Atorvastatin and omega-3 fatty acids protect against activation of the coagulation system in patients with combined hyperlipemia.

Activation of factor (F)VII by tissue factor may represent a critical event during plaque rupture in acute coronary syndromes. Patients with combined hyperlipemia are at high risk for developing coronary heart disease and their tendency to thrombosis may be accelerated during postprandial hyperlipemia. In the present double-blind, placebo-controlled parallel study, 42 patients with combined hyperlipemia and serum triglycerides between 2.0 and 15.0 mmol L(-1 )and serum cholesterol >5.3 mmol L-1 at the end of a 3-month dietary run-in period were treated with atorvastatin at 10 mg day-1 for at least 10 weeks. During the last 5 weeks the patients were randomized into two groups receiving 1.68 g day(-1) omega-3 fatty acids (omega-3 FA) or placebo (corn oil). The fasting levels of FVII antigen (FVII-Ag) and FVII coagulant activity (FVII:C) were high compared with healthy males. The fasting levels of activated FVII (FVIIa) and FVII-Ag correlated both to serum triglycerides and apolipoprotein A1 (apoA1). FVIIa and FVII:C increased during postprandial hyperlipemia. This increase of FVIIa correlated to the fasting triglyceride and apoA1 levels, but not to the degree of postprandial hypertriglyceridemia. The concentrations of fasting FVIIa in these patients were reduced in parallel with a reduction of fasting triglycerides by treatment with atorvastatin + placebo. This treatment also reduced the postprandial level of FVIIa. omega-3 FA in addition to atorvastatin further reduced FVIIa concentrations, fasting and postprandially, and also significantly reduced FVII:C and FVII-Ag during postprandial hyperlipemia. Prothrombin fragment 1 + 2 (F1 + 2) increased during postprandial hyperlipemia. This increase was significantly reduced after treatment with atorvastatin plus omega-3 FA. The increase of F1 + 2 measured as incremental area under the curve (iAUC) during postprandial hyperlipemia correlated to the fasting levels of FVIIa, FVII:C and FVII-Ag and also to the levels of these factors during postprandial lipemia. In conclusion, patients with combined hyperlipemia are at risk for activation of the coagulation system, particularly during postprandial lipemia. This activation may be significantly reduced by statins and omega-3 FA.

Increased lipid peroxidation during long-term intervention with high doses of n-3 fatty acids (PUFAs) following an acute myocardial infarction.

OBJECTIVE: To assess the oxidative burden of a highly concentrated compound of n-3 PUFAs as compared to corn oil by measuring thiobarbituric acid-malondialdehyde complex (TBA-MDA) by HPLC. We also studied the influence on TBA-MDA of statins combined with n-3 PUFAs or corn oil. DESIGN: A prospective, randomised, double-blind, controlled study. SETTING: One hospital centre in Stavanger, Norway. SUBJECTS: A total of 300 subjects with an acute myocardial infarction (MI). INTERVENTIONS: Gelatine capsules, containing 850-882 mg EPA and DHA as concentrated ethylesters, or 1 g of corn oil, were ingested in a dose of two capsules twice a day for at least 1 y. Alpha-tocopherol (4 mg) was added to all capsules to protect the PUFAs against oxidation. RESULTS: After 1 y TBA-MDA increased modestly in the n-3 PUFA group (n=125), as compared to the corn oil group (n=130), P=0.027. Multiple linear regression analyses of fatty acids in serum total phospholipids (n=56) on TBA-MDA measured after 12 months intervention, showed no dependency. Performing best subsets regression, serum phospholipid concentration of arachidonic acid (20:4 n-6 PUFA) was identified as a predictor of TBA-MDA at 12 months follow-up, P=0.004. We found no impact of statins on TBA-MDA. CONCLUSION: TBA-MDA increased modestly after long-term intervention with n-3 PUFAs compared to corn oil post-MI, suggesting biological changes induced by n-3 PUFAs, rather than simply reflecting their concentration differences. The peroxidative potential of n-3 PUFAs was not modified by statin treatment. SPONSORSHIP: : Pharmacia A/S and Pronova A/S, Norway.

