N-3 fatty acids do not prevent restenosis after coronary angioplasty: results from the CART study. Coronary Angioplasty Restenosis Trial.
(9/2038)
OBJECTIVES: The aim of the study was to investigate whether omega-3 fatty acids (n-3 FA) reduce the occurrence of restenosis after percutaneous transluminal coronary angioplasty. BACKGROUND: Meta-analyses have shown significant reduction of restenosis after coronary angioplasty upon supplementation with n-3 FA. METHODS: In a prospective, placebo-controlled, double-blind study, 500 patients were randomly allocated to treatment with n-3 FA (Omacor, Pronova AS, Oslo, Norway) 5.1 g/day or corn oil (placebo) starting at least two weeks prior to elective coronary angioplasty. The treatment was continued until restenosis evaluation by quantitative coronary angiography after six months. Stenosis was defined as a minimal luminal diameter (MLD) < 40% of the reference diameter. Successful coronary angioplasty was defined as > or = 20% acute gain in MLD and a residual stenosis < 50%. Restenosis was defined as > or = 20% late loss of diameter and stenosis > 50% or an increase in stenosis of > or = 0.7 mm. Three-hundred ninety-two patients fulfilled the criteria for initial stenosis and successful coronary angioplasty, and, except four patients who died, none were lost for follow-up. RESULTS: Restenosis occurred in 108/266 (40.6%) of the treated stenoses in the Omacor group and in 93/263 (35.4%) in the placebo group (odds ratio [OR] 1.25, 95% confidence interval [CI] [0.87-1.80] p = 0.21). In the Omacor group one or more restenoses occurred in 90/196 (45.9%) patients as compared with 86/192 (44.8%) in the placebo group (OR 1.05, 95% CI [0.69-1.59] p = 0.82). CONCLUSIONS: Supplementation with 5.1 g n-3 FA/day for six months, initiated at least two weeks prior to coronary angioplasty did not reduce the incidence of restenosis. (+info)
(n-3) fatty acid supplementation in moderately hypertriglyceridemic adults changes postprandial lipid and apolipoprotein B responses to a standardized test meal.
(10/2038)
The effects of (n-3) fatty acids on the postprandial state were investigated by monitoring the alimentary responses to identical test meals fed to adults [n = 11; fasting triacylglycerol (TG) 2.55 +/- 0.24 mmol/L; mean +/- SEM] after a self-selected diet baseline period (BLP) and then after a 6-wk (n-3) fatty acid period (FOP) [ approximately 5.2 g (n-3) fatty acids] and a 6-wk control oil period (COP) administered in random order. Samples were drawn immediately prior to the test meal (time 0) and then hourly from 2 to 6 h postmeal. Postprandial plasma triacylglycerol (TG) and TG-rich lipoprotein (TRL) TG apo B48, and B100 absolute concentrations were significantly lower after FOP than after COP or BLP, while plasma cholesterol was unchanged. Normalizing the results as increments over time 0 eliminated the diet effect on all but plasma TG. Time remained a significant effect for plasma TG, TRL TG, and TRL TC. Finally, only absolute TRL B48 and absolute and incremental plasma TG concentrations displayed significant time-diet interactions. These results suggest that postprandial TRL apo B reductions are likely caused by (n-3) fatty acid suppression of both hepatic and intestinal apoB secretion/synthesis. Altered TRL metabolism, i.e. changes in postprandial TG, cholesterol, apo B48, and increase in LDL particle size, may represent an additional mechanism for the reduced heart disease risk associated with fish [(n-3) fatty acid] consumption. (+info)
The effect of supplementation with omega-3 fatty acids on soluble markers of endothelial function in patients with coronary heart disease.
