Andrew Huberman: Journal Club with Dr. Peter Attia - Metformin for Longevity and The Power of Belief Effects

The video is about a journal club discussion between Andrew Huberman and Peter Attia, where they discuss two papers on Metformin and the placebo effect. The first paper is about the potential role of Metformin in longevity, and the second paper is about the placebo effect and how it can follow a dose response. The discussion covers the existing peer-reviewed research on these topics and how scientists and clinicians approach these issues. The podcast is separate from Huberman's teaching and research roles at Stanford and is part of his effort to bring zero-cost consumer information about science and science-related tools to the general public.

This video by Andrew Huberman was published on Sep 11, 2023.
Video length: 02:21:19.

The video is about a journal club discussion between Andrew Huberman and Peter Attia, where they discuss two papers on Metformin and the placebo effect.

The first paper is about the potential role of Metformin in longevity, and the second paper is about the placebo effect and how it can follow a dose response. The discussion covers the existing peer-reviewed research on these topics and how scientists and clinicians approach these issues.

The podcast is separate from Huberman's teaching and research roles at Stanford, and is part of his effort to bring zero-cost consumer information about science and science-related tools to the general public.

• The video is about a journal club discussion between Andrew Huberman and Peter Attia.
• The discussion covers two papers on Metformin and the placebo effect.
• The first paper is about the potential role of Metformin in longevity.
• The second paper is about the placebo effect and how it can follow a dose response.
• The discussion is based on existing peer-reviewed research on these topics.
• Metformin is a medication used to lower blood sugar levels.
• It has been studied for its potential role in longevity.
• The paper discussed in the journal club suggests that Metformin may have a protective effect on the liver and kidneys.
• It also suggests that Metformin may reduce the risk of certain types of cancer.
• The paper highlights the need for more research to fully understand the potential benefits of Metformin for longevity.
• The placebo effect is the phenomenon where a person experiences an improvement in their symptoms or health, even though they have received a treatment that has no therapeutic effect.
• The paper discussed in the journal club suggests that the placebo effect can follow a dose response.
• This means that the effectiveness of the placebo can be influenced by the dosage of the medication.
• The paper highlights the importance of understanding the placebo effect in medical research and treatment.
• It also suggests that the placebo effect may be related to the psychological and social aspects of healthcare.
• The journal club discussion highlights the importance of monitoring blood glucose levels and understanding how different foods and food combinations can impact blood glucose levels.
• It also emphasizes the need for more research on the potential benefits of Metformin for longevity and the placebo effect.
• The discussion highlights the importance of understanding the psychological and social aspects of healthcare.
• It also emphasizes the need for more research on the placebo effect and its potential influence on medical treatment.
• Overall, the journal club discussion provides valuable insights into the importance of monitoring blood glucose levels and understanding the potential benefits of Metformin and the placebo effect.

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

Introduction

• Welcome to the Huberman Lab podcast
• Discusses science and science-based tools for everyday life
• Hosted by Andrew Huberman and Peter Attia
• First online collaborative Journal Club episode
• Two papers discussed: Metformin and the placebo effect

Section 1: Metformin and Longevity

• Peter Attia discusses a paper on Metformin and its potential role in longevity
• Compares the paper to previous findings on Metformin
• Advises whether or not he would take Metformin based on the data in the paper
• Discusses whether or not other people might be well advised or ill-advised to take Metformin

Section 2: The Placebo Effect

• Andrew Huberman presents a paper about the placebo effect
• Discusses how the placebo effect can follow a dose response
• Scales the degree of placebo effect depending on whether or not a person thinks they are taking low, moderate, or high doses of a particular drug
• Nicotine is the drug discussed in the paper

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

Section 3: Conducting a Journal Club

• Observes how a Journal Club is conducted
• Parses the papers and discusses them
• Argues in the papers at times
• Learns a lot of science and health practices

Section 4: Sponsors

• First sponsor is Helix Sleep
• Helix Sleep makes customized mattresses to give you the best possible night's sleep
• Takes a two-minute quiz to match you to a mattress that's ideal for your sleep needs
• Offers up to 350 off any mattress order and two free pillows

Section 1: Introduction

• The video is about a journal club discussion between Andrew Huberman and Peter Attia.
• The discussion covers two papers on Metformin and the placebo effect.
• The first paper is about the potential role of Metformin in longevity.
• The second paper is about the placebo effect and how it can follow a dose response.
• The discussion is based on existing peer-reviewed research on these topics.