Statins and omega-3 fatty acids in the treatment of dyslipidemia and coronary heart disease.

Dyslipidemia including hypercholesterolemia and hypertriglyceridemia often associated with low levels of HDL-cholesterol is a common and important cluster of risk factors for coronary heart disease. Dyslipidemia is also commonly associated with hypertension, hyperinsulinemia and central obesity in the metabolic syndrome. Lifestyle adjustments including increased physical activity and dietary modifications leading to weight reduction are important first steps in the prevention of coronary heart disease in patients with such abnormalities in lipid metabolism. When these adjustments are insufficient to achieve desirable results, the combined treatment with statins and omega-3 fatty acids is an efficient treatment alternative. Both statins and omega-3 fatty acids have documented their effects against coronary heart disease (CHD) both in primary and secondary prevention trials. The mechanisms involved are only partly explained, however, the synergistic effects of statins and omega-3 fatty acids significantly reduce the risk for CHD in patients with dyslipidemia.

[Antithrombotic treatment of atrial fibrillation in hospital]. / Antitrombotisk behandling av atrieflimmer i sykehus.

BACKGROUND: In clinical guidelines regarding atrial fibrillation, oral anticoagulation is recommended for patients over the age of 65 or with additional risk factors. The aim of the present study was to investigate how these recommendations are followed in clinical practice. MATERIAL AND METHODS: A retrospective study was conducted among patients hospitalized for atrial fibrillation at Tromsø University Hospital from 1995 to 1998. Data were obtained from hospital files. RESULTS: 362 patients with atrial fibrillation (57% men), mean age 68.4 years (range 24-96), were included. 23.5% had their first atrial fibrillation event. 224 (62%) patients experienced successful cardioversion during hospitalization(s), while 138 (38%) were discharged from hospital with chronic atrial fibrillation. 97 (70%) of these patients were given warfarin at discharge. Previous stroke and atrial fibrillation were significant predictors for warfarin prescription. Prescription did not increase with age. 28 (20%) of patients with chronic atrial fibrillation received acetylsalicylic acid, while 16 (12%) were not given antithrombotic treatment. INTERPRETATION: This study indicates a high degree of implementation of guidelines for antithrombotic treatment of patients with chronic atrial fibrillation in hospital practice.

Effects of atorvastatin and omega-3 fatty acids on LDL subfractions and postprandial hyperlipemia in patients with combined hyperlipemia.

BACKGROUND AND AIM: The aim of the present study was to see whether a moderate dose of omega-3 fatty acids (FA) potentiates the beneficial effects of statins on the high risk for coronary heart disease (CHD) in patients with combined hyperlipemia. METHODS AND RESULTS: In the present double-blind parallel study, 42 patients with combined hyperlipemia with serum triglycerides 2-15 mmol/L-1 and serum total cholesterol > 5.3 mmol/L-1 at the end of a three-month dietary run-in period were treated with 10 mg/d atorvastatin for 10 or more weeks. During the last 5 weeks they were randomized into two groups that received either 1.68 g/d omega-3 FA as ethylesters of eicosapentaenoic (45%) and docosahexaenoic acids (39%), or placebo (corn oil). As expected, atorvastatin significantly reduced serum total LDL-cholesterol (LDL-C), triglycerides and apolipoproteins B, E, CII and CIII, whereas HDL-cholesterol (HDL-C) was increased. Addition of omega-3 FA further increased HDL-C (p < 0.03), and reduced systolic blood pressure (< 0.03), while the small dense LDL-particles (LDL III) (p < 0.05) and postprandial hypertriglyceridemia (p < 0.01) were reduced compared with the baseline, though there were no significant differences to the placebo group. This may be related to the large individual variation in these parameters and the small number of patients. No significant effects on basic or postheparin activities of lipoprotein lipase or hepatic lipase were observed after atorvastatin with or without addition of omega-3 FA. CONCLUSIONS: This study indicates that addition of a low dose of omega-3 FA may further improve the risk profile for CHD in patients with combined hyperlipemia treated with atorvastatin. The effect is related to reduction of postprandial hyperlipemia and redistribution of LDL subfractions.

n-3 polyunsaturated fatty acids and cardiovascular diseases.

