versus experience or environmental factors? [17:00]; Reasons for genetic testing [22:30]; What exactly is being measured by a genetic test? [29:15]; Testing for monogenic disorders [35:15]; Understanding polygenic risk [39:30]; Is genetic testing more important for someone who doesn’t know their family history? [40:45]; What does it mean to be positive for a particular variant? [43:00]; What does it mean to be negative for a particular variant? [45:45]; How does someone get genetic testing through their healthcare provider, and how are these tests performed? [48:15]; The financial cost of various genetic tests [54:30]; Could having a risk allele for a disease result in an increase in one’s insurance premium? [57:15]; Other risks associated with genetic testing [59:00]; How do commercial, direct-to-consumer genetic tests compare to the information one might receive from clinical genetic testing? [1:01:45]; Are certain direct-to-consumer tests better than others? [1:03:45]; How long until whole genome sequencing becomes genuinely useful? [1:16:00]; How useful are personalized dietary recommendations based on genetics? [1:18:15]; Final thoughts and advice regarding genetic testing [1:20:00]; and More.  Connect With Peter on Twitter, Instagram, Facebook and YouTube

#266 - AMA #50: Genetics: how they impact disease risk, what you can do about it, testing, and more

View the Show Notes Page for This Episode  Become a Member to Receive Exclusive Content  Sign Up to Receive Peter’s Weekly Newsletter Oliver Burkeman is the author of The New York Times best-seller Four Thousand Weeks: Time Management for Mortals. In this episode, Oliver delves into the pervasive idea that time can be mastered, exploring whether maximizing productivity is an attainable goal or a perpetual trap. He discusses the allure of attempting to control time—and, therefore, the future—and shares his personal journey of experimenting with diverse time management techniques that failed to deliver the emotional satisfaction he sought. Ultimately, they explore the mismatch between being a finite human and existing in a world of infinite possibilities and how all of these concepts intertwine with finding a sense of purpose and meaning. Additionally, Oliver shares insights from his book on productivity, using our time wisely, and embracing our finitude to live a more fulfilling life. We discuss:  Oliver’s experience that led him to write the book Four Thousand Weeks [3:15]; Human’s relationship with time and the struggle with the finite nature of time [7:15]; How productivity can be a trap [11:00]; The fallacy that being more efficient will open up more time and bring a feeling of control [16:45]; The paradoxical nature of trying too hard to be present in the current moment [22:45]; The value of relationships in meaningful experiences and fulfillment, and how time gets its value from being shared [26:45]; The importance of time synchronicity [36:00]; Identifying your biggest priorities and the paradox of wanting to do more than you have time for [41:00]; Oliver’s moment of clarity in 2014 [47:15]; The role of a sense of purpose in fulfillment [50:15]; Reconciling the finite nature of time and letting go of trying to master your time [59:00]; Why we tend to have a future-focused attitude and how to combat that with atelic activities [1:05:45]; The power of shifting your perspective about time and your experiences [1:12:45]; How to operationalize the three principles for the dilemma of finite time [1:20:15]; Harnessing the power of patience in the face of a problem or experience [1:28:00]; The value of incrementalism for being productive [1:34:15]; Embracing your finitude with curiosity [1:38:00]; Acting on an idea in the moment rather than letting the idea be the obstacle [1:41:15]; and More.  Connect With Peter on Twitter, Instagram, Facebook and YouTube

#265 - Time, productivity, and purpose: insights from Four Thousand Weeks | Oliver Burkeman

