Eicosapentaenoic Acid To Arachidonic Acid Research Articles

A Low Omega-3 Index and High AA/EPA Ratio in American College Football Players are Both Improved Following 5 Weeks of DHA-Rich Algae Oil Supplementation

Abstract Purpose Many athletes are deficient in long chain omega-3 polyunsaturated fatty acids (LC n-3 PUFA). A consequent low Omega-3 Index (O3I) and high arachidonic acid/eicosapentaenoic acid (AA/EPA) ratio increase cardiovascular disease risk and inflammation. Algae oil is a plant-based, sustainable source of LC n-3 PUFA, suitable for vegans and vegetarians. Effects of algae oil supplementation on whole blood fatty acids among athletes has not been previously reported. This study evaluated the effects of 5 weeks of DHA-rich algae oil supplementation on the whole blood fatty acid profile, O3I and AA/EPA ratio of omnivorous Division I American College Football (ACF) players. Methods: Data, including a spot blood sample, were collected at baseline for all participants (n = 47), then for a subset of players (n = 22) following a 5-week control period (usual diet) and 5 weeks of algae oil supplementation (usual diet + 1575 mg docosahexaenoic acid (DHA) + eicosapentaenoic acid (EPA) 5 days/week; average 1125 mg/day). Results: Baseline O3I was 4.3% ± 0.1% and AA/EPA ratio was 45.6 ± 23.8. After 5 weeks of algae oil supplementation, the O3I was 6.1% ± 1.0% and the AA/EPA ratio was 25.1 ± 11.6. The O3I was significantly higher and the AA/EPA ratio was significantly lower (P < 0.0001 for both) compared with both baseline and the end of the control period. The increase in O3I from baseline was correlated with calculated DHA + EPA dose per unit body mass (R = 0.641, P = 0.001). Conclusions: Algae oil supplementation for 5 weeks improved both the low baseline O3I and high AA/EPA ratio among ACF players, with body mass specific dose effects.

Impact of serum eicosapentaenoic acid/arachidonic acid ratio on overall survival in lung cancer patients treated with pembrolizumab: a pilot study

This pilot study analyzed the dietary patterns of patients with non-small cell lung cancer undergoing initial pembrolizumab, an immune checkpoint inhibitor (ICI), treatment in the month before treatment. Serum fatty acid fractions and their associations with ICI treatment efficacy were also investigated. The results showed that long-term survivors (those who survived for ≥ 3 years) consumed significantly more seafood than short-term survivors (those who survived for < 3 years). Furthermore, the serum levels of eicosapentaenoic acid (EPA) as well as the ratio of EPA to arachidonic acid (EPA/AA) were higher in the long-term survivors than those in the short-term survivors. The group with a high serum EPA/AA ratio had a significantly higher overall survival rate after ICI treatment than the group with a low serum EPA/AA ratio. In conclusion, higher dietary seafood consumption may improve OS in lung cancer patients treated with ICI and the serum EPA/AA ratio may be a useful biomarker for determining the efficacy of ICI treatment. Thus, supplements that increase the serum EPA/AA ratio could serve as new nutritional interventions for enhancing the efficacy of ICI treatment. However, further large-scale case and intervention studies are required.

Linear isomer but not branched isomers of perfluorooctane sulfonate in plasma is associated with eicosapentaenoic acid, a seafood consumption biomarker.

Per- and polyfluoroalkyl substances (PFAS) are global contaminants. Seafood consumption is a possible PFAS exposure route to humans while the isomer specific analysis has not been conducted. Perfluorooctane sulfonate (PFOS), perfluoroheptane sulfonate (PFHpS) and perfluorohexane sulfonate (PFHxS) were investigated in residents of Kyoto, Japan (n = 51). The relationship between plasma PFAS and seafood consumption biomarker, the ratio of eicosapentaenoic acid to arachidonic acid (EPA/AA) was examined by multiple regression analysis. Linear PFOS concentrations showed a significant positive correlation with the EPA/AA ratio in plasma samples (β = 6.80, p = 0.0014). Linear PFHpS was marginally associated with EPA/AA ratio (β = 0.178, p = 0.0874). Branched PFOS isomers and PFHxS had no associations with EPA/AA ratios. Seafood intake may be a significant exposure pathway for PFAS, such as PFOS but the isomers differ.

