Plasma EPA Research Articles

VERY LOW INTAKES OF [formula omitted]-3 FATTY ACIDS INCORPORATED INTO BOVINE MILK REDUCE PLASMA TRIACYLGLYCEROL AND INCREASE HDL-CHOLESTEROL CONCENTRATIONS IN HEALTHY SUBJECTS

Eight normolipidaemic volunteers, habitual partial skim milk drinkers and non-eaters of fish during the study, were given 500 ml day−1of partial skim milk for 1 month; they were then switched to 500 ml day−1of a novel commercially available milk preparation, supplying 400 mg of N-3 fatty acids—of which 300 mg were EPA+DHA—and 15 mg vitamin E, for 6 weeks. No changes in plasma lipid parameters were observed after the first run-in month; at 3 and 6 weeks on the N-3-rich milk, marked increments of plasma EPA (44 and 31%, respectively) and DHA (13 and 31%, respectively) were observed. Triacylglycerol (TG) concentrations decreased by 19% and high-density lipoprotein (HDL) concentrations increased by 19% at 6 weeks; plasma vitamin E rose by 21% while the susceptibility of plasma to oxidation was unaffected. Correlations were found between plasma EPA or DHA and TG, cholesterol, and HDL. In conclusion, the intake of a milk preparation providing low amounts of EPA+DHA to healthy individuals led to marked increases of N-3 fatty acids and vitamin E in plasma and in associated favourable changes in HDL and TG.

EDITORIAL: TUMOUR NECROSIS FACTOR AS A POTENTIAL TARGET FOR THE TREATMENT OF CONGESTIVE HEART FAILURE

Eight normolipidaemic volunteers, habitual partial skim milk drinkers and non-eaters of fish during the study, were given 500 ml day−1of partial skim milk for 1 month; they were then switched to 500 ml day−1of a novel commercially available milk preparation, supplying 400 mg of N-3 fatty acids—of which 300 mg were EPA+DHA—and 15 mg vitamin E, for 6 weeks. No changes in plasma lipid parameters were observed after the first run-in month; at 3 and 6 weeks on the N-3-rich milk, marked increments of plasma EPA (44 and 31%, respectively) and DHA (13 and 31%, respectively) were observed. Triacylglycerol (TG) concentrations decreased by 19% and high-density lipoprotein (HDL) concentrations increased by 19% at 6 weeks; plasma vitamin E rose by 21% while the susceptibility of plasma to oxidation was unaffected. Correlations were found between plasma EPA or DHA and TG, cholesterol, and HDL. In conclusion, the intake of a milk preparation providing low amounts of EPA+DHA to healthy individuals led to marked increases of N-3 fatty acids and vitamin E in plasma and in associated favourable changes in HDL and TG.

Antihypertensive Effect of All-cis-5,8,11,14,17-Icosapentaenoate of Aged Rats Is Associated with an Increase in the Release of ATP from the Caudal Artery

Fish oils have been shown to lower blood pressure in hypertensive subjects. All-cis-5,8,11,14,17-icosapentaenoate (EPA), one of the ω–3 polyunsaturated fatty acids, is known to be one of the major active components in fish oil that has beneficial effects on the cardiovascular system. However, little is known about the antihypertensive effect of EPA alone on blood pressure. In the present study, we have determined the spontaneous and noradrenaline-evoked release of ATP, ADP, AMP, and adenosine from caudal arteries of aged (100 weeks old) Wistar rats which were fed a standard diet or a high cholesterol diet, treated with EPA. Dietary EPA administration increased plasma and caudal arterial EPA concentrations and repressed increases in blood pressure with advancing age in both aged rats with and without hypercholesterolemia. In addition, noradrenaline (1 µmol/l) evoked a significantly greater release of purines from the caudal arteries of EPA-administered aged rats compared to both sets of control rats. Regression analysis revealed a significant relationship between the total amount of purines released from the artery and blood pressure. These results suggest that administration of EPA to aged rats increases the release of ATP from the vascular endothelial cells, leading to repression of the blood pressure rise seen with advancing age.