View the Show Notes Page for This Episode  Become a Member to Receive Exclusive Content  Sign Up to Receive Peter’s Weekly Newsletter Adam Cohen is an orthopedic surgeon with expertise in sports medicine. In this episode, Adam breaks down the anatomy of the lower extremities: the hip, knee, ankle, and foot. He explains in detail the common injuries, sources of pain, and what leads to the development of arthritis. He lays out the non-surgical and surgical treatment options as well as the factors that determine whether surgery is appropriate. The discussion includes various procedures like hip replacement, knee replacement, ACL reconstruction, repair of meniscus tears, and more. Additionally, Adam sheds light on the utility of biological therapies like stem cells and platelet-rich plasma (PRP) and how they compare to more traditional approaches. We discuss:  Anatomy of the hip, hip dysplasia in infants, and the development of arthritis [3:00]; Diagnosing hip pain in people under 50, stress fractures in the femoral neck, and more [11:15]; Common hip injuries, gender differences, and problems that occur when the hip isn’t formed normally [19:30]; Advancements in hip replacement surgery [25:15]; Common hip problems in people over age 60 [27:30]; The importance of muscular strength around the hips for injury prevention [30:30]; Hip fractures due to osteopenia and osteoporosis [36:00]; The utility of biological therapies like stem cells and platelet-rich plasma (PRP) [40:30]; Cortisone as a treatment to delay the need for surgical intervention [53:30]; Anatomy of the knee [56:30]; Are activities like running that amplify forces bad for the knee? [59:45]; Risk of future knee issues and arthritis following an ACL tear or other substantial knee injury [1:04:30]; How the ACL injury happens and how it is repaired [1:08:30]; Arthritis of the knee [1:19:00]; Meniscus tears: how they happen and when surgery is appropriate [1:21:30]; Total knee replacement: when it’s appropriate and how the recovery process compares to hip replacement [1:30:30]; Learning from elite athletes, heart rate recovery, V02 max, and other metrics [1:58:45]; Surgical vs. non-surgical approaches to various knee injuries [1:40:45]; Achilles tendon: tendinitis, rupture of the Achilles tendon, and prevention strategies [1:44:15]; Anatomy of the ankle and foot [1:49:00]; Common injuries to the ankle and foot [1:51:15]; Tips for finding a good orthopedic surgeon [2:01:45]; and More.  Connect With Peter on Twitter, Instagram, Facebook and YouTube

#264 ‒ Hip, knee, ankle, and foot: common injuries, prevention, and treatment options

View the Show Notes Page for This Episode  Become a Member to Receive Exclusive Content  Sign Up to Receive Peter’s Weekly Newsletter Michael “Micky” Collins is an internationally renowned expert in sports-related concussions and a consultant for multiple professional sports organizations. In this episode, Mickey first explains the definition and diagnosis of a concussion, as well as the diverse signs and symptoms associated with different types of concussions. He discusses the risk factors that contribute to increased susceptibility and/or severity of concussions in certain individuals, emphasizes the significance of prompt treatment, and uses case studies to illustrate the latest in treatment protocols and recovery process. Additionally, Mickey provides insight into the evolving field of concussion treatments, including the exploration of hyperbaric oxygen and synthetic ketones. He gives advice to parents of kids who play sports and discusses the promising prospects in the realm of concussion management. We discuss:  Micky’s interest in concussion and how he started the first concussion clinic [3:15]; Concussion: definition, pathophysiology, and risk factors making someone more susceptible [9:45]; Symptoms of concussion, predictors of severity, and the importance of early and effective treatment [20:00]; The six types of concussion, the effectiveness of treatment, and factors that impact recovery [25:45]; The importance of seeing a specialist and the prognosis for recovery [30:00]; Case study of a racecar driver who suffered a vestibular concussion [32:15]; Why vestibular concussions are particularly problematic [42:45]; A treatment plan for the racecar driver, possible use of medications, and how to address the root cause [45:45]; Exploring alternative treatments: hyperbaric oxygen, synthetic ketones, and more [52:00]; The natural history of a concussion if untreated and the effect, if any, of concussion on subsequent risk of brain disease [57:15]; Chronic traumatic encephalopathy (CTE) [1:01:45]; Advice for parents of kids who play sports: when and where to seek treatment for a possible concussion [1:04:45]; Is there any evidence that the APOE4 genotype increases susceptibility to concussion or TBI? [1:10:15]; The increased risk of concussions in older adults and a case study of a 90-year-old patient who suffered a head injury in a fall [1:11:15]; Funding for concussion research and fellowship programs to train concussion specialists [1:15:30]; and More.  Connect With Peter on Twitter, Instagram, Facebook and YouTube

#263 ‒ Concussions and head trauma: symptoms, treatment, and recovery | Micky Collins, Ph.D.