(11/2038)
During progression of atherosclerosis the overlying endothelial cells alter their expression of some surface molecules. Circulating levels of such molecules may be quantified. We investigated the effect of omega-3 fatty acids (n-3 FA) on the levels of tissue plasminogen activator antigen, von Willebrand factor, and the soluble forms of thrombomodulin, P-selectin, E-selectin, and vascular cell adhesion molecule-1 in 54 patients with coronary heart disease. Twenty-three of the patients had taken 5.1 g/d n-3 FA for 6 months (group I) and 31 were given corn oil as placebo (group II). For another 4 weeks ("the study period") they all got 5.1 g/d of n-3 FA. Compliance was confirmed by demonstration of changes in relevant fatty acids in serum phospholipids. At baseline, significant differences between the groups were found with lower median values of von Willebrand factor (128% versus 147%) and soluble thrombomodulin (24.9 versus 32.5 ng/mL) and higher median values of soluble E-selectin (41.4 versus 35.5 ng/mL) and soluble vascular cell adhesion molecule-1 (573 versus 473 ng/mL) in group I. During the study period differences in changes between the groups were found; tissue plasminogen activator antigen and soluble thrombomodulin decreased (P for difference between the groups 0.001 and 0.015, respectively), whereas soluble E-selectin and soluble vascular cell adhesion molecule-1 increased (P for difference between the groups <0.01 for both) in group II relative to group I. Our results indicate that n-3 FA supplementation decreases hemostatic markers of atherosclerosis, whereas markers of inflammation may be increased. The latter may be the result of lipid peroxidation as a simultaneous decrease of vitamin E and increase in thiobarbituric acid-reactive substances were observed. (+info)
Cardiac (n-3) non-esterified fatty acids are selectively increased in fish oil-fed pigs following myocardial ischemia.
(12/2038)
The effect of fish oil supplementation on the nonesterified fatty acid (NEFA) concentration and composition in the normoxic and hypoxic myocardium of pigs was examined. Two groups of female pigs (n = 7) were fed a diet supplemented with either 5 g beef tallow/kg (as control) or 5 g fish oil/kg (MaxEPA) rich in (n-3) fatty acids. After 6 wk of supplementation, the pigs were anesthetized, hearts exposed by thoracotomy followed by occlusion of the left anterior descending artery. Normoxic and hypoxic regions of the heart were examined for NEFA concentration and composition by using a combination of thin layer and gas chromatography. Nonesterified (n-6) and (n-3) fatty acid concentration and composition differed significantly between the two groups in both the normoxic and hypoxic areas of the heart. Eicosapentaenoic and docosahexaenoic acid concentration in the NEFA fraction of the normoxic myocardium were higher in the fish oil group than in the beef tallow group (P < 0.001). In the fish oil-fed pigs, the (n-3) NEFA concentration was significantly higher in the hypoxic compared to the normoxic region of the heart. The fish oil-fed group had lower levels of arachidonic acid in the NEFA fraction compared to the beef tallow-fed group, whereas the hypoxic myocardium had higher levels of arachidonic acid, regardless of the dietary fat supplementation. Despite large differences in the proportions of saturated fatty acids in the experimental diets, there was little or no difference in the saturated fatty acid content of cardiac phospholipid and NEFA fractions. Following myocardial ischemia, (n-3) fatty acids in the NEFA fractions were selectively increased in the fish oil-fed pigs, implicating the possible role of nonesterified (n-3) polyunsaturated fatty acids in the prevention of arrhythmias. (+info)
An octaene fatty acid, 4,7,10,13,16,19,22,25-octacosaoctaenoic acid (28:8n-3), found in marine oils.
(13/2038)
We report structure determination of an octaene fatty acid, 4,7,10, 13,16,19,22,25-octacosaoctaenoic acid (28:8n-3). The molecular weight and double bond locations were determined using acetonitrile chemical ionization mass spectrometry (MS) and MS/MS and were confirmed by MS of hydrogenated and deuterogenated 28:8 and by argentation thin-layer chromatography. 28:8n-3 was 1.2 +/- 0.1%, in oil derived from the heterotrophic dinoflagellate Crypthecodinium cohnii and a commercial polyunsaturated fatty acid concentrate derived from fish oils (0.16 +/- 0.01%), both components of human dietary supplements. It was not found in whole bovine retina, cultured Y79 human retinoblastoma cells, or neonate baboon cerebral cortex. The long chain polyunsaturates present in the C. cohnii oil suggest a possible route for 28:8n-3 biosynthesis similar to that for biosynthesis of 22:6n-3. (+info)
Blockade by N-3 polyunsaturated fatty acid of the Kv4.3 current stably expressed in Chinese hamster ovary cells.
