Plasma Concentrations Of Eicosapentaenoic Acid Research Articles

Rationale for different formulations of omega-3 fatty acids leading to differences in residual cardiovascular risk reduction

Rationale for different formulations of omega-3 fatty acids leading to differences in residual cardiovascular risk reduction

Diurnal rhythm of plasma EPA and DHA in healthy adults

Knowledge of the diurnal variation in circulating omega-3 polyunsaturated fatty acids (n-3 PUFAs) may be an important consideration for the development of dosing protocols designed to optimise tissue delivery of these fatty acids. The objective of the current study was to examine the variation in plasma concentrations of eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3) over a 24-h period in healthy adults under eating and sleeping conditions generally approximate to a free-living environment. Twenty-one healthy participants aged 25–44 years took part in a single laboratory visit encompassing an overnight stay. EPA and DHA were measured in plasma samples collected every two hours from 22:00 until 22:00 the following day, with all meals being provided at conventional times. Cosinor analysis was used to estimate the diurnal variation in each fatty acid from pooled data across all participants. A significant diurnal variation in the pooled plasma concentrations of both fatty acids was detected. However, evidence of distinct rhythmicity was strongest for DHA. The timing of the peak concentration of DHA was 17:43 with a corresponding nadir at 05:43. In comparison, the observed acrophase for EPA was delayed by three hours, occurring at 20:41, with a nadir at 08:41. This is the first time that the diurnal variation in these important bioactive fatty acids has been described in a sample of healthy adults following a normal pattern of eating and sleeping. In the absence of any dietary intake of EPA and DHA, circulating levels of these fatty acids fall during the overnight period and reach their lowest point in the morning. Consumption of n-3 PUFAs at night time, which counteracts this pattern, may have functional significance.

Translating plasma eicosapentaenoic acid concentrations into erythrocyte percentages of eicosapentaenoic acid plus docosahexaenoic acid during treatment with icosapent ethyl

The Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT) study demonstrated that 4g/d of eicosapentaenoic acid (EPA) ethyl esters (icosapent ethyl [IPE]) reduced risk for major cardiovascular events by 25% in statin-treated patients with residual hypertriglyceridemia. How this treatment affected red blood cell (RBC) EPA and docosahexaenoic acid (DHA) levels (ie, the Omega-3 Index [O3I]) was not reported, but effects on plasma EPA concentrations were reported. The aim of the study was to estimate baseline and final O3I levels in REDUCE-IT. First, deidentified data from our laboratory on RBC and plasma EPA and DHA from 2311 patients with similar lipid profiles as those in REDUCE-IT were used to generate a regression equation, which was then used to estimate the O3I from plasma FA concentrations. Second, previously published data on the effects of IPE on RBC FA concentrations were also converted to the O3I. Both approaches (from calculations and prior publications) suggested that baseline and follow-up O3I levels were about 5% and 7%, respectively. In addition, plasma EPA levels (but not the O3I) were noted to be influenced by triglyceride levels. For patients using 4 g of IPE, an estimated O3I value of about 7% reflects a cardioprotective state. Plasma EPA concentrations may be ill-suited as treatment targets because they are confounded by triglyceride levels.

N-3 Docosapentaenoic Acid Intake and Relationship with Plasma Long-Chain n-3 Fatty Acid Concentrations in the United States: NHANES 2003-2014.

The long-chain n-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), play a crucial role in health, but previous National Health and Nutrition Examination Survey (NHANES) analyses have shown that EPA and DHA intake in the United States is far below recommendations (~250-500 mg/day EPA + DHA). Less is known about docosapentaenoic acid (DPA), the metabolic intermediate of EPA and DHA; however, evidence suggests DPA may be an important contributor to long-chain n-3 fatty acid intake and impart unique benefits. We used NHANES 2003-2014 data (n = 45,347) to assess DPA intake and plasma concentrations, as well as the relationship between intake and plasma concentrations of EPA, DPA, and DHA. Mean DPA intake was 22.3 ± 0.8 mg/day from 2013 to 2014, and increased significantly over time (p < 0.001), with the lowest values from 2003 to 2004 (16.2 ± 1.2 mg/day). DPA intake was higher in adults (20-55 years) and seniors (55+ years) compared to younger individuals. In regression analyses, DPA intake was a significant predictor of plasma EPA (β = 138.5; p < 0.001) and DHA (β = 318.9; p < 0.001). Plasma DPA was predicted by EPA and DHA intake (β = 13.15; p = 0.001 and β = 7.4; p = 0.002), but not dietary DPA (p = 0.3). This indicates that DPA intake is not a good marker of plasma DPA status (or vice versa), and further research is needed to understand the factors that affect the interconversion of EPA and DPA. These findings have implications for future long-chain n-3 fatty acids dietary recommendations.