The Impact of Maternal Dietary N-3 Fatty Acids Upon Blood Levels of Docosahexaenoic Acid in the Newborn and Breast-Fed Infant

The importance of the maternal diet in infant nutrition is well established. Less well understood is the vital role of maternal dietary docosahexaenoic acid (DHA; 22:6n-3) and other n-3 fatty acids in the optimal development of the fetus and the breast-fed infant. DHA is a vital component of the phospholipid membrane of the brain, retina and spermatozoa. Another n-3 fatty acid, eicosapentaenoic acid (EPA; 20:5n-3) is involved in prostaglandin metabolism. This study compares the effects of long chain fatty acids (DHA and EPA) in the maternal diet upon their levels in the blood of the newborn baby and the infant. Twenty-nine women were recruited during the third trimester of pregnancy. Maternal intake of n-3 fatty acids was assessed during pregnancy, at 2, 4 and 12 months post partum and twice post lactation. Maternal blood was collected during the third trimester, at delivery, 2, 4 and 12 months post partum and twice post lactation. Maternal and cord blood were obtained at delivery; breast milk and infant blood were collected at 2, 4 and 12 months post partum. Women consumed their typical diets throughout the study. Significant correlations occurred between maternal and infant blood and milk. Maternal plasma DHA correlated with milk DHA at 2 and 12 months (r=0.71; P<0.001 and r=0.77; 0.03, respectively). Also, at 2 months infant plasma DHA correlated with milk DHA (r=0.69; P<0.001). At 12 months, maternal plasma EPA correlated with milk EPA (P<0.001). Only one significant correlation was found between maternal diet and maternal blood n-3 fatty acids. Maternal dietary EPA and plasma EPA were correlated at 2 months (r=0.45; p=0.02). No significant correlations were found between maternal diet and infant blood. At 4 months. maternal and infant red blood cells were significantly correlated for DHA (r=0.50; p=0.03) and EPA (r<0.52; p=0.02). These data indicate there is a relationship between the n-3 long chain fatty acids in the maternal diet and the levels of these fatty acids in maternal and infant blood and breast milk from birth to 12 months.

Prolonged inhibition of platelet aggregation after n-3 fatty acid ethyl ester ingestion by healthy volunteers

This study addressed two questions: 1) whether a relatively low dose of n-3 fatty acid ethyl esters (n-3 FAs) administered to healthy volunteers for a prolonged period of time would exert beneficial effects on plasma lipids, platelet function, and thromboxane biosynthesis; and 2) whether a short-term loading treatment (6 wk) with 6 g n-3 FAs/d followed by 12 wk with 3 g/d results in more pronounced effects. After 6 wk treatment a reduction of plasma triglyceride concentration and an accumulation of EPA and DHA in plasma were observed. A longer period of treatment with n-3 FAs was necessary to affect platelet aggregation and thromboxane A2 biosynthesis. At 12 and 18 wk, platelet aggregation, thromboxane A2 formation, and the excretion of thromboxane metabolites in urine were reduced, particularly in subjects who received 6 g n-3 FAs/d during the initial 6 wk. After treatment ended, triglyceride and thromboxane A2 biosynthesis returned to baseline values within 4 wk, whereas platelet aggregation remained impaired for > or = 14 wk. The longlasting impairment in platelet aggregation was accompanied by the retention of n-3 FAs in platelet phospholipids.

Linolenic Acid Provides a Source of Docosahexaenoic Acid for Artificially Reared Rat Pups

