The Peter Attia Drive

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To support Tom's mission and work, please visit: https://africanmissionhealthcare.org/donation/catena/.

In this episode, Tom Catena, a missionary physician who runs Mother of Mercy Hospital in the Nuba Mountains in Sudan, describes some of his extraordinary work as the only doctor in a remote, war-torn region of Africa. In terms of individual lives saved, you could argue that there is no other person on the front lines doing more than Tom. Additionally, we explore the manner in which the Nuba people die, which is in striking contrast to the ubiquity of chronic disease and self-harm in the West, despite the extreme poverty and unimaginable suffering experienced by the Nuba people. Lastly, we discuss the lessons to be gleaned from the Nuba people, who, despite their suffering, live so harmoniously, happily, and resiliently.

We discuss:

• Background, medical training, and early days of missionary work in Africa [5:15];
• Tom arrives at Mother of Mercy Hospital in the Nuba Mountains of Sudan, civil war breaks out, and his staff evacuates [12:30];
• Learning surgery on the job and earning the trust of the community [37:00];
• The amazing people of Nuba, and why Nuba feels like home to Tom [47:45];
• NY Times article about Tom's work, and Tom's new venture on the board of the Aurora Prize Foundation, raising awareness and funds for other missionaries [59:45];
• Tom's mind-blowing ability to deal with chaos while seeing hundreds of patients per day [1:12:00];
• The most afraid Tom has ever been, and how he copes with the emotional trauma of his daily experiences [1:19:45];
• The basic tools, technologies, and medicines that Tom is lacking that could save many lives [1:30:00];
• The logistical challenge of helping Tom's hospital, and what Tom really needs [1:35:15];
• Diseases in the adult population [1:38:30];
• Living without possessions, finding meaning, and being a missionary [1:55:45];
• Happiness, sense of purpose, and suicide: contrasting the US with Nuba [2:07:15];
• Other than donations, is there a way people can help Tom and other similar causes? [2:15:15];
• The food in Nuba [2:18:30];
• Tom's annual bout of malaria [2:23:45];
• Patients Tom will never forget [2:26:00];
• Resources for people wanting to get involved in helping Tom's work [2:31:00];
• Peter tells a story that defines Tom [2:32:00]; and
• More.

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In this "Ask Me Anything" (AMA) episode, Peter explores various pharmacologic tools commonly utilized to improve metabolic health and treat diabetes, including SGLT-2 inhibitors, metformin, and GLP-1 agonists. He examines the available data on these drugs, assessing their comparative effectiveness and their potential in the context of lifestyle interventions. Additionally, he offers insights into whether SGLT2 inhibitors hold promise as geroprotective agents beyond their effects on glycemic control. Next, Peter analyzes the relationship between statin usage and the risk of developing insulin resistance and type 2 diabetes, investigating possible causal pathways and providing insights into strategies for risk reduction. He offers insights on monitoring adverse statin effects and evaluating the need for adjustments, ultimately weighing the trade-off between the risk to overall metabolic health against the benefits of reducing apoB levels through statin use.

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

We discuss:

• Pharmacologic tools for improving metabolic health, and the relationship between statins and insulin resistance [2:00];
• SGLT-2 inhibitors: how they work and help to manage type 2 diabetes [4:15];
• The history of SGLT2 inhibitors – from discovery to the current state [10:15];
• Comparing the various FDA-approved SGLT2 inhibitors [15:00];
• Other beneficial effects of SGLT2 inhibitors outside of glycemic control [20:15];
• Exploring SGLT2 inhibitors as potential geroprotective molecules [22:45];
• The side effects and risks associated with SGLT2 inhibitors [31:45];
• Medications, lifestyle interventions, and other considerations for treating diabetes and improving metabolic health [37:45];
• Metformin as a tool for pre-diabetics, and how metformin compares to lifestyle interventions [44:00];
• How GLP-1 agonists compare to metformin and SGLT2 inhibitors in terms of glycemic control and weight loss [49:15];
• Exploring the relationship between statin use and the risk of developing insulin resistance and type 2 diabetes [52:30];
• Possible mechanisms of statin-induced insulin resistance and diabetes, and potential mitigation strategies [1:04:30];
• How to monitor for adverse effects of statin use and assess the need for adjustments [1:11:45];
• Weighing the benefits and risks of statin use: does the diabetes risk outweigh the benefits of lowering apoB with a statin? [1:15:30];
• Parting thoughts [1:20:45]; and
• More.

