Serum Levels Of Eicosapentaenoic Acid Research Articles

Low serum eicosapentaenoic acid / arachidonic acid ratio in male subjects with visceral obesity.

BackgroundVisceral fat accumulation is caused by over-nutrition and physical inactivity. Excess accumulation of visceral fat associates with atherosclerosis. Polyunsaturated fatty acids have an important role in human nutrition, but imbalance of dietary long-chain polyunsaturated fatty acids, especially low eicosapentaenoic acid (EPA) / arachidonic acid (AA) ratio, is associated with increased risk of cardiovascular disease. The present study investigated the correlation between EPA, docosahexaenoic acid (DHA), AA parameters and clinical features in male subjects.FindingsThe study subjects were 134 Japanese with diabetes, hypertension and/or dyslipidemia who underwent measurement of visceral fat area (eVFA) by the bioelectrical impedance method and serum levels of EPA, DHA and AA. EPA/AA ratio correlated positively with age, and negatively with waist circumference and eVFA. Stepwise regression analysis demonstrated that age and eVFA correlated significantly and independently with serum EPA/AA ratio. Serum EPA/AA ratio, but not serum DHA/AA and (EPA+DHA)/AA ratios, was significantly lower in subjects with eVFA ≥100 cm2, compared to those with eVFA <100 cm2 (p=0.049). Subjects with eVFA ≥100 cm2 were significantly more likely to have the metabolic syndrome and history of cardiovascular diseases, compared to those with eVFA <100 cm2 (p<0.001, p=0.028, respectively).ConclusionsImbalance of dietary long-chain polyunsaturated fatty acids (low serum EPA/AA ratio) correlated with visceral fat accumulation in male subjects.Clinical trial registration numberUMIN000002271

Serum Eicosapentaenoic Acid/Arachidonic Acid Ratio Is Low in Patients with Pulmonary Thromboembolism

Recently n-3 polyunsaturated fatty acids (PUFAs) have been reported to play protective roles against cardiovascular diseases. Pulmonary thromboembolism (PTE) is one of the critical diseases in the circulatory system. However the relationship between n-3 PUFAs and PTE has not been reported. A total of 144 outpatients of the division of cardiology, including 12 of PTE cases, were enrolled in the present study and serum levels of eicosapentaenoic acid (EPA) and arachidonic acid (AA) were analyzed. We found that the EPA/AA ratio of the patients with PTE (the PTE group) was significantly lower than that of the patients without PTE (the non-PTE group) (p=0.007 for log EPA/log AA ratio). Next, the PTE group was divided into two groups by the presence or absence of malignant carcinoma. The PTE without carcinoma group showed significantly lower EPA/AA ratio than that of the non-PTE group (p=0.002 for log EPA/log AA ratio). However, the PTE with carcinoma group did not show the statistical difference in EPA/AA ratio compared with the non-PTE group (p=0.39). These data indicate that PTE may be associated with a low EPA/AA ratio, although the presence of malignant carcinoma should be taken into account.

Highly Purified Eicosapentaenoic Acid May Increase Low-Density Lipoprotein Particle Size by Improving Triglyceride Metabolism in Patients With Hypertriglyceridemia

The purpose of this study was to evaluate the effect of highly purified eicosapentaenoic acid (EPA) in increasing low-density lipoprotein (LDL) particle size, as one of the possible mechanisms by which intake of EPA may prevent coronary events. Hypertriglyceridemic subjects were randomly assigned to a control group (n=72) or an EPA group (n=72; EPA regimen 1,800mg/day for 6 months). In the EPA group, the serum LDL-cholesterol and high-density lipoprotein cholesterol levels remained unchanged, but there was a significant increase in LDL particle size based on LDL-relative mobility measured on lipoprotein polyacrylamide-gel electrophoresis, and a significant decrease in serum triglyceride-rich lipoproteins (TRLs) level. None of these changes were observed in the control group. After adjustments for coronary risk factors, multivariate logistic regression analysis identified elevation of serum EPA-related markers (6-month EPA, 6-month EPA/arachidonic acid [AA] ratio, change in [Δ] EPA, and EPA/AA), and treatment with statins and EPA as independent variables associated with increase in LDL particle size. Negative correlations were found between ΔTRLs and ΔLDL particle size, suggesting that improvement in triglyceride metabolism was associated with an increase in LDL particle size. EPA increases LDL particle size by improving triglyceride metabolism; and serum EPA level and EPA/AA ratio after EPA treatment may be useful markers of increased LDL particle size.

