Qualy #52 - Insights about berberine

**Peter Attia** (0:05)
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Insights about Berberine. So berberine is a plant-derived extract that has two properties, one of which it gets a lot of attention for, one of which it might not be as well known. The first is that it is a weak AMP kinase activator.
And for those of you that have shown an interest in what metformin does, that's sort of the, that's probably the secret sauce of metformin, is its AMPK activation.
So berberine, when taken at sort of recommended OTC doses, which I don't even remember the doses anymore. I think it's like a, it might be actually a comparable dose to metformin. It might be like either 500 twice a day or 1,000 twice a day. It does have some of that weak AMPK activation. And what that, the net effect of that is it decreases hepatic glucose output.
So it's upregulating AMPK is telling the liver, hey, you can make less glucose. So send less glucose out of the body.
And so in that sense, it's a poor man's version of metformin. I don't find that that interesting. I prefer to just use metformin. If we're gonna go down that path, like let's do it pharmacologically with potent drugs that we understand that are consistent from batch to batch that have a much higher sort of oversight of regulation and that kind of stuff. The other thing about berberine, and this is when I still do use it in clinical practice, is it is also a weak inhibitor of the enzyme PCSK9, which any listener of this podcast is gonna be very well up to speed on what PCSK9 is. The word on the street is it probably only works in a subset of people who overexpress PCSK9. So if you, so PCSK9 is a protein that degrades LDL receptors. So if you overexpress this enzyme, you're gonna really degrade LDL receptors. You're gonna have a higher LDL particle number and probably a higher LDL cholesterol.
If you take that subset of patients, they seem to respond quite nicely to berberine. Now the question is, how do you know that? I don't think there's a test anymore to measure that. Atheritech, which I think might have got absorbed into VAP or something like that, I think used to have a test. But in the end, I was like, why am I gonna do some test on somebody to see if they over-express PCSK9 before I give them berberine? I'll just give them berberine, make no other change, and see if there's not a significant enough difference in their LDL, I don't care. And every once in a while, you look like a rock star. You get this patient whose LDL is really high, and you check your boxes. Like, their triglycerides aren't that high, their phytosterols are not that high, their stanols are not that high, their dysmosterol is not that high. Hey, they clearly have defective LDL clearance. Maybe they over-express PCSK9, which would be one of 1,000 reasons you could have high. Like, literally, there are 2,000 genetic mutations that can lead to an inability to clear LDL receptors. This is like one of them, but this one amounts to about 5% of them. And so in that patient, you hit them with berberine, and all of a sudden, like, everything's fixed. Do you see that with metformin at all? No, no, I don't think metformin possesses that piece of what berberine has. I hope you enjoyed today's Qualy.
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