U-shaped relationship between tissue docosahexaenoic acid and atrial fibrillation following cardiac surgery.

BACKGROUND/OBJECTIVES: Randomised controlled trials (RCTs) evaluating the effect of fish oil supplementation on postoperative atrial fibrillation (POAF) following cardiac surgery have produced mixed results. In this study, we examined relationships between levels of red blood cell (RBC) n-3 long-chain polyunsaturated fatty acids (LC-PUFAs) and the incidence of POAF. SUBJECTS/METHODS: We used combined data (n=355) from RCTs conducted in Australia and Iceland. The primary end point was defined as POAF lasting >10 min in the first 6 days following surgery. The odds ratios (ORs) for POAF were compared between quintiles of preoperative RBC n-3 LC-PUFA levels by multivariable logistic regression. RESULTS: Subjects with RBC docosahexaenoic acid (DHA) in the fourth quintile, comprising a RBC DHA range of 7.0-7.9%, had the lowest incidence of POAF. Subjects in the lowest and highest quintiles had significantly higher risk of developing POAF compared with those in the fourth quintile (OR=2.36: 95% CI; 1.07-5.24 and OR=2.45: 95% CI; 1.16-5.17, respectively). There was no association between RBC eicosapentaenoic acid levels and POAF incidence. CONCLUSIONS: The results suggest a 'U-shaped' relationship between RBC DHA levels and POAF incidence. The possibility of increased risk of POAF at high levels of DHA suggests an upper limit for n-3 LC-PUFAs in certain conditions.

Inflammatory response following heart surgery and association with n-3 and n-6 long-chain polyunsaturated fatty acids in plasma and red blood cell membrane lipids.

BACKGROUND: Open heart surgery is associated with a systemic inflammatory response. The n-3 long-chain polyunsaturated fatty acids (LC-PUFA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and the n-6 LC-PUFA arachidonic acid (AA) may contribute to modulation of the inflammatory response. OBJECTIVE: We investigated whether the preoperative levels of EPA, DHA and AA in plasma phospholipids (PL) and red blood cell (RBC) membrane lipids in patients (n=168) undergoing open heart surgery were associated with changes in the plasma concentration of selected inflammatory mediators in the immediate postoperative period. RESULTS AND CONCLUSIONS: The postoperative concentration of TNF-ß was lower (P<0.05) and those of hs-CRP, IL-6, IL-8, IL-18 and IL-10 higher (P<0.05) than the respective preoperative concentrations. We observed that the preoperative levels of EPA and AA in plasma PL and RBC membrane lipids were associated with changes in the concentration of pro-inflammatory and anti-inflammatory mediators, suggesting a complex role in the postoperative inflammatory process.

Relationship between high consumption of marine fatty acids in early pregnancy and hypertensive disorders in pregnancy.

OBJECTIVE: To investigate whether there is a relationship between maternal intake of cod-liver oil in early and late pregnancy and hypertensive disorders in pregnancy. DESIGN: An observational prospective study. SETTING: Free-living conditions in a community with traditional fish and cod-liver oil consumption. POPULATION: Four hundred and eighty-eight low-risk pregnant Icelandic women. METHODS: Maternal use of cod-liver oil, foods and other supplements was estimated with a semiquantitative food frequency questionnaire covering food intake together with lifestyle factors for the previous 3 months. Questionnaires were filled out twice, between 11 and 15 weeks of gestation and between 34 and 37 weeks of gestation. Supplements related to hypertensive disorders in pregnancy, i.e. gestational hypertension and pre-eclampsia, were presented, with logistic regression controlling for potential confounding. MAIN OUTCOME MEASURES: Gestational hypertension, pre-eclampsia, cod-liver oil and multivitamins. RESULTS: The odds ratio for developing hypertensive disorders in pregnancy for women consuming liquid cod-liver oil was 4.7 (95% CI 1.8-12.6, P= 0.002), after adjusting for confounding factors. By dividing the amount of n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) into centiles, the odds ratio for hypertensive disorders across groups for n-3 LCPUFA suggested a u-shaped curve (P = 0.008). Similar results were found for gestational hypertension alone. Further, the use of multivitamin supplements without vitamins A and D in late pregnancy doubled the odds of hypertensive disorders (OR 2.4, 95% CI 1.0-5.4, P= 0.044). CONCLUSIONS: Consumption of high doses of n-3 LCPUFA in early pregnancy, or other nutrients found in liquid cod-liver oil, may increase the risk of developing hypertensive disorders in pregnancy.

Inotropic response of rat heart papillary muscle to alpha 1- and beta-adrenoceptor stimulation in relation to dietary n-6 and n-3 polyunsaturated fatty acids (PUFA) and age.

