Why do omega-3 fatty acids lower serum triglycerides?Harris, William Sa,b; Bulchandani, DeeptibCurrent Opinion in Lipidology: August 2006 - Volume 17 - Issue 4 - p 387–393 doi: 10.1097/01.mol.0000236363.63840.16 Hyperlipidaemia and cardiovascular disease Abstract Author Information Purpose of review: Fish oils rich in n-3 fatty acids reduce serum triglyceride levels. This well known effect has been shown to be caused by decreased very low-density lipoprotein triglyceride secretion rates in kinetic studies in humans. Animal studies have explored the biochemical mechanisms underlying this effect. Triglyceride synthesis could be reduced by n-3 fatty acids in three general ways: reduced substrate (i.e. fatty acids) availability, which could be secondary to increase in β-oxidation, decreased free fatty acids delivery to the liver, decreased hepatic fatty acids synthesis; increased phospholipid synthesis; or decreased activity of triglyceride-synthesizing enzymes (diacylgylcerol acyltranferase or phosphatidic acid phosphohydrolase). Recent findings: Rarely were experimental conditions used in rat studies physiologically relevant to the human situation in which 1.2% energy as n-3 fatty acids lowers serum triglyceride levels. Nevertheless, the most consistent effect of n-3 fatty acids feeding in rats is to decrease lipogenesis. Increased β-oxidation was frequently, but not consistently, reported with similar numbers of studies reporting increased mitochondrial compared with peroxisomal oxidation. Inhibition of triglyceride-synthesizing enzymes was only occasionally noted. Summary: As the vast majority of studies fed unphysiologically high doses of n-3 fatty acids, these findings in rats must be considered tentative, and the mechanism by which n-3 fatty acids reduce triglyceride levels in humans remains speculative. aMid America Heart Institute, Saint Luke's Health System, USA bUniversity of Missouri–Kansas City School of Medicine, Kansas City, Missouri, USA Correspondence to William S. Harris, South Dakota Health Research Foundation, Nutrition and Metabolic Diseases, 1400 W. 22nd Street, Sioux Falls, SD 57105, USA E-mail: Bill.Harris@usd.edu © 2006 Lippincott Williams & Wilkins, Inc.