Effects of a Self–micro-emulsifying Delivery System Formulation Versus a Standard ω-3 Acid Ethyl Ester Product on the Bioavailability of Eicosapentaenoic Acid and Docosahexaenoic Acid: A Study in Healthy Men and Women in a Fasted State

PurposeIntakes of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are associated with several potential health benefits, but standard ethyl ester (EE) formulations of these ω-3 fatty acids require the co-ingestion of fat for adequate absorption. The objective of this research was to assess the relative bioavailability of EPA and DHA administered in a proprietary self–micro-emulsifying delivery system (SMEDS) formulation compared with EPA and DHA in a standard ω-3 acid EE product in healthy men and women in a fasted state. MethodsThis randomized crossover study investigated the bioavailability of 2 encapsulated formulations of EPA and DHA, a capsule containing 500 mg EPA + DHA administered in a SMEDS formulation (SMEDS treatment), and a capsule containing 840 mg EPA + DHA in a standard ω-3 acid EE formulation (EE treatment). Subjects consumed a single dose of their assigned capsule in a fasting state, and plasma was collected before and for 24 h after dosing. Subjects underwent a ≥14-day washout and were crossed over to the other treatment condition. Plasma concentrations of EPA, DHA, and EPA + DHA were assessed. FindingsTwenty-three subjects (11 women, 12 men; mean [SEM] age, 33.8 [2.1] years; and body mass index, 24.9 [0.7] kg/m2) completed the trial. The baseline-adjusted, dose-normalized, arithmetic means (SD) of the incremental (i)-AUC0–24h for EPA + DHA were 543 (266) and 102 (88.2) h · μg/mL/g for the SMEDS and EE formulations, respectively (P < 0.001). The iAUC0–24h least-squares geometric mean ratio (90% CI) for SMEDS:standard EE was 475/58 = 8.2 (4.8–13.9), indicating markedly higher bioavailability of EPA + DHA with the SMEDS formulation compared to the standard EE formulation. This finding was also true for EPA (geometric mean ratio [90% CI], 18.2 [11.3–29.3]) and DHA (geometric mean ratio [90% CI], 4.5 [2.9–7.0]). ImplicationsThe SMEDS delivery system markedly enhanced appearance in plasma of EPA and DHA, compared to a standard EE formulation, when ingested in the fasting state. ClinicalTrials.gov identifier: NCT03443076.

Importance of pancreatic exocrine dysfunction in patients with type 2 diabetes: A randomized crossover study

BackgroundLevels of faecal elastase-1 (FE-1), a marker of exocrine pancreatic function, are lower in patients with type 2 diabetes than without diabetes. We aimed to investigate the association between FE-1 and nutritional status, gastrointestinal symptoms, and lipid absorption. MethodsThis randomized, open-label, crossover study included 315 patients with type 2 diabetes aged 18–70 years treated with oral antidiabetics, with HbA1c 6.5–9.0% and BMI 18–40 kg/m2. Assessments included levels of FE-1 and blood biomarkers of nutrition, and Bristol Stool Scale and Gastrointestinal Symptom Rating Scale (GSRS) scores. Plasma exposure of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) after oral administration of free omega-3 carboxylic acids or ethyl esters with breakfast was investigated in patients with low, intermediate, and normal FE-1 levels. ResultsThe prevalence of low and intermediate FE-1 levels was 5.2% and 4.9%, respectively. Bristol Stool Scale scores and mean values of GSRS Diarrhoea and Indigestion domain symptoms were similar across groups, but patients with low FE-1 were heavier and reported lower stool frequency. FE-1 levels correlated positively with plasma levels of amylase, lipase, 25-hydroxy vitamin D, and albumin. Mean EPA + DHA exposure was similarly higher after intake of free vs. esterified omega-3 fatty acids in all FE-1 groups. ConclusionsThe prevalence of low FE-1 (<100 μg/g) as a measure of pancreatic exocrine insufficiency was infrequent in type 2 diabetes. Except for low plasma concentrations of EPA and 25-hydroxy vitamin D, type 2 diabetes patients with low FE-1 had no other signs of malabsorption or gastrointestinal disorders. Plasma levels of EPA and DHA after the intake of esterified versus free EPA and DHA did not correlate with FE-1 levels. Trial registrationClinicalTrials.gov NCT02370537.