Remarkable Response of Vildagliptin/Metformin (EquMet) for Diabetic Patient with Recovered Ratio of Eicosapentaenoic Acid/ Arachidonic Acid (EPA/AA) by EPA Intake

Remarkable Response of Vildagliptin/Metformin (EquMet) for Diabetic Patient with Recovered Ratio of Eicosapentaenoic Acid/ Arachidonic Acid (EPA/AA) by EPA Intake

Plasma fingerprint of free fatty acids and their correlations with the traditional cardiac biomarkers in patients with type 2 diabetes complicated by coronary heart disease.

Type 2 diabetes mellitus (T2DM) is a well-established risk factor for cardiovascular disease, with at least 2–3 fold higher risk of cardiovascular diseases than non-diabetics. Free fatty acids (FFAs) are believed to play important roles in the occurrence of cardiovascular disease in people with T2DM. The aim of this study was to investigate the fingerprint of plasma FFAs and their correlations with the tradition risk factors of cardiovascular disease in T2DM patients complicated by coronary heart disease (CHD-T2DM). A total of 401 participants, including healthy control (HC, n = 143), T2DM patients (n = 134), and CHD-T2DM patients (n = 126) were enrolled in this study. Plasma levels of 36 FFAs with carbon chain length ranged from 3 to 22 were quantified by using reverse phase ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS). Tradition risk factors of cardiovascular disease were tested in clinical laboratory, including homocysteine (HCY), creatine kinase (CK), high sensitivity C reactive protein (hsCRP), and N-terminal pro-brain natriuretic peptide (NT-proBNP) and so on. Almost all the FFAs with different carbon chain length and unsaturation were significantly upregulated in the T2DM-CHD groups, compared to the HC and T2DM groups. Both n-3 and n-6 polyunsaturated fatty acids (PUFA) were also found to be significantly upregulated in T2DM-CHD group compared to the T2DM group. However, no significantly differences of the n-6/n-3 PUFA ratio, arachidonic acid/eicosapentaenoic acid (AA/EPA) ratio, and arachidonic acid/docosahexaenoic acid (AA/DHA) ratio were observed between T2DM-CHD and T2DM groups. Plasma FFA levels were found to be positively correlated with HCY, CK, hsCRP, NT-proBNP and other tradition risk factors of CHD. Multivariate logistic regression analysis indicated that a dozens of FFAs were the independent risk factors of CHD after adjustment for confounding factors and other risk factors. Excessively high plasma levels of FFAs were demonstrated to be independent risk factors for CHD in patients with T2DM, despite of the differences in chain length, unsaturation, and double bond position.

The influence of a basic military training diet on whole blood fatty acid profile and the Omega-3 Index of Australian Army recruits.

This study described the whole blood fatty acid profile and Omega-3 Index (O3I) of Australian Army recruits at the commencement and completion of basic military training (BMT). Eighty males (17-34y, 77.4± 13.0kg, 43.5± 4.3mL/kg/min) and 37 females (17-45y, 64.3± 8.8kg, 39.3± 2.7 mL/kg/min) volunteered to participate (N= 117). Whole blood samples of each recruit were collected using a finger prick in weeks 1 and 11 (n= 82) and analysed via gas chromatography for the relative proportions of each fatty acid (mean [95% confidence interval]). The macronutrient characteristics of the diet offerings was also determined. At commencement there was a low omega-3 status (sum of omega-3; 4.95% [4.82-5.07]) and O3I (5.03% [4.90-5.16]) and no recruit recorded an O3I >8% (desirable). The omega-6/omega-3 (7.04 [6.85-7.23]) and arachidonic acid/eicosapentaenoic acid (AA/EPA) (18.70 [17.86-19.53]) ratios for the cohort were also undesirable. The BMT mess menu provided a maximum of 190mg/day of EPA and 260mg/day of docosahexaenoic acid (DHA). The O3I of the recruits was lower by week 11 (4.62% [4.51-4.78], p< 0.05), the omega-6/omega-3 increased (7.27 [7.07-7.47], p< 0.05) and the AA/EPA remained elevated (17.85 [16.89-18.81]). In conclusion, Australian Army recruits' omega-3 status remained undesirable during BMT and deserves nutritional attention. Novelty: Australian Army recruits' Omega-3 Index, at the commencement of BMT, was reflective of the Western-style diet. The BMT diet offered minimum opportunity for daily EPA and DHA consumption. Every recruit experienced a further reduction of their Omega-3 Index during BMT.