An expert round table discussion on the relationship between intake of n-3 polyunsaturated fatty acids (PUFA) mainly of marine sources and coronary heart disease at the 34th Annual Scientific Meeting of European Society for Clinical Investigation came to the following conclusions: 1. Consumption of 1-2 fish meals/wk is associated with reduced coronary heart disease (CHD) mortality. 2. Patients who have experienced myocardial infarction have decreased risk of total, cardiovascular, coronary, and sudden death by drug treatment with 1 g/d of ethylesters of n-3 PUFA, mainly as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The effect is present irrespective of high or low traditional fish intake or simultaneous intake of other drugs for secondary CHD prevention. n-3 PUFA may also be given as fatty fish or triglyceride concentrates. 3. Patients who have experienced coronary artery bypass surgery with venous grafts may reduce graft occlusion rates by administration of 4 g/d of n-3 PUFA. 4. Patients with moderate hypertension may reduce blood pressure by administration of 4 g/d of n-3 PUFA. 5. After heart transplantation, 4 g/d of n-3 PUFA may protect against development of hypertension. 6. Patients with dyslipidemia and or postprandial hyperlipemia may reduce their coronary risk profile by administration of 1-4 g/d of marine n-3 PUFA. The combination with statins seems to be a potent alternative in these patients. 7. There is growing evidence that daily intake of up to 1 energy% of nutrients from plant n-3 PUFA (alpha-linolenic acid) may decrease the risk for myocardial infarction and death in patients with CHD. This paper summarizes the conclusions of an expert panel on the relationship between n-3 PUFA and CHD. The objectives for the experts were to formulate scientifically sound conclusions on the effects of fish in the diet and the administration of marine n-3 PUFA, mainly eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3), and eventually of plant n-3 PUFA, alpha-linolenic acid (ALA, 18:3n-3), on primary and secondary prevention of CHD. Fish in the diet should be considered as part of a healthy diet low in saturated fats for everybody, whereas additional administration of n-3 PUFA concentrates could be given to specific groups of patients. This workshop was organized on the basis of questions sent to the participants beforehand, on brief introductions by the participants, and finally on discussion and analysis by a group of approximately 40 international scientists in the fields of nutrition, cardiology, epidemiology, lipidology, and thrombosis.

[Use of statins in hospitals after myocardial infarction]. / Bruk av statiner i sykehus etter hjerteinfarkt.

BACKGROUND: The objective of this study was to register the frequency of statin prescription during the initial hospitalization for acute myocardial infarction and therapeutic intensity at follow-up. MATERIAL AND METHODS: A retrospective study among patients aged below 70 of both sexes with acute myocardial infarction, who survived the initial hospitalization at the University Hospital of Tromsø during 1995-1998. RESULTS: 473 patients with acute myocardial infarction, 76% men, mean age 57.4 (range 33-70 yrs) were included. Statin treatment was started in 55% of the patients within discharge from the hospital. Total cholesterol (odds ratio 0.51, 0.41-0.64; 95% CI) and decreasing age (1.60, 1.21-2.10) were significant predictors for statin prescription. Statin treatment started during hospitalization increased gradually from 42% in 1995 to 91% in 1998 (p < 0.001) among patients with total cholesterol above 5.0 mmol/l at admission. 54% of the statin users achieved the treatment goal at their first outpatient control 8-12 weeks after discharge. INTERPRETATION: The proportion of statin users has increased satisfactory during 1995-98, but the therapeutic intensity is unsatisfactory compared to guidelines for cholesterol-lowering treatment of patients with acute myocardial infarction.

Relationship between apolipoprotein E polymorphism, postprandial hyperlipemia and hemostatic variables in patients with combined hyperlipemia.

