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Abstract
A number of epidemiological/observational studies, as well as large-scale randomized intervention studies, have been conducted to provide evidence for the efficacy of ω-3 fatty acids against atherosclerotic diseases. Currently, ω-3 fatty acids are commercially available in many parts of the world containing the same active ingredients as Lotriga® (ω-3-acid ethyl esters 90 [O3AE highly concentrated ω-3 fatty acid ethyl esters, consisting of eicosapentaenoic acid-ethyl ester and docosahexaenoic acid-ethyl ester [EPA-E/DHA-E]). A recent head-to-head comparative study of O3AEE90 versus EPA-E demonstrated that O3AEE90 4g/day led to a significantly greater reduction in triglycerides (TG) than EPA-E 1.8g/day and that O3AEE90 2g/day produced comparable effects on TG to those with EPA-E 1.8g/day. While both agents were shown to be useful in lowering TG, the hallmark feature of O3AEE90, that is, the presence of the DHA-E component versus its absence in EPA-E, needs to be further examined for its clinical implications.
Financial & competing interests disclosure
I Tatsuno received lecture fees from Takeda Pharmaceutical Company Ltd, Eli Lilly Japan K.K., and Boehringer Ingelheim Japan; received research grants from Takeda Pharmaceutical Company, Johnson & Johnson K.K., and Taisho Pharmaceutical Co., Ltd; and was endowed a course at his affiliation by Fukuda Denshi Co., Ltd. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Key issues
The roles of ω-3 fatty acids in the prevention of atherosclerotic diseases have been established with the large-scale epidemiological studies, clinical outcomes trials, and meta-analyses.
Although ω-3 fatty acids were not clearly shown to be effective in the recent secondary prevention trials in patients with multiple cardiovascular disease risk factors, one reason for the failure may be that the study subjects had been heavily treated with pharmacotherapy, which may have led to reductions in the efficacy of ω-3 fatty acids against cardiac death.
A meta-analysis demonstrated that docosahexaenoic acid is superior to eicosapentaenoic acid in reducing TG, probably through the reduction of apo C-III production by regulating different hepatic transcription factors than eicosapentaenoic acid.
The potent anti-inflammatory lipid mediators such as resolvins and neuroprotectins were discovered to be produced from ω-3 fatty acids, particularly docosahexaenoic acid, at the end of an inflammatory process.
The roles of these anti-inflammatory mediators will be necessary to study in not only human atherosclerosis, but also inflammatory diseases.