How Vascepa (EPA) works to lower CVD event risk...
The edited version...
The most important effect of adding 4 grams of EPA to the diet is it changes the EPA/AA ratio..AA stands for Arachidonic Acid which is an omega-6 PUFA.
Changes in the EPA/AA ratio have profound effect on the sensitivity of systemic inflammation (SI). To understand how V works you need to understand how SI works..
SI is a complex system that includes the inflammatory system and a to a degree the immune system...The system is very ancient dating back to the very first multi cellular animals. The SI is designed to protect the multi cellular animal from toxins, injuries, DNA disruptions and microbial invaders...SI does not remain at one constant level but varies its level of sensitivity and activity based on a number of factors in which diet plays the most important role.
SI is more sensitive if food is plentiful and less sensitive when food is scarce..This is logical because when food is scarce energy spent on combating potential threats must be conserved for activities needed to gather food..When food is abundant SI becomes more active. This increased sensitivity can become problematic. SI relies heavily on its ability to distinguish between self (host tissue). However the SI can and does attack host tissue sometimes when the SI sensitivity gets very high..And that results in destruction of host tissue..
The Si is not governed by any central gland...The SI system is present in every cell of the body except red cells..That is the way the design feature has to run...SI employs an arsenal of weapons no less impressive then the Pentagon..and most of these biological agents are too dangerous to be floating around in the blood stream..Inflammation needs to be limited to the areas where the the threat exists...Once its starts to go beyond that then it is no less dangerous than and outside threat..
SI is to a great degree controlled by cell membrane receptors (see The Eicosanoid System). The receptors are capable of reacting to a number of differing molecules depending on their three dimensional structure. The most important of these molecules are EPA and AA...EPA..is an omega-3 n-3 and AA is an omega-6, but both posses the correct molecular structure to interact with these cell membrane receptors. EPA and AA compete for these cell membrane receptors..A simplistic view is that if AA captures a receptor the result is to increase the sensitivity of SI and if EPA captures a receptor it tends to lower SI...This is called competitive inhibition..So when you add EPA to the diet it raise the blood EPA levels and increase the EPA/AA ratio if the AA levels are not increased...Higher EPA levels decrease the sensitivity and Activity of SI...And this has a profound effect on every cell in the body.. including platelets..
High CVD event risk is mainly a problem created by increased SI sensitivity..All the other the other factors including LDL-C, trigs, sugars...risk factors like high blood pressure, smoking...obesity are just "puppets"...It is SI that is pulling the strings..even though most people, including doctors, don't know the science...The science is very strong...
Insulin Resistance (IR). Is the root problem in T2DM.. Scientists have established that IR is caused by elevated SI..That means T2 diabetes is directly caused by elevated SI. T2 Diabetics are known to be at significantly higher risk for CVD events tha non diabetics with otherwise matched risk factors. How does IR increase CVD event risk? The answer is that IR lowers insulin's ability to lower blood sugar which causes effected individuals to increase insulin production to get the sugar to normal levels..A problem arises however because insulin has effects other than just lowering blood sugar efficiently as it should be...so the body starts making more insulin..The problem is that insulin has other actions that don't involve sugar lowering...Insulin also accelerates the synthesis of AA and that further increases SI..Creating a viscous cycle.
The same thing happens in patients with elevated trigs...The problem there is not insulin, but another enzyme which has insulin like effects on trigs. The enzyme is Fatty Acid Synthase(S) which controls trig levels the same way that Insulin controls blood sugar levels, The interesting fact is that FAS's activity is also lowered by elevvated SI like and this cause elevatin if blood trigs,, That is why elevated trigs are a marker for increased DSI and increase CVD event risk..And also explains why if you do not lower trigs by lowering SI you get very little benefit from the trig lowering.. ..
Elevated SI has many direct effect when it comes to the heart and blood vessels...Elevated SI means higher inflammation at the blood vessel lumen where oxidized lipoproteins meet the endothelium and start the whole plaque process..Without inflammation the plaques are very limited inn their ability to create catastrophic events as they do when inflammation makes them pop like a pimple and spill their highly inflammatory contents into the circulation...Increased inflammation means greater platelet activity which means greater platelet adhesion..
High SI also very likely increases the amount of damage caused by ischemia...Of note is the amazing lowering of ischemic strokes seen in RI..31% RRR...This means fewer ischemic events...but also means that lowering SI likely decreases the zone on injury in the brain and turns minor CNS ischemic interruptions into non events..
When asked how EPA works to create the amazing clinical benefits seen in R-I...The answer is very simple....It increases the EPA/AA ratio...and if you don't believe that...Then you need to study the Japanese population and their EPA/AA ratios and their CVD event risk...
"":>) JL