Section 2: Metformin and Longevity

• Metformin is a medication used to lower blood sugar levels.
• It has been studied for its potential role in longevity.
• The paper discussed in the journal club suggests that Metformin may have a protective effect on the liver and kidneys.
• It also suggests that Metformin may reduce the risk of certain types of cancer.
• The paper highlights the need for more research to fully understand the potential benefits of Metformin for longevity.

Section 3: The Placebo Effect

• The placebo effect is the phenomenon where a person experiences an improvement in their symptoms or health, even though they have received a treatment that has no therapeutic effect.
• The paper discussed in the journal club suggests that the placebo effect can follow a dose response.
• This means that the effectiveness of the placebo can be influenced by the dosage of the medication.
• The paper highlights the importance of understanding the placebo effect in medical research and treatment.
• It also suggests that the placebo effect may be related to the psychological and social aspects of healthcare.

Section 4: Conclusion

• The journal club discussion highlights the importance of monitoring blood glucose levels and understanding how different foods and food combinations can impact blood glucose levels.
• It also emphasizes the need for more research on the potential benefits of Metformin for longevity and the placebo effect.
• The discussion highlights the importance of understanding the psychological and social aspects of healthcare.
• It also emphasizes the need for more research on the placebo effect and its potential influence on medical treatment.
• Overall, the journal club discussion provides valuable insights into the importance of monitoring blood glucose levels and understanding the potential benefits of Metformin and the placebo effect.

Section 1: Introduction to Yerba Mate

• The speaker is discussing the drink Yerba Mate, which is a traditional drink from Uruguay and other parts of the world.
• The speaker has been drinking Yerba Mate since they were young and it is not heavily caffeinated.
• The speaker collects dew off the leaves of Yerba Mate every morning.
• The speaker has had some transformative dreams recently.
• The speaker has had a dream that allowed them to feel something they had never felt before and has catalyzed important decisions.

Section 2: Dream Exploration

• The speaker has been exploring their dreams recently.
• The speaker has had some transformative dreams that have impacted their life.
• The speaker has had to do a lot of work to prepare for the dream to take place.
• The speaker has had to work with a skilled psychiatrist to analyze the dream.
• The speaker has had to take a walk while waking to realize that their brain was going to keep working on the dream.

Section 3: Metformin and Type 2 Diabetes

• The speaker is discussing a paper titled "Reassessing the Evidence of a Survival Advantage in Type 2 Diabetics Treated with Metformin Compared with Controls without Diabetes: A Retrospective Cohort Study."
• The paper is important because it is a retrospective cohort study that reassesses the evidence of a survival advantage in type 2 diabetics treated with metformin compared with controls without diabetes.
• The paper is important because it is a retrospective cohort study that reassesses the evidence of a survival advantage in type 2 diabetics treated with metformin compared with controls without diabetes.
• The paper is important because it is a retrospective cohort study that reassesses the evidence of a survival advantage in type 2 diabetics treated with metformin compared with controls without diabetes.
• The paper is important because it is a retrospective cohort study that reassesses the evidence of a survival advantage in type 2 diabetics treated with metformin compared with controls without diabetes.

Section 4: Metformin and Glucophage

• The speaker is discussing the drug Glucophage, which is a brand name for metformin.
• Glucophage is a generic drug today.
• The mechanism by which metformin works is debated, but it is known to inhibit complex one of the mitochondria.
• The mitochondria are the cellular engine for making ATP, the most efficient way to make ATP is through oxidative phosphorylation.
• The speaker has been drinking Yerba Mate since they were young and it is not heavily caffeinated.

The Role of Metformin in Longevity

• Metformin is a drug that works at the first of four electron transport chain complexes in the mitochondria.
• It is not a complete inhibitor of the process, but rather a weak blocker that changes the ratio of adenosine monophosphate to adenosine diphosphate.
• The net effect of this change is to reduce the amount of glucose that the liver puts out, which is one of the fundamental problems in type 2 diabetes.
• Metformin seems to do this by tamping down on high glucose output from the liver.
• The ability of the liver to regulate glucose output is important for maintaining metabolic health.