Association Between Serum Levels of n-3 Polyunsaturated Fatty Acids and Coronary Plaque Detected by Coronary Computed Tomography Angiography in Patients Receiving Statin Therapy

Intensive lipid-lowering therapy with statins reduces cardiovascular events, but residual cardiovascular risks remain. Intake of n-3 polyunsaturated fatty acids (PUFAs) has been associated with cardiovascular events. We examined the relationships between serum n-3 PUFAs and coronary atherosclerotic findings on computed tomography angiography (CTA) in patients undergoing statin treatment. We enrolled 172 subjects (mean age: 68.2 years; 64% men) prior to statin treatment for 6 months. Serum PUFAs, including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid, were measured. When the patients were divided into 2 groups according to the median EPA level (61.3 μg/ml), the low-EPA group showed higher incidences of 3-vessel plaque involvement (62% vs. 43%, P=0.015), noncalcified plaques (NCPs) (74% vs. 52%, P=0.0016), extensive NCPs (≥ 2 segments) (56% vs. 34%, P=0.0036), and high-risk plaques (minimum CT density <39 HU and remodeling index >1.05) (43% vs. 22%, P=0.0034). Multivariate analyses revealed that low EPA levels were an independent factor for these coronary plaque findings. The DHA levels were not independently associated with these findings. Low serum EPA level, but not serum DHA, is associated with the presence and extent of NCPs and high-risk plaques detected by coronary CTA in patients undergoing lipid-lowering therapy with statins.

Low Levels of Serum n-3 Polyunsaturated Fatty Acids Are Associated With Worse Heart Failure-Free Survival in Patients After Acute Myocardial Infarction

Intake of long-chain n-3 polyunsaturated fatty acids (n-3 PUFA), including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), is associated with a lower risk of atherosclerotic cardiovascular events, particularly acute myocardial infarction (AMI). However, limited data are available regarding the association between serum n-3 PUFA levels and heart failure (HF) events in survivors of AMI. We evaluated whether serum DHA and EPA levels were associated with HF-free survival and HF hospitalization rates after AMI. A total of 712 patients were divided into 3 groups according to their tertile serum levels of DHA and EPA (Low, Middle, and High). Propensity-score-stratified Cox regression analysis revealed that DHA- and EPA-Low groups presented statistically significant worse HF-free survival (hazard ratio (HR) 1.68, 95% confidence interval (CI) 1.03-2.72, P=0.0358, and HR 1.69, 95% CI 1.05-2.72, P=0.0280, respectively), with the EPA-Low group having a higher risk of HF hospitalization (HR 2.40, 95% CI 1.21-4.75, P=0.0097) than the DHA-Low group (HR 1.72, 95% CI 0.86-3.45, P=0.1224). The relationship between a low DHA or EPA level and decreased HF-free survival was almost common to all subgroups; however, the effect of low serum EPA on HF hospitalization was prominent in male patients, and those with low levels of high-density lipoprotein cholesterol or without statin therapy. Low levels of circulating n-3 PUFA are associated with decreased HF-free survival in post-AMI patients.

Highly Purified Eicosapentaenoic Acid Increases Interleukin-10 Levels of Peripheral Blood Monocytes in Obese Patients With Dyslipidemia

