Replies to post #102419 on Amarin Corp Plc (AMRN)

[Flounderguy]

JL, I can only respond with an anecdotal response. My trigs in Jan. of 2016 were at 337. After only three months of V and a slightly better diet, my trigs fell to 78. Along the way I realized that my plantar fasciitis in my left heel went away. Along with the heel relief I also noticed a resumption of "morning hellos". This all came about within four weeks of being on the 4gms a day regime. Reading this board and using V has literally saved my life. So I would like to thank all the naysayers as well as all the scientific reporting and truth telling by a few on this board. I look forward to meeting all of the men and women here who have made a profound effect in my health. My son and I can not thank you enough. All the in fighting amongst the board members is unnecessary, but highly informative

[Pyrrhonian]

EPA vs DHA on Systemic Inflammation, etc

Have to chime in one more time on this one...

EPA acts to lower systemic inflammation and DHA does not and therefore EPA is much more effective in lowering CVD risk.. --JL

I know you are an advocate of the Zone diet, but not everything Dr Sears says is true. DHA is actually better than EPA at reducing markers of systemic inflammation. You are once again completely wrong.

Randomized, crossover, head-to-head comparison of EPA and DHA supplementation to reduce inflammation markers in men and women: the Comparing EPA to DHA Study1,2,3

Background: To date, most studies on the anti-inflammatory effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in humans have used a mixture of the 2 fatty acids in various forms and proportions.

Objectives: We compared the effects of EPA supplementation with those of DHA supplementation (re-esterified triacylglycerol; 90% pure) on inflammation markers (primary outcome) and blood lipids (secondary outcome) in men and women at risk of cardiovascular disease.

Design: In a double-blind, randomized, crossover, controlled study, healthy men (n = 48) and women (n = 106) with abdominal obesity and low-grade systemic inflammation consumed 3 g/d of the following supplements for periods of 10 wk: 1) EPA (2.7 g/d), 2) DHA (2.7 g/d), and 3) corn oil as a control with each supplementation separated by a 9-wk washout period. Primary analyses assessed the difference in cardiometabolic outcomes between EPA and DHA.

Results: Supplementation with DHA compared with supplementation with EPA led to a greater reduction in interleukin-18 (IL-18) (-7.0% ± 2.8% compared with -0.5% ± 3.0%, respectively; P = 0.01) and a greater increase in adiponectin (3.1% ± 1.6% compared with -1.2% ± 1.7%, respectively; P < 0.001). Between DHA and EPA, changes in CRP (-7.9% ± 5.0% compared with -1.8% ± 6.5%, respectively; P = 0.25), IL-6 (-12.0% ± 7.0% compared with -13.4% ± 7.0%, respectively; P = 0.86), and tumor necrosis factor-a (-14.8% ± 5.1% compared with -7.6% ± 10.2%, respectively; P = 0.63) were NS. DHA compared with EPA led to more pronounced reductions in triglycerides (-13.3% ± 2.3% compared with -11.9% ± 2.2%, respectively; P = 0.005) and the cholesterol:HDL-cholesterol ratio (-2.5% ± 1.3% compared with 0.3% ± 1.1%, respectively; P = 0.006) and greater increases in HDL cholesterol (7.6% ± 1.4% compared with -0.7% ± 1.1%, respectively; P < 0.0001) and LDL cholesterol (6.9% ± 1.8% compared with 2.2% ± 1.6%, respectively; P = 0.04). The increase in LDL-cholesterol concentrations for DHA compared with EPA was significant in men but not in women (P-treatment × sex interaction = 0.046).

Conclusions: DHA is more effective than EPA in modulating specific markers of inflammation as well as blood lipids. Additional studies are needed to determine the effect of a long-term DHA supplementation per se on cardiovascular disease risk.

http://m.ajcn.nutrition.org/content/early/2016/06/01/ajcn.116.131896.abstract

Literally EVERYTHING was better with DHA alone. Maybe this is because more of it is almost always present in fish. We've evolved to benefit from eating fish, which of course has loads of DHA.

Also it would help validate your statements greatly if you could quote peer reviewed sources and provide links like I do. No one's word is bond, not even a judge in a courtroom. And especially not a random in a chat room.

Let's recap, and add this one in with the other observations made previously:

DHA is beneficial for one's health, and should not be omitted from fish oil just because of LDL-C worries. It is the fatty acid responsible for lowering blood pressure (BP) and resting heart rate (HR), interfering with oxLDL uptake by macrophages, interfering with LDL synthesis, increasing LDL particle size and decreasing LDL-P concentration (far more implicated in MACE than LDL-C), increasing HDL-C and especially HDL2, and is much better than EPA at lowering VLDL-C. It is also better than EPA at reducing markers of systemic inflammation. Lastly, DHA has no effect on fasting glucose levels.

EPA taken alone on the other hand has no effect on BP or HR, has modest lowering effects on LDL-C at doses of 4g/d (although the above study showed it increased LDL-C slightly at the same dose), may decrease LDL particle size (atherogenic), increases oxLDL uptake by macrophages, decreases HDL-C and especially HDL3, and increases fasting glucose levels in T2Ds. And is worse than DHA at reducing markers of systemic inflammation.

(see: https://investorshub.advfn.com/boards/read_msg.aspx?message_id=129440107 )

So I do not think it wise to take 4g/d EPA only. Or any dose of EPA only. Risk reduction is apparent when peoples cut back on atherogenic foods and replace them with cardio-protective foods (this is even true of LA containing foods). Replacing mammalian meats and dairy with non-fried fish is clearly cardio-protective, and of course lots of DHA and DPA etc are naturally present in the fish along with EPA.

This over-focus on LDL-c imo misses the forest for the trees.

Lastly, even with DHA, it appears that isolated fish oils at higher doses (4g/d+) have mixed benefit. Although lipid profiles improve, there are a number of atherogenic markers that increase, including TBARS and decreased serum vit E.

One placebo-controlled study of around 300 subjects that tried a dose of 4g/d n-3 failed, and actually showed a trend towards increased MACE risk in fish oil group:

http://ajcn.nutrition.org/content/74/1/50.long

The authors (experienced cardiologists) hypothesized that, among other possibilities for the failure, optimal dose statins and low dose aspirin may "mask the potential of n-3 to show benefit." And so what is left is the potential harm, which they also hypoethsized may result due to increased lipid peroxidation at high dosages.

Net net, I think REDUCE-IT will overwhelmingly fail (and I haven't even touched on dropouts going on fenofibrate or OTC n-3 while remaining ODIS). But I hope I'm wrong. It would be a nice consolation for losing money on my future short positions if that happens.

Cheers