The goal of the present study was to determine the effectiveness of linolenic acid for enriching docosahexaenoic acid (DHA) in infant rats. Seven-day-old rat pups were artificially reared and fed intragastrically for 8 d a milk substitute containing either 1) corn oil, high in linoleic acid (35.6 g/100 g fatty acids, 775 kJ/L); 2) menhaden oil, high in DHA (3 g/100 g, 67 kJ/L) and eicosapentaenoic acid (EPA, 6 g/100 g, 132 kJ/L); or 3) linseed oil, rich in linolenic acid (34 g/100 g, 750 kJ/L). Growth rates were comparable among the artificially fed pups and those raised by lactating dams. Feeding the DHA precursor linolenic acid enriched EPA in plasma, erythrocytes and liver, but enriched DHA only in the liver, compared with feeding corn oil. The proportion of liver DHA in the pups fed the linolenic acid-rich substitute was twice that detected in the corn oil-fed pups and 60% of the level found in the pups fed the preformed DHA. The significant elevation of hepatic DHA indicates active desaturation and elongation in the developing rat liver. The failure to enrich erythrocyte DHA suggests the need for caution in the use of erythrocytes as an index of DHA status in tissues capable of in situ synthesis. The artificial rearing of rat pups was proven suitable for studying the interaction of dietary manipulation and tissue accretion of essential fatty acids during the postnatal development.

Changes of n − 3 and n − 6 fatty acids in plasma and circulating cells of normal subjects, after prolonged administration of 20:5 (EPA) and 22:6 (DHA) ethyl esters and prolonged washout

Eight normal volunteers (four men and four women) were treated with 3 × 1 g capsules of n − 3 fatty acid ethyl esters for a period of 18 weeks, followed by a 24 week washout. Fatty acids of plasma, platelets, monocytes and red blood cells were analyzed at 0, 6, 12 and 18 weeks of treatment and at 4, 14 and 24 weeks of washout. During treatment, accumulation of EPA in plasma and cells was almost maximal at 6 weeks, whereas that of DHA reached a peak at 18 weeks. Arachidonic acid declined somewhat at 12 weeks in plasma and more markedly at 18 weeks in red blood cells and monocytes. During washout, EPA returned rapidly toward pretreatment values in all compartments, but it remained significantly higher in plasma and platelets at the end of washout. DHA declined more slowly, maintaining higher than basal values in plasma and platelets and lower than basal in red blood cells, at the end of washout. Rebound increments of AA occurred in platelets and plasma. Finally, the plasma levels of AA, but not those of the n − 3 fatty acids, were more markedly modified in males than in females. The presented results suggest interactions between circulating fatty acids in the different compartments after n − 3 FA administration, and indicate that very long washouts are necessary for a complete recovery from the induced fatty acid modifications.

Influence of intravenous n‐3 lipid supplementation on fatty acid profiles and lipid mediator generation in a patient with severe ulcerative colitis

N-3 fatty acids were supplied to a 36-year-old female patient suffering from ulcerative colitis and severe steroid side-effects, in a sequence of parenteral and enteral administration. During a moderately active period of disease, 200 ml d-1 fish oil-derived lipid emulsion (eicosapentaenoic acid [EPA], 4.2 g; docosahexaenoic acid [DHA], 4.2 g) was infused for 9 days, in parallel with rapid tapering of the steroid dose. Disease activity declined rapidly, and the patient was subsequently provided with 16 fish oil capsules per day (EPA, 2.9 g; DHA, 1.9 g) for 2 months. At the end of this period of therapy, severe colitis recurred with intestinal and extraintestinal manifestations. The n-3 lipid emulsion was then used for intravenous alimentation (29 days, maximum dose 300 ml per day); during this time, marked improvement of the inflammatory bowel disease was noted. During both periods of parenteral n-3 lipid administration, total plasma EPA and DHA contents increased several-fold, surpassing that of arachidonic acid; this plasma n-3 fatty acid enrichment was only maintained to a minor extent during the intermediate period of dietary fish oil supplementation. The intravenously administered EPA-containing triglycerides were rapidly hydrolyzed, as evidenced by the appearance of substantial quantities of EPA in the plasma free fatty acid fraction. Platelet and neutrophil total membrane content of EPA and DHA as well as n-3 fatty acid/AA membrane ratios similarly increased during the periods of intravenous n-3 lipid administration and declined during oral fish oil uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

The influence of a fish oil high in docosahexaenoic acid on plasma lipoprotein and vitamin E concentrations and haemostatic function in healthy male volunteers.