BACKGROUND AND AIM: Combined hyperlipemia is a common lipid abnormality associated with coronary heart disease (CHD). Aim of this study was to investigate the relationship between this abnormality and hemostatic risk factors related to thrombosis. METHODS AND RESULTS: Forty-one patients were examined in the fasting state and during postprandial hyperlipemia. They had high levels of factor VIIc in the fasting state. During postprandial hyperlipemia a highly significant (p < 0.001) increase of activated factor (VIIa) occurred. This activation was not correlated to the increase in free fatty acids, but to the degree of postprandial hypertriglyceridemia. The absolute postprandial triglyceridemia was highest in subjects with the apolipoprotein (apo) E2 allele. Tissue factor pathway inhibitor activity (TFPIa) was correlated to LDL cholesterol and apo B concentrations and was highest in subjects with genotypes containing the E4 allele. CONCLUSIONS: Subjects with combined hyperlipemia may have an increased thrombotic risk related to activation of factor VII during postprandial hyperlipemia. Subjects with genotypes including the apoE4 allele may have a high lipid risk profile associated with high levels of LDL cholesterol.

Dietary supplementation with highly purified eicosapentaenoic acid and docosahexaenoic acid does not influence PAI-1 activity.

Impaired fibrinolysis due to elevated levels of plasminogen activator inhibitor type 1 (PAI-1) is a risk factor for atherothrombotic disease. Many studies have reported a positive correlation between serum triglycerides and PAI-1 activity. Dietary intervention with very long n-3 fatty acids from marine sources is known to decrease serum triglycerides, but an adverse increase in PAI-1 activity has been reported in some studies. A double blind, placebo controlled study was conducted among 224 middle-aged (ages 36-56), healthy, non-smoking men in which the participants were randomly assigned to daily supplementation with 3.8 g eicosapentaenoic acid/d, 3.6 g docosahexaenoic acid/d, or 4.0 g corn oil/d (placebo) for 7 weeks. PAI-1 activity increased by 2.35+/-6.24 U/ml (28%), 1.15+/-6.74 U/ml (14%), and 1.33+/-5.64 U/ml (22%) during dietary supplementation with eicosapentaenoic acid, docosahexaenoic acid, and corn oil, respectively, but the changes were not significantly different between groups. There was no relationship between change in concentrations of serum triglycerides or phospholipid n-3 fatty acids and change in PAI-1 activity. At baseline, analysis was performed to investigate the influence of dietary lipids, blood lipids, and serum fatty acids on plasma concentrations of PAI-1 activity. Dietary intake of saturated fat correlated directly with PAI-1 both in crude analysis and after adjustment for age and body mass index (kg/m(2)). Furthermore, PAI-1 was associated with body mass index, apo-B100, serum triglycerides, and the concentration of n-6 polyunsaturated fatty acids in serum. In a multiple regression analysis, 21% of the variation in PAI-1 activity could be explained by these variables. Plasma PAI-1 activity did not correlate with dietary intake or serum concentrations of n-3 polyunsaturated fatty acids. In a review of 17 trials, including 935 subjects that assessed the effect of n-3 fatty acids on PAI-1 activity, an overall 17.7% increase in PAI-1 activity was estimated by n-3 supplementation. However, only two studies were able to demonstrate a significant increase in PAI-1 attributable to n-3 fatty acid supplementation. We conclude that there is no strong evidence for an unfavourable, clinically relevant effect of n-3 fatty acids on PAI-1 activity in plasma.

Effect of omega-3 fatty acids and simvastatin on hemostatic risk factors and postprandial hyperlipemia in patients with combined hyperlipemia.

