The Peter Attia Drive

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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>
• 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.

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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'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'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 testosterone, and more [2:02:30];
• Post-finasteride syndrome [2:09:00];
• The role of testosterone in prostate cancer and addressing the notion that TRT could increase risk [2:16:15];
• The effects of testosterone as an adjunct to therapy for estrogen-sensitive breast cancer in women [2:27:15];
• Resources for those looking for healthcare providers [2:28:45]; and
• More.

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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'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's launch of our complementary podcast on men's sexual health.

We discuss:

• Sharon'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'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'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];
• Age 65 and beyond, and resources for finding a provider [2:37:30]; and
• More.

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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.

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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.

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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.

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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.

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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.

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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.

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Rhonda Patrick, Ph.D., is a scientist with expertise in the areas of aging, cancer, and nutrition who translates complex scientific topics into actionable insights on her podcast, Found My Fitness. In this episode, Rhonda provides her latest thinking as it relates to Alzheimer's disease including the possibility of a vascular hypothesis as well as the factors that can impact disease risk such as type 2 diabetes, blood pressure, omega supplementation, exercise, sauna, and more. She also touches on cancer risk including the relationship between cancer and exercise as well as the link between alcohol consumption and cancer. Additionally, Rhonda explains her new focus on exercise and protein consumption as well as how her perspective has shifted as it pertains to fasting and time-restricted feeding.

We discuss:

• Alzheimer's disease: Rhonda's evolved thinking on neurodegenerative diseases [2:30];
• The breakdown of the blood-brain barrier in neurodegenerative disease [8:45];
• An explanation for the observation that type 2 diabetes increases risk of Alzheimer's disease [15:45];
• The role of omega-3 fatty acids (EPA and DHA) in brain health and prevention of neurodegeneration [19:45];
• Comparing the preventable nature of type 2 diabetes, atherosclerosis, cancer, and dementia [32:15];
• Blood pressure: an important modifiable lifestyle factor that can affect Alzheimer's disease risk [35:15];
• Rhonda's outlook on "precision medicine" as it pertains to one's genetic predispositions [38:45];
• Possible mechanisms by which exercise reduces the risk of Alzheimer's disease [45:45];
• Building your aerobic pyramid: neurobiological effects of exercise, benefits of lactate peaks, and more [53:45];
• Maximizing mitochondrial biogenesis: alternative training approaches and strategies [58:45];
• Possible brain benefits of sauna, and Rhonda's personal protocol [1:09:30];
• The relationship between cardiorespiratory fitness and dementia risk [1:15:30];
• How exercise may reduce the risk of cancer [1:20:30];
• The overarching impact of exercise on health, and the importance of focusing the factors that matter most [1:33:15];
• Impact of alcohol consumption on breast cancer risk and overall health [1:37:15];
• Exercise as an intervention for poor sleep habits [1:42:30];
• The longevity benefits of consuming adequate protein and strength training to preserve muscle mass and strength [1:46:30];
• How to get enough of the right kind of protein in your diet [2:05:15];
• Fasting: weighing the risk vs. reward [2:12:15];
• How Rhonda's views have shifted on diet and exercise [2:15:30];
• How to follow Rhonda's work and more about the benefits of lactate for the brain [2:21:00]; and
• More.

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