Effect of polyunsaturated fatty acids of the n-3 and n-6 series on lipid composition and eicosanoid synthesis of platelets and aorta and on immunological induction of atherosclerosis in rabbits

The effect of dietary fish oil (rich in n-3 polyunsaturated fatty acids (PUFA], corn oil (rich in n-6 PUFA) and coconut oil (low in n-3 and n-6 PUFA) on the induction of atherosclerosis by serum sickness in rabbits was investigated over a 12-month period. Dietary fish oil led to a significant increase in the level of eicosapentaenoic acid (EPA) in all platelet phospholipid fractions and to a significant reduction in the level of platelet phosphatidylethanolamine arachidonic acid (AA). In aortic total phospholipids, rabbits given fish oil showed a significant reduction in AA and a significant increase in EPA. Rabbits given fish oil showed significantly lower collagen-induced platelet thromboxane A2 release and aortic production of 6-keto-PGF1 alpha. Serum total immune complex levels and anti-horse serum IgG levels were not influenced by diet. There was a significant reduction in total aortic atherosclerosis in fish oil-fed animals compared with coconut oil fed animals.     

Docosahexanoic acid and docosapentanoic acid incorporation into human platelets after 24 and 72 hours: Inhibitory effects on platelet reactivity

Short-term in vitro platelet membrane lipid enrichment studies and feeding trials of human subjects with eicosapentanoic acid (EPA) and docosahexanoic acid (DHA) have shown a decreased reactivity in the platelet response to collagen. In this study, exogenous albumin-bound n-3 polyunsaturated fatty acids (PUFAs), namely EPA, DHA and docosapentanoic acid (DPA) were added to platelet suspensions and maintained at 22 ° C for 24 and 72 hours. Subsequently, the aggregation response to agonist stimulation and the morphological appearance of the platelets were evaluated. A significant enrichment of platelet phospholipids (PL) in n-3 fatty acids occurred upon incubation with n-3 PUFAs in vitro, which was accompanied by a decrease in the aggregation response to collagen and preservation of platelet morphology compared with non-supplemented control platelet preparations. The inhibitory effect of the n-3 PUFAs appeared to be surface mediated in the case of DHA and DPA because the platelet response to agonist returned when the fatty acids were removed by washing. The platelet aggregation response after storage at 22 ° C was also evaluated in platelet suspensions collected from healthy individuals before and after 42 days of dietary supplementation with seal oil, rich in DPA and DHA. Unlike the in vitro supplementation, in vivo modification and enrichment of platelet PLs by ingestion of seal oil did not appear to improve platelet function during storage relative to the placebo group.     

Docosahexaenoic acid and docosapentanoic acid incorporation into human platelets after 24 and 72 hours: inhibitory effects on platelet reactivity

Short-term in vitro platelet membrane lipid enrichment studies and feeding trials of human subjects with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have shown a decreased reactivity in the platelet response to collagen. In this study, exogenous albumin-bound n-3 polyunsaturated fatty acids (PUFAs), namely EPA, DHA and docosapentanoic acid (DPA) were added to platelet suspensions and maintained at 22 degrees C for 24 and 72 hours. Subsequently, the aggregation response to agonist stimulation and the morphological appearance of the platelets were evaluated. A significant enrichment of platelet phospholipids (PL) in n-3 fatty acids occurred upon incubation with n-3 PUFAs in vitro, which was accompanied by a decrease in the aggregation response to collagen and preservation of platelet morphology compared with non-supplemented control platelet preparations. The inhibitory effect of the n-3 PUFAs appeared to be surface mediated in the case of DHA and DPA because the platelet response to agonist returned when the fatty acids were removed by washing. The platelet aggregation response after storage at 22 degrees C was also evaluated in platelet suspensions collected from healthy individuals before and after 42 days of dietary supplementation with seal oil, rich in DPA and DHA. Unlike the in vitro supplementation, in vivo modification and enrichment of platelet PLs by ingestion of seal oil did not appear to improve platelet function during storage relative to the placebo group.     