The Placebo Effect

• The placebo effect is the phenomenon where a person experiences an improvement in their symptoms or health, even though they have received a treatment that has no therapeutic effect.
• This can occur because the act of receiving treatment can trigger changes in the brain and body that lead to improvements in symptoms or health.
• The placebo effect has been observed in a variety of conditions, including pain, depression, and anxiety.
• The placebo effect can be influenced by factors such as the expectations of the patient, the context in which the treatment is administered, and the relationship between the patient and the healthcare provider.
• Understanding the placebo effect is important for medical research and clinical practice, as it can help to distinguish between real and imagined effects of treatments.

Insulin Resistance

• Insulin is a peptide that binds to a receptor on a cell, responsible for most glucose disposal.
• Glucose is toxic and needs to be put away, with most of it stored in muscles (75-80%).
• When insulin binds to the insulin receptor, a chemical reaction takes place inside the cell that leads to a phosphorylation, requiring energy.
• Insulin is responsible for placing a little straw into the membrane to allow glucose to flow into the cell.
• Insulin resistance occurs when the cell becomes resistant to the effect of insulin, requiring more and more insulin to get the transporter up.

Insulin Resistance and Type 2 Diabetes

• Insulin resistance is the early mark of type 2 diabetes, with an increase in insulin being the canary in the coal mine.
• Over time, insulin resistance can lead to a system where the body needs a boatload of insulin to get glucose out of the circulation.
• The liver becomes insulin resistant as well, leading to overproduction of glucose and difficulty regulating it.
• The muscles that can't dispose of the excess glucose can lead to a vicious cycle.
• Inflammation in the pancreas due to fat accumulation can lead to less effective insulin production, requiring exogenous insulin in some cases.

Causes of Type 2 Diabetes

• Accumulating too much fat is an enormous cause of type 2 diabetes.
• Inactivity or insufficient activity is probably the single most important cause of insulin resistance.
• Exercise is one of the most important things to do to ward off insulin resistance.
• Sleep deprivation has a profound impact on insulin resistance.

The Effects of Sleep Deprivation on Glucose Disposal

• Sleep deprivation for just one week can reduce glucose disposal by about half.
• Hypercortisolemia, energy imbalance, and accumulation of excess energy in the body are also factors that exacerbate the problem.
• When excess energy is stored in subcutaneous fat cells, liver, pancreas, and muscle, it can lead to insulin resistance.

Metformin as a First-Line Drug for Type 2 Diabetes

• Metformin is a first-line drug for type 2 diabetes, as it addresses the problem of insulin resistance.
• Unlike other drugs that increase insulin sensitivity, metformin tamps down glucose by addressing the glucose disposal channel.

The Role of Metformin in Longevity

• Metformin has been shown to increase insulin sensitivity, which can lead to improved glucose disposal and potentially increase lifespan.
• Metformin has been shown to reduce the risk of cardiovascular disease, which is a major contributor to mortality in older adults.

The Power of Belief Effects

• Placebo effects can be powerful, as they can lead to real improvements in health and well-being.
• Placebo effects can be influenced by factors such as the patient's expectations, the doctor's behavior, and the context in which the treatment is administered.

Background

• The study was conducted in the future and looked at the past.
• The study used informative censoring, which excluded patients who deviated from the inclusion criteria.
• The study only considered patients who were on Metformin, stayed on Metformin, and never progressed to a more significant drug.
• The study found a crude death rate of 14.4 deaths per thousand patient years in the group of people with type 2 diabetes who were on Metformin.
• The control group had a crude death rate of 15.2.

Interesting Result

• The crude death rate in the group of people with type 2 diabetes who were on Metformin was lower than the control group.
• The difference in lifespan between the two groups was only about one year and a half.
• Taking Metformin on average will shorten your life by six years.
• The people in the Metformin group had a far worse outcome, but the fact that it was statistically significant in the other direction was remarkable.
• The people who took Metformin and had diabetes had a 15% relative reduction in lifespan.

Limitations

• The study only considered patients who were on Metformin, stayed on Metformin, and never progressed to a more significant drug.
• The study used informative censoring, which excluded patients who deviated from the inclusion criteria.

Conclusion

• The study found a crude death rate of 14.4 deaths per thousand patient years in the group of people with type 2 diabetes who were on Metformin.
• The difference in lifespan between the two groups was only about one year and a half.
• Taking Metformin on average will shorten your life by six years.
• The people in the Metformin group had a far worse outcome, but the fact that it was statistically significant in the other direction was remarkable.
• The people who took Metformin and had diabetes had a 15% relative reduction in lifespan.