Patients with combined hyperlipemia have lipid abnormalities associated with an increased tendency to develop atherosclerosis and thrombosis. This tendency may be accelerated during postprandial hyperlipemia. In the present double-blind parallel study, 41 patients with combined hyperlipemia and serum triacylglycerols between 2.0 and 15.0 mmol/L and serum total cholesterol >5.3 mmol/L at the end of a 3-month dietary run-in period were treated with simvastatin at 20 mg/d for at least 10 weeks; patients were then randomized into 2 groups receiving simvastatin+omega-3 fatty acids at 3.36 g/d or placebo (corn oil) for an additional 5 weeks. Hemostatic variables that have been associated with increased thrombotic tendency were evaluated with subjects in the fasting state and during postprandial hyperlipemia before and after combined treatment. Supplementation of omega-3 fatty acid reduced tissue factor pathway inhibitor antigen (P<0.05) in the fasting state, reduced the degree of postprandial hyperlipemia (P<0.005), and reduced activated factor VII concentration appearing during postprandial hyperlipemia. In conclusion, omega-3 fatty acids given in addition to simvastatin to patients with combined hyperlipemia reduced the free tissue factor pathway inhibitor fraction in the fasting state and inhibited the activation of factor VII occurring during postprandial lipemia, thus representing a potential beneficial effect on the hemostatic risk profile in this patient group.

[Use of statins following myocardial infarction before and after the 4S study]. / Bruk av statiner etter hjerteinfarkt i sykehus før og etter 4S-studien.

The 4S study was followed by guidelines for statin treatment of patients with manifest coronary heart disease recommending statins for patients with serum cholesterol above 5.5 mmol/l, age below 70 years, and more than three years life expectancy. The purpose of the present study was to investigate how these guidelines were implemented in clinical practice. A retrospective registration was conducted on two cohorts of patients; patients with myocardial infarction in 1994 (before 4S) (n = 101) and 1996 (n = 100). Risk factors for coronary diseases and the use of statins were registered from the patients records. No significant differences in risk factors between the two cohorts were observed. The proportion of patients given statins increased from 4% in 1994 to 40% in 1996, whereas 50% of patients with serum cholesterol above 5.5 mmol/l were given statins in 1996. Statin treatment was usually instituted during hospitalization. Awareness of actual prescription and handling of statin treatment, and adaption of knowledge from clinical studies to clinical practice is probably needed for further improvement of statin treatment.

Dietary fatty acids and coronary heart disease.

The effects of dietary fats have been established in epidemiological and intervention studies and through relationship to risk factors for development of coronary heart disease (CHD). During a period where the impressive effects of hydroxymethylglutaryl-CoA reductase inhibitors on the mortality of CHD dominate the medical journals, it is important to realize the major effects of dietary fatty acids on a series of events included in the multifactorial disorder of CHD.

Lipid peroxidation of isolated chylomicrons and oxidative status in plasma after intake of highly purified eicosapentaenoic or docosahexaenoic acids.

Fourteen healthy male volunteers were given two separate high-saturated-fat meals with and without the addition of 4 g highly purified ethyl esters of either eicosapentaenoic acid (EPA) (95% pure, n = 7) or docosahexaenoic acid (DHA) (90% pure, n = 7) supplied as 1-g capsules each containing 3.4 mg vitamin E. The chylomicrons were isolated 6 h after the meals, at peak concentrations of n-3 fatty acids (FA). Addition of n-3 FA with the meal caused a 10.4-fold increase in the concentration of n-3 FA in chylomicrons compared to the saturated fat meal without addition of n-3 FA. After the saturated-fat meal, the concentration of thiobarbituric acid-reactive substances (TBARS) was 327.6 +/- 34.6 nmol/mmol triacylglycerol (TAG), which increased to 1015.8 +/- 212.0 nmol/mmol TAG (P < 0.0001, n = 14) after EPA and DHA were added to the meal. There was no significant correlation between the concentrations of TBARS and vitamin E in the chylomicrons collected 6 h after the test meal. The present findings demonstrate an immediate increase in chylomicron peroxidation ex vivo provided by intake of highly purified n-3 FA. The capsular content of vitamin E was absorbed into chylomicrons, but the amount of vitamin E was apparently not sufficient to protect chylomicrons against lipid peroxidation ex vivo. Daily intake of 4 g n-3 FA either as EPA or DHA for 5 wk did not change the plasma concentration of TBARS. Although not significantly different between groups, DHA supplementation decreased total glutathione in plasma (P < 0.05) and EPA supplementation increased plasma concentration of vitamin E (P < 0.05). The other lipid-soluble and polar antioxidants in plasma remained unchanged during 5 wk of intervention with highly purified n-3 FA.