OBJECTIVEIt has recently been highlighted that proinflammatory (M1) macrophages predominate over anti-inflammatory (M2) macrophages in obesity, thereby contributing to obesity-induced adipose inflammation and insulin resistance. A recent clinical trial revealed that highly purified eicosapentaenoic acid (EPA) reduces the incidence of major coronary events. In this study, we examined the effect of EPA on M1/M2-like phenotypes of peripheral blood monocytes in obese dyslipidemic patients.RESEARCH DESIGN AND METHODSPeripheral blood monocytes were prepared from 26 obese patients without and 90 obese patients with dyslipidemia. Of the latter 90 obese patients with dyslipidemia, 82 patients were treated with or without EPA treatment (1.8 g daily) for 3 months.RESULTSMonocytes in obese patients with dyslipidemia showed a significantly lower expression of interleukin-10 (IL-10), an M2 marker, than those without dyslipidemia. EPA significantly increased serum IL-10 and EPA levels, the EPA/arachidonic acid (AA) ratio, and monocyte IL-10 expression and decreased the pulse wave velocity (PWV), an index of arterial stiffness, compared with the control group. After EPA treatment, the serum EPA/AA ratio was significantly correlated with monocyte IL-10 expression. Only increases in monocyte IL-10 expression and serum adiponectin were independent determinants of a decreased PWV by EPA. Furthermore, EPA significantly increased the expression and secretion of IL-10 in human monocytic THP-1 cells through a peroxisome proliferator–activated receptor (PPAR)γ-dependent pathway.CONCLUSIONSThis study is the first to show that EPA increases the monocyte IL-10 expression in parallel with decrease of arterial stiffness, which may contribute to the antiatherogenic effect of EPA in obese dyslipidemic patients.

Effect Of Epa Ethyl Ester On Fatty Acid Profile In Hemodialysis Patients With Low Epa/Aa Ratio

Large amounts of n-3 polyunsaturated fatty acids are known to lower the risk of cardiovascular events (CVE). Serum eicosapentaenoic acid (EPA) / arachidonic acid (AA) ratio may potentially be a predictor of CVE which is the most common cause of death in hemodialysis (HD) patients. Therefore, we estimated the effect of EPA ethyl ester on fatty acid profile in HD patients. Fatty acid profile and high sensitivity CRP (hs-CRP) were measured in 131 patients receiving maintenance HD. Among these, 64 patients (F:M=25:39) with both low EPA/AA ratio (≦0.4) and negative CRP were enrolled in this randomized study (Group A, EPA administrated group, n=30; Group B, EPA non-administrated group, n=34). The mean age of the patients was 66.5 ± 11.9 years old and the duration of HD was 8.4 ± 7.9 years. The serum levels of EPA, AA, docosahexaenoic acid (DHA), and dihomogammalinolenic acid (DHL-A) were measured by gas chromatography (SRL, Tokyo, Japan). The mean levels of EPA/AA ratio, DHA/AA ratio, DHL-A, non HDL-C and GNRI (Geriatric Nutritional Risk Index) were 0.28±0.13, 0.62±0.15, 22.7±8.4 μg/ml, 112.2±31.0 mg/dl and 93.6±5.5, respectively. After one month of treatment with EPA in group A, EPA/AA ratio was significantly increased (0.30±0.15 vs. 0.95±0.45, p<0.0001) and DHL-A significantly decreased (22.7±7.4 vs. 15.7±6.8, p= 0.0003), but DHA/AA ratio, serum non HDL-C and phosphate levels did not change. EPA/AA ratio was significantly higher and DHL-A lower in group A compared with group B after one month of the start of study. Medication of EPA for one month increases EPA/AA ratio, and decreases DHL-A level without the change of serum phosphate level in HD patients with low EPA/AA ratio.

Predicting efficacy of dipeptidyl peptidase-4 inhibitors in patients with type 2 diabetes: Association of glycated hemoglobin reduction with serum eicosapentaenoic acid and docosahexaenoic acid levels.

This study was initiated to identify clinical and dietary parameters that predict efficacy of dipeptidyl peptidase-4 inhibitors. A total of 72 untreated Japanese patients with type 2 diabetes who received DPP-4 inhibitors (sitagliptin, alogliptin or vildagliptin) for 4 months were examined for changes of glycated hemoglobin (HbA1c) and body mass index (BMI), and self-administered 3-day food records, as well as serum levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). DPP-4 inhibitors significantly reduced HbA1c (before initiation of DPP-4 inhibitors 7.2 ± 0.7%, 4 months after initiation of DPP-4 inhibitors 6.7 ± 0.6% [paired t-test, P < 0.01 vs before]). Multiple regression analysis showed that changes of HbA1c were significantly correlated with baseline HbA1c, as well as estimated intake of fish. Furthermore, changes of HbA1c were significantly correlated with serum levels of EPA (r = -0.624, P < 0.01) and DHA (r = -0.577, P < 0.01). HbA1c reduction by DPP-4 inhibitors is significantly correlated with estimated intake of fish and serum levels of EPA and DHA. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2012.00214.x, 2012).