Greater Change in the Eicosapentaenoic Acid to Arachidonic Acid Ratio Is Associated With Decreased Incidence of Cardiovascular Events in Acute Coronary Syndrome Patients With Elevated Triglyceride Levels.

This study investigated whether the percentage change (%Δ) in the eicosapentaenoic acid to arachidonic acid (EPA/AA) ratio is associated with cardiovascular event rates among acute coronary syndrome (ACS) patients receiving contemporary lipid-lowering therapy other than polyunsaturated fatty acids (PUFAs).Methods and Results:This post hoc subanalysis of the HIJ-PROPER study included PUFA-naïve patients for whom EPA/AA ratio data were available at baseline and after 3 months. Patients were categorized into 2 groups based on the median %ΔEPA/AA ratio: Group 1, change less than the median; and Group 2, change greater than or equal to the median. The 3-year rates of the primary endpoint, a composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, and unstable angina pectoris, were compared between the 2 groups. The median %ΔEPA/AA ratio in Groups 1 and 2 was -26.2% (n=482 patients [49.9%]) and 42.2% (n=483 patients [50.1%]), respectively. At the 3-year follow-up, the occurrence of the primary endpoint was significantly lower in Group 2 than in Group 1 (29/483 [6.0%] vs. 53/482 [11.0%]; hazard ratio 0.53, 95% confidence interval 0.33-0.82; P=0.005). The same trend was observed after adjusting for patient factors (P=0.02). Among ACS patients receiving contemporary lipid-lowering therapy other than PUFAs, a greater change in the EPA/AA ratio was associated with a lower incidence of cardiovascular events.

Refining omega‐3 supplementation trials in APOE4 carriers for dementia prevention

AbstractBackgroundDespite the observed association of the omega‐3s docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) intake or blood levels with Alzheimer’ disease (AD) incidence and cognitive outcomes, omega‐3 clinical trials have largely been negative. Carrying the APOE4 allele is the strongest genetic risk factor for AD. Therefore, identifying how APOE4 affects the response to omega‐3 supplementation can help refine newer and more personalized trials. DHA supplementation increases EPA levels and EPA has strong anti‐inflammatory effects. The ratio of EPA to arachidonic acid (EPA/AA) is a marker of tissue inflammation.MethodWe examined the effect of APOE4 on the change in plasma and cerebrospinal fluid (CSF) EPA/AA in two different clinical trials: the ADCS‐sponsored DHA trial in patients with mild AD (n=402), and the Brain DHA Delivery Pilot trial in cognitively normal participants (n=33). In both trials, participants were randomized to high doses of algal DHA (2 grams per day). A subset of the ADCS‐sponsored study underwent MRIs for measurement of hippocampal volumes (n=86).ResultPlasma EPA/AA was significantly lower in APOE4 carriers compared to non‐carriers after high dose DHA supplementation in both trials. CSF EPA/AA differed by APOE4 genotype in the Brain DHA Delivery Pilot, with APOE4 non‐carriers having two times greater increase in CSF EPA/AA than APOE4 carriers (30 vs. 14% increase, p=0.001) after supplementation. Greater increase in plasma EPA/AA was positively correlated with less decline in the right hippocampal volume (r=0.31, p=0.03) with APOE4 modifying this association (interaction p value, p=0.01, Figure 1).ConclusionAPOE4 appears to limit the conversion of DHA to EPA after DHA supplementation by promoting EPA’s mitochondrial oxidation. These changes start before the onset of dementia. We propose that the plasma EPA/AA can serve as a biomarker for DHA supplementation efficacy. Prospective validation of this biomarker can guide the development of more personalized omega‐3 interventions designed to reduce the increased AD risk with APOE4.