Differential effect of unfractionated heparin and low molecular weight heparin on intravascular tissue factor pathway inhibitor: evidence for a difference in antithrombotic action.

Tissue factor pathway inhibitor (TFPI) is a potent inhibitor of tissue factor (TF)-induced blood coagulation, which is increased several-fold in post-heparin plasma and thought to contribute significantly to the antithrombotic action of heparin. In the present study we investigated whether subcutaneous (s.c.) administration of a low molecular weight heparin (LMWH), enoxaparin, had a different effect on intravascular pools of TFPI compared with continuous i.v. infusion of unfractionated heparin (UFH). 18 healthy male volunteers were randomly assigned to continuous i.v. infusion with UFH (initially 450 U/kg/24 h, n = 6) or to s.c. treatment with LMWH once daily (enoxaparin, 1.5 mg/kg, n = 12) for 72 h. A bolus injection of 5000 IU UFH i.v. caused an 8-13-fold increase in plasma-free TFPI antigen (TFPI Ag), followed by a progressive decrease (81 +/- 4%, P<0.001) during the 72 h infusion with UFH. 4 h after discontinuation of the infusion, basal free TFPI Ag and heparin-releasable TFPI were significantly decreased compared with the concentrations before the infusion (30 +/- 9%, and 27 +/- 7%, respectively). In contrast, LMWH treatment did not reduce either basal or heparin-releasable TFPI Ag. The changes in plasma TFPI Ag by UFH and LMWH were statistically different between groups both in pre- (P<0.001) and post-heparin (P<0.0001) plasma. The differential effect of UFH and LMWH on intravascular pools of TFPI may contribute to the understanding of the apparent superior efficacy of LMWHs in the treatment of both arterial and venous thrombosis.

Effects of Simvastatin and omega-3 fatty acids on plasma lipoproteins and lipid peroxidation in patients with combined hyperlipidaemia.

OBJECTIVES: Patients with combined hyperlipidemia are at increased risk for development of coronary heart disease. The purpose of this study was to evaluate the efficiency and the safety of treatment with Simvastatin and omega-3 fatty acids in patients with this lipid disorder. DESIGN: A double-blind placebo controlled, randomized study evaluating the effects of Simvastatin separately and in combination with omega-3 fatty acids in 41 healthy patients with defined hyperlipidemia. After a 16 weeks dietary run-in period the patients were treated in periods of 5 weeks. RESULTS: As expected Simvastatin (20 mg day[-1]) reduced serum total cholesterol, triacylglycerols, apolipoproteins B and E and increased HDL-cholesterol and apolipoprotein A1. Addition of omega-3 fatty acids (4 g day[-1]) further decreased serum triacylglycerols (P = 0.007), total cholesterol (P = 0.052) and apolipoprotein E (P = 0.035). No significant changes attributable to supplementation of polyunsaturated fatty acids on the content of lipid peroxides in plasma and in the various lipoprotein fractions were observed. CONCLUSIONS: The combined treatment of Simvastatin and omega-3 fatty acids seems to be an efficient and safe alternative for patients with combined hyperlipidemia.

Effects of highly purified eicosapentaenoic acid and docosahexaenoic acid on fatty acid absorption, incorporation into serum phospholipids and postprandial triglyceridemia.

