<p><a href="https://peterattiamd.com/andrewhuberman2/?utm_source=podcast-feed&utm_medium=referral&utm_campaign=230911-pod-andrewhuberman2&utm_content=230911-pod-andrewhuberman2-podfeed"> View the Show Notes Page for This Episode</a></p> <p><a href="https://peterattiamd.com/subscribe/?utm_source=podcast-feed&utm_medium=referral&utm_campaign=230911-pod-andrewhuberman2&utm_content=230911-pod-andrewhuberman2-podfeed"> Become a Member to Receive Exclusive Content</a></p> <p><a href="https://peterattiamd.com/newsletter/?utm_source=podcast-feed&utm_medium=referral&utm_campaign=230911-pod-andrewhuberman2&utm_content=230911-pod-andrewhuberman2-podfeed"> Sign Up to Receive Peter's Weekly Newsletter</a></p> <p>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'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 "belief effect" from a placebo effect and highlighting its exciting implications for the future.</p> <p><strong>We discuss:</strong></p> <ul type="disc"> <li>The motivation behind this journal club conversation [2:45];</li> <li>Why Peter chose a paper on metformin, how metformin works, and why it generated excitement as a longevity-enhancing agent [9:00];</li> <li>Defining insulin resistance and its underlying causes [16:15];</li> <li>Metformin as a first-line treatment for type 2 diabetes, and Peter's evolving interest in metformin as a geroprotective drug [22:00];</li> <li>Defining the term "geroprotection" [24:45];</li> <li>The 2014 study that got the anti-aging community interested in metformin [26:00];</li> <li>Peter presents the 2022 paper that repeats the analytical approach from the 2014 Bannister study [33:15];</li> <li>Greater mortality in the metformin group: how results differed between the 2022 paper and the 2014 paper [40:00];</li> <li>Understanding statistical significance, statistical power, sample size, and why epidemiology uses enormous cohorts [51:45];</li> <li>Interpreting the hazard ratios from the 2022 metformin study, and the notable takeaways from the study [56:45];</li> <li>Drugs that may extend lifespan, why Peter stopped taking metformin, and a discussion of caloric restriction [1:08:45];</li> <li>Current thoughts on the use of metformin for longevity [1:21:00];</li> <li>Could there be any longevity benefit to short periods of caloric restriction? [1:22:45];</li> <li>Peter and Andrew's process for reading scientific papers [1:26:45];</li> <li>The biological effects of belief, and how "belief effects" differ from placebo effects [1:32:30];</li> <li>The neurobiology of nicotine: a precursor conversation before delving into the paper Andrew chose [1:39:45];</li> <li>Andrew presents a paper that demonstrates the impact of belief [1:45:30];</li> <li>Analyzing the fascinating results of the Perl paper [1:54:30];</li> <li>Exciting implications of the findings about "belief" reported by Perl and colleagues [2:03:15]; and</li> <li>More.</li> </ul> <p>Connect With Peter on <a href="https://twitter.com/PeterAttiaMD">Twitter</a>, <a href="https://www.instagram.com/peterattiamd/">Instagram</a>, <a href="https://www.facebook.com/peterattiamd/">Facebook</a> and <a href="https://www.youtube.com/channel/UC8kGsMa0LygSX9nkBcBH1Sg">YouTube</a></p>
Actionable Insights
1. Leverage Belief Effects
Recognize that your beliefs about drug doses and effects can biologically impact your physiology and brain activation, not just subjectively.
2. Deep Self-Analysis
Engage in intensive analysis, potentially with a skilled professional, to explore your subconscious and catalyze transformative life decisions and experiences.
3. Exercise for Insulin Sensitivity
Prioritize regular exercise as it is one of the most important actions to ward off insulin resistance and maintain metabolic health.
4. Sleep for Insulin Sensitivity
Ensure adequate sleep, as sleep deprivation can profoundly reduce glucose disposal and induce insulin resistance.