Long-term saturated fat supplementation in the rat causes an increase in PGI2/TXB2 ratio of platelet and vessel wall compared to n-3 and n-6 dietary fatty acids

The effect of long-term manipulation of dietary lipid intake on platelet and vessel wall lipid composition and eicosanoid synthesis was investigated. Rats were fed a standard diet (REF diet) supplemented (12% w/w) with either sheep fat (SF), sunflower seed oil (SSO) or tuna fish oil (TFO) for a period of 15 months. Significant compositional changes both in the aorta and platelets were observed following dietary lipid treatment and differences between these tissues were particularly apparent with regard to the incorporation and conversion of n-3 fatty acids. For example, platelets displayed a selective accumulation of eicosapentaenoic acid (EPA, 20:5 n-3) over docosahexaenoic acid (DHA, 22:6, n-3), but in the aorta the proportion of DHA was considerably higher than that of EPA. In both tissues, compared to REF diet, n-3 dietary fatty acids replaced the n-6 unsaturates 20:4 and 22:4, but did not affect the proportion of linoleic acid. In contrast to aorta, the unsaturation index for platelet membrane varied significantly between dietary groups. The capacity of aorta and platelets to generate PGI2-like activity and thromboxane was unaltered by the SSO diet. However, changes were seen following SF and TFO supplementation. Rats fed the SF diet displayed a greater synthetic capacity whilst in animals maintained on TFO diet the synthesis of these two eicosanoids was considerably suppressed. The SF group displayed the highest value for PGI2/TXB2 ratio whereas TFO diet fed rats showed the lowest which may partly be due to synthesis of TXA3. The reduction in eicosanoids following the tuna fish oil supplementation can be explained on the basis of concurrent compositional changes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparative effects of feeding different fats on fatty acid composition of major individual phospholipids of rat hearts

Comparative effects of feeding dietary linoleic (corn oil), oleic (olive oil), alpha-linolenic (soybean oil) and polyunsaturated fatty acids (fish oil) on lipid content and fatty acid composition of major individual phospholipids of rat hearts were examined. Feeding different diets did not result in lipid accumulation in the heart. Total triglyceride, nonesterified fatty acid, cholesteryl ester and phospholipid levels of heart tissue were not affected by the type of dietary fatty acid. However, heart free cholesterol levels decreased in both animals fed the olive and the fish oil diets. The percentage of individual phospholipids, phosphatidylcholine (PC), phosphatidylethanolamine (PE) and cardiolipin (CL) did not modify by changes in the dietary fat composition. Heart tissue from animals fed on olive oil were enriched with 18:1 (n-9 + n-7) fatty acid in all phospholipid fractions. Animals fed corn oil contained higher proportions of 18:2 (n-6) for PC, PE and CL, and the ingestion of the soybean oil diet increased 18:2 (n-6) for PC and CL in the same proportion as the ingestion of the corn oil diet. The levels of 22:6 (n-3) were increased in the fish oil-fed group, accompanied by both a decrease in total (n-6) fatty acids and an increase in total (n-3) fatty acids in the three phospholipid fractions. The 20:5 (n-3) was only detected in these animals. These results show that olive oil is as effective as fish oil in reducing heart cholesterol content and support earlier works suggesting the role of fish oil in preventing cardiovascular disease.     

Alterations in the lipids and prostaglandins in mouse spleen following the ingestion of menhaden oil

Two groups of male mice were fed for 2 weeks with a semisynthetic diet supplemented with either 10% hydrogenated coconut oil or 10% menhaden oil. The spleen from animals fed with menhaden oil contained significantly higher amounts of polyunsaturated n-3 fatty acids. The n-3 fatty acids reciprocally replaced arachidonic acid in the phospholipids. The synthesis of 6-keto prostaglandin F1 alpha and prostaglandin E2 by spleen tissues were significantly depressed (70-80%) in mice consuming menhaden oil. These studies indicated that n-3 fatty acids can effectively displace arachidonic acid from spleen lipids and thereby affect the synthesis of prostaglandins. The implications of these observations are discussed.     