Relationship between RBC Mercury Levels and Serum n3 Polyunsaturated Fatty Acid Concentrations among Japanese Men and Women

Aims. To evaluate potential health risk and benefits of fish consumption, the association of fish consumption with total mercury levels in red blood cells (RBCs) and serum eicosapentaenoic acid (EPA) concentrations was examined. Subjects and Methods. Study subjects were 269 Japanese (98 men and 171 women) living in a remote island of Kagoshima, and their blood was drawn in 1994. Results. Total mercury levels were related to weekly fish consumption among women (P = 0.035) but not among men (P = 0.643). However, serum EPA levels were not related to fish consumption in both women and men. In contrast, EPA levels in the high-density ipoprotein (HDL) fraction of the sera were significantly related to fish consumption (P values for men and women were 0.014 and 0.073, resp.). Interestingly, mercury levels were related to serum EPA levels and EPA in the HDL fraction of the sera (P = 0.001) among women (P = 0.005) but not among men. Sex differences in fish species consumed may be an explanation for the observed sex difference. Conclusion. Those findings suggest that the health benefit of fish consumption can be maximized by the careful selection of fish species consumed.

Regional Differences in Hypertensive Cardiovascular Remodeling Between Fishing and Farming Communities in Japan

Effects of dietary n-3 polyunsaturated fatty acids (n-3 PUFA) intake on the cardiovascular system have been reported, and thus we hypothesized that the prevalence of hypertensive cardiovascular remodeling would be lower in a fishing than a farming community. We recruited 263 essential hypertensives from a fishing and 333 from a farming village; all subjects were ≥40 years (mean 73 years; 42% men). They were cross-sectionally examined for serum eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), asymmetric dimethylarginine (ADMA) levels, left ventricular mass index (LVMI), and common-carotid artery (CCA) and internal-carotid artery (ICA) intima-media thickness (IMT). Compared to the patients in the farming village, those in the fishing village had higher serum EPA and DHA levels (63.3 vs.70.9 µg/ml, 137.2 vs.157.8 µg/ml) and lower ADMA levels (0.49 vs.0.47 nmol/ml; all P < 0.05). LVMI and both CCA-IMT and ICA-IMT levels were lower in the fishing than the farming village (113.2 vs.121.6 g/m(2), 0.88 vs.0.94 mm, 1.10 vs.1.17 mm: all P < 0.01) even after adjustment for age, sex, body mass index (BMI), duration of hypertensive medication, number of antihypertensive medications, and 24-h systolic blood pressure (SBP) level. The differences in LVMI and IMT levels between these communities also remained unchanged (all P < 0.01) after additional adjustment for the regional differences in EPA, DHA, and ADMA levels. A multivariable linear regression analysis showed that the difference in place of residence was independently associated with LVMI as well as with both CCA-IMT and ICA-IMT levels (all P < 0.01). The prevalence of cardiovascular remodeling was significantly lower in patients in the fishing community than in those in the farming community. Further investigations are required to explain the mechanisms underlying this association.

Enteral Nutrition Enriched With Eicosapentaenoic Acid (EPA) Preserves Lean Body Mass Following Esophageal Cancer Surgery: Results of a Double-Blinded Randomized Controlled Trial