View the Show Notes Page for This Episode  Become a Member to Receive Exclusive Content  Sign Up to Receive Peter's Weekly Newsletter In this "Ask Me Anything" (AMA) episode, Peter goes into depth on the topic of brain health, starting with how Alzheimer's disease is diagnosed, the significance of blood-based biomarkers in diagnosis, and what the various APOE gene variants mean in terms of a person's risk of developing Alzheimer's disease. Next, Peter discusses the various strategies for preventing Alzheimer's disease and neurodegeneration. He touches briefly on exercise as a potent tool, but focuses more on lesser-known factors that could impact brain health, such as nutrition supplementation, lipid management, brain games, sauna, oral health, hearing loss, and more. 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 #49 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits  here. We discuss:  Topics: exercise, kidneys, and brain health [1:30]; Rucking: advice for beginners, proper load, packs, and shoes [4:30]; Rucking for women, bone health, using a treadmill, zone 2, and more [11:45]; Building vs. maintaining: when and how to transition from the goal of building muscle and strength to focusing on maintenance [16:00]; Should you lift weights before or after a cardio session? [24:00]; Heart rate recovery: defining heart rate recovery and how it relates to cardiovascular fitness [28:45]; How to measure heart rate recovery, and what is considered a "good" heart rate recovery [33:15]; How kidney health and function typically measured [42:30]; Differentiating between creatine and creatinine [48:15]; The cystatin C blood test as a practical way to assess kidney health [52:45]; How kidney function impacts lifespan and the five stages of kidney disease [59:15]; Slowing the decline of kidney function [1:08:15]; The main drivers of kidney disease [1:11:15]; The importance of managing homocysteine levels for brain health [1:14:00]; The relationship between alcohol consumption and brain health [1:21:30]; and More.  Connect With Peter on Twitter, Instagram, Facebook and YouTube

#262 - AMA #49: Heart rate recovery, strength training, rucking, kidney function, and brain health

View the Show Notes Page for This Episode  Become a Member to Receive Exclusive Content  Sign Up to Receive Peter’s Weekly Newsletter In this special episode filmed live in front of readers of Outlive, Peter answers questions revolving around his concept of the centenarian decathlon. He starts by defining the “marginal decade” and how that shapes his training for the events and activities that make up his personal centenarian decathlon. Peter explains how he coaches patients through the challenges of customizing their own list and building out a training plan, including how to set fitness goals early in life in preparation for the marginal decade. From there, he dives into training within the four pillars (zone 2, VO2 max, stability, and strength), including the minimum effective dose, how to split your time, his personal protocols, and other considerations. Additionally, he touches on bone mineral density, female-specific considerations, working through injuries, and the profound impact training can have on the overall quality of life. We discuss:  The best interventions for longevity [2:15]; The marginal decade and the centenarian decathlon [4:45]; Peter’s personal list of events for his “centenarian decathlon” and how he helps patients create their own list [8:00]; Determining your fitness goals early in life in preparation for the marginal decade, metrics to track, and more [15:00]; How does playing sports like tennis, basketball, or golf fit into training for the centenarian decathlon? [24:15]; Training within the four pillars: minimum effect dose, how to split your time, and other considerations [27:45]; Advice for the older person and why it’s never too late to start [33:45]; Bone mineral density and other female-specific concerns and considerations [36:15]; Training advice for those with minimal access to a gym or equipment [39:30]; Injuries: prevention and working through existing conditions [41:00]; Cardiorespiratory training: how to split time between zone 2 and VO2 max training, and different modalities for a true zone 2 workout [44:15]; VO2 max training: modalities, Peter’s protocol, and how to monitor progress [54:45]; The profound impact training can have on the overall quality of life [58:15]; and More.  Connect With Peter on Twitter, Instagram, Facebook and YouTube

#261 ‒ Training for The Centenarian Decathlon: zone 2, VO2 max, stability, and strength | Peter Attia, M.D.