Comparative changes in the fatty-acid composition of rat cardiac phospholipids after long-term feeding of sunflower seed oil- or tuna fish oil-supplemented diets

The fatty-acid composition of rat heart phospholipids was examined after long-term, i.e. more than 12 months, feeding of diets supplemented with n-6 fatty acids as sunflower seed oil (SSO), or n-3 fatty acids as tuna fish oil (TFO) which is a particularly rich source of docosahexenoic acid (DHA). Although some small changes occurred in the relative proportions of palmitic and stearic acids and in the ratio of total saturates to total unsaturates, the most important changes were in the relative proportions of 18:2 n-6 and 20:4 n-6 to 20:5 n-3 and 22:6 n-3. In general, the n-6/n-3 ratio of phosphatidylcholine (PC), phosphatidylethanolamine (PE) and diphosphatidyl glycerol (DPG) was altered in favour of the family of fatty acids administered, although the proportions of the individual long-chain polyunsaturated fatty acids which contributed to this ratio varied from one class of phospholipids to another. In cardiac PC and PE, feeding TFO supplements reduced the proportions of arachidonic acid (AA) and significantly elevated (p less than 0.01) the proportions of DHA but produced relatively little change in those of eicosapentenoic acid (EPA). In DPG, feeding TFO led to a significant increase in the proportion of AA as well as an increase in DHA. The level of EPA was relatively low in PC, PE and DPG even after TFO feeding and never reached comparable levels with that of either AA or DHA. Nevertheless the n-6/n-3 ratio in all these classes of major cardiac phospholipids was significantly reduced by feeding TFO compared to the SSO diet or the commercial rat chow (CC) reference group. In contrast to the reports of other workers who have studied the fatty-acid composition of platelet membranes after feeding various fish oil supplements, in the rat heart the major effect of tuna fish oil is an increase in the proportion of DHA rather than EPA in the cardiac phospholipids.     

The Effect of Cod Liver Oil in Two Populations with Low and High Intake of Dietary Fish

ABSTRACT Two subgroups of healthy males from an inland and a coastal community in Norway with a traditionally low and high consumption of dietary fish were given a dietary supplement of 20 ml cod liver oil rich in n-3 polyunsaturated fatty acids for 3 weeks. Cod liver oil induced an increase in serum high density lipoprotein (HDL) cholesterol in men from the inland. Both groups showed a prolonged primary bleeding time, whereas platelet aggregation and thromboxane A₂ production induced by collagen were mainly unaffected. Platelet phospholipid fatty acids showed similar changes in both groups with a decrease in n-6 and an increase in n-3 polyunsaturated fatty acids. No changes were observed in total cholesterol or platelet phospholipid content. This study shows that dietary supplement with cod liver oil induces changes in serum lipids and platelets that may reduce the tendency to thrombosis both in subjects with a low and in those with a high intake of dietary fish. The effects were more pronounced in the subjects with a traditionally low fish consumption.     

Fatty acid compositions of serum lipids, erythrocytes, and platelets in insulin-dependent diabetic women

The fatty acid composition of serum lipids, erythrocytes, platelets, and diet was studied in women with insulin-dependent diabetes (IDDM) and in normal subjects matched for age, sex, body weight, and serum lipid levels. The dietary intake of linoleic acid was higher in IDDM patients than in the normal subjects. The linoleic acid content of serum triglycerides, cholesterol esters, and phospholipids and of red cells and platelets were elevated in patients with IDDM proportionately to their dietary linoleate intake. The linoleic acid content of serum lipids, but not of diet, was significantly correlated with glycosylated hemoglobin A1c in IDDM patients. However, the serum lipid content of arachidonic acid and other n-6 polyunsaturated fatty acids, which are metabolites of linoleic acid, was decreased in IDDM patients, but these metabolites were normal or increased in their cell membranes. The contents of n-3 polyunsaturated fatty acids were decreased in serum and platelet lipids and tended to be increased in erythrocyte membranes of diabetic patients. The results suggest that elongation and desaturation of essential fatty acids, linoleic acid in particular, are decreased in women with IDDM.     

