E-EPA reduces cardiovascular disease risk factors in diabetics

E-EPA reduces cardiovascular disease risk factors in diabetics

Ethyl esterified eicosapentaenoic acid (E-EPA, 1.800mg/day) reduces newly discovered risk factors of cardiovascular diseases in men and women with metabolic syndrome. These risk factrors are: small dense low density lipoprotein (sdLDL), remnant lipoprotein particles, and C-reactive protein. The new findings were reported by Japanese scientists (Kyoto Medical Center and Tokyo Medical and Dental Hospital) in Diabetes Care (January 2007). These observations confirm earlier studies suggesting that diabetics may benefit from E-EPA as dietary supplement.

The doctors sought to determine whether EPA has an effect independent of DHA on lipoprotein subclass profiles and inflammation individuals with metabolic syndrome, a precursor of cardiovascular disease (CVD).

The study included 44 type 2 diabetics with the diagnostic criteria of the metabolic syndrome. Participants were divided to receive a standard diet designed for cardiovascular disease, or diet plus 1.800mg E-EPA daily for three months. Body mass index, serum EPA and arachidonic acid (AA, an omega-6 fatty acid associated with inflammation) levels, remnant lipoprotein particle cholesterol and triglycerides, plasma cholesteryl ester transfer protein (CETP) activity, LDL cholesterol subfractions, and C-reactive protein were measured before and after the treatment regimen.

At the conclusion of the study, serum EPA levels were elevated while arachidonic acid levels were decreased in the group that received E-EPA. In other words, the AA/EPA ratio improved. Remnant lipoprotein triglycerides, CETP activity, small dense LDL, and CRP levels were significantly lowered in the group that received EPA compared to the group treated by diet alone. Decreases in in CRP were correlated with reductions in remnant lipoprotein cholesterol and small dense LDL.

"The present study is the first to demonstrate that purified EPA reduces sdLDL, remnants, and CRP, thereby potentially leading to the reduction in development of atherosclerosis and CVD in metabolic syndrome," the authors conclude.

Satoh N, Shimatsu AS, Kotani, K et al. Purified Eicosapentaenoic Acid Reduces Small Dense LDL, Remnant Lipoprotein Particles, and C-rective Protein in Metabolic Syndrome Diabetes Care 2007;30: 144-146 [Abstract]

The intima (the inner wall) of the arteries gets thick and stiff impairing the blood circulation and may cause a total obstruction. Regular intake of E-EPA (1.800mg/day) seems to stop the process and reverse it. E-EPA antagonizes – in addition to the above mentioned risk factors – the neurohormonal substance endothelin, which conbtributes to the thickening and stiffening of the arteries (more).

E-EPA protects the diabetics´ arteries

E-EPA protects the diabetics´ arteries

Stiffening and thickening of the arteries and heart failure are frequent complications in diabetes. Latest research sheds light on the biochemical mechanism of these changes and on the other hand illustrates that a fatty acid found in fish oil, EPA, fights effectively these pathological alterations.

One of the main culprits in arteriosclerosis seems to be a neurohormonal mediator called endothelin (ET). It is a protein excreted by the cells in the inner lining, called endothelium, of the arterial walls. Unfortunately insulin – administered to all type 1 diabetics and many type 2 diabetics – stimulates excessive production of ET. Its overproduction results in dramatic structural changes in the blood vessels, including inflammation, vasoconstriction and thickening of the arterial wall causing arterial disease, elevated blood pressure and heart failure.

Arteriosclerosis. The intima (the inner wall) of the arteries gets thick and stiff impairing the blood circulation and may cause a total obstruction. Regular intake of E-EPA (1.800mg/day) seems to stop the process and reverse it. E-EPA antagonizes the neurohormonal substance endothelin, which is cause the thickening and stiffening of the arteries.

Scientists have looked into this problem and found that a fatty acid present in fish oil, EPA, antagonizes the hazardous effects of ET (Shimojo et al 2006). A Japanese research team showed recently that supplementation with a special EPA product called E-EPA (1800 mg/day) not only prevented but even reversed the pathological alterations observed in the carotid arteries of type 2 diabetics (more). The explanation lies probably by EPA´s capacity to fight endothelin.

A recents Swiss study suggests that altered activity of retinal endothelin-1 (ET-1) and nitric oxide may play a causal role in the hemodynamic and histopathological changes of diabetic retinopathy (Shaw et al 2006). These new studies give an impetus to recommend E-EPA as a dietary supplement for all diabetics irrespective of the diet and health status.