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Harold (Hal) Burstein is an internationally renowned breast cancer expert. In this episode, Hal discusses a broad range of topics related to breast cancer, starting with the intricacies of breast anatomy and the endocrinological factors at play. He covers the spectrum of breast cancer, from precancerous lesions to invasive breast cancer, classifying these conditions into a helpful framework. He delves into various screening methods, including self-exams, mammograms, ultrasounds, and MRIs, and addresses the ongoing debate surrounding early screening and detection. Hal provides insights into the latest advancements in cancer treatment, offering valuable guidance for individuals to understand their unique circumstances within the three primary categories of breast cancer. Finally, Hal delves into the role of genetics in breast cancer and brings attention to the less commonly addressed issue of male breast cancer.

We discuss:

• The prevalence and mortality rate of breast cancer in women [4:15];
• The anatomy of the breast and the complex factors behind breast cancer development [6:30];
• The three main categories of breast cancer [16:45];
• Breast cancer risk: the impact of menopause, estrogen, breast density, obesity, and more [21:15];
• Finding and evaluating lumps in the breast [25:30];
• Identifying and treating precancerous lesions like ductal carcinoma in situ (DCIS) [31:00];
• Post-lumpectomy for DCIS: standard of care, future risk of cancer, and pros and cons of radiation and other preventative options [41:15];
• Lobular carcinoma in situ (LCIS): how it differs from DCIS in terms of treatment and future risk of invasive cancer [55:00];
• Breast cancer screening: mammography, ultrasound, MRI, and more [1:03:45];
• Invasive breast cancer: pathology report, surgery, and survival [1:11:00];
• The argument for aggressive screening for breast cancer [1:22:15];
• Advances in the treatment of breast cancer, adjuvant therapy, and neoadjuvant therapy [1:27:00];
• The use of hormone replacement therapy in women who are in remission from breast cancer [1:41:15];
• The role of genetics in breast cancer [1:44:45];
• The importance of multidisciplinary care delivered by cancer centers [1:53:15];
• Breast cancer in men [2:03:30];
• Parting thoughts and takeaways [2:05:45]; and
• More.

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Kari Nadeau is a physician scientist with expertise in treating food allergies. In this episode, Kari first explains the fascinating workings of the immune system, exploring how it adeptly defends against bacteria and viruses but how the same system can lead to food allergies. She proceeds to explore the complexities of food allergies, detailing their typical developmental patterns, underscoring the significance of preventative approaches like early exposure, and highlighting the potentially life-threatening nature of severe food allergies. Kari illuminates the latest advancements in immunotherapies that not only mitigate allergy severity but also hold the potential to completely cure the patient. Additionally, Kari shares her concerns about the increasing levels of air pollution, elucidating its adverse effects on health while providing valuable suggestions for reducing exposure.

We discuss:

• Kari's motivation to study food allergies [4:00];
• Overview of the immune system and the family of immunoglobulins [9:00];
• How our immune system fights viruses, bacteria, or fungi, and some exceptions to the rule [13:00];
• Why our immune system is generally better at fighting viruses than bacterial infections [18:45];
• Differentiating a food sensitivity from a food allergy, and a discussion about celiac disease [25:30];
• How food allergies develop, why they can be lethal, and factors contributing to the uptrend in food allergies [35:45];
• The role of environmental factors in the onset of food allergies and strategies for prevention [50:15];
• How immunotherapy helps to overcome, and even cure, food allergies [1:04:15];
• Can immunotherapy work for environmental allergens like pollen? [1:24:00];
• Air pollution: impact on health and tips for reducing your risk [1:25:30];
• Resources for those wanting to learn more or find clinical trials related to food allergies [1:40:45]; and
• More.