Prepartum fatty acid supplementation in sheep. II. Supplementation of eicosapentaenoic acid and docosahexaenoic acid during late gestation alters the fatty acid profile of plasma, colostrum, milk and adipose tissue, and increases lipogenic gene expression of adipose tissue.

The objectives of this study were as follows: 1) to establish whether feeding a source of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) to ewes during late gestation changes the fatty acid profile of colostrum, milk, ewe adipose tissue, and plasma and subsequently lamb plasma and red blood cells (RBC), and 2) to investigate the effects of EPA and DHA on mRNA expression in ewe adipose tissue. Eighty-four gestating ewes (28 pens, three per pen) were blocked by lambing day and assigned to a diet with an addition of fat at 0.39% of the DM during the last 50 d of gestation using Ca salts of a palm fatty acid distillate (PFAD) high in palmitic and oleic acids or EPA + DHA. Blood samples were taken from ewes on days 20, 1 (parturition), and 30 and from lambs on days 1 and 30 for plasma fatty acid analysis. Fatty analysis of lamb RBC was performed on day 1. Colostrum samples were taken at lambing and milk samples on day 30 for fatty acid analysis. Subcutaneous adipose tissue biopsies were taken from one ewe per pen on day 20 for fatty acid analysis and gene expression analysis of 27 genes. Treatment × day interactions (P < 0.10) were observed for several isomers of C18:1, with concentrations that were greater in plasma of EPA + DHA ewes on day 20, but were not different on day 1 or 30. Plasma concentrations of EPA tended to be greater (P = 0.07), whereas DHA was greater (P < 0.001) in EPA + DHA ewes compared with PFAD ewes. There was no difference in EPA or DHA in adipose tissue with EPA + DHA vs. PFAD supplementation (P > 0.10). Concentrations of fatty acids with 6 to 10 carbons were significantly increased (P < 0.05) in colostrum and milk of EPA + DHA ewes. There was a treatment × day interaction with EPA + DHA ewes yielding greater EPA (P = 0.03) and DHA (P = 0.04) concentrations than PFAD in colostrum, but not in milk. Treatment × day interactions (P < 0.05) were observed for several C18:1 isomers with concentrations that were greater in EPA + DHA ewe colostrum, but were not different between treatments in milk. In lamb plasma and RBC, EPA and DHA were not different between treatments (P > 0.10). The expression of fatty acid synthase and leptin was significantly increased (P < 0.05), whereas the expression of diacylglycerol acyltransferase 2 tended to be increased (P = 0.08) by supplementation of EPA + DHA vs. PFAD. These results suggest that supplementation with EPA and DHA to ewes during late gestation alters the fatty acid profile of plasma, colostrum, and milk and may increase lipogenesis.

Effects of aspirin in combination with EPA and DHA on HDL-C cholesterol and ApoA1 exchange in individuals with type 2 diabetes mellitus