The Role of Metformin in Longevity

• The study found a 15% reduction in all-cause mortality over 2.8 years.
• There is no clear explanation for this effect, except for the belief that metformin is doing something beyond just lowering blood glucose.
• Metformin is a weak inhibitor of mTOR and reduces inflammation, potentially tamping down on senescent cells and their secretory products.
• There are many things that metformin could be doing that are off-target, and it might be that these things are conferring the advantage.
• The speaker mentions that they take ag1 daily, a vitamin mineral probiotic drink designed to meet all of your foundational nutrition needs.

The Placebo Effect

• The placebo effect is the phenomenon where a person experiences an improvement in their symptoms or health, even though they have received a treatment that has no therapeutic effect.
• The placebo effect can follow a dose response, meaning that the greater the dose of the placebo, the greater the effect.
• The speaker mentions that they have experienced the placebo effect themselves, and that it can be a powerful tool in managing pain and other symptoms.
• The speaker also mentions that the placebo effect can be used in clinical trials to help researchers better understand the effects of a particular treatment.
• The speaker emphasizes the importance of understanding the placebo effect in order to better design and interpret clinical trials.

Introduction

• The TAME trial is a clinical trial that aims to study the role of metformin in longevity.
• The study will use a random assignment method to study the effects of metformin on aging.
• The study will use a different cohort of people than the Banister study, which used a larger sample from a Danish Health registry.
• The study will use a twin trick analysis to study the effects of metformin on aging.
• The study will also use a sensitivity analysis with and without informative censoring to study the effects of metformin on aging.

Twin Trick Analysis

• The twin trick analysis is a method used to study the effects of metformin on aging.
• The study will use same-sex twins that only differ in that one has diabetes and one doesn't.
• The study will use genetic and environmental factors during childhood to study the effects of metformin on aging.
• The study will use a degree of genetic similarity and environmental factors during childhood to study the effects of metformin on aging.
• The study will use a sensitivity analysis with and without informative censoring to study the effects of metformin on aging.

Medication List

• The medication list is an important limitation of the study.
• The study cannot match the medication list perfectly.
• The study will use a sensitivity analysis with and without informative censoring to study the effects of metformin on aging.
• The study will use a twin trick analysis to study the effects of metformin on aging.
• The study will use a degree of genetic similarity and environmental factors during childhood to study the effects of metformin on aging.

Conclusion

• The TAME trial is a clinical trial that aims to study the role of metformin in longevity.
• The study will use a random assignment method to study the effects of metformin on aging.
• The study will use a twin trick analysis to study the effects of metformin on aging.
• The study will use a sensitivity analysis with and without informative censoring to study the effects of metformin on aging.
• The study will use a degree of genetic similarity and environmental factors during childhood to study the effects of metformin on aging.

Section 1: Crude Mortality Rates

• The video discusses the crude mortality rate in each group of the study.
• The most important row in the table is the one that says crude mortality per thousand person years.
• The control group in the study had a crude mortality rate of 15.86 per thousand person years.
• The non-twins who were not diabetic had a crude mortality rate of 16.86 per thousand person years.
• The single The Singletons with without so the non-twins who were not diabetic had a crude mortality rate of 16.86 per thousand person years.

Section 2: Normalizing Mortality Rates

• The video explains that mortality rates are normalized to make comparisons between different groups.
• When we talk about the mortality from a disease in the population, we report it as what's the mortality rate per 100,000 persons.
• The reason we can do it that way is because we're literally looking at how many people died this calendar year and we divide it by the number of people in that age group.
• The majority of deaths in absolute terms probably occur in the seventh decade.
• To say something like you know we have a crude death rate of five deaths per thousand person years one way to think about that is if you had a thousand people and you followed them for one year you'd expect five to die.

Section 3: Epidemiology vs. Experimental Studies

• The video explains that epidemiology is way more complicated than following the basics of experimental studies.
• When you adjust for age, the crude death rate of the people on Metformin who are not twins versus who are twins is almost identical.
• The first thing that jumps out at you when you look at this is there's clearly a difference here.
• The parentheses after every one of these numbers offer the 95 confidence interval.
• If a 95 confidence interval does not cross the number zero, it's statistically significant.