Nine healthy male subjects consumed a daily fish oil supplement providing 2.1 g docosahexaenoic acid (22:6 n-3; DHA) and 0.8 g eicosapentaenoic acid (20:5 n-3; EPA) for 6 weeks. The proportion of EPA and DHA in plasma, erythrocytes, leucocytes and platelet phospholipids was increased by the supplement. Plasma concentration of triacylglycerol and very-low-density-lipoprotein-cholesterol were lowered and those of high-density-lipoprotein (HDL)- and HDL2-cholesterol and apoprotein B were increased. Platelet aggregation and thromboxane B2 production induced by collagen were partially inhibited. Both systolic and diastolic blood pressure fell during treatment and rose following withdrawal of the supplement. Statistically significant reductions in erythrocyte counts, packed cell volume and haemoglobin and increases in total leucocyte and monocyte counts occurred with the supplement. Plasma alpha-tocopherol concentrations fell below the normal range during the period of supplementation. It is suggested that future studies consider components other than EPA in fish oil. Further studies are needed to investigate the extent to which fish oil increases the requirement for antioxidant nutrients.

血せんと脂質に関する研究 Ｖ ＥＰＡの脂質および凝固系におよぼす影響について

The purpose of the study was to investigate the effect of eicosapentaenoic acid (c20: 5, ω3; EPA) on the serum lipids and fatty acid profiles, platelet functions and coagulation systems.Highly concentrated (75%) EPA ethylester, which was isolated and purified from sardine oil, was given to 17 patients suffering from hyperlipoproteinemia and/or hypertension for at least 16 weeks. Daily doses of EPA were 0.9g in 6, 1.8g in 7 and 2.7g in 4 patients. Initial mean total cholesterol level (TC) was 270.9±45.0mg/dl and reduction rates of TC were 4.4% at 4 week-period, 5.8% at 8 week-period, 3.1% at 16 week-period and 6.4% at 12 month-period of the treatment. Triglyceride level fell significantly, 20.9% at 4 week-period, 13.0% at 16 week-period and 18.6% at 12 month-period. HDL-cholesterol did not significantly change throughout the treatment. Changes in plasma main fatty acid profiles were shown in fig 1. plasma EPA increased from 1.84mol% to 5.41mol% after 4 weeks and 4.77mol% after 16 weeks, while other polyunsaturated fatty acids except arachidonate inclined to decrease. Above all, plasma linoleate fell significantly after taking EPA. No correlation between ΔTG and Δlinoleate suggests that exogenous EPA bound mainly to β-position of triglyceride and phospholipids in competition with other polyunsaturated fatty acids.As for platelet functions, no significant changes in platelet adhesiveness and collagen induced aggregation were observed. 1μM ADP induced aggregation lowered from 46.6% in maximal amplitued before the treatment to 29.0% at 16 week-period, 7.1% at 6 month-period and 27.3% at 12 month-period. Over 5mol% of EPA in plasma inhibited ADP induced aggregation. Coagulability expressed by thromboelastogram tended to be reduced, however, prothrombin time, PTT, antithrombin III, α2 macroglobulin and α1 antitrypsin did not alter.In conclusion, EPA reduced both serum lipids and ADP induced aggregation, which would be favourable for the prevention of atherosclerotic thrombotic diseases.

Effects of orally administered ethyl ester of eicosapentaenoic acid (EPA; C20:5, ω-3) on PGI 2-like substance production by rat aorta

A highly purified ethyl ester of EPA (EPAEE) (74%) was manufactured from sardine oil. Sixty mg/kg/day of EPAEE was given orally to male Wishar rats for 8 weeks. No side effect or toxicity from the administration of EPAEE was observed. Plasma EPA concentration and the ratio of EPA to arachidonic acid were significantly increased, compared with control Wistar rats. An enhancement of PGI 2-like substance production by aortas obtained from rats fed EPAEE was noted. Conversion of EPA to Λ 17-6-keto-PGF 1α, a stable metabolite of PGI 3, could not be detected by an incubation study of 14C-EPA and aortas either from rats fed EPAEE or from control rats. Therefore, PGI 2-like substance produced by rat aorta is most likely to be PGI 2. itself and not PGI 3.