Dietary linolenic acid-mediated increase in vascular prostacyclin formation

Wagner

et al. 2004

Herz

Self Cite

The identification of risks associated with sudden cardiac death requires further investigations. The question was addressed whether parameters can be established which not only describe an increased risk for an enhanced electrical instability of the heart but also of inflammatory events underlying plaque rupture. Emphasis is placed on dose-dependent effects of the long-chain omega-(omega-)3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Since free acids of EPA and DHA are required for most of their biological effects, it appears essential not only to build up stores in the body for release of these fatty acids, but also to provide a sustained uptake of EPA and DHA in the form of ethyl esters. In contrast to rapidly absorbed triacylglycerols from fish, ethyl esters are taken up more slowly within 24 h. For the administration of 1 g/day highly purified EPA+DHA ethyl esters (Omacor) to healthy volunteers, it is shown that EPA is increased from 0.6% to 1.4% within 10 days, while DHA is increased from 2.9% to 4.3%. After withdrawal, EPA and DHA approach baseline values within 10 days. A gas chromatographic procedure was established which requires only 10 microl of whole blood for the identification of more than 35 fatty acids. Evidence is summarized strengthening the concept that a low "EPA+DHA level" presents a risk for sudden cardiac death and that the administration of 840 mg/day of EPA+DHA ethyl esters raises the "EPA+DHA level" to approximately 6% that is associated with a marked protection from sudden cardiac death. For reducing pro-inflammatory eicosanoids and cytokines, a higher "EPA+DHA level" is required which can be achieved with an intake of 2-4 g/day of 84% EPA+DHA ethyl esters. For assessing influences from pro-inflammatory eicosanoids and cytokines, the EPA/arachidonic acid ratio ("EPA/AA ratio") was identified as diagnostic parameter. To assess the dietary EPA+DHA intake, fatty acids were determined in fish dishes of the cafeteria of the Philipps University Hospital Marburg, Germany. The EPA+DHA content of the popular Alaska Pollock was 125 +/- 70 mg/100 g. A once daily fish dish can thus not provide the 840 mg/day EPA+DHA administered in the GISSI Prevention Study in the form of ethyl ester which markedly reduced the risk of sudden cardiac death in postmyocardial infarction patients. Nonetheless, at least two preferably oily fish meals per week should be consumed as preventive measure by persons without coronary artery disease. With documented coronary heart disease, it was advised to consume approximately 1 g/day of EPA+DHA.

Section: Epa and Dha Conversion From α-Linolenic Acidmentioning

confidence: 83%

“…*p < 0.05 versus rats fed a control chow. Data are adapted from [65]. would be the finding that sustained ventricular tachycardia can be reduced by infusion of 3.8 g ω-3 marine triacylglycerols in patients with implanted cardioverter defibrillators [71].…”

Section: Mechanisms Of Antiarrhythmogenic Action Of Epa and Dha Free mentioning

confidence: 99%

Risk Stratification by the ?EPA+DHA Level? and the ?EPA/AA Ratio?

Wagner

et al. 2004

Herz

Self Cite

“…The content of ALA in the aorta rose by 12% while the concentration of EPA was unaltered. Vascular prostacyclin synthesis increased, resulting in lower blood pressure (Rupp et al, 1996). Apparently, ALA can be converted into EPA and subsequently alters prostanoid production, without raised EPA concentration in cell membranes.…”

Section: Discussionmentioning

confidence: 99%

Associations of alpha-linolenic acid and linoleic acid with risk factors for coronary heart disease

et al. 2000

Background: Prevention of coronary heart disease (CHD) in high-risk subjects. Objective: To investigate the associations of dietary intake of alpha-linolenic acid (ALA) and linoleic acid (LA) as assessed by food frequency questionnaire and in the plasma cholesteryl ester (CE), with CHD risk factors. Design: Baseline data of a double-blind, randomized placebo-controlled trial. Subjects have hypercholesterolemia (6.0 ± 8.0 mmolal) and at least two other CHD risk factors (n 266). Results: The reported dietary ALA and LA intakes and the LAaALA ratio were associated with the contents in the CE (r 0.37, r 0.21, and r 0.42, respectively; P`0.01). In multivariate analysis, CE ALA was inversely associated with diastolic blood pressure (r 7 0.13; P`0.05) and positively with serum triacylglycerol (r 0.13; P`0.05), and CE LA was inversely associated with serum triacylglycerol (r 7 0.32; P`0.01). The CE LAaALA ratio was strongly inversely associated with CE ALA (r 7 0.95; P`0.01). In the lowest quintile of CE ALA, mean dietary intake was 0.4 energy % ALA (1.2 gaday), 8.4 energy % LA and an LAaALA ratio of 21, and in the highest quintile 0.6 energy % ALA (1.7 gaday), 6.8 energy % LA and 12 (ratio). In the lowest quintile of CE ALA the diastolic blood pressure was 4 mmHg lower (P trend`0.05), and the serum triacylglycerol 0.3 mmolal higher (P trend NS) when compared with the top quintile. Conclusions: In a CHD high-risk population with LA-rich background diet, these cross-sectional data suggest that replacing LA in the diet by ALA may decrease diastolic blood pressure, and may increase serum triacylglycerol concentration. Sponsorship: Dutch Prevent fund grant no. 28-2757; Unilever (margarine). Descriptors: alpha-linolenic acid; linoleic acid; plasma cholesteryl ester; CHD risk factors; blood pressure; serum triacylglycerol European Journal of Clinical Nutrition (2000) 54, 865±871 IntroductionThe MARGARIN study is a prevention project of coronary heart disease (CHD) through a high-risk approach. The study group is composed of 266 hypercholesterolemic subjects with at least two other CHD risk factors. Our project was inspired by the Lyon Diet Heart Study. In this secondary prevention trial among patients who had a myocardial infarction, a 70% reduction in CHD events was observed in the experimental group on an alphalinolenic acid (ALA; 18 : 3n-3) rich Mediterranean diet. In the ®nal report, plasma ALA content was associated with improved prognosis (de Lorgeril et al, 1994(de Lorgeril et al, ,1999. Also, several large observational studies have reported on the preventive effect of dietary ALA on CHD events (Ascherio et al, 1996;Hu et al, 1999).ALA is the vegetary precursor of the marine long chain n-3 fatty acids eicosapentaenoic acid (EPA; 20 : 5n-3) and docosahexaenoic acid (DHA; 22 : 6n-3). ALA competes with its n-6 counterpart linoleic acid (18 : 2n-6) for desaturation and chain-elongation. Linoleic acid (LA) is in this pathway converted to arachidonic acid (AA; 20 : 4n-6).In recent years, hypercholesterolemic subjects have b...

