Amarin Corp Plc (AMRN)

[jessellivermore]

What was obvious, is obvious, and why it was not obvious..and still is not easily understood..and while Singer's work is excellent on legal basis it does not actually explain the why EPA's actions were so unexpected...

First the facts..

Fact 1) Triglycerides (trigs) are a fraction of the blood lidids..they are three fatty acid chains tied together by a glycerol molecule...and as such are the main source of the bodies fuel..Even though diet and liver synthesis (trigs are synthesized by the liver) can increase blood trig levels..Trig levels are mainly controlled by the rate they are removed from the blood stream...From a clinical standpoint when and if a patient has high trigs..it is not because he is eating too many fats its because he can not dissolve the trigs out of his blood stream and store them in his body fat...

Fact 2)..All fats are lipids and not soluble in aqueous solutions like the blood...Therefore they must be transported in lipoproteins that have a polar external surface and a non polar internal surface..The lipoprotein which carries pricipally trigs is the Very Low Density Lipoprotein (VLDL) fraction. The VLDL fraction also carries some LDL-C and as such is defined principally by the cargo it carries..The confusion here is created by the fact that if the VLDL particle loses a significant fraction of its trigs.(50%) then it is no longer a VLDL particle, but is converted into a LDL particle..And this is why lowering trigs in most cases results in an increase in LDL particles..

Fact 3)..There is an equation (The Friedewald Equation) which defines the correct ratios of the main lipid components of the blood..The Friedewald equation has been determined in large clinical studies (30 thousand patients) to very accurate although it does require some changes in the constant at very high trig levels..

The Friedwald Equation says LDL = TotalChol - (Triglycerides / 5) - HDL

From this very simple algebraic formula we can see that if all other parameters remain constant then lowering the trigs by any method should cause an increase in LDL. LDL being a well known risk factor now and back in the early 2000s it seems obvious that if EPA lowered the trig level it must increase the LDL...The fact it did not was anything but obvious and is still not obvious 20 years later...it is a mystery to most..

The reason why EPA could lower Trig levels and not raise LDL could be because EPA lowers Trigs by lowering Systemic Inflammation (SI)..As noted earlier trig levels are controlled mainly by the rate trigs are removed from the blood stream and not by the rate they are introduced into the blood stream and this is very similar to how blood sugar levels are controlled by the body..

In type 2 Diabetes...the root problem is the patient's insulin is not very efficient at removing sugar from the blood stream..A situation called "Insulin Resistance" (IR)..It is a proven fact that IR is the direct result of elevated SI...Elevated trigs result in a similar fashion to those seen in the blood sugar in t2DM because the enzymes that expedite the removal of trigs from the blood (Fatty acid synthases) (FAS) are effected by elevated SI in the same way Insulin is effected in T2DM...In both cases the culprit is elevated Systemic Inflammation..So elevated blood sugar in T2DM is a marker for elevated SI and elevated trigs are also a marker for SI..And as we on this board understand elevated SI is what causes the events in Cardiac and vascular diseases..

So there was no obviousness about the Marine results back in 2010..Ten years later and it is still a puzzle..Lowering trigs and not significantly rising LDL-C..should not be possible..Most likely there is a statin like effect resulting from the lowering of SI..

Du and even Fisher and certainly the other judges are way over their heads on these issues. There was no obviousness and still no obviousness.
Mother medicine can hold on to her secrets..The questions never change..only the answers...

":>) JL