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In this special episode of The Drive, Peter discusses a variety of topics, breaking away from the typical deep-dive format to explore a wide range of common questions submitted by listeners. Peter tackles subjects like the viability of living to 120 and beyond, addressing some of the optimistic theories regarding achievement of this remarkable feat. Peter then shares his drug and supplement regimen while emphasizing how individualized these protocols need to be. The conversation also touches on lowering apoB, the long-term use of statins, the myth of good vs. bad cholesterol, the complexities of nutrition research, the quest for the ideal diet, and Peter's strategies for hitting daily protein goals. Peter finishes with a discussion about his favorite health-tracking wearables, the role of CGM in non-diabetics, and more.

We discuss:

• Overview of topics and previous episodes of a similar format [2:45];
• The viability of living to 120 and beyond: some optimistic theories [4:45];
• The potential of mTOR inhibition as a mid-life intervention, and longevity potential for the next generation [13:30];
• A framework for thinking about geroprotective drugs and supplements in the context of a lack of aging biomarkers [17:00];
• Supplements Peter takes and how his regimen has changed in the last year [26:15];
• Pharmacologic strategies to lower ASCVD risk, the limitations of statins, nutritional interventions, and more [36:15];
• Misnomers about cholesterol [48:00];
• Why nutritional research is so challenging, some general principles of nutrition, and why Peter stopped doing prolonged fasts [50:45];
• Optimizing protein intake [59:45];
• Wearables for sleep and exercise, continuous glucose monitors (CGM), and a continuous blood pressure monitor on the horizon [1:04:45]; and
• More.

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In this "Ask Me Anything" (AMA) episode, the discussion zeroed in on the practical application of hormone replacement therapy in women. Peter walks through the signs, symptoms, and hormonal changes in women approaching – and going through – menopause. He provides an overview of the FDA-approved HRT formulations and explains how women might go about choosing the right option for themselves. Peter also describes the significant changes in testosterone levels in women over time and the options, as well as the considerations and challenges of testosterone replacement therapy (TRT) for women. Lastly, Peter highlights the necessary role of compounding pharmacies in HRT, underscores concerns regarding the quality and sterility of compounded drugs, and offers guidance on locating a trustworthy pharmacy.

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

We discuss:

• Why hormone replacement therapy is such an important topic [2:00];
• The onset of menopause: symptoms, blood tests, and when to consider HRT [6:00];
• Tests that may provide indications of perimenopause and their implications for fertility [9:15];
• Vasomotor symptoms: hormonal changes that cause hot flashes/night sweats, and HRT therapies that can help [13:45];
• The role of estrogen in menopausal HRT [17:30];
• The limited role of progesterone in HRT protocols [25:15];
• What is a "bioidentical" hormone? [28:30];
• Overview of the FDA-approved HRT formulations [31:45];
• Determining HRT dosing and considerations for perimenopausal women [37:45];
• Choosing the right HRT formulation: pros and cons [43:30];
• Examining the link between certain forms of estrogen and breast cancer [46:45];
• Changes in testosterone levels in women over time and why it matters [50:00];
• Recognizing low testosterone in women: common symptoms and diagnosis [53:45];
• Testosterone replacement therapy for women: options, considerations, and challenges [57:30];
• The long-term use of testosterone in women: examining the limited data [1:00:15];
• What is a compounding pharmacy? [1:09:30];
• Reasons to opt for a compounding pharmacy over a pharmacy that adheres to stricter regulations [1:16:00];
• The tragic incidents that heightened concerns about compounding pharmacies [1:20:45];
• Tips for finding a reputable compounding pharmacy [1:27:45]; and
• More.