Background/synopsisLow-dose aspirin is an effective drug for the prevention of cardiovascular disease (CVD) events but individuals with diabetes mellitus can be subject to ‘aspirin resistance’. Thus, aspirin's effect in these individuals is controversial. Higher blood levels of seafood-derived omega-3 polyunsaturated fatty acids (ω3) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) also have beneficial effects in reducing risk of CVD events but few studies have examined the interaction of plasma EPA and DHA with aspirin ingestion. Objective/purposeOur study examined the combinatory effects of EPA, DHA, and aspirin ingestion on HDL-cholesterol (HDL-C) and apoA-I exchange (shown to be associated with CVD event risk). Methods30 adults with Type 2 diabetes mellitus ingested aspirin (81mg/day) for 7 consecutive days, EPA+DHA (2.6g/day) for 28 days, then both for 7 days. Plasma was collected at baseline and at 5 subsequent visits including 4h after each aspirin ingestion. Mixed model methods were used to determine HDL-C-concentrations and apoA-I exchange compared to the baseline visit values. LOWESS curves were used for non-linear analyses of outcomes to help discern change patterns, which was followed by piecewise linear functions for formal testing of curvilinear relationships. ResultsSignificant changes (p < 0.05) compared to baseline in both HDL-C-concentrations and apoA-I exchange were present at different times. After 7 days of aspirin-only ingestion, apoA-I exchange was significantly modified by increasing levels of DHA concentration, with increased apoA-I exchange observed up until log(DHA) of 4.6 and decreased exchange thereafter (p = 0.03). These LOWESS curve effects were not observed for EPA or HDL-C (p > 0.05). Aspirin's effects on apoA-I exchange were the greatest when EPA or DHA concentrations were moderate compared to high or low. Comparison of EPA, DHA, and EPA+DHA LOWESS curves, demonstrated that the majority of the effect is due to DHA. ConclusionOur results strongly suggest that plasma concentrations of EPA and DHA influence aspirin effects on lipid mediators of CVD event risk where their concentrations are most beneficial when moderate, not high or low. These effects on HDL-C cholesterol and apoA-I exchange are novel. Personalized dosing of DHA in those who take aspirin may be a beneficial option for patients with type 2 diabetes mellitus.

Nutrigenetics of Japanese Vegetarians with Polymorphism in the Fatty Acid Desaturase

This review investigates how the genotype of vegetarians controls lipid metabolism responses to the dietary intake of n-3 fatty acids. While health indices of Japanese vegetarians are superior to those of omnivores, the effects of genetics have not been studied. The lipid intake of Japanese omnivores and vegans is less than that of Western vegans. Mongolian carnivores and Inuit piscivores have shorter lifespans compared to other Asians who consume a rice diet or taro-fish diet. Our genetic studies on Mongoloids in Asia Pacific regions revealed similar allele frequencies of genes related to diabetes and cardiovascular diseases, which are increasing with recent Westernization because of genetic differences between Mongoloids and Caucasoids. Long-chain n-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), play a role in preventing these diseases, yet vegetarians consume nearly 0 g per day. Conversion of plant-derived α-linolenic acid (ALA) to EPA and DHA, and linoleic acid to arachidonic acid (AA) requires the Δ5 desaturase. Thus, plasma concentrations of EPA, DHA and AA in vegetarians are lower than those in omnivores, especially vegans with the C allele of the Δ5 desaturase polymorphism rs174547. The following hypotheses have been proposed to explain the health of C homozygote vegans: 1. They are unable to survive, 2. They cease the vegan diet, 3. They preferentially preserve EPA/DHA by lowered catabolism, 4. Their Δ5 desaturase is activated by specific factors, and 5. Their EPA/AA ratio is elevated and harmful LDL-C and inflammation etc. is reduced. This review does not support hypotheses 1 and 2, but partially accepts 3 and 4 and completely confirms 5. In future, genotype-specific personalized dietary recommendations for optimal health span based on telomere length will be developed. Currently, the pesco-vegetarian diet, which is similar to the traditional Japanese (Washoku) diet, is the healthiest for the majority of subjects.

Fish Oil Supplements Lower Serum Lipids and Glucose in Correlation with a Reduction in Plasma Fibroblast Growth Factor 21 and Prostaglandin E2 in Nonalcoholic Fatty Liver Disease Associated with Hyperlipidemia: A Randomized Clinical Trial.

