Prescription omega-3 fatty acids and their lipid effects: physiologic mechanisms of action and clinical implications

Expert Rev Cardiovasc Ther. 2008 Mar;6(3):391-409. doi: 10.1586/14779072.6.3.391.

Abstract

Hypertriglyceridemia is a risk factor for atherosclerotic coronary heart disease. Very high triglyceride (TG) levels (> or =500 mg/dl [5.65 mmol/l]) increase the risk of pancreatitis. One therapeutic option to lower TG levels is omega-3 fatty acids, which are derived from the oil of fish and other seafood. The American Heart Association has acknowledged that fish oils may decrease dysrhythmias, decrease sudden death, decrease the rate of atherosclerosis and slightly lower blood pressure, and has recommended fish consumption or fish oil supplementation as a therapeutic strategy to reduce cardiovascular disease. A prescription omega-3-acid ethyl esters (P-OM3) preparation has been available in many European nations for at least a decade, and was approved by the US FDA in 2004 to reduce very high TG levels (> or =500 mg/dl [5.65 mmol/l]). Mechanistically, most evidence suggests that omega-3 fatty acids reduce the synthesis and secretion of very-low-density lipoprotein (VLDL) particles, and increase TG removal from VLDL and chylomicron particles through the upregulation of enzymes, such as lipoprotein lipase. Omega-3 fatty acids differ mechanistically from other lipid-altering drugs, which helps to explain why therapies such as P-OM3 have complementary mechanisms of action and, thus, complementary lipid benefits when administered with statins. Additional human studies are needed to define more clearly the cellular and molecular basis for the TG-lowering effects of omega-3 fatty acids and their favorable cardiovascular effects, particularly in patients with hypertriglyceridemia.

Publication types

  • Review

MeSH terms

  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / mortality
  • Cardiovascular Diseases / prevention & control
  • Cholesterol, HDL / drug effects
  • Cholesterol, LDL / drug effects
  • Cholesterol, VLDL / drug effects
  • Coronary Artery Disease / etiology
  • Coronary Artery Disease / mortality
  • Coronary Artery Disease / prevention & control*
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Approval
  • Drug Prescriptions / statistics & numerical data
  • Eicosapentaenoic Acid / therapeutic use*
  • Fatty Acids, Omega-3 / therapeutic use*
  • Female
  • Humans
  • Hypertriglyceridemia / complications*
  • Hypertriglyceridemia / diagnosis
  • Hypertriglyceridemia / drug therapy*
  • Male
  • Prognosis
  • Randomized Controlled Trials as Topic
  • Risk Assessment
  • Severity of Illness Index
  • Survival Analysis
  • Treatment Outcome
  • United States
  • United States Food and Drug Administration

Substances

  • Cholesterol, HDL
  • Cholesterol, LDL
  • Cholesterol, VLDL
  • Fatty Acids, Omega-3
  • Eicosapentaenoic Acid