The effect of fish oil on hypertension, plasma lipids and hemostasis in hypertensive, obese, dyslipidemic patients with and without diabetes mellitus C. Yosefy, 1 J. Reuven Viskoper, 1 A. Laszt, 1 R. Priluk, 1 E. Guita, 1 D. Varon, 2 Z. Illan, 1 E. M. Berry, 3 N. Savion, 4 Y. Adan, 5 G. Lugassy, 1 R. Schneider, 1 A. Raz 5 1 WHO Collaborative Center for Prevention of Cardiovascular Disease and the Department of Medicine B, Barzilai Medical Center, Ashkelon, affiliated with Ben-Gurion University of the Negev, Beer-Sheva, Israel 2 National Hemophilia Center, Sheba Medical Center, Tel-Hashomer, Israel 3 Department of Human Nutrition and Metabolism, Hadassah Medical Center, Jerusalem, Israel 4 Goldschleger Eye Research Institute, Sheba Medical Center and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel 5 Department of Biochemistry, Tel Aviv University, Tel Aviv, Israel Summary We have recently reported that dietary fish oil supplementation (n-3) polyunsaturated fatty acid (PUFA) led to a reduction in blood pressure (BP) and serum triglycerides (TG), in addition to the normalization of the hypercoagulable state in subjects with obesity, hypertension and dyslipidemia without diabetes mellitus (OHD-DM). The aim of the present study was to explore the mechanism of this amelioration by comparing the previous results to those obtained from 19 subjects who, in addition to the conditions described above, also suffer from diabetes mellitus (OHD+DM) and proteinuria. In both the non-diabetic and diabetic groups, a similar reduction was observed in BP (from 158.7/80.8 to 146/72.9 mmHg, and from 157.6/83.2 to 141.9/75.6 mmHg, respectively, P<0.001) and TG levels (from 159.2 to 108.0 mg/dl and from 208.7 to 153.1 mg/dl, respectively, P<0.001). However, a favorable reduction in hemostasis parameters (platelet aggregation on extracellular matrix and (α 2 -antiplasmin) was only seen among the nondiabetic patients (from 12.1±4.9 to 4.2±3.2%, P<0.001). This difference may stem from a less efficient exchange between n-3 and n-6 PUFA in serum phospholipid of the OHD+DM patients. Overall, this 13-day fasting/refeeding method developed by us has proven to cause the rapid exchange of arachidonic acid for eicosapentaenoic acid. It appears to be an effective regimen for the reduction of cardiovascular risk factors (BP, TG and hemostatic variables) in OHD-DM patients and to a lesser extent in OHD+DM patients. 83 Prostaglandins, Leukotrienes and Essential Fatty Acids (1999) 61(2), 83–87 © 1999 Harcourt Publishers Ltd Article no. plef.1999.0075 INTRODUCTION Patients with metabolic diseases such as obesity, hyper- tension, hypercholesterolemia, hypertriglyceridemia, im- paired glucose tolerance, Type I and Type II diabetes, are at a high risk for the development of atherothrombosis and coronary heart disease. 1,2 In addition, an elevated level of serum triglycerides (TG), combined with a low level of high-density lipoprotein cholesterol (HDL-CHO) is often seen in conjunction with a hypercoagulable state resulting from a higher plasma concentration of fib- rinogen and clotting factors (e.g. factor X) and reduced fibrinolytic activity. 2 A meta-analysis, comprised of 17 studies, 3 showed a fish oil dose-related effect on blood pressure (BP) that was restricted to subjects with atherosclerotic disease. This effect was suggested to result from changes in the composition of platelet phospholipid n-3 and n-6 poly- unsaturated fatty acid (PUFA). 4 We have previously 5 described a protocol for the enhanced exchange of n-3 for n-6 PUFA in serum phos- pholipids when fish oil was administered together with intermittent one-day fasting, promoting the depletion of Received 29 April 1999 Accepted 4 May 1999 Correspondence to: C. Yosefy, WHO Collaborative Center for Prevention of Cardiovascular Diseases, Barzilai Medical Center, Ashkelon, Israel. Tel.: +972 7 6745871; Fax: +972 7 6712733