View the Show Notes Page for This Episode  Become a Member to Receive Exclusive Content  Sign Up to Receive Peter’s Weekly Newsletter In this episode, radiologist/engineer, Raj Attariwala, explains how he was able to apply his engineering background to create a unique MRI scanner that is capable of constructing whole-body images with a resolution that is unmatched in the industry. Peter and Raj discuss the implications of such a robust, radiation-free imaging tool on the early detection of cancer. They dive deep into cancer screening and define terms such as sensitivity and specificity that are necessary to really understand this complex space. They then describe the biggest risks involved in this type of screening (false positives) and how Raj’s unique technology and process might drive down this risk substantially. But before that, they discuss all the common imaging technology from X-ray, to CT scan, to PET scans, to ultrasound, to MRI, and more. They touch on the history of each, how they work, the usefulness and limitations of each of them, as well as the varying risks involved such as radiation exposure. If you are interested in cancer screening and/or you’ve ever wondered how any radiology tool works, this episode is for you. We discuss:  Raj’s road from engineering to radiology [2:45]; How X-ray works, the risk of radiation exposure, and the varying amounts of radiation associated with the different imaging technologies [13:00]; Computed tomography scans (CT scans): The history of CT, how it works, and why we use contrast [22:45]; Ultrasound: Benefits and limitations, and a special use for the heart [36:00]; Detecting breast cancer with mammography: When is works, when you need more testing, and defining ‘sensitivity’ and ‘specificity’ [46:15]; Magnetic resonance imaging (MRI): How it works, defining terms, and looking at the most common types of MRI [59:00]; Brain aneurysms: Using MRI to find them and save lives [1:18:45]; Raj’s unique MRI technology [1:25:15]; The risk of false positives in cancer detection, and how Raj’s MRI can reduce the number of false positives (i.e., increase specificity) [1:38:45]; The unique software Raj created to pair with his MRI machine [1:46:15]; Comparing the radiation exposure of a whole-body PET-CT to Raj’s equipment (DWIBS-MRI) [1:48:45]; How diffusion-weighted magnetic resonance imaging (DW-MRI) has revolutionized cancer screening [1:50:15]; Why a DW-MRI is still not a perfect test [1:54:15]; The potential for advancing MRI technology: Where does Raj think it could improve in the next 5-10 years? [1:58:00];/li&gt; Are there any commercially available scanners that can match the resolution of Raj’s images? [2:01:00]; Machine learning: When and where might machine learning/AI impact the field of radiology? [2:03:45]; and More.  Connect With Peter on Twitter, Instagram, Facebook and YouTube

Cancer screening with full-body MRI scans and a seminar on the field of radiology | Rajpaul Attariwala, M.D., Ph.D. (#61 rebroadcast)