The effect of dietary n-6 and n-3 polyunsaturated fatty acids (PUFA) and age on inotropic responses of heart papillary muscle to alpha 1-or beta-adrenoceptor stimulation was examined in young (4 months), middle-aged (12 months) and senescent (27 months) male Wistar rats. From the age of two months the rats were fed a diet containing 2% or 12% of fat by weight varying in PUFA type: a) standard low-fat n-6 PUFA diet, b) high-fat n-6 PUFA diet or c) high-fat n-3 PUFA diet. The inotropic responses to alpha 1-adrenoceptor stimulation with phenylephrine were triphasic (positive, negative, then positive). Young, high-fat n-3 PUFA-fed rats exhibited significantly lower negative and higher positive responses to phenylephrine stimulation, and higher positive responses to isoprenaline stimulation than young, high-fat n-6 PUFA-fed rats. On the other hand, no such dietary-related difference was found between young rats fed a high-fat n-3 PUFA diet and a standard low-fat n-6 PUFA diet. The young high-fat n-6 PUFA-fed rats exhibited inotropic responses similar to those of the middle-aged and senescent rats within the three dietary groups. The time to peak force and the time of half relaxation did not differ within dietary and age groups. The findings indicate that dietary n-6 PUFA-rich supplementation at a young age induces changes resembling the effects of age, as evidenced by decreasing cardiac responses to adrenoceptor agonists, such as phenylephrine or isoprenaline.

Plasma fatty acids and lipids in two separate, but genetically comparable, Icelandic populations.

Levels of serum lipids and lipoproteins, and the fatty acid composition of plasma phospholipids, were measured in two genetically comparable, but widely separated, populations. The 1975 mortality rates for ischemic heart disease were significantly higher in one of these populations, the Manitoban residents of pure Icelandic descent, than in the other, a rural population from Northeastern Iceland. Two study populations, Icelanders and Icelandic-Canadians, were drawn from these larger populations. The study populations were matched for age and sex and divided into three age groups, 20-39, 40-59, and 60-69 years. In comparison to the Icelandic-Canadians, the Icelanders exhibited significantly higher levels of total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol, but lower triglyceride levels. Their plasma phospholipids contained significantly lower levels of saturated fatty acids (SFA), monounsaturated fatty acids, and n-6 polyunsaturated fatty acids (PUFA); but their n-3 PUFA levels were three times as high. It was additionally found that fatty acid composition of plasma phospholipids differed among Icelanders of different ages. SFA levels were significantly lower, and n-6 PUFA levels significantly higher, in the 20-39 year group than in the 60-69 year group, possibly due to different dietary fat consumption patterns between generations. No corresponding age-related difference in the fatty acid composition of plasma phospholipids was found in the Icelandic-Canadian study population. As the Icelandic and Icelandic-Canadian groups are assumed to be genetically similar, the biochemical differences between them are evidently due to environmental, probably dietary, differences. The findings indicate that n-3 PUFA may be cardioprotective in the context of an otherwise atherogenic diet.

Effects of dietary oils and methyl ethyl ketone peroxide on in vivo lipid peroxidation and antioxidants in rat heart and liver.

Weanling male Sprague-Dawley rats were fed diets for four weeks which differed in their content of n-6 (corn oil; CO) and n-3 fatty acids (fish oil; FO), but were similar in their content of saturated and monounsaturated fatty acids and vitamin E. At the end of the four-week feeding period, each dietary group was subdivided into two groups. One group received a single placebo injection of alpha-tocopherol-stripped corn oil (TSCO); the other group received a single injection of the free radical generator; methyl ethyl ketone peroxide (MEKP), in TSCO. Twenty-four hours after injection, the effect of dietary oil and MEKP treatment on endogenous lipid peroxide (LPO) production (measured as methylene blue formed by the "Determiner LPO" assay), glutathione (GSH) and vitamin E content, and fatty acid composition of phosphatidylcholine and phosphatidylethanolamine in heart and liver from unfasted animals were measured. FO-fed rats had significantly heavier hearts and livers, increased levels of n-3 fatty acids in membrane phospholipids, and higher liver LPO levels than CO-fed rats. MEKP treatment resulted in significantly lower body weights and liver GSH levels. The data indicate that dietary n-3 fatty acids increase lipid peroxidation in liver somewhat more than in heart. The study also demonstrates that the effect of induced oxidative stress due to a single dose of MEKP on lipid peroxide formation and antioxidant status in tissues from unfasted animals was independent of the dietary oils.

Influence of dietary cod liver oil on fatty acid composition of plasma lipids in human male subjects after myocardial infarction.

A randomized crossover study was carried out to investigate the fatty acid profile and concentrations of plasma lipids in male patients with myocardial infarction (MI) who supplemented their diet with 20 ml cod liver oil daily for 6 weeks. Subjects were divided into two groups, A and B. Group A received cod liver oil daily for 6 weeks after hospital discharge, but none for the subsequent 6 weeks. Group B did not start taking cod liver oil until 6 weeks after hospital discharge, and they then took cod liver oil for 6 weeks. Diet, medication or smoking habits were kept as constant as possible during the study. During the period of cod liver oil intake, eicosapentaenoic acid (20:5 (n-3), EPA) and docosahexaenoic acid (22:6 (n-3), DHA) increased significantly in phospholipids (PL), triglycerides (TG) and cholesterol esters (CE), whereas linoleic acid (18:2 (n-6), LA), dihomo-gamma-linolenic acid (20:3 (n-6), DHGLA) and arachidonic acid (20:4 (n-6), AA) were significantly decreased in phospholipids. The plasma level of TG was significantly decreased during the cod liver oil intake. Total cholesterol, high density lipoprotein (HDL) cholesterol, and levels of apolipoproteins A1 and B were not affected by cod liver oil in these MI patients.