Fish oil has been used effectively in the treatment of cardiovascular disease via triglyceride reduction and inflammation modulation. This study aimed to assess the effects of fish oil on patients with nonalcoholic fatty liver disease (NAFLD) associated with hyperlipidemia. Eighty participants with NAFLD associated with hyperlipidemia were randomly assigned to consume fish oil (n=40, 4 g/d) or corn oil capsules (n=40, 4 g/d) for 3 months in a double-blind, randomized clinical trial. Blood levels of lipids, glucose and insulin, liver enzymes, kidney parameters and cytokines at baseline and the end of the study were measured. Seventy people finished the trial. Plasma concentrations of eicosapentaenoic acid and docosahexaenoic acid significantly increased in the fish oil group after intervention. After adjustment for age, gender and BMI, fish oil significantly decreased fasting serum concentrations of total cholesterol, triglyceride, apolipoprotein B and glucose (by (mean±SD) 0.49±0.43 mmol/L, 0.58±0.89 mmol/L, 0.28±0.33 g/L and 0.76±0.56 mmol/L, respectively, P<0.05), as well as alanine aminotransferase and γ-glutamyl transpeptidase levels (by (median (interquartile)) 9.0(0.5, 21.5) and 7.0(2.2, 20.0) IU/L, respectively, P<0.05), significantly increased serum adiponectin levels (by 1.29±0.62 μg/mL, P<0.001), and reduced serum levels of tumor necrosis factor α, leukotrienes B4, fibroblast growth factor 21 (FGF21), cytokeratin 18 fragment M30 and prostaglandin E2 (by 1.70±1.18 pg/mL, 0.59±0.28 ng/mL, 121±31 pg/mL, 83±60 IU/L and 10.9±2.3 pg/mL, respectively, P<0.001). Corn oil had no effect except for increasing serum creatinine concentrations by 7.7±8.9 μmol/L (P=0.008). The effects of fish oil on lipids, glucose and γ-glutamyl transpeptidase were positively correlated with the reductions of serum FGF21 and prostaglandin E2 concentrations after adjustment for age, gender and BMI (r = 0.275 to 0.360 and 0.261 to 0.375, respectively, P<0.05). In conclusion, our findings suggest that fish oil can benefit metabolic abnormalities associated with NAFLD treatment.Trial Registration ChiCTR-TRC-12002380

The effects of aspirin on platelet function and lysophosphatidic acids depend on plasma concentrations of EPA and DHA

Aspirin׳s prevention of cardiovascular disease (CVD) events in individuals with type 2 diabetes mellitus is controversial. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and aspirin all affect the cyclooxygenase enzyme. The relationship between plasma EPA and DHA and aspirin׳s effects has not been determined. Thirty adults with type 2 diabetes mellitus ingested aspirin (81mg/day) for 7 days, then EPA+DHA (2.6g/day) for 28 days, then both for another 7 days. Lysophosphatidic acid (LPA) species and more classic platelet function outcomes were determined. Plasma concentrations of total EPA+DHA were associated with 7-day aspirin reduction effects on these outcomes in a “V”-shaped manner for all 11 LPA species and ADP-induced platelet aggregation. This EPA+DHA concentration was quite consistent for each of the LPA species and ADP. These results support aspirin effects on lysolipid metabolism and platelet aggregation depending on plasma EPA+DHA concentrations in individuals with a disturbed lipid milieu.

Eicosapentaenoic Acid Attenuates Coronary Atherosclerotic Plaque Volume in Patients with Coronary Artery Disease

Although eicosapentaenoic acid (EPA) has been shown to reduce cardiovascular events, its mechanisms are unknown. The aim of this study was to investigate the effects of EPA on atherosclerotic plaque volume in patients with coronary artery disease. 20 patients were enrolled in this study. 11 patients were administrated EPA as EPA group and 9 patients without EPA administration were served as control group. The plasma concentrations of EPA and arachidonic acid (AA), adiponectin and cholesterol profiles were examined before and after observation.

Relationship between diet and plasma long-chain n-3 PUFAs in older people: impact of apolipoprotein E genotype

The main risk factors for Alzheimer's disease, age and the ε4 allele of the APOE gene (APOE4), might modify the metabolism of n-3 PUFAs and in turn, their impact on cognition. The aim of this study was to investigate the association between dietary fat and plasma concentrations of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in elderly persons, taking the APOE4 genotype into account. The sample was composed of 1,135 participants from the Three-City study aged 65 years and over, of whom 19% were APOE4 carriers. Mean plasma proportions of EPA [1.01%, standard deviation (SD) 0.60] and DHA (2.41%, SD 0.81) did not differ according to APOE4. In multivariate models, plasma EPA increased with frequency of fish consumption (P < 0.0001), alcohol intake (P = 0.0006), and female gender (P = 0.02), and decreased with intensive consumption of n-6 oils (P = 0.02). The positive association between fish consumption and plasma DHA was highly significant whatever the APOE genotype (P < 0.0001) but stronger in APOE4 noncarriers than in carriers (P = 0.06 for interaction). Plasma DHA increased significantly with age (P = 0.009) in APOE4 noncarriers only. These findings suggest that dietary habits, gender, and APOE4 genotype should be considered when designing interventions to increase n-3 PUFA blood levels in older people.

