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Omega-3 fatty acids: new insights into the pharmacology and biology of docosahexaenoic acid, docosapentaenoic acid, and eicosapentaenoic acid

Davidson, Michael H.a,b

doi: 10.1097/MOL.0000000000000019
THERAPY AND CLINICAL TRIALS: Edited by Anton F. Stalenhoef and John J.P. Kastelein

Purpose of review Fish oil contains a complex mixture of omega-3 fatty acids, which are predominantly eicosapentaenoic acid (EPA), docosapentaenoic acid, and docosahexaenoic acid (DHA). Each of these omega-3 fatty acids has distinct biological effects that may have variable clinical effects. In addition, plasma levels of omega-3 fatty acids are affected not only by dietary intake, but also by the polymorphisms of coding genes fatty acid desaturase 1-3 for the desaturase enzymes that convert short-chain polyunsaturated fatty acids to long-chain polyunsaturated fatty acids. The clinical significance of this new understanding regarding the complexity of omega-3 fatty acid biology is the purpose of this review.

Recent findings FADS polymorphisms that result in either lower levels of long-chain omega-3 fatty acids or higher levels of long-chain omega-6 polyunsaturated fatty acids, such as arachidonic acid, are associated with dyslipidemia and other cardiovascular risk factors. EPA and DHA have differences in their effects on lipoprotein metabolism, in which EPA, with a more potent peroxisome proliferator-activated receptor-alpha effect, decreases hepatic lipogenesis, whereas DHA not only enhances VLDL lipolysis, resulting in greater conversion to LDL, but also increases HDL cholesterol and larger, more buoyant LDL particles.

Summary Overall, these results emphasize that blood concentrations of individual long-chain polyunsaturated fatty acids, which reflect both dietary intake and metabolic influences, may have independent, but also complementary- biological effects and reinforce the need to potentially provide a complex mixture of omega-3 fatty acids to maximize cardiovascular risk reduction.

aPritzker School of Medicine, The University of Chicago, Chicago, Illinois

bOmthera Pharmaceuticals, Princeton, New Jersey, USA

Correspondence to Michael H. Davidson, MD, FACC, FNLA, Department of Medicine, Pritzker School of Medicine, The University of Chicago, 150 East Huron Street, Suite 900, Chicago, IL 60611, USA. Tel: +1 773 834 4150; fax: +1 312 494 2217; e-mail: mdavidso@medicine.bsd.uchicago.edu

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