View the Show Notes Page for This Episode  Become a Member to Receive Exclusive Content  Sign Up to Receive Peter’s Weekly Newsletter Mohit Khera is a world-renowned urologist with expertise in sexual medicine and testosterone therapy. In this episode, Mohit provides a comprehensive overview of male sexual health. He begins with an in-depth exploration of erectile dysfunction, shedding light on its prevalence across different age groups, diagnostic methods, and its intriguing connection to cardiovascular disease. He then ventures into Peyronie&#39;s disease, penile fractures, penile enlargement treatments, prolonged erections, premature ejaculation, and anorgasmia. Shifting gears, Mohit delves into the intricate workings of testosterone, DHT, and estrogen, emphasizing their physiological significance and interplay. He explains blood tests for diagnosing low testosterone, the correlation between symptoms and blood levels in cases of low testosterone, and the pros and cons of different methodologies for increasing testosterone. He concludes with a thought-provoking conversation about the role of testosterone in patients with prostate cancer and addresses concerns surrounding DHT, finasteride, and post-finasteride syndrome. We discuss:  Mohit’s career path and interest in sexual medicine and infertility [3:00]; The anatomy of the male genitalia [5:45]; The prevalence of sexual dysfunction, its impact on quality of life, and the importance of seeking help [7:15]; Erectile dysfunction (ED): definition, diagnosis, pathophysiology, and more [11:00]; The history of medications to treat ED and the mechanisms of how they work [15:30]; Relationship between aging and erectile dysfunction and Mohit&#39;s approach to treating patients and prescribing medications [20:00]; The impact of lifestyle on sexual health and the association between ED and cardiovascular disease [29:30]; Causes and treatments for Peyronie’s Disease, penile fracture, and more [37:30]; The value of ultrasound for ED diagnosis and management strategies [47:45]; Various treatment options for ED: injections, penile prosthesis, and more [50:15]; Priapism (prolonged erection): what is happening and when to seek treatment [57:15]; Shockwave therapy as a treatment for ED [1:02:45]; Stem cell therapy for ED [1:08:15]; Platelet-rich plasma (PRP) injections as a treatment for ED [1:12:00]; Premature ejaculation (PE): prevalence, pathophysiology, and treatment [1:14:45]; Anorgasmia: causes and treatment [1:22:00]; The interplay of sex hormones, the impact of aging, symptoms of low testosterone, and considerations for testosterone replacement therapy (TRT) [1:26:45]; Methods for increasing endogenous testosterone [1:38:45]; Testosterone replacement therapy: various forms of exogenous testosterone, weighing risk vs. reward, and more [1:52:30]; The physiology and purpose of testosterone and DHT, why some men feel fine even with “low” testosterone, personalized approaches to treating low testo

#260 ‒ Men’s Sexual Health: why it matters, what can go wrong, and how to fix it | Mohit Khera, M.D., M.B.A., M.P.H.

View the Show Notes Page for This Episode  Become a Member to Receive Exclusive Content  Sign Up to Receive Peter&#39;s Weekly Newsletter Sharon Parish is a Professor of Medicine in Clinical Medicine and Clinical Psychiatry at Weill Cornell Medical College and a prominent sexual medicine specialist who has been practicing for 30 years. In this episode, Sharon tackles the topic of women&#39;s sexual health, including the conditions associated with decreased sexual function and desire and available treatment options. She explores the influence of sexual health on overall well-being while also examining the potential effects of childbirth, birth control, metabolic health, and more on sexual function and desire. Through case studies, Sharon teases apart the differences between desire and arousal, explains the various factors that affect them, and walks through hypothetical treatment plans for the case study patients. In addition, she delves into the subject of menopause, addressing its impact on sexual health as well as the misguided fears around hormone replacement therapy. Stay tuned for next week&#39;s launch of our complementary podcast on men&#39;s sexual health. We discuss:  Sharon&#39;s interest in sexual medicine and the current state of the field [3:00]; How hormones change in women over time and how that impacts sexual function [8:15]; Changes after childbirth and its impact on sexual function [11:00]; The role of metabolic health and systemic vascular health in sexual health [20:15]; Conditions associated with decreased sexual function and the importance of sexual health for overall wellbeing [26:15]; Sexual dysfunction case study #1: A 41-year-old mother of two, the sexual response cycle, and the difference between arousal and desire [38:45]; Medications that may reduce sexual desire [49:45]; The effect of birth control pills on sexual desire [56:30]; The importance of testosterone in women for sexual function and desire, and why the FDA hasn&#39;t approved exogenous testosterone as a therapeutic [1:01:15]; Challenges faced by physicians who are open to prescribing off-label testosterone for women, and Sharon&#39;s approach in managing this aspect with her patients [1:14:30]; A hypothetical treatment plan for the patient in case study #1 [1:26:45]; The role of DHEA (a precursor to testosterone) in female sexual health [1:32:15]; Case study #2: A 30-year-old woman with anorgasmia (inability to orgasm) [1:38:30]; Resources for helping women and their partners to enhance the pleasure experienced during sex, overcome anxiety, and increase desire [1:51:30]; Two drugs for premenopausal women with low desire [1:59:30]; Why treatments are potentially underutilized for both desire and genitourinary syndrome of menopause [2:13:15]; Case study #3: A menopausal woman with symptoms [2:19:00]; Addressing the misguided fears around hormone replacement therapy and cancer [2:24:15]; Symptoms and treatment of genitourinary syndrome of menopause [2:32:45];

#259 - Women's sexual health: Why it matters, what can go wrong, and how to fix it | Sharon Parish, M.D.

