Atherosclerosis 175 (2004) 333–343 Effects of oils rich in eicosapentaenoic and docosahexaenoic acids on the oxidizability and thrombogenicity of low-density lipoprotein Maria Dolores Mesa, Richard Buckley, Anne Marie Minihane, Parveen Yaqoob ∗ The Hugh Sinclair Unit of Human Nutrition, School of Food Biosciences, The University of Reading, Whiteknights, P.O. Box 226, Reading RG6 6AP, UK Received 14 January 2004; received in revised form 22 March 2004; accepted 20 April 2004 Available online 15 June 2004 Abstract Consumption of oily fish and fish oils is associated with protection against cardiovascular disease. Paradoxically, long-chain polyunsaturated fatty acids present in low-density lipoprotein (LDL) are suggested to be susceptible to oxidation. It is not clear whether eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have similar effects on the susceptibility of LDL to oxidation or whether they affect the thrombogenicity of oxidized LDL. This study examined the influence of highly purified preparations of EPA and DHA on LDL oxidizability and LDL-supported thrombin generation in healthy human volunteers. Forty-two healthy volunteers were randomly assigned to receive olive oil (placebo), an EPA-rich oil or a DHA-rich oil for 4 weeks at a dose of 9g oil/day. EPA and DHA were incorporated into LDL phospholipids and cholesteryl esters during the supplementation period, but were progressively lost during ex vivo copper-mediated oxidation. Following supplementation, the EPA treatment significantly increased the formation of conjugated dienes during LDL oxidation compared with baseline, whereas the DHA treatment had no effect. Neither treatment significantly affected the lag time for oxidation, oxidation rate during the propagation phase or maximum diene production. Neither EPA nor DHA significantly affected the thrombotic tendency of oxidized LDL compared with the placebo, although DHA tended to decrease it. In conclusion, there are subtle differences in the effects of EPA and DHA on the oxidizability and thrombogenicity of LDL. DHA does not appear to increase the susceptibility of LDL to oxidation to the same degree as EPA and has a tendency to decrease LDL-supported thrombin generation. © 2004 Elsevier Ireland Ltd. All rights reserved. Keywords: Fish oil; Docosahexaenoic acid; Eicosapentaenoic acid; Oxidized LDL; Thrombin 1. Introduction There is epidemiological evidence that consumption of fish or of long-chain n-3 polyunsaturated fatty acids (PUFA), found in oily fish and fish oils, protects against cardiovascu- lar disease in Western populations [1–5]. Secondary preven- tion studies, providing long-chain n-3 PUFA to patients who had already suffered a myocardial infarction (MI), demon- strate significant benefit [6–8]. This effect might be due to anti-thrombotic [9] and anti-arrhythmic actions of n-3 PUFA [10] or to an increase in plaque stability [11]. Long-chain n-3 PUFA, such as EPA and DHA, are usu- ally consumed in small quantities, and are therefore found ∗ Corresponding author. Tel.: +44 118 378 8720; fax: +44 118 931 0080. E-mail address: p.yaqoob@reading.ac.uk (P. Yaqoob). in relatively low proportions in plasma and tissue lipids. However, increased consumption of these fatty acids is marked by an increase in their proportion in various blood and tissue lipid pools, including LDL cholesteryl esters and phospholipids [12]. Paradoxically, enrichment of LDL with n-3 PUFA is thought to enhance the susceptibility of LDL for oxidation [13–19]. The susceptibility of LDL to oxidation is influenced by its PUFA content (amount of substrate available for oxidation) and its antioxidant content (confer resistance to oxidation). Thus, at a given antioxi- dant content, increasing the PUFA content (or the number of double bonds) of LDL should increase its susceptibility to oxidation. A number of studies have investigated the effects of dietary or supplemented fish oil on the suscep- tibility of LDL to oxidation and demonstrated a marked reduction in the lag phase for oxidation of LDL by fish oil [13–19]. However, not all studies agree that n-3 PUFA 0021-9150/$ – see front matter © 2004 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.atherosclerosis.2004.04.004