USEFULNESS OF EICOSAPENTAENOIC ACID TO ARACHIDONIC ACID RATIO AS DIFFERENTIATION OF STEMI AND NSTEMI/UAP

Polyunsaturated fatty acids (PUFAs) are known to be associated with cardiovascular event. However, the relationship between serum eicosapentaenoic acid to arachidonic acid (EPA/AA) ratio and patients of acute coronary syndrome (ACS) is unclear. The purpose of this study is to examine the difference

Omega-3 Fatty Acid Supplementation Reduces Intervertebral Disc Degeneration.

BackgroundIntervertebral disc (IVD) degeneration is a common cause of lower back pain, which carries substantial morbidity and economic cost. Omega-3 fatty acids (n-3 FA) are known to reduce inflammatory processes with a relatively benign side effect profile. This study aimed to investigate the effect of n-3 FA supplementation on IVD degeneration.Material/MethodsTwo non-contiguous lumbar discs of 12 Sprague Dawley rats were needle-punctured to induce disc degeneration. Post-surgery, rats were randomly assigned to either a daily n-3 FA diet (530 mg/kg/day of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in a 2: 1 ratio, administered in sucrose solution) or control diet (sucrose solution only), which was given for the duration of the study. After 1 month, blood serum arachidonic acid/eicosapentaenoic acid (AA/EPA) ratios were analyzed. After 2 months, micro-MRI (magnetic resonance imaging) analysis and histological staining of disc explants were performed to analyze the IVD.ResultsA reduction of blood AA/EPA ratios from 40 to 20 was demonstrated after 1 month of daily supplementation with n-3 FA. Micro-MRI analysis showed an injury-induced reduction of IVD hydration, which was attenuated in rats receiving n-3 FA. Histological evaluation demonstrated the destruction of nucleus pulposus tissue in response to needle puncture injury, which was less severe in the n-3 FA diet group.ConclusionsThe results of this study suggest that n-3 FA dietary supplementation reduces systemic inflammation by lowering AA/EPA ratios in blood serum and has potential protective effects on the progression of spinal disc degeneration, as demonstrated by reduced needle injury-induced dehydration of intervertebral discs and reduced histological signs of IVD degeneration.

P824The clinical impact of polyunsaturated fatty acid on clinical outcomes in acute coronary syndrome with dyslipidemia: HIJ-PROPER sub-analysis

Abstract Background Polyunsaturated fatty acids, especially omega-3 and -6 series, are key essential nutrients that play an important role in humans to maintain cell membranes and function. A recent randomized trial reported that adding eicosapentaenoic acid (EPA) to statins was beneficial to cardiovascular disease patients who had a residual risk factor. Further, several studies have reported that the low baseline value for EPA to arachidonic acid (AA) ratio is related to worse clinical outcome and plaque vulnerability in coronary artery disease patients. However, effects of baseline EPA/AA ratio on clinical outcomes in ACS patients have not been thoroughly evaluated. Objectives This study aimed to examine the impact of baseline eicosapentaenoic acid to arachidonic acid (EPA/AA) ratio on clinical outcomes of acute coronary syndrome (ACS) patients and how lipid-lowering therapy affects serum EPA/AA levels in these patients. Methods This is a sub-analysis of HIJ-PROPER assessing the effect of aggressive low-density lipoprotein cholesterol (LDL-C)-lowering treatment with pitavastatin+ezetimibe in 1,734 ACS patients with dyslipidemia. Patients were divided into two groups based on EPA/AA level on admission (cut-off: 0.34 μg/mL; median of baseline EPA/AA level) and clinical outcomes were examined. Results Percent reduction of LDL-C from baseline to follow-up and mean LDL-C level during follow-up were similar regardless of baseline EPA/AA ratio. In the low EPA/AA group, the Kaplan–Meier estimate for the primary endpoint at 3 years was 27.2% in the pitavastatin+ezetimibe group, compared with 36.6% in the pitavastatin-monotherapy group [hazard ratio (HR), 0.69; 95% confidence interval (CI), 0.52–0.93; P=0.015). However, in the high EPA/AA group, there was no significant reduction in the primary endpoint by pitavastatin+ezetimibe therapy (HR, 0.92; 95% CI, 0.70–1.20; P=0.52). Conclusions Aggressive lipid-lowering therapy with ezetimibe had a positive effect on clinical outcomes in the low EPA/AA group of ACS patients with dyslipidemia, but not in the high EPA/AA group. This effect was independent of LDL-C reduction and suggests that EPA/AA measurement on admission in ACS patients contributes to a “personalized” lipid-lowering approach.