View the Show Notes Page for This Episode  Become a Member to Receive Exclusive Content  Sign Up to Receive Peter’s Weekly Newsletter In this “Ask Me Anything” (AMA) episode, Peter delves into the critical subject of blood pressure, which is one of the three primary causes of atherosclerosis, along with high apoB and smoking. He begins by unraveling the nature of high blood pressure, its prevalence, and why it often goes undiagnosed. Peter describes in detail the proper way to accurately measure blood pressure and what determines a diagnosis. Next, Peter discusses the actionable steps one can take in response to high blood pressure, shedding light on the extent to which factors like weight loss, exercise, and nutrition can make an impact. He also explores the pharmacological options available and offers valuable insights on how to approach them. 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 #48 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here. We discuss:  Blood pressure and other risk factors for cardiovascular disease [2:30]; Defining blood pressure and the purpose and meaning of a blood pressure measurement [5:45]; The implications of high blood pressure and the importance of maintaining an optimal level [10:30]; The importance of accurate measurements of blood pressure and how Peter approaches the care of patients at the very top range of “normal” [21:45]; The prevalence of high blood pressure—a hidden epidemic? [24:30]; The consequences of high blood pressure on cardiovascular health, brain health, kidneys, and more [27:45]; Low blood pressure: symptoms and consequences [35:30]; How to properly measure blood pressure [37:45]; Daily variance in blood pressure and the transient changes in blood pressure during exercise [48:00]; Primary hypertension vs. secondary hypertension: what to look for [51:45]; Lifestyle factors impacting blood pressure: weight loss, exercise, and sodium [57:45]; Impact of insulin resistance and type 2 diabetes on blood pressure [1:04:45]; How sleep impacts blood pressure [1:06:45]; Pharmacologic options for managing blood pressure [1:08:00]; and More.  Connect With Peter on Twitter, Instagram, Facebook and YouTube

#258 - AMA #48: Blood pressure—how to measure, manage, and treat high blood pressure

View the Show Notes Page for This Episode  Become a Member to Receive Exclusive Content  Sign Up to Receive Peter’s Weekly Newsletter Tommy Wood is an Assistant Professor of Pediatrics at the University of Washington, where he studies brain injury and how lifestyle choices and environmental factors contribute to brain health, cognitive function, and chronic disease. In this episode, Tommy delves into the complexities of age-related cognitive decline and explores interventions to counteract it. Drawing from his experience working with Formula 1 drivers, he highlights the connection between cognitive function and the right type of demands and training leading to improvement. Next, he explores the various theories on the different types of pathology in dementia and neurodegeneration. He makes the case that a large fraction of dementia is preventable through lifestyle choices and nutrient status, and provides an in-depth overview of interventions and supplements that support cognitive function. Finally, he provides a comprehensive overview of head injuries, including concussions and traumatic brain injuries (TBIs), discussing symptoms, how to mitigate damage following an incident, and long-term management. We discuss:  Tommy’s professional work, unique skill sets, and interests [3:00]; Age-related decline in cognitive function and memory [5:45]; Improving brain function with the right level and type of demand [20:15]; Formula 1 as a model for how to perform under high cognitive demand and how to increase multitasking capacity [31:30]; Advice for the person reaching middle life looking to mitigate cognitive decline [37:45]; Tasks and activities that support and improve cognitive function [45:30]; Neuropathology of Alzheimer’s disease: exploring the role of amyloid and tau proteins [49:30]; Why Tommy believes dementia research funding should be focused on environmental and lifestyle-based risk factors [1:05:15]; Benefits of lowering homocysteine and boosting omega-3’s, and evidence-based supplements that support cognitive function [1:09:00]; A unifying theory of dementia [1:20:45]; How muscular strength can help with both the prevention and survivability of dementia [1:24:15]; Head injuries: comparing concussions against traumatic brain injuries (TBIs), mitigating the damage after an incident, and the long-term management of head injuries [1:29:15]; Is hyperbaric oxygen treatment helpful after a TBI? [1:45:45]; Supplements that aid recovery from a TBI: creatine, DHA, and choline [1:49:30]; Demands faced by F1 drivers, and testing interventions to improve their performance [1:57:30]; and More.  Connect With Peter on Twitter, Instagram, Facebook and YouTube

#257 ‒ Cognitive decline, neurodegeneration, and head injuries: mitigation and prevention strategies, supplements, and more | Tommy Wood, M.D., Ph.D.

