Abstract-Animal studies suggest that the 2 major 3 fatty acids found in fish, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), may have differential effects on blood pressure (BP) and heart rate (HR). The aim of this study was to determine whether there were significant differences in the effects of purified EPA or DHA on ambulatory BP and HR in humans. In a double-blind, placebo-controlled trial of parallel design, 59 overweight, mildly hyperlipidemic men were randomized to 4 g/d of purified EPA, DHA, or olive oil (placebo) capsules and continued their usual diets for 6 weeks. Fifty-six subjects completed the study. Key Words: eicosapentaenoic acid Ⅲ docosahexaenoic acid Ⅲ fatty acids Ⅲ blood pressure Ⅲ heart rate C urrent evidence from epidemiological studies, clinical trials, and experimental animal studies suggests that 3 fatty acids of marine origin may be protective against cardiovascular disease. 1 Most studies that assessed the potential cardiovascular benefits of 3 fatty acids have focused largely on the importance of eicosapentaenoic acid (EPA), with little attention given to the relative effect of docosahexaenoic acid (DHA). This is probably attributable to the fact that the majority of commercial marine oil preparations as well as most, but not all, fish species contain more EPA than DHA. In addition, EPA, unlike DHA, is a substrate for the cyclooxygenase and lipoxygenase enzymes involved in eicosanoid metabolism.Fish oil supplementation in humans results in substantial increases in plasma and tissue 3 fatty acids, particularly EPA and DHA, but with variable incorporation in different phospholipid classes in different tissues. In vitro animal and human studies have shown that EPA and DHA are differentially incorporated into plasma, 2 platelet, 3,4 and tissue lipids. 4 These differences may play an important role in the utilization and metabolism of the 2 fatty acids. For example, EPA and DHA differ in their effects on membrane fluidity and the activities of membrane-bound enzymes 5 and on neutrophilmediated endothelial detachment. 6 Compelling evidence shows that in vitro DHA but not EPA decreased cytokine-induced expression of endothelial leukocyte adhesion molecules. 7 Recent reports have described differences in lipid metabolism 8,9 and platelet aggregation. 10 An antihypertensive effect of fish oils has been demonstrated in hypertensive patients, 11-14 although generally only when relatively large doses of fish oils have been used. We recently reported that daily fish meals that provide 3.65 g/d of 3 fatty acids significantly reduced blood pressure (BP) in overweight, treated hypertensives. 15 This study addresses the question of whether EPA and DHA have differential effects on BP and heart rate (HR) in humans. In support of a differential effect of EPA and DHA on BP control, McLennan et al 16 recently reported that DHA was more effective than EPA at retarding the development of hypertension in spontaneously hypertensive rats (SHR) but not in adult SHR with already established hyperten...

Incorporating a daily fish meal into a weight-loss regimen was more effective than either measure alone at improving glucose-insulin metabolism and dyslipidemia. Cardiovascular risk is likely to be substantially reduced in overweight hypertensive patients with a weight-loss program incorporating fish meals rich in n-3 fatty acids.

Abstract-Obesity is a major factor contributing to hypertension and increased risk of cardiovascular disease. Regular consumption of dietary fish and 3 fatty acids of marine origin can lower blood pressure (BP) levels and reduce cardiovascular risk. This study examined the potential effects of combining dietary fish rich in 3 fatty acids with a weight loss regimen in overweight hypertensive subjects, with ambulatory BP levels as the primary end point. Using a factorial design, 69 overweight medication-treated hypertensives were randomized to a daily fish meal (3.65 g 3 fatty acids), weight reduction, the 2 regimens combined, or a control regimen for 16 weeks. Sixty-three subjects with a meanϮSEM body mass index of 31.6Ϯ0.5 kg/m 2 completed the study. Weight fell by 5.6Ϯ0.8 kg with energy restriction. Dietary fish and weight loss had significant independent and additive effects on 24-hour ambulatory BP. Effects were greatest on awake systolic and diastolic BP (PϽ0.01); relative to control, awake pressures fell 6.0/3.0 mm Hg with dietary fish alone, 5.5/2.2 mm Hg with weight reduction alone, and 13.0/9.3 mm Hg with fish and weight loss combined. These results also remained significant after further adjustment for changes in urinary sodium, potassium, or the sodium/potassium ratio, as well as dietary macronutrients. Dietary fish also significantly reduced 24-hour (Ϫ3.1Ϯ1.4 bpm, Pϭ0.036) and awake (Ϫ4.2Ϯ1.6 bpm, Pϭ0.013) ambulatory heart rates. Weight reduction had a significant effect on sleeping heart rate only (Ϫ3.2Ϯ1.7 bpm, Pϭ0.037). Combining a daily fish meal with a weight-reducing regimen led to additive effects on ambulatory BP and decreased heart rate. The effects were large, suggesting that cardiovascular risk and antihypertensive drug requirements are likely to be reduced substantially by combining dietary fish meals rich in 3 fatty acids with weight-loss regimens in overweight medication-treated hypertensives. The reduction in heart rate seen with dietary fish suggests a cardiac/autonomic component, as well as vascular effects, of increased consumption of 3 fatty acid from fish. (Hypertension. 1998;32:710-717.) Key Words: fish Ⅲ 3 fatty acids Ⅲ weight control Ⅲ blood pressure Ⅲ obesity S everal randomized controlled trials have shown that fish oils may lower blood pressure (BP), 1-4 although the effects have been most clear-cut in hypertensive subjects treated with relatively large doses of 3 fatty acids. 5,6 On the other hand, population studies suggest that regular consumption of even small amounts of fish may reduce the risk of coronary heart disease, 7 an effect presumed to be due to actions of 3 fatty acids on a variety of mechanisms underlying atherosclerosis. 8 Obesity is a major factor contributing to hypertension, and weight loss reduces BP in overweight hypertensives. 9 In addition, hypertension and obesity are both associated with impaired endothelial function. 10,11 Because 3 fatty acids improve endothelial dilator function and vascular reactivity, 12,13 we hypothesized that combining weight ...