5. Prevent Excess Fat Accumulation
Avoid accumulating excess fat, especially its spillover into muscles, liver, and pancreas, as this exacerbates insulin resistance.
6. Maintain Glucose Homeostasis Through Lifestyle
Achieve glucose homeostasis and energy balance through good sleep hygiene, consistent exercise, and thoughtful eating, without necessarily relying on caloric deficit.
7. Reframe Stress Positively
Reframe your perception of stress by believing it enhances performance, which can lead to improved outcomes compared to viewing it as limiting.
8. Reframe Drug Side Effects
View drug side effects as evidence that the medication is working, which can make the experience less negative and potentially increase perceived relief from primary symptoms.
9. Dosage Belief Alters Response
Understand that your belief about a drug’s dose can significantly alter your brain’s physiological response, influencing how your body reacts.
10. Influence Satiety Through Belief
Recognize that your belief about a food’s caloric content and nutritional value can influence physiological responses like ghrelin suppression and satiety.
11. Believe in Exercise Benefits
Actively acknowledge and believe in the health benefits of your daily physical activity, as this belief alone can lead to greater positive physiological outcomes like weight loss.
12. Avoid Nocebo Effect
Be cautious about dwelling on potential negative side effects of a drug, as this can trigger the nocebo effect, leading to the subjective experience of those side effects.
13. Structured Paper Reading
When reading scientific papers, identify the questions, understand the approach, note the findings, and critically assess if conclusions are substantiated by the data.
14. Research Scientific Methods
When encountering unfamiliar scientific methods in a paper, look up their purpose online to significantly aid comprehension.
After reading the title and abstract, first review the figures to digest visual information before delving into the main text for deeper understanding.
16. Adapt Paper Reading Strategy
Adjust your paper reading approach based on familiarity; for new topics, use figures to generate questions, then read methods for clarity.
17. Review Supplemental Paper Info
Always check the supplemental information of scientific papers, as crucial data or analyses are often placed there due to journal length constraints.
18. Start a Journal Club
Engage in or resume a formal journal club (e.g., monthly) to review scientific papers, as it’s a great way to learn and develop interpretation skills.
19. Interpret Scientific Papers
Develop the skill of reading and interpreting scientific papers to understand research findings and think like scientists and clinicians.
20. Don’t Rely Solely on Abstracts
Avoid relying solely on a paper’s abstract for full understanding, as it’s usually insufficient to grasp the complete findings and implications.
21. Titrate Drug Dosages
When starting a new medication, titrate the dose up gradually rather than starting at a full dose to avoid severe side effects.
22. Manage Cortisol Levels
Be aware that hypercortisolemia (high cortisol) can contribute to insulin resistance, implying a need to manage stress or other factors that elevate cortisol.
Consider that metformin has not shown success in the ITP for geroprotection, suggesting re-evaluation of its use solely for anti-aging purposes in insulin-sensitive individuals.
24. Monitor Resting Lactate
If taking a weak mitochondrial inhibitor, monitor resting fasted lactate levels (aim for 0.3-0.6 millimole) as elevated levels may indicate increased shunting of glucose to lactate.
Be aware that metformin may attenuate hypertrophy and strength gains, which could be a factor for individuals prioritizing muscle mass and exercise performance.
26. Explore SGLT2 Inhibitors
Consider SGLT2 inhibitors as a potential drug for glucose disposal, based on mechanistic studies, ITP results, and human trials showing benefits even in non-diabetics.
27. Eat Unprocessed Foods
Focus on consuming most nutrients from unprocessed or minimally processed food sources, as this approach can enhance satiety and allow for greater food intake.
28. Acknowledge Longevity Biomarker Gaps
Understand that current longevity interventions lack reliable biomarkers to indicate whether they are effectively moving one in the right direction or at the correct dosage.
29. Gradual Nicotine Reduction
When attempting to quit nicotine, consider progressively reducing the actual dose while maintaining the belief that the dose is consistent to mitigate reward pathway disruption.
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