View the Show Notes Page for This Episode  Become a Member to Receive Exclusive Content  Sign Up to Receive Peter’s Weekly Newsletter In this special episode of The Drive, Peter provides a comprehensive overview of the various endocrine systems: the thyroid system, the adrenal system, and the sex hormone system (for both men and women). He walks through the basic biology and the feedback cycles that regulate the production of these hormones and discusses the various options for the treatment of hormone deficiencies. In addition, Peter delves into hormone replacement therapy (HRT), providing nuanced insights into its appropriate usage and the clinical approach he adopts when working with patients.   Peter supplements these explanations with whiteboard illustrations. For a more complete understanding, we highly recommend watching these videos over just listening. The videos can be found on our YouTube channel or on the show notes page. We discuss:  The thyroid system [2:15]; The adrenal system [15:45]; The female sex hormone system [27:00]; The male sex hormone system [40:00]; and More.  Connect With Peter on Twitter, Instagram, Facebook and YouTube

#256 ‒ The endocrine system: exploring thyroid, adrenal, and sex hormones | Peter Attia, M.D.

View the Show Notes Page for This Episode  Become a Member to Receive Exclusive Content  Sign Up to Receive Peter’s Weekly Newsletter John Kastelein is a renowned expert in lipoprotein metabolism and atherosclerotic cardiovascular disease (ASCVD) research. In this discussion, John delves deep into familial hypercholesterolemia (FH), a genetic disorder characterized by high levels of LDL cholesterol in the blood that increases the risk of developing heart disease. He covers its definition, genetic underpinnings, and clinical identification. He then explores the therapeutic options available for the prevention and treatment of cardiovascular disease, including the captivating history of CETP inhibitors. He explains the past shortcomings of previous CETP inhibitors before underscoring the compelling potential of the latest iterations, not only for cardiovascular disease but also for conditions like Alzheimer's disease and type 2 diabetes. Moreover, he unveils the intricate role of APOE, shedding light on why the APOE4 isoform codes for a protein that significantly increases the risk of Alzheimer's disease and cardiovascular disease. Concluding the discussion, John shares a profound sense of optimism, envisioning the possibility of targeted therapeutic interventions for high-risk patients in the near future. We discuss:  Familial hypercholesterolemia (FH): a genetic condition [4:30]; Differentiating between phenotype and genotype when it comes to FH [9:45]; The pathophysiology related to mutations of FH [15:30]; Clinical presentations, physical manifestations, and diagnosis of FH [22:00]; Why a small fraction of people with FH do not develop premature ASCVD [34:15]; Treatment and prevention for those with FH [39:45]; Addressing the assertion by some that elevated LDL is not casual in cardiovascular disease [52:45]; The history of CETP inhibitors, and the role of the CETP protein [55:45]; The thrifty gene hypothesis and why genes underlying FH may have been preserved [1:09:00]; The compelling potential of the latest CETP inhibitor (obicetrapib) [1:13:00]; Promising results from phase 3 trials exploring obicetrapib [1:27:45]; Why the APOE4 allele increases the risk of Alzheimer’s disease, and the connection to blood lipids [1:41:30]; The role of APOE in cardiovascular disease [1:51:45]; Takeaways and looking ahead [1:57:00]; and More.  Connect With Peter on Twitter, Instagram, Facebook and YouTube

#255 ‒ Latest therapeutics in CVD, APOE’s role in Alzheimer’s disease and CVD, familial hypercholesterolemia, and more | John Kastelein, M.D., Ph.D.