Decreasing atherogenic risks by an eicosapentaenoic acid-rich diet

(n-3) diets rich in polyunsaturated fatty acids (PUFA) reduce the atherogenic lipoproteins, especially the VLDL (very low density lipoproteins) rich in triglycerides but also the LDL, more effectively than (n-6) PUFA-rich diets. Moreover also other parameters such as high blood pressure and aggregation of thrombocytes are positively influenced, similarly like after (n-6) PUFA-rich diet. Eicosapentaenoic acid (20:5, n-3) has a triglyceride- and cholesterol-reducing effect by inhibition of the VLDL-synthesis (apolipoprotein B, triglycerides) in the liver, inhibition of lipogenic liver enzymes, accelerated elimination of VLDL from the circulation, increased excretion of steroids and bile acids into the stools and amelioration of the fat tolerance. The prolongation of the period of haemorrhage and the decrease of the aggregation of thrombocytes is associated with the enrichment of EPA in the platelet membrane. In these cases the decreased thrombocyte-vascular vessel-interaction shall be caused by a changed metabolism of the eicosanoids (secondary products of unsaturated fatty acids with 20 carbon atoms) and eicosanoid-independent mechanisms.     

Diets rich in saturated n-9 and n-3 fatty acids differentially affect the fatty acid composition of phospholipids and function of rat platelets

The aim of the present study was to determine whether dietary intake of monounsaturated or long chain n-3 fatty acids could be effective in lowering platelet responsiveness through modulation of platelet phospholipid composition. Rats were fed diets containing 20% fat with equal cholesterol and 13a-tocopherol contents. These diets were supplemented with saturated, oleic or n-3 fatty acids, n-3 polyunsaturated fatty acids being added either pure, as eicosapentaenoic and docosahexaenoic ethyl esters, or as MaxEPA oil. Dietary n-3 fatty acids did not affect the oxidation status of plasma lipids. Oleic acid- and saturated fatty acid-rich diets led to similar enrichment of platelet phospholipids in arachidonic acid and to comparable thromboxane A(2) generation on stimulation with collagen or thrombin. Platelets of n-3-fed groups were differently enriched in eicosapentaenoic and docosahexaenoic acids at the expense of arachidonic acid. These groups displayed similar thromboxane A(2) production, although levels were lower than those for groups fed with oleic- or saturated fatty acid-rich diets. Only the MaxEPA diet led to a reduction in platelet reactivity, measurable as a small decrease in the aggregation induced by collagen. This diet was also responsible for a high cholesteroUphospholipid ratio and low a-tocopherol content in platelets. Overall results indicated that (i) only MaxEPA reduced platelet reactivity and (ii) this effect was moderate and apparently unrelated to platelet arachidonic acid content, membrane cholesterol to phospholipid ratio or thromboxane A(2) production.     

Effects of Dietary Supplementation with n-6 and n-3 Long-chain Polyunsaturated Fatty Acids on Serum Lipoproteins and Platelet Function in Hypertriglyceridaemic Patients

ABSTRACT Twenty-seven patients with hypertriglyceridaemia were given dietary supplementation either with evening primrose oil rich in gammalinolenic acid (GLA, 18: 3 n-6) (n=13) or a marine oil concentrate containing n-3 fatty acids (n=14) in a double-blind cross-over design during 8+8 weeks with olive oil as placebo. During GLA supplementation, increases in GLA and dihomogammalinolenic acid (20: 3 n-6) were found in plasma lipid esters and platelet phospholipids, whereas platelet function and serum lipoproteins were unaffected. During supplementation with n-3 fatty acids there was a significant decrease in triglycerides in all lipoprotein fractions with a slight increase in high density lipoprotein and low density lipoprotein cholesterol. A marked increase in the long-chain n-3 fatty acids was found both in plasma and platelets, mainly at the expense of the n-6 fatty acids. No pronounced effects on platelet reactivity could be demonstrated. Our results confirm a triglyceride-lowering effect of n-3 fatty acids, whereas no such effect of GLA could be demonstrated.     

