Increased consumption of fish/seafood containing long-chain omega-3 polyunsaturated fatty acids as EPA (eicosapentaenoic acid) plus DHA (docosahexaenoic acid) has long been associated with a reduced risk of various diseases and a favourable attenuation of risk factors associated with these chronic disorders. The vast majority of the numerous placebo-controlled clinical trials as published in leading medical and nutrition journals which have reported the benefits of omega-3 supplementation on these chronic disorders have employed supplements containing a mixture of EPA plus DHA. During the past few years, concentrated EPA supplements (containing predominantly EPA) have become available for controlled clinical trials and for use by both health care professionals and consumers. The purpose of the present review is to briefly report upon the findings from published clinical trials in peer-reviewed journals wherein EPA supplementation has been studied.
During the past decade, evidence has been forthcoming on the potential effectiveness of long-chain omega-3 fatty acid supplementation in those individuals with various psychiatric disorders. The strongest evidence in this field has been obtained in mood disorders where, in particular, the prevention and improvement of depressive symptoms with omega-3 fatty acids as EPA plus DHA has been reported. In some of the studies, omega-3 supplementation was provided in addition to conventional medical management (including pharmaceutical treatment).
Interestingly, extensive review of numerous clinical trials indicated that EPA may be more efficacious than DHA in treating depression. The level of supplemental EPA consumed (without DHA or with DHA amounts much lesser than the EPA) in these various studies showing benefit in those with depressive disorders has often been in the range of 1000 – 2000 mg per day over periods ranging from 4 to 12 weeks. The apparent effectiveness of supplemental EPA in depressive disorders is rather surprizing since DHA and not EPA is the major omega-3 fatty acid in the brain. However, EPA is readily taken up from the circulation into the brain and rapidly metabolized therein to bio-active products which likely contributes to its neuroprotective effects. EPA may also exhibit its beneficial effect via physiological effects that promote fuel supply to the brain. It is also known that EPA can be converted into bio-active products (including Resolvin E1) which can limit brain inflammation.
Cardiovascular Disease Protection and Management
Impressive clinical trials from Japan (referred to as JELIS – The Japan Lipid Intervention Study) have shown rather dramatic benefits of EPA supplementation (at a level of 1800 mg/day) over a period of 4.6 years in patients with elevated blood cholesterol levels. This long-term trial was performed on 18,645 patients (including both those without or with pre-existing coronary artery disease (CAD)) who were receiving pharmaceutical statin treatment for blood-cholesterol lowering. Those who had a history of CAD and were given EPA supplements had their risk of unstable angina and non-fatal heart attacks lowered by 18% and 30 %, respectively, as compared to the control group not receiving EPA. Furthermore, the sub-group of mostly disease-free patients with abnormal (elevated) levels of blood serum triglyceride levels plus low HDL-cholesterol levels and at much higher risk for CAD showed a dramatically lower risk for developing CAD (by 53 % overall) if they received the EPA supplementation. A previous article in this series has outlined some of the risk factors for CAD which are favourably affected by supplementation with long-chain omega-3 fatty acids as EPA/DHA.
There are two major trials in progress using supplemental EPA in cardiovascular care. The Reduce-IT trial is designed to determine if 4 grams (4000 mgs) daily of EPA will reduce ischemic cardiac events in patients at increased risk for cardiovascular disease who are already being treated with statins (for blood cholesterol-lowering). The EVAPORATE trial will employ statin-treated patients with elevated blood triglyceride levels to determine if 4000 mgs daily of EPA can retard the progression of atherosclerotic plaques.
Stroke recurrence is a major public health problem despite aggressive pharmaceutical interventions in those having suffered their first stroke. In addition to conventional treatment, the aforementioned JELIS trial assigned 457 stroke patients on a placebo (control) supplement and 485 patients on daily supplementation providing 1800 mg EPA per day over a 5 year period. A markedly lower stroke recurrence occurred in the EPA group ( 6.8 % of patients) as compared to those in the placebo group (10.5 % of patients).
Evidence is emerging that long-chain omega-3 fatty acids may reduce both the risk and progression of various cancers (breast, pancreatic, lung, leukemia) and particularly gastrointestinal cancer. As example, patients at high risk for colorectal cancer were subjected to endoscopic evaluation before and after 6 months of supplementation with either placebo capsules (lacking EPA) or with EPA-containing capsules providing 2 grams (2000 mgs) EPA daily. The EPA-supplemented patient group experienced an overall reduction (by 22.4 %) in polyp number and in polyp volume (by 39.6 %) whereas the polyp burden worsened in the placebo group.
Finally, population studies over several years have reported that those with higher levels of EPA in their circulation (eg., blood plasma phospholipid) had a correspondingly lower risk for all-cause mortality and received extra years of life. The lower mortality risk as found with those in the top 20 % with respect to EPA levels in the circulation was mainly due to fewer cardiovascular deaths.
There is extensive evidence from peer-reviewed publications in medical and nutrition journals that EPA omega-3 fatty acid can provide considerable benefit in the prevention and management of various chronic disorders. Many clinical trials have employed EPA supplementation as a complementary addition to standard medical treatment in these human studies. It is noted that the aforementioned benefits of EPA were reported with daily intakes that were considerably greater than the very low background dietary intakes averaging only approximately 50 mgs/person/day in North America.
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