Esophagectomy represents an exemplar of controlled major trauma, with marked metabolic, immunologic, and physiologic changes as well as an associated high incidence of complications. Eicosapentaenoic acid (EPA) enriched enteral nutrition (EN) modulates immune function and limits catabolism in patients with advanced cancer, but its impact in the peri-operative period is unclear. To examine the effects of perioperative EPA enriched EN on the metabolic, nutritional, and immuno-inflammatory response to esophagectomy, and on postoperative complications. In a double-blind design, patients were randomized to a standard EN formula or a formula enriched with 2.2 g EPA/d for 5 days preoperatively (orally) and 21 days postoperatively (jejunostomy). Segmental bioelectrical impedance analysis was performed preoperatively and on POD 21. Postoperative complications were monitored, as well as the acute phase response, coagulation markers, and serum cytokines. Fifty-three patients (28 EPA, 25 standard) completed the study, and both groups were well matched. Serum and peripheral blood mononuclear cell (PBMC) membrane EPA levels were significantly increased in the EPA group. There was no difference in the incidence of major complications. The EPA group maintained all aspects of body composition postoperatively, whereas patients in the standard EN group lost significant amounts of fat-free mass (1.9 kg, P = 0.030) compared with the EPA group [leg (0.3 kg, P = 0.05), arm (0.17 kg, P = 0.01), and trunk (1.44 kg, P = 0.03)]. The EPA group had a significantly (P < 0.05) attenuated stress response for TNFalpha, IL-10, and IL-8 compared with the standard group. EPA supplemented early EN is associated with preservation of lean body mass post esophagectomy compared with a standard EN. These properties may merit longer-term study to address its impact on recovery of function and quality of life in models of complex surgery or multimodal cancer treatment regimens.

Omega-3 Fatty Acid Effect on Alveolar Bone Loss in Rats

Gingival inflammation and alveolar bone resorption are hallmarks of adult periodontitis, elicited in response to oral micro-organisms such as Porphyromonas gingivalis. We hypothesized that omega (omega)-3 fatty acids (FA) dietary supplementation would modulate inflammatory reactions leading to periodontal disease in infected rats. Rats were fed fish oil (omega-3 FA) or corn oil (n-6 FA) diets for 22 weeks and were infected with P. gingivalis. Rats on the omega-3 FA diet exhibited elevated serum levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), documenting diet-induced changes. PCR analyses demonstrated that rats were orally colonized by P. gingivalis; increased IgG antibody levels substantiated this infection. P. gingivalis-infected rats treated with omega-3 FA had significantly less alveolar bone resorption. These results demonstrated the effectiveness of an omega-3 FA-supplemented diet in modulating alveolar bone resorption following P. gingivalis infection, and supported that omega-3 FA may be a useful adjunct in the treatment of periodontal disease.

Exposure to the fish parasite Anisakis causes allergic airway hyperreactivity and dermatitis

Several case reports show allergy and anaphylactic reactions to the fish parasite Anisakis in the domestic and occupational setting. Further research is needed on the prevalence and mechanisms of disease. To determine the prevalence of Anisakis sensitization and related symptoms among workers in 2 fish-processing factories, and to use gene-deficient mice to determine the working mechanisms of Anisakis allergy. A modified version of the European Community Respiratory Health Survey was used to interview 578 South African fish-processing workers. Sensitization to Anisakis, seafood, and common aeroallergens was determined by skin prick test. Lung function was measured by spirometry and methacholine challenge. Serum eicosapentaenoic acid levels were used as an index of seafood consumption. Sensitized wild-type, IL-4, or IL-4 receptor alpha-deficient mice were challenged orally with Anisakis extract. Allergic reactions, lung pathology, antibodies, cytokines, mast cell proteases, and histamine were evaluated. The prevalence of sensitization to Anisakis was higher than the prevalence of sensitization to fish (8% vs 6%). Anisakis-specific IgE reactivity was associated with bronchial hyperreactivity and dermatitis, and significantly increased with fish consumption. In mice, Anisakis infective larvae (L3) induced a striking T(H)2/type 2 response. Food-allergic-type reactions induced by oral challenge with Anisakis extract were absent in IL-4 receptor alpha knockout mice. Anisakis sensitization in fish-processing workers is associated with allergic symptoms and correlates with high levels of fish consumption. Anisakis proteins induce allergic reactions in sensitized mice by IL-4/IL-13-mediated mechanisms. Anisakis allergy should be considered in fish-processing workers with allergic symptoms.