Influence on serum lipids, lipoproteins and blood pressure of mackerel and herring diet in patients with type IV and V hyperlipoproteinemia

Eight patients with type IV and V hyperlipoproteinemia were put on a mackerel and herring diet of an isocaloric regimen for 2 weeks, in a cross-over design. At the end of the dietary periods a predominant increase of eicosapentaenoic acid (EPA - C20:5, n-3) in cholesterol esters and of docosahexaenoic acid (DHA - C22:6, n-3) in serum triglycerides, being more pronounced after mackerel as compared to herring diet, could be confirmed. After mackerel diet serum triglycerides and total cholesterol were significantly lower, returning to basal levels 3 months later. High density lipoprotein (HDL) cholesterol appeared slightly increased after mackerel diet and decreased to initial values thereafter. After herring diet, which contained half as much EPA as compared to mackerel diet, the differences were minor. The decline of free fatty acids (FFA) and insulin at the end of the mackerel period reached the level of significance 60 min and 120 min, respectively, after glucose load. A significantly lower systolic blood pressure in recumbent and upright position after the mackerel period could be found, whereas diastolic pressure and blood pressure after herring diet remained unchanged.     

Diets rich in saturated n-9 and n-3 fatty acids differentially affect the fatty acid composition of phospholipids and function of rat platelets

The aim of the present study was to determine whether dietary intake of monounsaturated or long chain n-3 fatty acids could be effective in lowering platelet responsiveness through modulation of platelet phospholipid composition. Rats were fed diets containing 20% fat with equal cholesterol and 13a-tocopherol contents. These diets were supplemented with saturated, oleic or n-3 fatty acids, n-3 polyunsaturated fatty acids being added either pure, as eicosapentaenoic and docosahexaenoic ethyl esters, or as MaxEPA oil. Dietary n-3 fatty acids did not affect the oxidation status of plasma lipids. Oleic acid- and saturated fatty acid-rich diets led to similar enrichment of platelet phospholipids in arachidonic acid and to comparable thromboxane A₂ generation on stimulation with collagen or thrombin. Platelets of n-3-fed groups were differently enriched in eicosapentaenoic and docosahexaenoic acids at the expense of arachidonic acid. These groups displayed similar thromboxane A₂ production, although levels were lower than those for groups fed with oleic- or saturated fatty acid-rich diets. Only the MaxEPA diet led to a reduction in platelet reactivity, measurable as a small decrease in the aggregation induced by collagen. This diet was also responsible for a high cholesteroUphospholipid ratio and low a-tocopherol content in platelets. Overall results indicated that (i) only MaxEPA reduced platelet reactivity and (ii) this effect was moderate and apparently unrelated to platelet arachidonic acid content, membrane cholesterol to phospholipid ratio or thromboxane A₂ production.     

Effects of long-chain polyunsaturated fatty acids on the contraction of neonatal rat cardiac myocytes.

Because of the ability of certain long-chain polyunsaturated fatty acids (PUFAs) to prevent lethal cardiac arrhythmias, we have examined the effects of various long-chain fatty acids on the contraction of spontaneously beating, isolated, neonatal rat cardiac myocytes. The omega 3 PUFA from fish oils, eicosapentaenoic acid [EPA; C20:5 (n-3)] and docosahexaenoic acid [DHA; C22:6 (n-3)], at 2-10 microM profoundly reduced the contraction rate of the cells without a significant change in the amplitude of the contractions. The fatty acid-induced reduction in the beating rate could be readily reversed by cell perfusion with fatty acid-free bovine serum albumin. Addition of either oxygenase inhibitors or antioxidants did not alter the effect of the fatty acids. Arachidonic acid [AA; C20:4 (n-6)] produced two different effects on the beating rate, an increase or a decrease, or it produced no change. In the case of the increased or unchanged beating rate in the presence of AA, addition of AA oxygenase inhibitors subsequently reduced the contraction rate. The nonmetabolizable AA analog eicosatetraynoic acid (ETYA) always reduced the beating rate, as did EPA or DHA. Two other PUFAs, linoleic acid [C18:2 (n-6)] and linolenic acid [C18:3 (n-3)] also exhibited similar but less potent effects compared with EPA or ETYA. In contrast, neither the monounsaturated fatty acid oleic acid [C18:1 (n-9)] nor the saturated fatty acids stearic acid (C18:0), myristic acid (C14:0), and lauric acid (C12:0) affected the contraction rate. The inhibitory effect of these PUFAs on the contraction rate was similar to that produced by the class I antiarrhythmic drug lidocaine. The fatty acids that are able to reduce the beating rate, particularly EPA and DHA, could effectively prevent and terminate lethal tachyarrhythmias (contracture/fibrillation) induced by high extracellular calcium concentrations or ouabain. These results suggest that free PUFAs can suppress the automaticity of cardiac contraction and thereby exert their antiarrhythmic effects.     