(14/2038)
1. The Kv4.3 gene is believed to encode a large proportion of the transient outward current (Ito), responsible for the early phase of repolarization of the human cardiac action potential. There is evidence that this current is involved in the dispersion of refractoriness which develops during myocardial ischaemia and which predisposes to the development of potentially fatal ventricular tachyarrhythmias. 2. Epidemiological, clinical, animal, and cellular studies indicate that these arrhythmias may be ameliorated in myocardial ischaemia by n-3 polyunsaturated fatty acids (n-3 PUFA) present in fish oils. 3. We describe stable transfection of the Kv4.3 gene into a mammalian cell line (Chinese hamster ovary cells), and using patch clamp techniques have shown that the resulting current closely resembles human Ito. 4. The current is rapidly activating and inactivating, with both processes being well fit by double exponential functions (time constants of 3.8 +/- 0.2 and 5.3 +/- 0.4 ms for activation and 20.0 +/- 1.2 and 96.6+/-6.7 ms for inactivation at +45 mV at 23 degrees C). Activation and steady state inactivation both show voltage dependence (V1/2 of activation= -6.7+/-2.5 mV, V1,2 of steady state inactivation= -51.3+/-0.2 mV at 23 degrees C). Current inactivation and recovery from inactivation are faster at physiologic temperature (37 degrees C) compared to room temperature (23 degrees C). 5. The n-3 PUFA docosahexaenoic acid blocks the Kv4.3 current with an IC50 of 3.6 micromol L(-1). Blockade of the transient outward current may be an important mechanism by which n-3 PUFA provide protection against the development of ventricular fibrillation during myocardial ischaemia. (+info)
Heart rate variability and fatty acid content of blood cell membranes: a dose-response study with n-3 fatty acids.
(15/2038)
BACKGROUND: Dietary intake of long-chain n-3 polyunsaturated fatty acids (PUFA) may protect against sudden cardiac death, an event that may be predicted by measurement of heart rate variability (HRV). OBJECTIVE: The objectives of this study were to 1) examine the correlations between the content of fatty acids in blood cell membranes (platelets and granulocytes) and HRV in healthy subjects, and 2) assess the effect on HRV of dietary intervention with n-3 PUFA in different doses. DESIGN: Sixty healthy volunteers (25 women and 35 men) were randomly assigned to 3 treatment groups in a double-blind design. Subjects received a daily supplement of either 6.6 g n-3 PUFA, 2.0 g n-3 PUFA, or placebo (olive oil). A 24-h Holter recording was obtained for each subject before supplementation and after 12 wk of supplementation; the 24-h HRV was then related to the content of fatty acids in granulocytes and platelets. RESULTS: Before supplementation, positive correlations were observed in men between the content of docosahexaenoic acid in cell membranes and HRV indexes (r = 0.50, P < 0.01), whereas such correlations were not found in women. Dietary intervention revealed a dose-dependent effect of n-3 PUFA on HRV in men, whereas no effect was found in women. CONCLUSION: The study showed a beneficial effect of n-3 PUFA on HRV in healthy men, suggesting an antiarrhythmic effect of n-3 PUFA. No such effect was observed in healthy women. (+info)
trans Fatty acids in human milk are inversely associated with concentrations of essential all-cis n-6 and n-3 fatty acids and determine trans, but not n-6 and n-3, fatty acids in plasma lipids of breast-fed infants.
(16/2038)
BACKGROUND: Human milk fatty acids vary with maternal dietary fat composition. Hydrogenated dietary oils with trans fatty acids may displace cis n-6 and n-3 unsaturated fatty acids or have adverse effects on their metabolism. The effects of milk trans, n-6, and n-3 fatty acids in breast-fed infants are unclear, although n-6 and n-3 fatty acids are important in infant growth and development. OBJECTIVE: We sought to determine the relations between trans and cis unsaturated fatty acids in milk and plasma phospholipids and triacylglycerols of breast-fed infants, and to identify the major maternal dietary sources of trans fatty acids. DESIGN: We collected milk from 103 mothers with exclusively breast-fed 2-mo-old infants, blood from 62 infants, and 3-d dietary records from 21 mothers. RESULTS: Mean (+/-SEM) percentages of trans fatty acids were as follows: milk, 7.1 +/- 0.32%; infants' triacylglycerols, 6.5 +/- 0. 33%; and infants' phospholipids, 3.7 +/- 0.16%. Milk trans fatty acids, alpha-linolenic acid (18:3n-3), arachidonic acid (20:4n-6), docosahexaenoic acid (22:6n-3) (P < 0.001), and linoleic acid (18:2n-6) (P = 0.007) were each related to the same fatty acid in infant plasma phospholipids. Milk trans fatty acids were inversely related to milk 18:2n-6 and 18:3n-3, but not to milk or infant plasma 20:4n-6 or 22:6n-3. trans Fatty acids represented 7.7% of maternal total fat intake (2.5% of total energy); the major dietary sources were bakery products and breads (32%), snacks (14%), fast foods (11%), and margarines and shortenings (11%). CONCLUSIONS: There were comparable concentrations of trans fatty acids in the maternal diet, breast milk, and plasma triacylglycerols of breast-fed infants. Prepared foods were the major dietary source of trans fatty acids. (+info)