MON-061 Association between the ratio of serum eicosapentaenoic acid or docosahexaenoic acid to arachidonic acid and life expectancy in hemodialysis patients

It is reported that n-3 polyunsaturated fatty acids as represented by eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) ameliorates the incidence of cardiovascular disease (CVD) event in population with dyslipidemia and that a higher serum EPA/AA (eicosapentaenoic acid to arachidonic acid) ratio is associated with a lesser risk of CVD event in a general Japanese population. On the contrary, it is well known that CKD itself contributes to the incidence of CVD event and life expectancy, however, the association between the ratio of serum EPA/AA or DHA/AA and the incidence of CVD event or life expectancy in hemodialysis patients remains to be investigated. 84 hemodialysis patients at our dialysis unit were examined on January, 2014. Along with regular blood examination at the beginning of the month, fatty acid four fractions (EPA, DHA, DHLA, AA) were collected. Also age, sex, dialysis-duration, clinical histories and existence or nonexistence of the administration of EPA/DHA-drug product were examined in the medical cords. The life expectancy was followed for three years prospectively. EPA/DHA-drug product was administered to only two patients, all the rest patients took no EPA/DHA-drug product. Comparing between patients with or without the administration of EPA/DHA-drug product, there was no significant difference in DHA/AA ratio, on the other hand, there was significant difference in EPA/AA ratio (the former: 1.58 vs the latter: 0.49) as well as in EPA+DHA/AA ratio. Hereinafter, the data was investigated on patients with the administration of EPA/DHA-drug product. On univariate analysis, there was significant positive correlation between age and the three ratios, respectively, however no correlation between clinical histories and the three ratios. On logistic regression analysis, there was significant positive correlation between age and EPA/AA or EPA+DHA/AA ratio, respectively. There was significant correlation between three-year life expectancy and the three ratios, respectively. Our findings suggest that a higher serum EPA/AA and/or DHA/AA ratio is associated with a better life expectancy in hemodialysis patients.

Body composition and sensory quality of wild and farmed brown-trout (Salmo trutta) and of farmed rainbow-trout (Oncorhynchus mykiss)

ABSTRACT: Body composition (total crude protein, lipid, ash, dry matter and moisture) and fatty acid profiles were compared between wild and farmed brown trout and between farmed rainbow trout. Farmed brown trout contained the highest amount of crude protein (18.39%), whereas farmed rainbow trout contained higher levels of crude lipid (2.35%). Thirty six fatty acids were found, including sixteen saturated fatty acids (SFA), nine monounsaturated fatty acids (MUFA) and eleven polyunsaturated fatty acids (PUFA). The most abundant SFA in all fish were palmitic acid and stearic acid. However, the most abundant fatty acids in all trout samples were MUFA and PUFA. MUFA were the most abundant fatty acid in farmed brown trout because of high abundance of oleic acid in this samples (35.46g / 100g fatty acids). PUFA were predominating in the samples of wild brown trout and of rainbow trout 56.16 and 56.29g/100g fatty acids, respectively). Linoleic acid was the most abundant fatty acid reported in the rainbow trout (47.17g/100g fatty acids). Significantly higher amounts of docosahexaenoic acid, α-linolenic acid, arachidonic acid and eicosapentaenoic acid were observed in the wild trout samples. Wild brown trout contained significantly more docosahexaenoic acid, α-linolenic acid, Eicosapentaenoic acidArachidonic acid. Sensory quality evaluation, by a consumers’ panel, revealed all samples were equally well accepted.