A Highly Bioavailable Omega-3 Free Fatty Acid Formulation Improves the Cardiovascular Risk Profile in High-Risk, Statin-Treated Patients With Residual Hypertriglyceridemia (the ESPRIT Trial)

BackgroundA novel omega-3 formulation in free fatty acid form (OM3-FFA) has as much as 4-fold greater bioavailability than ethyl ester forms and reduces triglyceride (TG) levels in patients with severe hypertriglyceridemia. ObjectiveThis study was designed to evaluate the efficacy of adding OM3-FFA (2 or 4 g/d) to statin therapy for lowering non–HDL-C and TG levels in subjects with persistent hypertriglyceridemia and at high risk for cardiovascular disease. MethodsIn this double-blind, parallel-group study, 647 diet-stable patients with fasting TG levels ≥200 mg/dL and <500 mg/dL (treated with a maximally tolerated dose of statin or statin with ezetimibe) and at high risk for cardiovascular disease were randomized to 6 weeks of treatment with capsules of control (olive oil [OO]) 4 g/d, OM3-FFA 2 g/d (plus 2 g/d OO), or OM3-FFA 4 g/d. Assessments included fasting serum levels of lipids and apolipoproteins (apo); plasma concentrations of eicosapentaenoic acid, docosahexaenoic acid, docosapentaenoic acid, and arachidonic acid; and laboratory safety values and adverse events. ResultsIn the 627 subjects in the intention to treat sample, non–HDL-C levels were reduced with OM3-FFA 2 g/d and OM3-FFA 4 g/d (–3.9% and –6.9%, respectively) compared with OO (–0.9%) (both, P < 0.05), as were TG levels (–14.6% and –20.6%, respectively, vs –5.9%; both, P < 0.001). LDL-C levels increased with OM3-FFA 2 g/d (4.6%) compared with OO (1.1%) (P = 0.025) but not with OM3-FFA 4 g/d (1.3%). Total cholesterol and VLDL-C concentrations were reduced compared with OO with both OM3-FFA dosages, and the total cholesterol/HDL-C ratio and apo AI and apo B levels were significantly lowered with OM3-FFA 4 g/d only (all at least P < 0.05). Percent changes from baseline in HDL-C did not differ between OO and either OM3-FFA group. Plasma concentrations of docosahexaenoic acid, eicosapentaenoic acid, and docosapentaenoic acid were significantly increased and arachidonic acid was significantly reduced in both OM3-FFA treatment groups compared with the OO responses (all, P < 0.001). Withdrawals related to treatment-emergent adverse events ranged from 0.9% with OO to 3.2% with OM3-FFA 4 g/d. ConclusionsOM3-FFA was well tolerated and lowered non–HDL-C and TG levels at both 2- and 4-g/d dosages in patients with persistent hypertriglyceridemia taking a statin, with the 4-g/d dosage providing incremental improvements compared with 2 g/d. ClinicalTrials.gov identifier: NCT01408303.

Estimation of eicosapentaenoic acid and docosahexaenoic acid intakes in pregnant Japanese women without nausea by using a self-administered diet history questionnaire

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) intakes during pregnancy affect fetal development and maternal mental health; therefore, an accurate assessment of EPA and DHA intakes is required. We hypothesized that a self-administered diet history questionnaire (DHQ) that was developed for non-pregnant adults could be used for estimating EPA and DHA intakes in pregnant Japanese women; thus, we evaluated the validity and reproducibility of the DHQ during pregnancy. We recruited 262 healthy participants with singleton pregnancies during their second trimester at a university hospital in Tokyo between June 2010 and July 2011. Plasma concentrations of EPA and DHA were measured as reference values. Fifty-eight women completed the DHQ twice, within a 4- to 5-week period to assess the reproducibility of the results. Among the participants without pregnancy-associated nausea (n = 180), significantly positive correlations were observed between energy-adjusted intakes and plasma concentrations of EPA (rs = 0.388), DHA (rs = 0.264), and EPA + DHA (rs = 0.328). More than 60% of the participants without nausea fell into the same or adjacent quintiles according to energy-adjusted intakes and plasma concentrations of EPA, DHA, and EPA + DHA. Meanwhile, among the participants with nausea, a low correlation for EPA and no correlation for DHA and EPA + DHA were found. Intraclass correlation coefficients for the 2-time DHQ measurements were 0.691 (EPA) and 0.663 (DHA). The results indicate that the DHQ has an acceptable level of validity and reproducibility for assessing EPA, DHA, and EPA + DHA intakes in pregnant Japanese women without nausea.

