270 ‒ Journal club with Andrew Huberman: metformin, power of belief, & how to read scientific papers

Bannister Study

Peter Attia and Andrew Huberman discuss the 2014 Bannister study, which sparked significant interest in metformin's potential as a geroprotective drug. Peter explains that the study used a registry from the UK to compare patients with type 2 diabetes on metformin to matched controls without diabetes. This study's methodology and its impact on the anti-aging community are highlighted.

This is almost ten years ago, and I'm sure many people have heard about this paper, even if they're not familiar with it, but they've heard the concept of the paper. And in many ways it's the paper that has led to the excitement around the potential for gero protection with metformin.

--- Peter Attia

The discussion also touches on the limitations of the study, such as informative censoring, which excluded patients who deviated from the inclusion criteria 1 2.

   

Statistical Methods

The episode delves into the statistical methodologies used in metformin studies, including the importance of understanding error bars and statistical power. Andrew Huberman emphasizes that overlapping error bars do not necessarily indicate a lack of significance, and Peter explains the concept of statistical power and its role in determining sample sizes.

Before you do an experiment, you have to have an expectation of what you believe the difference is between the groups, and you have to determine the number of samples you will need to assess whether or not that difference is there or not.

--- Peter Attia

They also discuss Kaplan-Meier curves, which are used to visualize mortality rates over time, and the complexities involved in interpreting these curves 3 4.

   

Geroprotection

Peter and Andrew explore the potential geroprotective benefits of metformin, referencing both epidemiological and animal studies. Peter mentions the TAME study, which aims to provide more definitive answers about metformin's impact on aging. He also shares his personal experiences with metformin and its effects on his exercise performance and lactate production.

If the Tame study ends up demonstrating that there is a geroprotective benefit of metformin I'll reconsider everything, right?

--- Peter Attia

They also touch on other drugs like rapamycin and 17-alpha estradiol, which have shown promise in extending lifespan in animal studies 5 6.

   

Health Metrics

The discussion shifts to how metformin affects various health metrics, including glucose levels, lactate levels, and liver function. Peter explains how metformin impacts lactate production, sharing his observations of elevated lactate levels during exercise.

If you have a weak mitochondrial toxin, what are you going to do? You're going to shunt more glucose into pyruvate and more pyruvate into lactate? I'm anaerobic.

--- Peter Attia

They also discuss the complexities of epidemiological studies and how mortality rates are calculated and normalized 7 8.