Altered levels of n-6/n-3 fatty acids in rat heart and storage fat following variable dietary intake of linoleic acid

Fat-supplemented dies enriched with linoleic acid by the addition of 12% w/w sunflower seed oil or proportionally reduced in linoleic acid by addition of 12% mutton fat were fed to rats for 18 months before the fatty acid composition of perirenal storage fat and myocardial membranes (phospholipids) was determined. Although the fatty acid composition of perirenal fat generally reflected that of the diet, there was an inverse relationship between the consumption of n-6 and the deposition of n-9 fatty acids. In addition, enhanced deposition of oleic acid (18:1, n-9) appears to be related to the dietary intake of stearic acid (18:0). In contrast, in myocardial membranes the n-3 polyunsaturated fatty acids are found to be increased when the intake of n-6 polyunsaturated fatty acids is reduced. This is particularly evident for docosahexaenoic acid (22:6, n-3) which is significantly increased in phosphatidylcholine, phosphatidylethanolamine, and diphosphatidylglycerol fractions of myocardial membranes, when the mutton fat diet was fed. After feeding the sunflower seed oil diet, the increased consumption of linoleic acid produced only small changes in the 18:2, n-6 content of cardiac phosphatidylcholine and phosphatidylethanolamine. These major classes of membrane phospholipids also showed only small increases in 20:4, n-6. In diphosphatidylglycerol, increased 18:2, n-6 also followed increased dietary intake, but this was not accompanied by increased 20:4, n-6. These changes in myocardial phospholipid fatty acid composition are similar to those observed after short-term feeding reported previously and confirm that changes in dietary n-6/n-3 fatty acid intake affect the fatty acid composition of both myocardial membranes and storage fat. These changes persist for the duration of the feeding period.     

Hepatic metabolism of dietary alpha-linolenic acid in suckling rats, and its possible importance in polyunsaturated fatty acid uptake by the brain

The presence of large amounts of long chain-polyunsaturated fatty acids (PUFA) in the brain implies an exogenous intake of unsaturated fatty acids, either as essential fatty acids, or in the form of higher homologues resulting from hepatic metabolism. To determine the influence of the diet upon the potential availability of polyunsaturated fatty acids to the brain, four different diets were used with comparable amounts of 18:2 n-6, but variable amounts of 18:3 n-3 (0.2, 1, 2 and 9%). These diets were administered to female rats from the day of mating and during the periods of gestation and lactation. Fifteen days after birth suckling animals were killed and the fatty acid distribution was studied in the serum in two lipoprotein classes (VLDL-LDL and HDL). On the whole, an increase in dietary 18:3 n-3 resulted in an increase of polyunsaturated fatty acids of the n-3 series and a decrease in fatty acids of the n-6 series. The modification chiefly concerned the terminal fatty acids in each series (22:5 n-6 and 22:6 n-3). It is noteworthy that the influence of exogenous 18:3 n-3 upon the 20:4 n-6 content of lipoproteins was not significant below 2% of 18:3 n-3 intake, a level that we have previously shown to be both necessary and sufficient to satisfy the requirements of the brain for fatty acids of the n-3 series. In the liver, the intermediary metabolism ensures an important release of long-chain polyunsaturated fatty acids, which may help to satisfy the lipid requirements of the brain.     

Alterations in molecular species of cholesterol esters formed via plasma lecithin-cholesterol acyltransferase in human subjects consuming fish oil