A longitudinal study of the association of the eicosapentaenoic acid/arachidonic acid ratio derived from fish consumption with the serum lipid levels: a pilot study.

It has been demonstrated that regular fish consumption is associated with a reduced mortality from atherosclerotic cardiovascular disease (ASCVD). However, data are scarce regarding the correlation between the changes in the serum eicosapentaenoic acid/arachidonic acid (EPA/AA) ratio associated with regular fish consumption and the changes in the serum lipid profile variables. This study was designed as a hospital-based longitudinal study to investigate the relationship between the changes in the serum EPA/AA ratio and changes of the serum lipid levels in patients with one or more risk factors for ASCVD. In 475 patients followed-up for at least 1year, univariable and multivariable regression analyses conducted after adjustments for the risk factors of ASCVD revealed that the absolute change of the EPA/AA ratio (∆EPA/AA ratio) was independently and significantly associated with the changes of the serum levels of low-density lipoprotein cholesterol (LDL-C) (β = - 0.129, p = 0.005), triglyceride (TG) (β = - 0.108, p = 0.019), non-high-density lipoprotein cholesterol (non-HDL-C) (β = - 0.149, p = 0.001), and TG/HDL-C ratio, a marker of the LDL particle size (β = - 0.104, p = 0.02), while not being correlated with any other lipid parameters. On the other hand, while the ∆ docosahexaenoic acid (DHA)/AA ratio was inversely correlated with the changes of the serum HDL-C level and positively correlated with the changes of the TG/HDL-C ratio, possibly serving to promote development of atherosclerosis. The results suggest that an increase of the EPA/AA ratio might be associated with decrease of the serum levels of LDL-C, TG and non-HDL-C levels, as well as with an increase of the TG/HDL-C ratio, which represents increased LDL particle size, all of which play a role in the development of ASCVD. A high EPA/AA ratio, but not DHA/AA ratio, derived from fish consumption might reduce the risk of ASCVD through reducing the risk of development of atherosclerosis.Clinical Trial Registration Information: UMIN ( http://www.umin.ac.jp/ ), Study ID: UMIN000010603.

The Current Conditions and Lifestyles of Obese University Students.

BackgroundThe prevalence of cardiovascular diseases in Japan remains high, and the onset becomes early. Studies on the current conditions and lifestyles of obese university students may support early interventions to achieve lifestyle modification.Methods and ResultsThe results of periodic health examinations in 32,262 first-year university students revealed that 2,036 (6.3%) were obese. We performed a more detailed examination in 221 of these obese students (165 males and 56 females, age 19 ± 1 years) with study agreement from 2014 to 2016. In this study cohort, the percentage of students who exercised regularly was significantly higher among males than females. Body fat in males with well-exercised was lower than that in males with no exercise. In addition, serum level of high-density cholesterol in males with well-exercised was higher. Among females, there were no significant differences in these parameters between exercisers and non-exercisers. Forty-two obese students (40 males and two females) met the diagnostic criteria of metabolic syndrome (MetS). Among males, levels of body fat, uric acid, liver enzyme and insulin resistance in the MetS group were significantly higher than those in the non-MetS group. The average ratio of eicosapentaenoic acid to arachidonic acid (EPA/AA) was low (0.14).ConclusionsAlthough the proportions of students with obesity and/or MetS were not high, the EPA/AA ratio in obese young males was low, which may be associated with a high risk of coronary atherosclerosis. To prevent the onset of cardiovascular diseases early intervention to achieve lifestyle modification may be important.

