Do high levels of n-3 polyunsaturated fatty acids in cell membranes increase the risk of postoperative atrial fibrillation?

OBJECTIVES: Postoperative atrial fibrillation (POAF) has been associated with an inflammatory response to the surgical procedure. n-3 long-chain polyunsaturated fatty acids (LC-PUFA) have been proposed for the prevention of POAF. We investigated the relationship between the plasma concentration of inflammatory mediators, levels of n-3 LC-PUFA in red blood cell (RBC) membrane lipids, and the risk of POAF after coronary artery bypass grafting (CABG). METHODS: A total of 125 patients who underwent CABG were studied. Inflammatory mediators in plasma and the content of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in RBC membranes were assessed. RESULTS: Sixty-two patients (49.6%) developed POAF. The POAF group had higher RBC levels of total n-3 LC-PUFA and DHA than did patients remaining in sinus rhythm (p < 0.05). Of the inflammatory mediators, only postoperative interleukin-6 levels differed, being higher in the POAF group (p < 0.05). Inflammatory mediators were not independent predictors of POAF by multivariable logistic regression analysis. Higher levels of DHA and total n-3 LC-PUFA in RBC membranes, measured immediately prior to CABG and on postoperative day 3, were linearly associated with an increased risk of POAF (p < 0.05). CONCLUSIONS: Our findings suggest that inflammatory mediators are not associated with the occurrence of POAF. Interestingly, high n-3 LC-PUFA levels in RBC membranes appear to increase the risk of POAF.

Plasma n-3 and n-6 fatty acids and the incidence of atrial fibrillation following coronary artery bypass graft surgery.

BACKGROUND: The anti-inflammatory or anti-arrhythmic effects of n-3 long-chain polyunsaturated fatty acids (LC-PUFA) may decrease the risk of postoperative atrial fibrillation (POAF), but interventional studies have yielded conflicting results. We examined the association between n-3 LC-PUFA and n-6 LC-PUFA in plasma phospholipids (PL) and POAF in patients undergoing coronary artery bypass grafting (CABG). METHODS: A total of 125 patients undergoing CABG were enrolled in the study. The levels of fatty acids in PL were measured preoperatively and on the third postoperative day. The endpoint was defined as POAF lasting ≥5 min. The incidence of POAF was compared between quartiles of the level of each fatty acid in plasma PL by univariate and multivariable analysis. RESULTS: The incidence of POAF was 49·6%. By univariate analysis, the incidence of POAF increased significantly with each higher quartile of pre- and postoperative docosahexaenoic acid (DHA) and diminished significantly with each higher quartile of pre- and postoperative arachidonic acid (AA). For postoperative total n-3 LC-PUFA, there was a significant U-curve relationship where the second quartile had the lowest incidence of POAF or 25·8%. In multivariable analysis, this U-curve relationship between n-3 LC-PUFA levels and POAF risk was not significant, whereas the association between POAF and DHA or AA remained statistically significant. CONCLUSIONS: This study suggests that n-3 LC-PUFA supplements might prevent POAF in CABG patients with low baseline levels of these fatty acids in plasma PL, but may be harmful in those with high levels. AA may play an important role in electrophysiological processes.

Does treatment with n-3 polyunsaturated fatty acids prevent atrial fibrillation after open heart surgery?

AIMS: To examine the effect of n-3 polyunsaturated fatty acid (PUFA) treatment on the incidence of post-operative atrial fibrillation (POAF). METHODS AND RESULTS: A prospective, randomized, double-blinded, placebo-controlled trial was conducted in patients admitted for coronary artery bypass grafting and/or valvular repair surgery. The patients received either n-3 PUFA capsules, containing a daily dose of 1240 mg eicosapentaenoic acid and 1000 mg docosahexaenoic acid, or olive oil capsules for 5-7 days prior to surgery and post-operatively until hospital discharge. The endpoint was POAF, defined as an episode detected by continuous electrocardiographic monitoring, lasting >5 min. A total of 170 patients were enrolled in the study, and 168 patients underwent surgery. Their median age was 67 (range 43-82) years, and 79.2% were males. There was no difference in baseline characteristics between the n-3 PUFA group (n = 83) and the placebo group (n = 85), and the incidence of POAF was 54.2 and 54.1% (P = 0.99), respectively. Factors associated with POAF included advanced age, peak post-operative C-reactive protein level, valvular surgery, lower body mass index, and non-smoking, but n-3 PUFA concentration in plasma lipids was not associated with POAF. CONCLUSION: There is no evidence for a beneficial effect of treatment with n-3 PUFA on the occurrence of POAF in patients undergoing open heart surgery.

Red blood cell n-3 polyunsaturated fatty acids in first trimester of pregnancy are inversely associated with placental weight.