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We discuss:

• Derek's interest in weightlifting and experimentation with anabolic steroids at a young age [3:15];
• Derek's experience acquiring steroids from underground labs and the potential long-term fertility concerns early in his bodybuilding career [12:00];
• The backstory on More Plates, More Dates and Derek's unique ability to blend scientific knowledge with personal observation [17:00];
• Growth hormone – from extreme use-cases to the more typical – and the misconception that it's the "elixir of life" [21:30];
• Growth hormone 101: definition, where it comes from, and the challenges of measuring it [28:45];
• Does exogenous growth hormone compromise one's ability to make endogenous growth hormone? [40:00];
• The use of growth hormone in restoration of tissue during periods of healing [42:00];
• Growth hormone-releasing peptides to increase endogenous GH: various peptides, risks, benefits, and comparison to exogenous growth hormone [48:45];
• The role of growth hormone in building muscle and burning fat, as well as its effects on sleep and daytime lethargy [1:02:30];
• The evolution of drug use in the sport of bodybuilding [1:10:30];
• What explains the protruding abdomens on some bodybuilders and athletes? [1:20:30];
• Death of bodybuilders [1:26:00];
• The complex interplay of hormones, and the conversion of testosterone into metabolites like DHT and estrogen [1:33:45];
• Post-finasteride syndrome and how Derek successfully treated his hair loss [1:43:15];
• Testosterone replacement therapy: compelling use-cases, side effects, and optimal dosing schedules [1:57:15];
• Aromatase inhibitors to suppress estrogen, and the misconceptions around estrogen in men [2:16:00];
• Other hormones beyond testosterone for male sex hormone replacement [2:21:00];
• The history of anabolic compounds, and the differing effects of various anabolic testosterone derivatives and related drugs [2:24:30];
• Use of SARMs by bodybuilders [2:29:45];
• Anabolic steroid and testosterone regimens of professional bodybuilders and the downstream consequences [2:36:15];
• The challenge of accurate hormone testing in the presence of anabolic steroids and supplements [2:44:45];
• The use of Clomid, hCG, and enclomiphene [2:47:15];
• Concerns about fertility: comparing the use of testosterone and hCG [3:00:30];
• The use of BPC-157 peptide for healing injuries [3:12:00]; and
• More.

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Ted Schaeffer is an internationally recognized urologist who specializes in prostate cancer. In this episode, Ted delves deep into the realm of prostate health, starting with strategies for vigilance and effective management of the issues that can arise with aging, including urinary symptoms, prostatitis, pelvic pain, and prostate inflammation. Ted sheds light on the popular drug finasteride, renowned for its dual purpose in prostate shrinkage and hair loss prevention, as well as the contentious topic of post-finasteride syndrome. Ted then shifts to the topic of cancer, explaining how androgens, genetics, and non-genetic factors contribute to the pathogenesis of prostate cancer. He provides valuable insights into cancer screening, examining blood-based screening tools like PSA and the use of MRI in facilitating biopsies and their interpretation. Finally, he explores the various treatment options for prostate cancer, including surgical interventions, androgen deprivation therapy, and more.

We discuss:

