Timing metformin to avoid negative effects on exercise adaptation: plausibility | Rhonda Patrick

Yeah. Do you think this is something where eventually, you know, we— because we do want this activation of AMPK, right? That's a positive thing. So here's the thing. So activation of AMPK— Can we pulse it? So the activation of— so here's the thing. That's the question, right? Well, what if you time your metformin, right? There's things to consider other than the half-life of metformin or, you know, the important thing is— so for example, exercise activates AMP kinase. The activation is relatively transient, but the effects of exercise last about 48 hours. Metformin activates AMP kinase and the effects of metformin last about 36 hours after the last dose. So is it the AMP kinase activation that's responsible for these effects? We don't even know. Like that's not even— it's not even known.

Or how long is the complex I inhibition lasting after you take your last dose? Is that also 36 hours after? We don't know. They're open questions, right? Right. Not to mention that there was just, I don't know, a couple of months ago, another randomized double-blind controlled trial showing metformin. This was also in healthy adults that were doing resistance training, and they were older adults. Both of these studies were older adults, 65, you know, age 65 years and older. But this study also showed that after 14 weeks of taking about 1,700 milligrams of metformin, which is quite high, that it— and this gets back to your friend's anecdote— the participants that took the placebo gained more lean muscle— lean body mass and also thigh muscle mass compared to those who took metformin.

So metformin blunted some of the gains in muscle mass. Right. It also diminished the strength, but those results were not significant, statistically significant. So it's trending towards your friend's anecdote, what he— what he found with his power and output and stuff.