Shimojo N, Jesmin S, Zaedi S et al. Effect of eicosapentaenoic acid on the different endothelin system components in endothelin-1-induced hypertrophied cardiomyocytes. Exp Biol Med (Maywood) 2006 [PubMed]

Shaw, SG, Boden JP, Biecker E et al. Endothelin antagonism prevents diabetic retinopathy in NOD mice: a potential role of the angiogenic factor adrenomedullin. Exp Biol Med (Maywood). 2006;231(6):1101-5 [PubMed].

You may read more about endothelin at
http://www.endothelinscience.com/
and view a short video at http://www.endothelinscience.com/era.cfm#playVideo

E-EPA reverses arteriosclerosis in type 2 diabetes

E-EPA reverses arteriosclerosis in type 2 diabetes

A Japanese study shwes that progress of arteriosclerosis in persons with type 2 diabetics can be stopped and reversed by taking daily 1.800 mg E-EPA – a novel fish oil preparation. These sensational results were published in the 5th April 2006 issue of the journal Athrerosclerosis.

The researches at the Department of Medicine, Metabolism and Endocrinology, Juntendo University School of Medicine (Tokyo , Japan) investigated the effect of highly purified eicosapentaenoic acid (E-EPA) on the progression of hardening of the arteries (diabetic macroangiopathy), in an open-label randomized prospective trial.

A total of 81 Japanese type 2 diabetes were randomly assigned to the EPA (1.800mg/day) treated group or the control group. Carotid intima-media thickness (IMT) and brachial-ankle pulse wave velocity (baPWV) were evaluated before and after treatment in both groups. Sixty patients (EPA group, n=30; control group, n=30) completed this study.

During the study period of 2.1 years, the mean IMT and max IMT of the EPA treated group showed a significant annual decrease compared with that of the control group*. The baPWV was also improved significantly in the EPA treated group compared with the control group**. Multiple regression analysis showed that the administration of E-EPA was a significant and independent factor associated with an annual improvement of mean IMT (R(2)=0.067).

In summary, this is the first demonstration that administration of purified EPA improves the carotid IMT and the baPWV in patients with type 2 diabetes.

* Mean IMT decreaes in the E-EPA group by -0.029+/-0.112mm versus 0.016+/-0.109mm, in the control group, respectively, P=0.029;
Max IMT decreased in the E-EPA group by -0.084+/-0.113mm versus -0.005+/-0.108mm in the control group, respectively, P=0.0008).

**baPWV decreased in the E-EPA group by -22.1+/-127.9cm/s versus 62.3+/-223cm/s in the control group, respectively, P=0.021).

Arteriosclerosis. The intima (the inner wall) of the arteries gets thick and stiff which impairs the blood circulation and may cause a total obstruction. Regular intake of E-EPA (1.800mg/day) seems to stop the process and reverse it. E-EPA antagonizes the neurohormonal substance endothelin, which is causes the thickening and stiffening of the arteries.

Mita T, Watada H, Ogihara T et al. Eicosapentaenoic acid reduces the progression of carotid intima-media thickness in patients with type 2 diabetes. Atherosclerosis. 2006 Apr 5;[PubMed]

Images of carotid artery (Wikipedia)
Ultrasound method described (Wikipedia)

Dr Tolonen´s comment
The results are most interesting, as arterisclerotic changes have not been considered reversible but rather proggessive. The results in absolute figures of this study are even more convingeing than just the statistical significance. Regular intake of relatively large daily dose (1.800mg) E-EPA seems to improve the considerably the prognosis of diabetic angiopathy (blood vessel disease). The explanation lies probably by EPA´s capacity to fight endothelin (read study report).

E-EPA has been prescribed in Japan for complementary treatment of diabetes for more than ten years, and it has been shown to protect against diabetic nephropaty (kidney damage) (Shimizu et al. 1995). Recently world´s largest fish oil study – the Japanese JELIS – indicated that supplementation with E-EPA (1.800mg/day) significantly recudes cardiovascular mortality and morbidity in people who are taking statins (anticholesterol medication). E-EPA seems to exert its beneficial effects in the arteries partly by improving the lipid profile and partly by supressing chronic low-grade inflammation.

"Carotid intima-medial thickness measurements have been proven to provide incremental data to traditional risk prediction based on clinical data. It is the only imaging test recommended by the American Heart Association for this purpose."
- President, American Heart Association

Shimizu H, Ohtani K, Tanaka Y, et al. Long-term effect of eicosapentaenoic acid ethyl (EPA-E) on albuminuria of non-insulin dependent diabetic patients. Diabetes Research and Clinical Practice 1995;28(1):35-40 [PubMed]