The roles of specific dietary fatty acids with respect to general health and atherosclerotic cardiovascular disease (ASCVD) have been thoroughly elucidated. It has been long acknowledged that omega-3 polyunsaturated fatty acids (omega-3s) can have prominent roles towards attenuation of hyperlipidemias, inflammation and ASCVD. With pharmaceutical competition in the “fish oil” market, specific prescriptive (Rx) omega-3 formulations are recommended over now taboo high quality fish oil products.
Much epidemiologic data indicate that consumption of oily fish or fish oil appears to promote general health and decreased incidence of cardiovascular disease. Many, but not all, large randomized controlled trials indicate beneficial effects of fish oils in patients with prior coronary artery disease, stroke, or major vascular events. Omega-3s decrease the levels of VLDL TG, cholesterol and apoB via lower hepatic secretion and enhanced clearance (lipolysis).
Hypercholesterolemia with elevated LDL-C has been long held as the primary lipid risk factor for ASCVD, but small dense LDL (sdLDL) and oxidized LDL (oxLDL) have emerged as the more granular lipoprotein culprits. Statin drugs certainly increase LDL (apo B) clearance, appear to have vascular protective anti-oxidant effects, and may contribute to decreased hepatic synthesis and secretion of apo B. However, statins have very little if any impact on sdLDL since they don’t effectively lower plasma TG.
Cold water fish oils are rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and ethyl esters and carboxylic acid forms of those omega-3s have recently been developed as drugs. Highly purified Rx omega-3 formulations at doses of 4 g/day 9 (EPA+DHA, ethyl esters) have recently been recommended for significant reduction in plasma TG, and further reduction in plasma cholesterol for patients on “moderate high intensity” statin therapy. However based on recent pharmaceutical trials, superiority has been touted for an EPA only formulation. That suggestion is tenuous and inconsistent with a crossover study in which 2.7 gm/day EPA verses DHA were given for 10 weeks. Both EPA and DHA markedly lowered plasma TG, but DHA actually elicited greater lowering of sdLDL, and increased turnover of LDL (apoB). Further, the DHA only formulation did not significantly increase LDL-C as propagated in the literature. Regardless of hypolipidemic effects, combined Rx EPA+DHA formulations have been reported to be associated with statistically increased atrial fibrillation (vs. corn oil). It should be noted that all of the Rx omega-3 clinical trials included only patients with high (>200 mg/dL) to very high (500-1,500 mg/dL) plasma TG, and almost all patients were taking statin drugs.
An abundance of patients today present with metabolic inflexibility, excessive visceral adiposity and Metabolic syndrome- without familial hyperlipidemia. In those conditions, elevated plasma free fatty acids are associated with moderately elevated plasma TG levels due to increased hepatic TG secretion and compromised TG clearance. Traditional use of high quality fish oil, along with lifestyle changes, and perhaps niacin, have great potential for attenuating such hypertriglyceridemia and dyslipoproteinemia. However, for patients with more severe hyperlipidemias despite non-pharmaceutical intervention and statin therapy, an Rx omega-3 product might be appropriate. Currently it seems extreme to advise against use of high quality fish oil, or Rx omega-3 preparations containing both EPA and DHA.