Change of heart: Mixed evidence on omega-3 FAs

In 2010, Americans spent more than $1 billion on nonprescription fish oil products. These dietary supplements remain the most commonly used natural products. Fish oil can be used as a source of long chain omega-3 polyunsaturated fatty acids (FAs), but data for their cardiovascular benefits are conflicting. Omega-3 FAs may have antiplatelet activity and may lower triglyceride concentrations and decrease the risk of arrhythmias. In the past 12 months, clinical trials, observational studies, and a meta-analysis have evaluated the potential value of omega-3 FAs on cardiovascular outcomes and all-cause mortality, with varying results. In July 2012, results from the Outcome Reduction With an Initial Glargine Intervention (ORIGIN) study were published.1.ORIGIN trial investigatorsn-3 fatty acids and cardiovascular outcomes in patients with dysglycemia.N Engl J Med. 2012; 367: 309-318Crossref PubMed Scopus (648) Google Scholar The study evaluated the potential benefits of long-term use of omega-3 FA 1 g/d in patients with type 2 diabetes or at high risk of developing diabetes. Researchers followed more than 12,000 patients for 6 years. Between 50% and 70% of participants were taking statins, antiplatelet agents, beta blockers, and ACE inhibitors or angiotensin-receptor blockers. The study's primary outcome, death from cardiovascular causes, was not reduced by omega-3 FA, despite a 14.5 mg/dL decrease in triglyceride concentrations. The negative results may have been due to patients already being on optimal therapy, an inadequate dosage of omega-3 FA, or patients not at high enough cardiovascular risk.■Patients seeking omega-3 fatty acid supplementation are best served by adding fish to their diet.■For effective primary and secondary prevention of cardiovascular disease, patients should focus on reducing risk factors. ■Patients seeking omega-3 fatty acid supplementation are best served by adding fish to their diet.■For effective primary and secondary prevention of cardiovascular disease, patients should focus on reducing risk factors. In September 2012, a group of researchers conducted a meta-analysis of omega-3 FA studies including 20 randomized clinical trials involving almost 70,000 people.2.Rizos E.C. Ntzani E.E. Bika E. et al.Association between omega-3 fatty acid supplementation and risk of major cardiovascular disease events: a systematic review and meta-analysis.JAMA. 2012; 308: 1024-1033Crossref PubMed Scopus (810) Google Scholar The studies included primary or second prevention trials of at least 1 year in duration and assessed the effects of omega-3 FA through either diet or supplements on all-cause mortality, sudden death, myocardial infarction (MI), or stroke. Two-thirds of studies were secondary prevention, and the mean dosage of omega-3 FA was 1.51 g/d. Overall, the meta-analysis identified no benefits from omega-3 FA. In April 2013, researchers published data from the Cardiovascular Health Study.3.Mozaffarian D. Lemaitre R.N. King I.B. et al.Plasma phospholipid long-chain omega-3 fatty acids and total and cause-specific mortality in older adults: a cohort study.Ann Intern Med. 2013; 158: 515-525Crossref PubMed Scopus (214) Google Scholar Unlike most other studies, in which participants eat a diet supplemented with omega-3 FA or use dietary supplements, this study's investigators used measurements of plasma concentrations of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and docosapentaenoic acid from almost 2,700 adults 74 years and older without documented cardiovascular disease. Their analysis also incorporated assessments of cardiovascular risk factors first measured in 1992 and data on outcomes collected until 2008. The researchers found that individuals with the highest concentrations of omega-3 FA were associated with a 27% reduction in risk of all-cause death. The decrease was due primarily to a reduced risk of cardiovascular death—specifically, death due to arrhythmias. DHA concentrations had the strongest inverse association with arrhythmic deaths, and EPA levels were inversely correlated with risk of nonfatal MI. The ingestion of fish oil and omega-3 FA supplements has increased dramatically in the past 24 years since the first reports of their benefits. The original studies demonstrating large benefits predated the current widespread use of statins, however. Newer studies have yielded contradictory data due to different designs and populations (primary vs. secondary prevention), concomitant use of drugs, self-reports of dietary omega-3 FA ingestion, and variable dosages and quality of some fish oil products. Encourage patients interested in omega-3 FA supplementation to substitute fish such as salmon or sea trout, in appropriately sized portions, for red meat once or twice a week. For secondary prevention of cardiovascular disease, omega-3 FA supplements likely have little additional benefit when combined with optimal therapies, including statins and ACE inhibitors. For primary prevention, especially in older patients, omega-3 FA supplementation may offer some benefits, although evidence remains conflicting. As always, patients interested in effective primary and secondary prevention should focus on reducing cardiovascular risk factors, especially smoking cessation.