Section 4: Metformin and Longevity

• The video discusses the potential role of Metformin in longevity.
• The non-twins who were not diabetic had a crude mortality rate of 16.86 per thousand person years.
• The single The Singletons with without so the non-twins who were not diabetic had a crude mortality rate of 16.86 per thousand person years.
• The crude mortality rate of the people on Metformin who are not twins versus who are twins is almost identical.
• The first thing that jumps out at you when you look at this is there's clearly a difference here.

Summary of Section 1

• The study compares the mortality rates of people with type 2 diabetes who took metformin to those who did not take it.
• The study found that people with type 2 diabetes who took metformin had a higher mortality rate compared to those who did not take it.
• The study also found that the difference in mortality rate was statistically significant after adjusting for age.
• The study used a Kaplan-Meier curve to visualize the mortality rates over time.
• The Kaplan-Meier curve showed that people with type 2 diabetes who took metformin had a higher mortality rate compared to those who did not take it.

Summary of Section 2

• The study used a placebo control group to compare the effectiveness of metformin.
• The placebo group received a sugar pill that looked identical to metformin.
• The study found that people who took metformin had a higher mortality rate compared to those who took the placebo.
• The study also found that the difference in mortality rate was statistically significant after adjusting for age.
• The study used a Kaplan-Meier curve to visualize the mortality rates over time.

Summary of Section 3

• The study used a twin group to compare the effectiveness of metformin.
• The twin group consisted of identical twins, one of whom took metformin and the other who did not take it.
• The study found that people who took metformin had a higher mortality rate compared to those who did not take it.
• The study also found that the difference in mortality rate was statistically significant after adjusting for age.
• The study used a Kaplan-Meier curve to visualize the mortality rates over time.

Summary of Section 4

• The study used a Kaplan-Meier curve to visualize the mortality rates over time.
• The Kaplan-Meier curve showed that people who took metformin had a higher mortality rate compared to those who did not take it.
• The study also found that the difference in mortality rate was statistically significant after adjusting for age.
• The study used a placebo control group to compare the effectiveness of metformin.
• The placebo group received a sugar pill that looked identical to metformin.

Section 1: Understanding Confidence Intervals

• Confidence intervals give a sense of how much range is expected for a given population.
• They are used to account for variability in a data set.
• The variability is how many people in each group die within a given year.
• The median was typically three or four years at a time in the study.
• The study used a complicated type of mathematics called A Cox proportional Hazard to generate Hazard ratios.

Section 2: Understanding Error Bars

• Error bars give a sense of how much range is expected for a given population.
• They are used to account for variability in a data set.
• The variability is how many people in each group die within a given year.
• The median was typically three or four years at a time in the study.
• The study used a complicated type of mathematics called A Cox proportional Hazard to generate Hazard ratios.

Section 3: Understanding Significance

• Determining significance is important in determining whether a result is due to chance or not.
• P-values are used to determine significance.
• P-values less than 0.05 are considered statistically significant.
• When dealing with repeated measures over time, statistical power is important.
• Statistical power is the expectation of what you believe the difference is between the groups and the number of samples needed to assess whether or not that difference is there or not.

Section 4: Understanding Statistical Power

• Statistical power is an important concept that is not often discussed.
• Before doing an experiment, you need to have an expectation of what you believe the difference is between the groups.
• You need to determine the number of samples needed to assess whether or not that difference is there or not.
• A power table can be used to determine the number of samples needed.
• The number of samples needed depends on the expected difference, the level of significance, and the level of power desired.

Section 1: Introduction

• The video is about a journal club discussion between Andrew Huberman and Peter Attia, where they discuss two papers on Metformin and the placebo effect.
• The first paper is about the potential role of Metformin in longevity, and the second paper is about the placebo effect and how it can follow a dose response.
• The discussion covers the existing peer-reviewed research on these topics and how scientists and clinicians approach these issues.

Section 2: Epidemiology vs. Randomized Prospective Experiments

• Epidemiology and randomized prospective experiments are two different approaches to studying health and disease.
• Epidemiology is the study of patterns of disease in populations, while randomized prospective experiments are controlled studies that follow a group of individuals over time.
• Both approaches have their strengths and weaknesses, and it's important to understand their limitations when interpreting research findings.

Watch the video on YouTube:
Journal Club with Dr. Peter Attia | Metformin for Longevity & The Power of Belief Effects - YouTube