The influence of a dietary supplement of n-3 polyunsaturated fatty acids containing eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) on the molecular species of cholesteryl esters (CE) formed via the plasma lecithin (phosphatidylcholine)-cholesterol acyltransferase (LCAT; EC 2.3.1.43) reaction was evaluated. For this purpose, one group of eight subjects received an encapsulated fish lipid concentrate (MaxEPA) and another group of eight volunteers in the control group received encapsulated olive oil for 22 days. Plasma lipid profiles and fatty acid compositions of plasma phosphatidylcholine (PC) and CE were measured at day 0 and day 22 in all subjects. A decrease in plasma triglyceride (by 34%) and a moderate rise in high-density lipoprotein (HDL)-cholesterol (by 13%) was observed in the MaxEPA group. For characterization of the plasma LCAT-derived reaction products formed in vitro, [14C]cholesterol was used as the substrate and the newly formed molecular species of [14C]CE were separated by argentation thin-layer chromatography. Marked shifts were found in the abundance of the various classes of LCAT-derived products in the MaxEPA group whereas no significant changes were observed in the controls. The proportion of the [14C]CE as pentaenoic (EPA) species rose by 9-fold (from 1.5% at day 0 to 14.4% at day 22) as the dienoic (linoleate) species fell (from 50.6 to 39.2%); a moderate rise in the hexaenoic (DHA) species (from 1.7 to 2.4%) with no significant change in the tetraenoic (arachidonate) (AA) species was observed. The LCAT results were in the order of the observed shifts in the fatty acid patterns of the plasma CE.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma Lipoproteins and Fatty Acid Composition during a Moderate Eicosapentaenoic Acid Diet

ABSTRACT. The effect of a diet rich in marine fatty acids, especially eicosapentaenoic acid, on plasma lipids (total plasma cholesterol, HDL cholesterol, total triglycerides and apolipoproteins A and B) and fatty acid composition in plasma phosphatidylcholine (PC) was studied in 10 healthy men. They were maintained for 11 weeks on their normal diet which was partly replaced by 150–200 g of fatty fish per day. In the same individuals this diet had previously caused a delay in primary haemostasis and a decrease in platelet aggregability similar to that caused by acetylsalicylic acid, a known inhibitor of thromboxane A₂ formation. Apart from its effect on haemostasis, the fish diet substantially reduced serum triglycerides (by 43%, p < 0.01) but caused no changes in total plasma or HDL cholesterol or apolipoproteins A and B. After three weeks on the diet the proportion of plasma PC ω-3 polyunsaturated fatty acids increased (C20: 5 and C22: 6) and ω-6 fatty acids decreased (C18: 2 and C20:3). The relative plasma PC content of arachidonic acid was unaffected throughout. These alterations in plasma PC fatty acid composition were principally in accordance with those seen in platelet membrane PC. There was a linear correlation between the content of ω-3 and of ω-6 fatty acids in plasma PC with that of platelet PC as well as in predominate individual fatty acids of the two series. Six weeks after the volunteers had resumed their usual diet, total triglycerides and the fatty acid composition of plasma PC had returned to the original state.     

Dietary N-3 polyunsaturated fatty acids decrease biliary cholesterol saturation in gallstone disease.

Because fatty acid composition of biliary phospholipids influences cholesterol secretion into bile, we investigated whether replacement of n-1 monounsaturated or n-6 polyunsaturated fatty acids with n-3 polyunsaturated fatty acids in biliary phosphatidylcholines reduces supersaturation with cholesterol and prevents precipitation of cholesterol crystals in bile of gallstone patients. Seven patients with radiolucent gallstones in functioning gallbladders were studied before (control) and after 5 wk of dietary supplementation with marine fish oil (11.3 gm/day = 3.75 gm n-3 polyunsaturated fatty acids/day). Duodenal bile was collected for analysis during intravenous infusion of cholecystokinin. Gallbladder emptying in response to cholecystokinin was comparable before and during intake of n-3 polyunsaturated fatty acids. Intake of n-3 polyunsaturated fatty acids increased (p less than 0.001) the fractions of eicosapentaenoic and docosahexaenoic acids and decreased the fractions of linoleic (p less than 0.001) and arachidonic acids (p less than 0.02) in biliary phospholipids. Concomitantly, the molar ratio of cholesterol to phospholipids decreased (-19%; p less than 0.05). As a consequence, the cholesterol saturation index was reduced by -25% (p = 0.01), from 1.60 +/- 0.44 to 1.24 +/- 0.38. However, in vitro nucleation time of duodenal bile was not prolonged. The decrease in cholesterol saturation was not sufficient to prevent nucleation of cholesterol crystals in bile of gallstone patients. In conclusion, our data suggest that cholesterol saturation can be influenced by the fatty acid composition of the phosphatidylcholines secreted in bile.