“…However, it has been suggested that the hypotensive effects of linolenic acid could be mediated through its influence on arachidonic acid and eicosanoids synthesis, leading to an anti-inflammatory response and to vasodilation. 6,9 We used data collected on 4594 white participants of the National Heart, Lung, and Blood Institute (NHLBI) Family Heart Study to assess whether dietary consumption of higher amounts of total linolenic acid (␣-linolenic and ␥-linolenic acid) was associated with a lower prevalence of hypertension and lower resting blood pressure. …”

mentioning

confidence: 99%

“…Animal and human studies on the association between linolenic acid and blood pressure have been inconsistent. Rupp et al 6 showed that a diet supplemented with ␣-linolenic acid lowered systolic blood pressure (SBP) by 6 mm Hg after 7 weeks in 28 spontaneous hypertensive rats. In a crosssectional study of 399 male subjects aged 20 to 78 years, a 1% higher adipose tissue ␣-linolenic acid was associated with a 5 mm Hg lower SBP and diastolic blood pressure (DBP).…”

mentioning

confidence: 99%

Dietary Linolenic Acid Is Associated With a Lower Prevalence of Hypertension in the NHLBI Family Heart Study

et al. 2005

Abstract-Dietary linolenic acid has been shown to be associated with coronary artery disease. However, limited data are available on its effects on blood pressure. We used data from 4594 white participants (aged 25 to 93 years) in the National Heart, Lung, and Blood Institute (NHLBI) Family Heart Study to evaluate whether dietary linolenic acid was associated with prevalent hypertension and resting blood pressure. We used generalized estimating equations to determine the prevalence odds ratios (ORs) of hypertension and adjusted means of systolic and diastolic blood pressure across quartiles of linolenic acid. [1][2][3][4][5] limited data are available on its effects on hypertension among subjects in a community setting. Animal and human studies on the association between linolenic acid and blood pressure have been inconsistent. Rupp et al 6 showed that a diet supplemented with ␣-linolenic acid lowered systolic blood pressure (SBP) by 6 mm Hg after 7 weeks in 28 spontaneous hypertensive rats. In a crosssectional study of 399 male subjects aged 20 to 78 years, a 1% higher adipose tissue ␣-linolenic acid was associated with a 5 mm Hg lower SBP and diastolic blood pressure (DBP). 7 In the Kuopio Ischemic Heart Disease Risk Factor Study, 8 dietary intake of linolenic acid, assessed by a 4-day food record, was associated inversely with SBP and mean blood pressure but not with DBP. Physiological mechanisms by which dietary linolenic acid might lower blood pressure are not well understood. However, it has been suggested that the hypotensive effects of linolenic acid could be mediated through its influence on arachidonic acid and eicosanoids synthesis, leading to an anti-inflammatory response and to vasodilation. 6,9 We used data collected on 4594 white participants of the National Heart, Lung, and Blood Institute (NHLBI) Family Heart Study to assess whether dietary consumption of higher amounts of total linolenic acid (␣-linolenic and ␥-linolenic acid) was associated with a lower prevalence of hypertension and lower resting blood pressure. Subjects and Methods Study PopulationParticipants in this project were members of the NHLBI Family Heart Study, which is a multicenter, population-based study designed to identify and evaluate genetic and nongenetic determinants of CAD, preclinical atherosclerosis, and cardiovascular risk factors. A detailed description of the NHLBI Family Heart Study has been published. 10 Briefly, families in the study had been chosen randomly (a random group) or based on a higher-than-expected risk of CAD (a high-risk group) from previously established population-based co-