• Changes to the prostate with age and problems that can develop [3:45];
• Behavioral modifications to help manage nocturnal urinary frequency and other lower urinary tract symptoms [8:30];
• Pharmacologic tools for treating nocturnal urinary frequency and lower urinary tract symptoms [16:30];
• Surgical tools for treating symptoms of the lower urinary tract [26:15];
• HoLEP surgery for reducing prostate size [32:30];
• Prostate size: correlation with cancer and considerations for small prostates with persistent symptoms [40:30];
• Prostatitis due to infection: symptoms, pathogenesis, and treatment [46:45];
• Prostatitis caused by factors besides infection [58:45];
• How to minimize risk of urosepsis in patients with Alzheimer's disease [1:05:00];
• Prostate cancer: 5-alpha reductase inhibitors, how androgens factor into pathogenesis, and more [1:10:00];
• Post-finasteride syndrome [1:18:15];
• The relationship between testosterone and DHT and the development of prostate cancer over a man's lifetime [1:26:30];
• How genetic analysis of a tumor can indicate the aggressiveness of cancer [1:35:15];
• Pathogenesis and genetic risk factors of prostate cancer and the use of PSA to screen for cancer [1:37:45];
• Non-genetic risk factors for prostate cancer [1:45:45];
• Deep dive into PSA as a screening tool: what is PSA, definition of terms, and how to interpret results [1:56:30];
• MRI as a secondary screening tool and the prostate biopsy options [2:13:15];
• Ted's ongoing randomized trial comparing different methods of prostate biopsy [2:24:00];
• Determining when a biopsy is necessary, interpreting results, explaining Gleason score, and more [2:27:00];
• Implications of a Gleason score of 7 or higher [2:46:45];
• Metastasis of prostate cancer to different body locations, treatment options, staging, and considerations for patients' quality of life and survival [2:53:30];
• How prostate cancer surgery has improved [3:09:30];;
• Questions to ask your neurologist if you are considering prostatectomy for cancer [3:21:45]; and
• More.

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In this episode of The Drive, Peter welcomes guests David Sabatini and Matt Kaeberlein, two world-leading experts on rapamycin and mTOR. David and Matt begin by telling the fascinating story of the discovery of rapamycin and its brief history as a pharmacological agent in humans. They then unravel the function of mTOR, a central regulator of numerous biological processes, and they discuss the pathways through which rapamycin exerts its potential benefits on lifespan. They touch upon initial studies that suggested rapamycin may have geroprotective effects and the ongoing research that continues to shed light on this unique molecule. Furthermore, they discuss the elusive details surrounding the frequency and dosing of rapamycin use in humans, and Peter emphasizes his reservations about indiscriminately prescribing rapamycin as a longevity drug for patients.

We discuss:

• David and Matt's expertise in mTOR and rapamycin [3:00];
• The discovery of rapamycin and its first use in humans as an immunosuppressant [13:15];
• The emergence of rapamycin as a molecule with the potential to prolong lifespan [19:30];
• The groundbreaking rapamycin study on mouse lifespan extension and the open questions about the timing and frequency of dosing [26:00];
• Explaining mTOR and the biology behind rapamycin's effects [35:30];
• Differences in how rapamycin inhibits mTOR complex 1 (MTORC1) versus mTOR complex 2 (MTORC2) [45:15];
• Reconciling the biochemical mechanism of rapamycin with its longevity benefit [49:15];
• Important discoveries about the interplay of amino acids (leucine in particular) and mTOR [54:15];
• Reconciling rapamycin-mediated mTOR inhibition with mTOR's significance in building and maintaining muscle [1:01:30];
• Unanswered questions around the tissue specificity of rapamycin [1:08:30];
• What we know about rapamycin's ability to cross the blood-brain barrier and its potential impacts on brain health and neurodegeneration [1:13:45];
• Rapamycin may act as an immune modulator in addition to immunosuppressive effects [1:21:30];
• Might rapamycin induce changes in T cell methylation patterns, potentially reversing biological aging? [1:34:15];
• Rapamycin side effects and impacts on mental health: fascinating results of Matt's survey on off-label rapamycin use [1:42:00];
• The impact of taking rapamycin in people who contracted COVID-19: more insights from Matt's survey [1:51:15];
• What David would like to study with mTOR inhibitors [1:54:45];
• Joan Mannick's studies of RTB101 and other ATP-competitive inhibitors of mTOR [2:00:30];
• The impact of mTOR inhibition on autophagy and inflammation and a discussion of biomarkers [2:10:00];
• The Dog Aging Project: what we've learned and what's to come from testing rapamycin in companion dogs [2:17:30];
• Preliminary results of primate studies with rapamycin [2:24:45];
• Dosing of rapamycin [2:27:45];
• The effect of rapamycin on fertility [2:36:45];
• The outlook for future research of rapamycin and the development of rapalogs [2:39:00]; and
• More.

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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.

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