linoleic-acid and Myocardial-Ischemia

The role of n-6 polyunsaturated fatty acids (PUFAs) in ischemic heart disease (IHD) is controversial, and dietary guidelines vary. Observationally, lower saturated fat intake and higher intake of vegetable oils rich in linoleic acid (LA), the main n-6 PUFA, is associated with lower IHD and diabetes; however, randomized controlled trials have not fully corroborated these benefits. We assessed how genetically predicted LA affected IHD and its risk factors, including diabetes, lipids, and blood pressure. We also assessed the role of LA in reticulocyte count, the red blood cell precursor, which has recently been identified as a possible causal factor in IHD.. Two-sample instrumental variable analysis with genetic instruments, i.e., Mendelian randomization, was used to obtain unconfounded estimates using genetic variants strongly (p value < 5 × 10. Genetically predicted LA was not associated with IHD or systolic blood pressure. Genetically predicted higher serum LA was associated with lower diabetes (odds ratio (OR) 0.97 per percentage in total fatty acid increase in LA, 95% confidence interval (CI) 0.96 to 0.99) and lower lipids (low-density lipoprotein, high-density lipoprotein, and total cholesterol), but may be associated with higher diastolic blood pressure. The findings were robust to different single nucleotide polymorphism (SNP) selections, analytic methods, and correction for multiple testing.. Our novel study suggests a benefit of LA for diabetes and lipids but no benefit for IHD, blood pressure, or reticulocyte count. Explicating these paradoxical findings would facilitate identification of effective new interventions for diabetes and IHD.

Topics: Female; Humans; Linoleic Acid; Male; Mendelian Randomization Analysis; Middle Aged; Myocardial Ischemia; Risk Factors

The role of n-6 (ω-6) polyunsaturated fatty acids (PUFAs) in type 2 diabetes (T2D) is inconclusive. In addition, little is known about how factors involved in PUFA metabolism, such as zinc, may affect the associations.. We investigated the associations of serum n-6 PUFAs and activities of enzymes involved in PUFA metabolism, Δ5 desaturase (D5D) and Δ6 desaturase (D6D), with T2D risk to determine whether serum zinc concentrations could modify these associations.. The study included 2189 men from the prospective Kuopio Ischaemic Heart Disease Risk Factor Study, aged 42-60 y and free of T2D at baseline in 1984-1989. T2D was assessed by self-administered questionnaires, by fasting and 2-h oral-glucose-tolerance test blood glucose measurement at re-examination rounds 4, 11, and 20 y after baseline, and by record linkage to the hospital discharge registry and the reimbursement register on diabetes medication expenses. Multivariate-adjusted Cox proportional hazards regression models were used to analyze associations.. During the average follow-up of 19.3 y, 417 men developed T2D. Those with higher estimated D5D activity (extreme-quartile HR: 0.55; 95% CI: 0.41, 0.74; P-trend < 0.001) and higher concentrations of total n-6 PUFAs (HR: 0.54; 95% CI: 0.41, 0.73; P-trend < 0.001), linoleic acid (LA; HR: 0.52; 95% CI: 0.39, 0.70; P-trend < 0.001), and arachidonic acid (AA; HR: 0.62; 95% CI: 0.46, 0.85; P-trend = 0.007) had a lower risk and those with higher concentrations of γ-linolenic acid (GLA; HR: 1.28; 95% CI: 0.98, 1.68; P = 0.021) and dihomo-γ-linolenic acid (DGLA; HR: 1.38; 95% CI: 1.04, 1.84; P-trend = 0.005) and higher D6D activity had a higher (HR: 1.50; 95% CI: 1.14, 1.97; P-trend < 0.001) multivariate-adjusted risk of T2D. Zinc mainly modified the association with GLA on T2D risk, with a higher risk observed among those with serum zinc concentrations above the median (P-interaction = 0.04).. Higher serum total n-6 PUFA, LA, and AA concentrations and estimated D5D activity were associated with a lower risk of incident T2D, and higher GLA and DGLA concentrations and estimated D6D activity were associated with a higher risk. In addition, a higher serum zinc concentration modified the association of GLA on the risk of T2D.

