Journal Club with Dr. Peter Attia | Metformin for Longevity & The Power of Belief Effects

In this journal club episode, my guest is Stanford and Johns Hopkins-trained physician, Dr. Peter Attia, M.D., who is also the host of The Drive podcast and the author of the bestselling book "Outlive: The Science & Art of Longevity."

We each present a scientific paper and discuss the findings' strengths, weaknesses and actionable takeaways.

First, we discuss an article that addresses whether taking the drug metformin can enhance longevity. Then, we discuss an article on belief effects (similar to placebo effects), showing how the effects of a drug on the brain and cognition depend on one's belief about the dose of the drug taken, not the actual dose.

Our conversation also highlights how to read, interpret and critique scientific studies. This episode ought to be of interest to those curious about health and longevity, medicine and psychology and for anyone seeking to better understand how to read and digest scientific findings.

#HubermanLab #Science

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Timestamps
00:00:00 Dr. Peter Attia, Journal Club
00:03:27 Sponsors: Helix Sleep & Levels
00:06:11 Dreams
00:12:36 Article #1, Metformin, Mitochondria, Blood Glucose
00:19:47 Type 2 Diabetes & Causes, Insulin Resistance
00:25:30 Type 2 Diabetes Medications, Metformin, Geroprotection, Bannister Study
00:36:19 Sponsor: AG1
00:37:15 TAME Trial; Demographics, Twin Cohort
00:44:27 Metformin & Mortality Rate
00:51:28 Kaplan-Meier Mortality Curve, Error Bars & Significance, Statistical Power
01:01:17 Sponsor: InsideTracker
01:02:23 Hazard Ratios, Censoring
01:09:00 Metformin Advantage?, Variables, Interventions Testing Program
01:16:02 Berberine, Acarbose, SGLT2 Inhibitors
01:23:48 Blood Glucose & Energy Balance; Caloric Restriction, Aging Biomarkers
01:32:22 Tool: Reading Journal Articles, 4 Questions, Supplemental Information
01:38:10 Article #2, Belief Effects vs. Placebo Effect
01:45:22 Nicotine Effects
01:51:07 Nicotine Doses & Belief Effects, fMRI Scan
02:00:07 Biological Effects, Dose-Dependent Response & Belief Effects
02:05:14 Biology & Beliefs, Significance, Dopamine Response, Non-Smokers
02:10:57 Dose-Dependence & Beliefs, Side Effects, Nocebo Effect
02:19:06 Zero-Cost Support, YouTube Feedback, Spotify & Apple Reviews, Sponsors, Momentous, Neural Network Newsletter, Social Media

[Itsme-ej]

We are so fortunate living in an era that people like Attia and Huberman have a platform to provide valuable information to health conscious people. We can educate ourselves about health so we can make the best decisions for us.

[Iskra]

Andrew, it would be great if you could do a podcast about PCOS, where metformin is first line drug prescribed, even to patients that are not insulin resistant. PCOS is an issue of almost 20% of young woman and still there is no simply answer what causes it and how to cure it.
Very informative podcast as always :)

[Random-zz]

Andrew never disappoints. Every time he make our life better. Respect

[karlbabaji]

I'm a person, 64 years old, who doesn't have diabetes but have a problem with sugar as my HEMOGLOBIN A1C WITH MPG last test was 5.9% and fasting Glucose was 99 mg/dL. I started taking Metaformin and my appetite and food/sugar cravings greatly reduced. Previously temptation was hard to resist.
Thus this feels revolutionary to me and I'm taking advantage of the opportunity to start new habits of exercise, diet and not eating myself into a stupor.
I think the factor of why someone was taking metformin would be a factor in the results that unfolded from doing so.
It's too early to report fat loss but early enough to say diet and exercised changed in ways that previously were unattainable

[beatrisbeatris]

Never stop being grateful for this kind of content, ever.

[Mariahmcam]

This is an absolutely an amazing idea for a podcast. Showing us in real time how to dissect academic papers. What a life time skill to learn. Thank you so much!

[TribeOfCooks]

Peter always leaves me speechless. His vocabulary and depth of knowledge is mind boggling.

[Ispeakyou]

Andrew and Peter you have no idea what a blessing you both are to all of us, thank you! 🙏❤️

[HarpaAI]

🎯 Key Takeaways for quick navigation:

00:00 📜 This is the Huberman Lab podcast's Journal Club episode with Dr. Peter Attia, focusing on scientific papers and discussions.
01:11 📄 They will discuss two papers: One about Metformin's potential role in longevity, and the other about the placebo effect, specifically with nicotine.
06:18 🎙️ Dr. Peter Attia and Andrew Huberman are excited to discuss and dissect scientific papers in real-time.
12:40 🧪 The first paper discussed is about metformin and its potential survival benefits for type 2 diabetics.
21:15 🧬 Insulin uses a "straw" mechanism to transport glucose into cells, and insulin resistance occurs when more insulin is needed to move the "straw, " leading to elevated insulin levels.
23:43 🩺 Insulin resistance can lead to type 2 diabetes, impacting glucose regulation in muscles and the liver, as well as causing inflammation in the pancreas.
34:23 📊 Metformin demonstrated a 15% relative reduction in all-cause mortality over 2.8 years in a study of individuals with type 2 diabetes, suggesting potential longevity benefits.
41:36 📈 The TAME trial uses both singletons and discordant twins to study metformin's effects, aiming for more robust results.
43:03 📊 Medication profiles in the study participants were not well-matched, particularly for diabetes-related medications, which is a significant limitation in this observational study.
01:06:15 🧬 In a twin study, one twin with diabetes on Metformin still had a 70-80% higher chance of death than the non-diabetic co-twin, even after adjustments.
01:13:23 🔄 Absent a randomized control trial, the true impact of Metformin on longevity and health remains uncertain. Such trials have not been conducted for hard outcomes.
01:16:14 🚫 Dr. Peter Attia stopped taking Metformin due to issues with nausea and high resting lactate levels, possibly related to weak mitochondrial function.
01:21:25 🌡️ An SGLT2 inhibitor is the only glucose disposal agent Dr. Attia currently takes due to its favorable mechanistic studies, results in the Interventions Testing Program (ITP), and benefits in non-diabetics, including heart failure.
01:24:55 🧪 This transcript discusses the role of energy balance in glucose homeostasis, emphasizing that macro composition may not matter as much as previously believed.
01:27:01 📊 The speaker mentions the "TAME" study, which could provide more definitive answers about Metformin's protective benefits, especially for non-diabetics.
01:28:23 💡 Short periods of caloric restriction or fasting may not have significant longevity benefits and lack clear biomarkers for tracking progress in anti-aging efforts.
01:30:41 🧬 The absence of biomarkers for aging is a major challenge in longevity research, hindering the ability to measure the effectiveness of interventions accurately.
01:32:07 📖 The recommended approach for reading scientific papers involves focusing on four key questions: the research question, the research methods, the findings, and whether the conclusions align with the findings.
01:38:23 🧠 The upcoming paper discussed in this transcript explores how beliefs about drugs can impact their effects at a biological level, differentiating belief effects from placebo effects.
01:45:14 🧠 Belief about nicotine strength affects brain activation: People's belief about the strength of nicotine they consumed in a vape pen influenced the activation of brain areas associated with attention, reward, and decision-making.
01:45:40 💨 Nicotine enhances cognitive performance: Nicotine can enhance cognitive performance by increasing the signal-to-noise ratio of sensory information coming into the brain, leading to improved perception and clarity.
01:49:23 🧒 ADHD medications and ventromedial prefrontal cortex: Stimulant medications used to treat ADHD, like Adderall and Ritalin, enhance the function of the ventromedial prefrontal cortex, which is crucial for focus and attention.
02:00:08 🧪 Dose-dependent belief effects: The study revealed a dose-dependent response in the brain to beliefs about nicotine strength, highlighting how expectations can shape physiological responses to drugs.
02:05:15 🧠 Belief effects can impact brain activity significantly, as seen in experiments with nicotine.
02:08:50 🧪 Small amounts of nicotine can activate pathways in the brain, especially in individuals naive to nicotine.

Made with HARPA AI

[flochfitness]

The scrutiny, experience, and precision that Dr. Attia brings to paper study analysis makes my head spin and gives me great confidence that when Attia gives recommendations on something, he knows what he’s talking about. 🙏🏻🙏🏻🙏🏻

[DivineGoddess-jusp]

The joy and delight exuding from Dr. Huberman is infectious, to say the least, and this is why we keep coming back to learn more about ourselves from this inspiring man and from his incredible guests. I also laughed pretty hard about the dream Peter had. 🤣

[magueysunset]

The book "Outlive" by Attia and the workbook "30 Days to Reduce Anxiety" by Harper Daniels have been instrumental in helping me develop a good daily routine for managing anxiety. Beside these two good books things like eliminating high caffeine drinks, cold showers, deep breathing, and long walks have helped a lot.

[optoutist]

How are we all so lucky to be able to just have access to these two wonderful humans and this journal club, I just can't believe it, that was so, so cool! Thank you, thank you thank you! <3

[Al_Ak-an]

I only at the beginning of the episode but I love how Dr. Huberman simplified Dr. Attia's explanation for us by asking questions so we can all understand everything correctly. Thank you so much!

[obinnamgbako]

Delighted to have these two thought leaders and scientists to help navigate this life continuum. Respect

[muntahafaiaaz]

This is the type of content that should be on YouTube

[nidhibr]

Outlive by Peter Attia is changing my life, for the better. Thank you Huberman (for the introduction) and Peter for enriching our regular lives.

[ZennyB]

As a shift worker, and as someone who has battled long term anosmia from covid, stumbling across this podcast has changed my life. This podcast is tremendously valuable and I always learn something new after listening. Thank you Andrew!

[Lazien]

WOW! Selfishly I hope and wish this series continues with unlimited episodes forever.

[MsDesseNoire]

27:01 FYI with metformin it is always first 7 days of nausea. You'd feel sick no matter the dose. My doctor prescribed me the smallest dose at first, and she warned me that I might feel nausea for a while at first. After a week it goes away. Then if you stop using it and start again in a few weeks, you'll have nausea again for a week. Thats my story