Berberine's interesting. Like Metformin, it's a mild ECT poison (not sure if it's complex 1 like Metformin, but probably) resulting in that boost of AMPK (changed ATP/ADP ratio). But it's also a mild PCSK9 inhibitor. PCSK9 is an enzyme your liver cells use to 'turn over' LDL receptors, end result being you have more receptors and so fewer LDL particles. It's unclear how this affects the different kinds of LDL (the large/buoyant are not an arteriosclerotic risk, the small/dense are). Everything I've seen indicates that it works the same on both (and maybe chylomicron remnants).

If you've got a high LDL particle count that seems resistant to changes in diet or statins (don't start me on the downsides of statins), it's worth at least trying Berberine to see if it sorts the issue.

I've also seen that Metformin reduces the positive effects of exercise (in the sense of increasing both muscle mass and per-cell average mitochondrial flux). Nothing so far on Berberine, but it probably does the same. There's a workaround for Metformin - at least for people not taking it for glucose control. Take advantage of its approx. 6.2 hour half-life, let it wash out overnight, exercise before pills. Again, I've seen nothing on the half-life of Berberine, just a vague "several hours" on healthline, which I wouldn't rely on, but it might be safe to assume 6-ish hours.

Just a thought.