Neuroprotective Effects of Omega-3 Polyunsaturated Fatty Acids in a Rat Model of Anterior Ischemic Optic Neuropathy.

The purpose of this study was to investigate the therapeutic effect of omega-3 polyunsaturated fatty acid (ω-3 PUFA) administration in a rat model of anterior ischemic optic neuropathy (rAION). The level of blood arachidonic acid/eicosapentaenoic acid (AA/EPA) was measured to determine the suggested dosage. The rAION-induced rats were administered fish oil (1 g/day EPA) or phosphate-buffered saline (PBS) by daily gavage for 10 consecutive days to evaluate the neuroprotective effects. Blood fatty acid analysis showed that the AA/EPA ratio was reduced from 17.6 to ≤1.5 after 10 days of fish oil treatment. The retinal ganglion cell (RGC) densities and the P1-N2 amplitude of flash visual-evoked potentials (FVEP) were significantly higher in the ω-3 PUFA-treated group, compared with the PBS-treated group (P < 0.05). The number of apoptotic cells in the RGC layer of the ω-3 PUFA-treated rats was significantly decreased (P < 0.05) compared with that of the PBS-treated rats. Treatment with ω-3 PUFAs reduced the macrophage recruitment at the optic nerve (ON) by 3.17-fold in the rAION model. The M2 macrophage markers, which decrease inflammation, were induced in the ω-3 PUFA-treated group in contrast to the PBS-treated group. In addition, the mRNA levels of tumor necrosis factor-alpha, interleukin-1 beta, and inducible nitric oxide synthase were significantly reduced in the ω-3 PUFA-treated group. The administration of ω-3 PUFAs has neuroprotective effects in rAION, possibly through dual actions of the antiapoptosis of RGCs and anti-inflammation via decreasing inflammatory cell infiltration, as well as the regulation of macrophage polarization to decrease the cytokine-induced injury of the ON.

PLASMA EICOSAPENTAENOIC ACID AND THE EICOSAPENTAENOIC ACID TO ARACHIDONIC ACID RATIO IN 8,010 PATIENTS WITH SEVERELY ELEVATED LDL-C (&gt;190 MG/DL): CAUSE FOR ALARM?

Background: In the Japan Eicosapentaenoic Acid (EPA) Lipid Intervention Study (JELIS) a low plasma EPA (<150 ug/mL) and a low EPA to arachidonic acid (EPA/AA) ratio (<0.75) were associated with increased major coronary events. In Japan, it has been proposed that patients who are either classified as

Influence of toll-like receptor 4 gene variants and plasma fatty acid profile on systemic inflammation: A population-based cross-sectional study

ObjectiveThe aim of this study was to investigate the interaction of toll-like receptor 4 (TLR4) gene single nucleotide polymorphism (SNP) and plasma fatty acid (FA) profile in modulating risk for systemic inflammation. MethodsIn all, 262 adult (19–59 y) participants of the Health Survey of São Paulo met the inclusion criteria. Anthropometric parameters, blood pressure, plasma inflammatory biomarker concentration, and fatty acid profile were measured and four SNPs of the TLR4 gene (rs4986790, rs4986791, rs11536889, and rs5030728) were genotyped. Multivariate cluster analysis was performed to stratify individuals based on levels of 11 plasma inflammatory biomarkers into two groups: inflammatory (INF) and noninflammatory (NINF). ResultsNo association was found between any of the SNPs studied and systemic inflammation. The INF cluster had higher palmitic acid levels (P = 0.039) and estimated stearoyl coenzyme A desaturase activity (P = 0.045) and lower polyunsaturated fatty acid (P = 0.011), ω-6 fatty acid (P = 0.018), arachidonic acid (P = 0.002) levels, and estimated δ-5 desaturase activity (P = 0.025) compared with the NINF cluster. Statistically significant interaction between rs11536889 and arachidonic acid/eicosapentaenoic acid (AA/EPA) ratio (P = 0.034) was found to increase the odds of belonging to the INF cluster when individuals had the variant allele C and were at the higher percentile of AA/EPA plasma ratio. ConclusionPlasma fatty acid profile modulated the odds of belonging to the INF cluster depending on genotypes of TRL4 gene polymorphisms.

