Andrew Huberman· PhD
When you inhibit cholesterol synthesis, the liver says, I want more cholesterol. So it puts more LDL receptors on its surface, and it pulls the LDL out of circulation.
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The evidence is convergent. Multiple independent sources reach the same conclusion, the underlying mechanism is well-characterized, and even the field's most cautious voices treat it as worth doing.
When you inhibit cholesterol synthesis, the liver says, I want more cholesterol. So it puts more LDL receptors on its surface, and it pulls the LDL out of circulation.
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I throw a statin at you and we started to talk about this that statin is not gonna budge your LP little a particle count at all but the statins going to dramatically lower your LDL so don't have a PO little a attached to it
my understanding is that sure statins directly target HMG co-reductase but then what ends up happening is because you're not producing so much sterols you turn on an entire srebp transcriptional program right and you bring more receptors to the surface of the liver that's right more of the statin efficacy is due to the LDL clearance than the reduction of cholesterol synthesis
if you give somebody a statin which is a very potent drug to lower ldl the primary mechanism by which it does so is by increasing hepatic clearance of ldl... and yet that does nothing to offset the amount of lp little a
if you give somebody a statin which is a very potent drug to lower ldl the primary mechanism by which it does so is by increasing hepatic clearance of ldl so you have more and longer lasting ldl receptors on the liver and they're pulling those ldl out of circulation which is lowering the plasma concentration
When we, as physicians, are recommending, particularly drug treatment, we should be monitoring those particles as a primary target of treatment because they are, and particularly smaller particles give us a much better handle on therapeutic benefit of any treatment.
So we've done... Now, we've studied almost every statin and shown that the effects on smaller LDL particles, particularly the very smallest LDL particles, are blunted compared with the larger LDL.