OBJECTIVE: To investigate pregnancy outcome in relation to red blood cell (RBC) level of long-chain n-3 polyunsaturated fatty acids (PUFA) in the first trimester of pregnancy and the influence of lifestyle factors on the RBC level of long-chain n-3 PUFA. DESIGN AND SETTING: Observational study in a community with traditional fish and cod liver oil consumption. POPULATION: Seventy-seven healthy pregnant women. METHODS: The PUFA composition of RBC was measured in the 11th to 15th week of pregnancy. The women answered food frequency and lifestyle questionnaires. Information on pregnancy outcome was collected from birth records. MAIN OUTCOME MEASURES: Placental weight, long-chain n-3 PUFA in diet and RBC, smoking. RESULTS: Of all the pregnancy outcome variables tested, placental weight was the only one associated with long-chain n-3 PUFA in RBC. Inverse association was found between the proportion of long-chain n-3 PUFA in RBC and placental weight, adjusted for birthweight (p=0.035). The proportion of long-chain n-3 PUFA in RBC was positively related to long-chain n-3 PUFA intake (p<0.001) and negatively related to smoking (p=0.011). CONCLUSION: The human fetus relies on maternal supply and placental delivery of long-chain n-3 PUFA for optimal development and function, particularly of the central nervous system. Given the importance of dietary n-3 PUFA during pregnancy, further studies are warranted to investigate the relationship between placental weight, maternal long-chain n-3 PUFA status and smoking.

Docosahexaenoic acid in red blood cells of women of reproductive age is positively associated with oral contraceptive use and physical activity.

Optimal intake of the long-chain n-3 polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA) and proper balance between intake of n-6 PUFA and n-3 PUFA are important for human health. Considerable evidence exists to show that DHA has a marked benefit during pregnancy. Lifestyle factors can affect the biosynthesis of DHA from dietary precursors, incorporation into membranes and degradation. The purpose of this study was to investigate the PUFA composition of red blood cells (RBCs) from women (n=40) in reproductive age, and how it is affected by diet and other lifestyle factors. Of all the lifestyle factors tested oral contraceptive use and physical activity were the ones correlated with DHA in RBCs, after adjustment for DHA intake. The findings indicate that oral contraceptive use and physical activity have a positive impact on the DHA status, as assessed by RBC level, of women in reproductive age.

Effect of dietary n-3 polyunsaturated fatty acids on brain lipid fatty acid composition, learning ability, and memory of senescence-accelerated mouse.

Animal studies have shown that a deficiency in brain of the n-3 polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA) is associated with memory loss and diminished cognitive function. The senescence-accelerated prone 8 (SAMP8) mouse develops impairments in learning and memory at 8-12 months of age. The effect of diet supplemented with n-3 PUFA on brain phospholipid DHA status, learning, and memory ability in aged SAMP8 mice was investigated. At the age of 10 months, SAMP8 mice were fed either a low-DHA or a high-DHA diet for 8 weeks. In comparison to SAMP8 mice fed the low-DHA diet, those fed a high-DHA diet had improved acquisition and retention in a T-maze foot shock avoidance test and a higher proportion of DHA in hippocampal and amygdala phospholipids. This study demonstrates that, in mature animals, DHA is incorporated into brain phospholipids and that dietary n-3 PUFA is associated with delay in cognitive decline.

Positive association between DNA strand breaks in peripheral blood mononuclear cells and polyunsaturated fatty acids in red blood cells from women.

Lipid peroxidation of polyunsaturated fatty acids (PUFA) generates reactive products that may cause DNA damage. To examine the possible relationship between DNA damage in peripheral blood mononuclear cells (PBMC) and the concentration of PUFA in red blood cells (RBC), endogenous DNA strand breaks, formamidopyrimidine DNA glycosylase (FPG) sites, and hydrogen peroxide (H2O2) sensitive sites were evaluated by the comet assay in blood samples from 98 Icelandic women. Fatty acid composition of RBC was analyzed by gas chromatography. Endogenous DNA strand breaks in PBMC correlated positively with the concentration of total PUFA, total n-3 PUFA, docosahexaenoic acid, linoleic acid, oleic acid, and palmitic acid in RBC. However, there was no association between FPG sites or H(2)O(2) sensitive sites in DNA in PBMC and the concentration of total PUFA or total saturated fatty acid in RBC. As there was no association between oxidative DNA damage or sensitivity of DNA to oxidative stress and the concentration of PUFA in RBC, the positive association between endogenous DNA strand breaks in PBMC and the concentration of total PUFA in RBC is probably not related to oxidative stress.

Effects of storage time and added antioxidant on fatty acid composition of red blood cells at -20 degrees C.