Eicosapentaenoic acid to arachidonic acid (EPA/AA) ratio as an associated factor of high risk plaque on coronary computed tomography in patients without coronary artery disease

Background and aimsCoronary computed tomography angiography (CCTA)-verified high risk plaque (HRP) characteristics including positive remodeling and low attenuation plaque have been associated with acute coronary syndromes. Several studies reported that the n-3 polyunsaturated fatty acids have been associated with cardiovascular events. However, the relationship between serum eicosapentaenoic acid to arachidonic acid (EPA/AA) ratio and CCTA-verified HRP in patients without known coronary artery disease (CAD) is unclear. We aimed at investigating the relation between EPA/AA and CCTA-verified HRP in patients without known CAD. MethodsWe included 193 patients undergoing CCTA without known CAD (65.5 ± 12.0 years, 55.0% male). No patient has been treated with EPA. The relation of coronary risk factors, lipid profile, high-sensitivity C-reactive protein, coronary artery calcification score (CACS), number of vessel disease, plaque burden, and EPA/AA with the presence of HRP was evaluated by logistic regression analysis. Incremental value of EPA/AA to predict HRP was also analyzed by C-index, NRI, and IDI. A Cox proportional hazards model was used to estimate the time to cardiovascular event. ResultsHRP was observed in 37 (19%) patients. Multivariable logistic regression analysis revealed that current smoking (OR 2.58; p=0.046), number of vessel disease (OR 1.87; p=0.031), and EPA/AA ratio (OR 0.65; p=0.0006) were independent associated factors of HRP on CCTA. Although the addition of EPA/AA to the baseline model did not significantly improve C-index, both NRI (0.60, p=0.0049) and IDI (0.054, p=0.0072) were significantly improved. Patients with HRP had significantly higher rate of events compared with patients without HRP (14% vs. 3%, Logrank p=0.0004). On multivariable Cox hazard analysis, baseline EPA/AA ratio was an independent predictor (HR 0.57, p=0.047). ConclusionsLow EPA/AA was an associated factor of HRP on CCTA in patients without CAD. In addition to conventional coronary risk factors and CACS, EPA/AA and CCTA might be useful for risk stratification of CAD.

Ankle-brachial index and eicosapentaenoic acid/arachidonic acid ratio in smokers with type 2 diabetes mellitus

BackgroundThe ankle-brachial index (ABI) is an indicator of peripheral arterial damage and a low (ABI ≤ 1.0) or borderline (ABI = 1.00–1.09) value is associated with risk of cardiovascular disease events. A low ratio of serum eicosapentaenoic acid to arachidonic acid (EPA/AA) is also a risk factor for cardiovascular disease events. This study examined associations between the ABI and the EPA/AA ratio in smokers and non-smokers with type 2 diabetes mellitus (T2DM).FindingsBlood data including EPA, AA, and ABI were measured in smokers and non-smokers with T2DM enrolled at Jichi Medical University (n = 116, male 86 %, mean age 59 yr). The patients were classified into two groups according to their ABI level: <1.1 (low to borderline) or ≥1.1 (high). The EPA/AA ratio in smoking patients with ABI < 1.1 (n = 26; EPA/AA = 0.25) was significantly lower than in those with ABI ≥ 1.1 (n = 32; EPA/AA = 0.34; p = 0.03), but was not significantly different in non-smoking patients. The EPA/AA ratio was independently, significantly, and positively correlated with the ABI level (β = 0.41; p < 0.01) after adjusting for multiple variables only in smoking patients with T2DM.ConclusionsThe EPA/AA ratio may be associated with subclinical peripheral arterial damage in smokers with T2DM. Further studies are warranted.