How does berberine reduce blood lipids and cholesterol?

As mentioned in the section above, berberine activates AMPK, which (among other things) suppresses the synthesis of lipids while promoting their breakdown, leading to a net reduction of their concentration in the blood.^[1][2]

Alongside its AMPK-dependent effects, berberine additionally benefits blood lipids by increasing the abundance of low-density lipoprotein receptors (LDLR). While it doesn’t increase expression of LDLR, it does increase the stability of the mRNA transcripts that go on to become LDLR proteins, which increases the abundance of LDLR receptors in cells and increases the rate at which they remove LDL cholesterol from the blood.^[3] Additionally, berberine also lowers cholesterol by interfering with its absorption in intestines and its release into the blood.^[4]

One noteworthy thing that berberine doesn’t do is interfere with cholesterol synthesis in the body. This contrasts with the most common class of cholesterol-lowering medications, statins, which directly inhibit the rate-determining enzyme of cholesterol synthesis, HMG-CoA reductase.^[3] Because its mechanism of action is distinct from that of statins, it means berberine has potential to be useful either in conjunction with, or as a replacement for, statins. Current clinical studies on this topic, while hopeful, are still unclear, due to inconsistent findings across the body of evidence.^[5][6][7]

In a similar vein, perhaps through its influence on blood lipids (or perhaps via effects on inflammation), berberine shows some promise as an antihypertensive when used as an add-on to standard of care treatments.^[8] There are few good-quality clinical studies on this topic though, so more evidence is needed.^[9]