By now, you've probably noticed that I'm a bit anti-statin. The "problem" with statins is that they reduce cholesterol synthesis in the liver by reducing the conversion of HydroxyMethylGlutarate (HMG) Co-enzyme A (CoA) into Mevalonate by inhibiting the enzyme HMG CoA reductase.
Reducing Mevalonate reduces lots of other things e.g. Coenzyme Q10 synthesis, terpenoid synthesis, protein prenylation, cell membrane maintenance, hormones, protein anchoring, N-glycosylation and steroid biosynthesis which leads to cholesterol synthesis. Paradoxically, although cholesterol synthesis is reduced, Vitamin D level is increased. See also Atorvastatin increases 25-hydroxy vitamin D concentrations in patients with polycystic ovary syndrome.
Some of the above changes are undesirable in terms of all-cause mortality, so what would be ideal is a drug that just reduces serum cholesterol without doing anything else. Enter....Squalestatin a.k.a. Zaragozic Acid. This reduces the conversion of Farnesyl Pyrophosphate into Squalene by inhibiting the enzyme Squalene synthase. This has no effect on Mevalonate, or any of the substances listed in the above paragraph. Perfect!
A Squalene synthase inhibitor called Lapaquistat (a.k.a. TAK-475) was developed and tested by Takeda Pharmaceutical Company Limited in 2008. So, why is this wonder drug not on the market today? According to Limited press release - Discontinuation of Development of TAK-475, A Compound for Treatment of Hypercholesterolemia:- " the profile of the compound is not superior to existing marketed drugs from both efficacy and safety viewpoints".
So, just reducing serum cholesterol without changing anything else is not superior to reducing serum cholesterol and changing loads of other things. Maybe statins reduce CHD mortality a bit because they change loads of other things, not because they reduce serum cholesterol. See Rosuvastatin to Prevent Vascular Events in Men and Women with Elevated C-Reactive Protein.
Statins are anti-inflammatory. So is Vitamin D3. I'd take Vitamin D3 instead of statins any day.