Topics: 8,11,14-Eicosatrienoic Acid; Adult; Arachidonic Acid; Diabetes Mellitus, Type 2; Fatty Acids, Omega-6; Finland; Follow-Up Studies; gamma-Linolenic Acid; Glucose Tolerance Test; Humans; Linoleic Acid; Linoleoyl-CoA Desaturase; Male; Middle Aged; Multivariate Analysis; Myocardial Ischemia; Proportional Hazards Models; Prospective Studies; Risk Factors; Zinc

n-3 (omega-3) PUFA has been proposed as having health-promoting effects, primarily in relation to ischemic heart disease (IHD). Whether these benefits can be achieved by both α-linolenic acid (ALA, 18:3n-3) and n-3 long-chain PUFA (LC-PUFA) is debatable.. The objective was to examine the association between ALA intake and risk of IHD in healthy subjects and to see if this was modified by intake of n-3 LC-PUFA or linoleic acid (LA, 18:2 n-6).. This was a prospective cohort study of 3277 healthy Danish women and men free of known IHD.. Four hundred seventy-one cases of IHD were observed during a median follow-up period of 23.3 y. Higher intake of ALA was not significantly associated with decreased risk of IHD among women or men. Although the HR of IHD was stepwise decreased with increasing ALA intake in men [0.84 (95% CI: 0.62, 1.14) in the medium compared with the lowest tertile (reference) and 0.83 (95% CI: 0.56, 1.24) in the highest compared with the lowest tertile], this change was far from significant (P-trend: 0.39). No evidence of effect modification by n-3 LC-PUFA or LA was observed. High n-3 LC-PUFA intake, in comparison with low intake, was inversely associated with risk of IHD; this trend was significant in women (P = 0.04; HR: 0.62; 95% CI: 0.40, 0.97) but not in men (P = 0.15; HR: 0.74; 95% CI: 0.51, 1.06). No associations were observed between intake of LA and risk of IHD.. This study suggests that there is no association between ALA intake and risk of IHD, but a high intake of n-3 LC-PUFA had a significant cardioprotective effect in women.

Topics: Adult; alpha-Linolenic Acid; Cohort Studies; Denmark; Diet; Diet Records; Fatty Acids, Omega-3; Female; Follow-Up Studies; Humans; Incidence; Linoleic Acid; Male; Middle Aged; Models, Statistical; Morbidity; Myocardial Ischemia; Prospective Studies; Risk; Sex Factors

The Jewish population of Israel consumes a diet rich in n-6 polyunsaturated fatty acids (PUFAs), principally linoleic acid. The consequences of this diet for ischemic heart disease (IHD) remain unclear.. We assessed the association of adipose tissue n-6 fatty acids, which are derived entirely from the diet, with acute myocardial infarction (AMI).. A total of 180 cases and 492 IHD-free controls aged 25-64 were included in a population-based case-control study of Jerusalem residents hospitalized with a first AMI. Diet was assessed by the use of a food-frequency questionnaire and adipose tissue fatty acids by gas chromatography of biopsy samples taken from subcutaneous gluteal tissue. The data were analyzed by multivariate logistic regression.. Dietary PUFAs (: 10.1% of energy) correlated (r = 0.43, P < 0.001) with adipose tissue linoleic acid, which constituted 25.6% of storage fatty acids. High intakes of linoleic acid were not associated with excess risk of AMI (age- and sex-adjusted odds ratio for the third versus the first tertile: 0.96; 95% CI: 0.62, 1.48; NS). In contrast, arachidonic acid, the long chain n-6 derivative of linoleic acid, was positively associated with AMI (age- and sex-adjusted odds ratio: 2.12; 95% CI: 1.33, 3.36; P = 0.004). With multivariate adjustment, there was no evidence for an adverse association of linoleic acid with AMI, whereas the risk associated with arachidonic acid persisted, albeit attenuated.. A very high linoleic acid intake does not appear to confer increased risk of nonfatal AMI. Nonetheless, the increased risk associated with arachidonic acid, a finding that requires confirmation, tempers an inference that diets rich in n-6 fatty acids are safe vis-à-vis coronary health.

Topics: Adipose Tissue; Adult; Arachidonic Acid; Case-Control Studies; Dietary Fats, Unsaturated; Fatty Acids, Omega-6; Fatty Acids, Unsaturated; Female; Humans; Jews; Linoleic Acid; Logistic Models; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia

Trimetazidine is an anti-ischemic compound devoid of hemodynamic effect, which was recently suspected to induce cardioprotection at the cellular level by a mechanism involving lipid metabolism. The effect on trimetazidine was evaluated in vivo by determination of rat cardiac fatty acid composition, and in vitro by investigation of the phospholipid metabolism in cultured rat cardiomyocytes. In rats, a 4-week trimetazidine treatment induced a significant decrease in the phospholipid content in linoleic acid, balanced by a small increase in oleic and stearic acids. These changes were not correlated with similar alterations in plasma fatty acid composition. In isolated cells, the time-dependent incorporation of labeled precursors of membrane phospholipid ([3H]inositol, [14C]ethanolamine, [14C]choline, [3H]glycerol, [14C]arachidonic acid, and [14C]linoleic acid 10 micromol/L) was compared in trimetazidine-treated cells and control cells. In trimetazidine-treated cells, arachidonic acid incorporation was increased in the phospholipid, but not in other lipid fractions. This enhanced fatty acid utilization elicited a net increase in the total arachidonic acid uptake. The incorporation of [14C] inositol in phosphatidylinositol was strongly stimulated by trimetazidine, although the uptake of inositol was not altered. The difference was significant within 30 minutes, and reached +70%(in trimetazidine-treated cells) after 150 minutes. A similar result was obtained with ethanolamine as phosphatidylethanolamine precursor, where turnover increased by 50% in trimetazidine-treated cells. Conversely, the incorporation of choline in phosphatidylcholine was not significantly affected by the presence of trimetazidine. In conclusion, trimetazidine appears to interfere with the metabolism of phospholipids in cardiac myocytes in a manner that could indicate an increased phosphatidylinositol turnover and a redirection of cytidine triphosphate (CTP) utilization toward phosphatidylethanolamine instead of phosphatidylcholine turnover. This overall phospholipid turnover increase may contribute to a reorganization of the fatty acid utilization balance in the heart, which could lead to a lowered availability of fatty acids for energy production.

Topics: Animals; Cells, Cultured; Choline; Chromatography, Gas; Ethanolamine; Fatty Acids; Inositol; Linoleic Acid; Myocardial Ischemia; Myocardium; Oleic Acid; Phosphatidylethanolamines; Phosphatidylinositols; Phospholipids; Rats; Rats, Wistar; Stearic Acids; Trimetazidine; Vasodilator Agents

An excess of Oxidative Stress can occur either through an increase in the generation of free radicals and their metabolites (which overwhelm the protective capacity of the normal defence mechanisms of the body) or through a decrease in the protective ability of the body to withstand normal Oxidative Stress or both. Excessive Oxidative Stress plays an important role in the pathogenesis of diabetes and its chronic complications like retinopathy and nephropathy. Through various mechanisms, it plays a prominent role in the progression and acceleration of atherosclerosis. Free radicals being highly unstable due to their high reactivity are very difficult to measure accurately. Recourse is therefore taken to measure the compounds that are formed due to the activity of these free radicals. These compounds are relatively more stable and therefore can be measured as diene congugate and lipid peroxides. Another valuable measurement is to measure the levels of reduced glutathione in serum. Measurements of these products can be an excellent parameter to judge the metabolic control of diabetes.

Topics: Adult; Aged; Antioxidants; Arteriosclerosis; Diabetes Mellitus; Diabetic Angiopathies; Diabetic Nephropathies; Diabetic Retinopathy; Disease Progression; Evaluation Studies as Topic; Female; Free Radicals; Glutathione; Humans; Linoleic Acid; Linoleic Acids; Lipid Peroxides; Male; Middle Aged; Myocardial Ischemia; Oxidative Stress

Seventeen patients with a more than 5-month-history of angina pectoris were allocated a diet for 4 weeks. The diet was supplemented with 6.15 g of omega 3-polyunsaturated fatty acids (PUFA) in 125 g canned Far-Eastern sardine. This increased the proportion of eicosapentaenic (EPA) and docosahexaenic acids from 1.28 +/- 0.72 to 9.02 +/- 2.83% and from 2.48 +/- 0.91 to 6.54 +/- 2.01%, respectively; p = 0.0003) in the total serum lipid fraction. The levels of omega 6-PUFA decreased due to linoleic acid (from 24.9 +/- 3.9 to 19.7 +/- 5.2%, p = 0.0014). The EPA/arachidonic acid ratio rose from 0.23 +/- 0.11 to 1.76 +/- 0.58 (p < 0.001). The levels of triglycerides decreased by 36.4% (from 162.3 +/- 55.2 to 103.9 +/- 42.4 mg/dl; p < 0.0005); those of very low density lipoproteins and total cholesterol by 36 and 6.8%, respectively (from 32.5 +/- 11.0 to 20.8 +/- 8.5 mg/dl; p < 0.0005 and from 234.8 +/- 43.2 to 218.4 +/- 39.7 mg/dl; p < 0.05, respectively). The concentrations of high density lipoproteins remained unchanged. Thus, a short-term supplementation of canned Far-Eastern sardine to the diet of patients with CHD caused a substantial changes in blood fatty acid composition and favourable shifts in the levels of lipids and lipoproteins. This allows the Far-Eastern sardine to be regarded as a valuable source of omega 3-PUFA which can be used in the secondary prevention of coronary heart disease.

Topics: Adult; Aged; Animals; Arachidonic Acid; Cholesterol; Docosahexaenoic Acids; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Fishes; Food Preservation; Food, Fortified; Humans; Linoleic Acid; Linoleic Acids; Lipoproteins, HDL; Lipoproteins, VLDL; Male; Middle Aged; Myocardial Ischemia; Time Factors; Triglycerides