Fourteen healthy volunteers were randomly allocated to receive 4 g highly purified ethyl esters of eicosapentaenoic acid (EPA) (95% pure, n = 7) or docosahexaenoic acid (DHA) (90% pure, n = 7) daily for 5 wk in supplement to their ordinary diet. The n-3 fatty acids were given with a standard high-fat meal at the beginning and the end of the supplementation period. EPA and DHA induced a similar incorporation into chylomicrons which peaked 6 h after the meal. The relative uptake of EPA and DHA from the meal was > 90% compared with the uptake of oleic acid. During absorption, there was no significant elongation or retroconversion of EPA or DHA in total chylomicron fatty acids. The concentration of EPA decreased by 13% and DHA by 62% (P < 0.001) between 6 and 8 h after the meal. During the 5-wk supplementation period, EPA showed a more rapid and comprehensive increase in serum phospholipids than did DHA. DHA was retroconverted to EPA, whereas EPA was elongated to docosapentaenoic acid (DPA). The postprandial triglyceridemia was suppressed by 19 and 49% after prolonged intake of EPA and DHA, respectively, indicating that prolonged intake of DHA is equivalent to or even more efficient than that of EPA in lowering postprandial triglyceridemia. This study indicates that there are metabolic differences between EPA and DHA which may have implications for the use of n-3 fatty acids in preventive and clinical medicine.

The effect of highly purified eicosapentaenoic and docosahexaenoic acids on monocyte phagocytosis in man.

The n-3 fatty acids (FA) from marine sources are known to exert antiinflammatory effects on monocyte function. There is still controversy whether n-3 FA may increase the susceptibility to infections. The present study was designed to assess the effect of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on monocyte phagocytosis and respiratory burst activity. Fifty-eight healthy men were randomized to take a daily supplement of 3.8 g highly purified EPA (n = 20), 3.6 g DHA (n = 19), or corn oil (n = 19) for 7 wk. Mononuclear leukocytes were collected, isolated, and cryopreserved prior to and after dietary supplementation. Paired samples were analyzed in the presence of autologous serum in a crossover design. Monocyte phagocytosis and respiratory burst activity were measured by flow cytometry after ingestion of Escherichia coli. Monocytes retained their phagocytic ability and respiratory burst activity after supplementation. No reduction in internalization of bacteria was registered. Dietary n-3 FA and particularly EPA improved bacterial adherence to the monocyte surface. In the crossover experiments, there was an adverse effect of serum enriched with n-3 FA on bacterial adherence. We conclude that monocytes retain their phagocytic potential after supplementation with purified EPA and DHA.

Highly purified eicosapentaenoic acid and docosahexaenoic acid in humans have similar triacylglycerol-lowering effects but divergent effects on serum fatty acids.

To compare the effects of highly purified ethyl ester concentrates of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on serum lipids, apolipoproteins, and serum phospholipid fatty acids in humans, we conducted a double-blind, placebo-controlled, parallel design intervention study. Healthy nonsmoking men (n = 234) aged 36-56 y were randomly assigned to dietary supplementation with 3.8 g EPA/d, 3.6 g DHA/d, or 4.0 g corn oil/d (placebo) for 7 wk. Serum triacylglycerols decreased 26% (P < 0.0001) in the DHA group and 21% (P = 0.0001) in the EPA group compared with the corn oil group. Although not significant, net decreases in serum triacylglycerols were consistently greater in the DHA group across all quartiles of baseline triacylglycerol concentrations. Serum high-density-lipoprotein cholesterol increased 0.06 mmol/L (P = 0.0002) in the DHA group. In the EPA group, serum total cholesterol decreased 0.15 mmol/L (P = 0.02) and apolipoprotein A-I decreased 0.04 g/L (P = 0.0003). In the DHA group, serum phospholipid DHA increased by 69% and EPA increased by 29%, indicating retroconversion of DHA to EPA. In the EPA group, serum phospholipid EPA increased by 297% whereas DHA decreased by 15%, suggesting that EPA is not elongated to DHA in humans. The serum phospholipid ratio of n-3 to n-6 fatty acids increased in both groups, whereas the relative changes in n-6 fatty acids suggested possible alterations in liver desaturation activity in the DHA group. We conclude that both DHA and EPA decrease serum triacylglycerols, but have differential effects on lipoprotein and fatty acid metabolism in humans.