View the Show Notes Page for This Episode  Become a Member to Receive Exclusive Content  Sign Up to Receive Peter’s Weekly Newsletter In this “Ask Me Anything” (AMA) episode, Peter delves deep into the data surrounding different forms of cold therapy, including cold water immersion, cryotherapy, and cold showers, aiming to unveil the potential benefits and drawbacks associated with cold therapy. He dissects the studies examining the effects of cold therapy on delayed onset muscle soreness (DOMS), activation of brown adipose tissue, and its potential impact on mood and as a therapeutic approach for depression. Furthermore, Peter discusses the potential negative impact cold therapy may have on muscular hypertrophy and offers his perspective on the extent to which the data support the notion of cold therapy providing longevity benefits. Finally, he also discusses the existing consensus, or lack thereof, regarding the optimal structure of an effective cold therapy protocol. 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 #47 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here. We discuss:  Overview of discussion on cold therapy (and a Formula 1 tangent) [1:45]; The most common cold exposure therapies [5:45]; Potential benefits of cold water immersion: a look at the data [9:30]; Comparing the effects of cold water immersion with whole-body cryotherapy [18:30]; The potential impact of cold exposure on mood and as a treatment for depression [20:45]; How do cold showers compare to cold water immersion? [28:15]; Cold exposure and the activation of brown adipose tissue (BAT) [34:15]; Things that clearly impact brain health: smoking, alcohol, sleep, head injuries, blood pressure, and more [34:15]; Exercising in cold temperatures: impact on exercise performance [38:30]; Potential downsides of cold therapy and its impact on hypertrophy, strength, and recovery [44:45]; Are the blunting effects of cold on hypertrophy due to the effects on inflammation? [50:45]; Does cold exposure offer any potential geroprotective benefits? [53:15]; Cold therapy protocols for delayed onset muscle soreness (DOMS) [56:30]; Summarizing the data and takeaways from Peter [1:01:00]; and More.  Connect With Peter on Twitter, Instagram, Facebook and YouTube

#254 - AMA #47: Cold therapy: pros, cons, and its impact on longevity

View the Show Notes Page for This Episode  Become a Member to Receive Exclusive Content  Sign Up to Receive Peter’s Weekly Newsletter JoAnn Manson is a world-renowned endocrinologist, epidemiologist, and Principal Investigator for the Women’s Health Initiative (WHI). In this episode, she dives deep into the WHI to explain the study design, primary outcome, confounding factors, and nuanced benefits and risks of hormone replacement therapy (HRT). JoAnn reflects on how a misinterpretation of the results, combined with sensationalized headlines regarding an elevated risk of breast cancer, led to a significant shift in the perception and utilization of HRT. From there, they take a closer look at the breast cancer data to separate fact from fiction. Additionally, JoAnn gives her take on how one should weigh the risks and benefits of HRT and concludes with a discussion on how physicians can move towards better HRT practices. We discuss:  The Women’s Health Initiative: the original goal of the study, hormone formulations used, and potential confounders [4:15]; Study design of the Women’s Health Initiative, primary outcome, and more [16:00]; JoAnn’s personal hypothesis about the ability of hormone replacement therapy to reduce heart disease risk prior to the WHI [26:45]; The relationship between estrogen and breast cancer [30:45]; Why the WHI study was stopped early, and the dramatic change in the perception and use of HRT due to the alleged increase in breast cancer risk [37:30]; What Peter finds most troubling about the mainstream view of HRT and a more nuanced look at the benefits and risks of HRT [45:15]; HRT and bone health [56:00]; The importance of timing when it comes to HRT, the best use cases, and advice on finding a clinician [59:30]; A discussion on the potential impact of HRT on mortality and a thought experiment on a long-duration use of HRT [1:03:15]; Moving toward better HRT practices, and the need for more studies [1:10:00]; and More.  Connect With Peter on Twitter, Instagram, Facebook and YouTube

#253 ‒ Hormone replacement therapy and the Women’s Health Initiative: re-examining the results, the link to breast cancer, and weighing the risk vs reward of HRT | JoAnn Manson, M.D.

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