The stability of PUFA in venous red blood cells (RBC) of women aged 25 to 55 years (n = 12) was investigated during storage at -20 degrees C. The RBC sample from each participant was divided into seven portions: one baseline with the antioxidant BHT, another without BHT, samples without BHT stored for 2, 4, 9, or 17 wk, and samples with BHT stored for 17 wk. No difference was found in proportions of PUFA at baseline and after storage for 2 and 4 wk without BHT, and 17 wk with BHT. After 9 wk without BHT the proportion of 22:6n-3 in RBC was lower, and after 17 wk without BHT proportions of all PUFA were lower than at baseline. High proportion of 22:6n-3 in RBC at baseline was associated with more stable concentration of total FA in RBC without BHT during 17 wk. The findings indicate that PUFA in RBC from healthy women are stable at -20 degrees C for 4 wk without BHT and for at least 17 wk with BHT.

Relationship between dietary intake of cod liver oil in early pregnancy and birthweight.

OBJECTIVE: To investigate the possible association between birth outcome and marine food and cod liver oil intake of healthy women in early (prior to 15 weeks of gestation) pregnancy. DESIGN: An observational study. SETTING: Free-living conditions in a community with traditional fish and cod liver oil consumption. POPULATION: Four hundred and thirty-five healthy pregnant Icelandic women without antenatal and intrapartum complications. METHODS: Dietary intake of the women was estimated with a semi-quantitative food frequency questionnaire (FFQ) covering food intake together with lifestyle factors for the previous three months. Questionnaires were filled out at between 11 and 15 weeks and between 34 and 37 weeks of gestation. The estimated intake of marine food and cod liver oil was compared with birthweight by linear and logistic regression controlling for potential confounding. MAIN OUTCOME MEASURES: Birthweight, cod liver oil intake, lifestyle factors (alcohol, smoking). RESULTS: Fourteen percent of the study population used liquid cod liver oil in early pregnancy. Regression analysis shows that these women gave birth to heavier babies (P < 0.001), even after adjusting for the length of gestation and other confounding. CONCLUSIONS: Maternal intake of liquid cod liver oil early in pregnancy was associated with a higher birthweight. Higher birthweight has been associated with a lower risk of diseases later in life and maternal cod liver oil intake might be one of the means for achieving higher birthweight.

Functional role, structure, and evolution of the melanocortin-4 receptor.

The melanocortin (MC)-4 receptor participates in regulating body weight homeostasis. We demonstrated early that acute blockage of the MC-4 receptor increases food intake and relieves anorexic conditions in rats. Our recent studies show that 4-week chronic blockage of the MC-4 receptor leads to robust increases in food intake and development of obesity, whereas stimulation of the receptor leads to anorexia. Interestingly, the food conversion ratio was clearly increased by MC-4 receptor blockage, whereas it was decreased in agonist-treated rats in a transient manner. Chronic infusion of an agonist caused a transient increase in oxygen consumption. Our studies also show that the MC-4 receptor plays a role in luteinizing hormone and prolactin surges in female rats. The MC-4 receptor has a role in mediating the effects of leptin on these surges. The phylogenetic relation of the MC-4 receptor to other GPCRs in the human genome was determined. The three-dimensional structure of the protein was studied by construction of a high-affinity zinc binding site between the helices, using two histidine residues facing each other. We also cloned the MC-4 receptor from evolutionary important species and showed by chromosomal mapping a conserved synteny between humans and zebrafish. The MC-4 receptor has been remarkably conserved in structure and pharmacology for more than 400 million years, implying that the receptor participated in vital physiological functions early in vertebrate evolution.

Hyperphagia modifies FA profiles of plasma phospholipids, plasma FFA, and adipose tissue TAG.

Hyperphagia was achieved by continuous intracerebroventricular infusion of a melanocortin receptor antagonist (HS024; Neosystem, Strasbourg, France) in rats. The effects of hyperphagia on FA composition and concentration of plasma phospholipids (PL), plasma FFA, and adipose tissue TAG were studied in rats for 8 d [short-term hyperphagia (STH); n = 8], or 28 d [long-term hyperphagia (LTH); n = 9]. The control rats were treated with artificial cerebrospinal fluid for 8 d (n = 8) or 28 d (n = 10). The rats were fed the same regular diet. In STH rats the plasma PL and fasting plasma FFA contained higher concentrations of saturated FA (SFA) and monounsaturated FA (MUFA), and plasma FFA contained lower n-6 PUFA than in the control rats. In LTH rats the plasma PL contained higher concentrations of SFA, MUFA, and n-3 PUFA and higher proportions of 16:1n-7 and 18:1n-9 at the expense of 18:2n-6 than in the control rats. In LTH rats the abundant dietary intake of 18:2n-6 did not enrich 18:2n-6 of the plasma PL or adipose tissue TAG. In LTH rats the fasting plasma FFA contained more than twofold higher concentrations of SFA and MUFA, and higher proportions of 16:1n-7 and 18:1n-9 at the expense of 18:2n-6 than in the control rats. This animal obesity model shows that LTH affects the FA composition and concentration of plasma PL, plasma FFA, and adipose tissue TAG, a result consistent with changes associated with increased risk of various diseases in humans. These results also demonstrate that LTH alters the FA composition of plasma PL and adipose tissue TAG in a way that does not reflect the FA composition of dietary fat.