Amarin Corp Plc (AMRN)

[jessellivermore]

mars..raf and other theorists...

We need to take the Pyrr/KIWIan conjecture seriously...That is, will these superstatin doses take a bite out of the Vascepa's rate reductions...

I have been doing a lot of serious thinking about this question which was raised in 2009...by the AHA after the JELIS trial...Would higher statin doses have reduced the RRRs and since we do have higher statin doses in R-I are they going to derail the train...

It goes to the issue of how similar are the statin effects to the EPA effects...Especially in regards to systemic inflammation (SI)..If statins can do EPA's job and does do EPA's job then maybe EPA is not needed...

Fortunately, I concluded..not based on some article, but from own deduction that statins act in method that is not tangential to EPA's mode of action and believe the statin effect on the RRRs will be quite minor...

We know how EPA lowers SI via cell and nuclear membrane receptors which are present in all cells except RBCs..We know that statins have no such receptors...So there must be another mechanism.

I have concluded that cholesterol behaves in a fashion similar to blood sugar (BS) and triglycerides. BS and trig levels elevations in T2DM and triglyceridemia are not caused by excess intake...If a patient with T2DM does not take his medication and eats the same amount of sugar I do...the T2's blood sugar will rise higher than mine (I do not have TDM)...This increase BS rise is not caused by greater sugar intake; but happens because his insulin is not removing the sugar from the blood and storing it in the fat tissue...like mine is...The same thing is seen in high trigs...it's not the dietary intake..its the inability to remove the trig which are made in the liver and then convert that into FFAs that can be stored..The root cause in both these situations is elevated SI which lowers the activity of insulin and FAS.

I believe the same thing holds for cholesterol. Another fat...Cholesterol(C) like trigs can be consumed or made in the liver...The body is very intelligent and once it comes up with a good idea it sticks with it..So if it works for carbs and trigs why wouldn't it work for C..There is probably an enzyme which converts excess cholesterol to some form of FA that allows it to be stored in the fat tissue.. When that enzyme slows down...then blood C levels start to go up just like sugar or trigs...And this enzyme is probably slowed down by elevated SI like the others.

Statins don't work the same way to lower C the way the body's own processes do. Which is to facilitate the conversion to FFAs that can be stored.

No, statins lower cholesterol by inhibiting the production of C in the liver..rather than facilitating their removal from the blood stream and storing them in the fat tissue..So statins attempt to by pass the the problem which is related to high SI...

Statins do lower SI but only in a restricted capacity..Unlike EPA's which effects all cells..statins lower SI by decreasing the LDL-C particle counts. LDL the carrier lipoprotein interfaces with the endothelium (the vessel lining).and this can result in oxidation. Oxidation being inflammatory by its very nature...So by lowering LDL-C particles statins lower inflammation...But this is only a local effect...That is why statins don't relieve extra vascular conditions like DES...

The important thing about this is it suggests the crossover effect between statins and EPA will not be very great...and we should hold our higher RRRs...EPA because it lowers SI should also increase the extent that C is removed from the blood stream and this explains why EPA alone can lower trigs and not raise LDL-C...The simple explanation being that lowering SI
promotes the body's ability to remove the cholesterol and store it in the fat tissue...And this fact actually will cut the dose needed for statins...

The inescapable conclusion is that EPA can replace the need for statins as it corrects the root problem which is elevated SI and statins don't...

All this represents my own thought processes and you will not find it in a journal or a textbook...

":>) JL