Impact of fish oil and melatonin on cachexia in patients with advanced gastrointestinal cancer: A randomized pilot study

Objective The effect of fish oil (FO), melatonin (MLT), or their combination and dietary advice on cachexia and biochemistry variables reflecting cachexia were investigated in patients with advanced gastrointestinal cancer. Methods Twenty-four patients not amenable to standard anticancer treatment and with documented weight loss and/or decreased serum albumin were included. They were randomized to 30 mL/d of FO, which provided 4.9 g of eicosapentaenoic acid and 3.2 g of docosahexanoic acid, or 18 mg/d of MLT for 4 wk. During the next 4 wk, all patients had FO and MLT. Serum or plasma was analyzed for tumor necrosis factor-α, interleukin-1β, soluble interleukin-2 receptor, interleukin-6, and interleukin-8 and the fatty acids eicosapentaenoic acid, docosahexanoic acid, arachidonic acid, and linoleic acid. Results Serum levels of eicosapentaenoic acid and docosahexanoic acid increased as expected with FO. No major changes in biochemical variables and cytokines were observed with any intervention. In the FO group, 5 of 13 patients (38%) showed weight stabilization or gain compared with 3 of 11 patients (27%) in the MLT group. After combining interventions, approximately 63% of patients showed such responses. Conclusions FO, MLT, or their combination did not induce major biochemical changes indicative of a strong anticachectic effect. Nonetheless, the interventions used may have produced a weight-stabilizing effect.

The role of socioeconomic status and serum fatty acids in the relationship between intake of animal foods and cardiovascular risk factors

Little is known regarding the relationship of serum fatty acids to cardiovascular risk factors in Nigerian populations. Civil servants with higher socioeconomic status (SES) in Nigeria appear to be in cultural transition toward a more Westernized lifestyle. For this study the food intakes of 397 civil servants were estimated from two 24-h recalls. Fatty acids in serum total lipids were measured in both absolute weight concentration and percentage composition. Daily meat intake was 43.5 g, and fish intake was 70.5 g. The intakes of meat, eggs, and milk were higher in high SES Nigerians than in low SES Nigerians. The concentration of total fatty acids (TFA, the sum of 12 serum fatty acids) was also higher in high SES men and women, as compared with low SES men and women (2064, 2060, 1831, and 1776 mg/L, respectively). There were significant direct associations between meat intake and serum level of arachidonic acid, and between fish intake and serum levels of eicosapentaenoic acid and docosahexaenoic acid. TFA was positively associated with cholesterol, low-density-lipoprotein cholesterol (LDLc), and triglycerides across gender and SES groups after adjustment for body mass index, fasting insulin level, and age. Nigerian women were compared with two groups of American women. We concluded that fatty acids in absolute weight concentration reflected the amount of fat intake. The level of TFA was directly related to cardiovascular risk factors in Nigerians. Follow-up of such populations in cultural transition can facilitate the understanding of the true roles of animal food intake in the early evolution of atherosclerosis.

Effects of low-dose marine oils on intimal hyperplasia in autologous vein grafts

The effects of low-dose cod-liver oil on intimal hyperplasia of vein grafts were examined in 45 adult mongrel dogs undergoing peripheral arterial reconstruction. Fifteen animals served as the control group, 15 animals were fed a fish-oil supplement containing 240 mg of eicosapentaenoic acid daily, and a further 15 animals received 480 mg of eicosapentaenoic acid daily. Segments of undistended external jugular vein were anastomosed to bilaterally divided femoral arteries. The grafts were harvested at 6 weeks and intimal thickness was measured with a computerized interactive image analyzing system. Serum cholesterol level, prothrombin time, partial thromboplastin time, bleeding time, and platelet counts were measured before the operation and at 2, 4, and 6 weeks after the operation. Plasma levels of thromboxane B2 and prostaglandin F1 alpha and serum levels of eicosapentaenoic acid were measured before and 4 weeks after the operation. Serum cholesterol level increased similarly and significantly in all animals. Serum levels of eicosapentaenoic acid rose proportionately with the oral ingestion of fish oil but did not affect coagulation parameters. Plasma thromboxane B2 and prostaglandin F1 alpha were not significantly affected by the ingestion of marine oils. Intimal thickness was 39 +/- 5 microns in the control dogs. Ingestion of 240 mg of eicosapentaenoic acid reduced intimal thickness to 24 +/- 3 microns at 6 weeks (p less than 0.01). Increasing the dose by a factor of 2 did not decrease intimal thickness further, the intima being 23 +/- 2 microns (p less than 0.005). Our data indicate that small doses of fish oil will reduce intimal proliferation in autologous vein grafts and that marine oils may exert their beneficial effects on intimal hyperplasia by a mechanism other than their known effects on prostanoid metabolism.