Comparison of eicosapentaenoic acid concentrations in plasma between patients with ischemic stroke and control subjects

Objectiveω-3 fatty acids, including eicosapentaenoic acid (EPA), prevent ischemic stroke. However, the clinical importance of EPA for ischemic stroke and its subtype has not been fully elucidated. MethodsIn a cross-sectional study, we determined whether ω-3 fatty acids were predictive factors for ischemic stroke. We compared common clinical parameters among 65 patients with ischemic stroke and 65 control subjects. The parameters included blood chemistry data; concentrations of EPA, docosahexaenoic acid, and arachidonic acid (AA); EPA/AA ratio; smoking; alcohol intake; fish consumption more than four times per week; and the incidence of underlying diseases. The comparisons were performed using the Mann-Whitney U test, and multiple logistic regression analysis was applied to the significant factors in the non-parametric test. We also applied the same approach to the ischemic stroke subtypes, cardioembolism and large-artery atherosclerosis. ResultsIn the multiple logistic regression analysis after the Mann-Whitney U test, a lower EPA concentration was one of the significant risk factors for ischemic stroke, as were a lower body mass index, lower high-density lipoprotein cholesterol, and smoking (sensitivity 0.846, specificity 0.831, positive predictive value 0.833). In the analysis of subtypes, a lower EPA/AA ratio and a lower body mass index were the significant risk factors for cardioembolism (sensitivity 0.800, specificity 0.733, positive predictive value 0.750). However, large-artery atherosclerosis was not related to the EPA concentration or the EPA/AA ratio. ConclusionsIn this study, the plasma EPA concentration and the EPA/AA ratio were potential predictive risk factors for ischemic stroke, especially for cardioembolism. Further prospective studies are necessary.

Plasma Fatty Acid Profile of Gestating Ewes Supplemented with Fishmeal

Problem statement: The very long chain n-3 polyunsaturated fatty acids (>18C) cannot be adequately synthesized by ruminant tissues to meet their requirements; therefore, their concentration in body depends on the supply through feed. It may be possible to improve the essential fatty acid status of ruminant animals, during gestation by manipulating the maternal diet with Fishmeal (FM). The objectives of this research were to (1) determine the effect of fishmeal supplementation on the plasma fatty acid profile of ewes during late gestation and (2) determine the status of the plasma docosahexaenoic acid (22:6n3) of lambs born to these ewes. Approach: Eight gestating ewes [Rideau-Arcott, 97±5 kg initial body weight, 100 days of gestation] were used in a completely randomized design. Ewes were individually-housed and fed either a control diet (supplemented with soybean meal) or a fishmeal supplemented diet. Blood samples were collected via jugular venipuncture for plasma fatty acids analysis on 100, 114, 128 and 142 days of gestation after morning feeding. Blood samples from the lambs were also collected via jugular venipuncture immediately after birth and before receiving their mothers’ colostrum. Plasma fatty acids were analyzed by gas-liquid chromatography. Results: The ewes from both groups, i.e., control and fishmeal supplemented, had a similar fatty acid profile prior to supplementation (at 100 days, p>0.05). Thereafter, there was an increase in eicosapentaenoic acid (20:5n3), docosahexaenoic acid, total n3-PUFA and total very long chain n3-PUFA (>C18) contents in plasma for the fishmeal supplemented ewes compared to the control (p 0.05) in total saturated fatty acids, total monounsaturated fatty acids, total conjugated linoleic acid, total trans-18:1, total cis-18:1, or total n6-PUFA contents in ewe plasma between control and fishmeal supplemented groups. Lambs born to ewes fed the fishmeal supplemented diet had greater (p<0.05) plasma concentrations of eicosapentaenoic acid (0.7 Vs 0.4, g/100 g FA), docosahexaenoic acid (1.6 Vs 0.9, g/100 g FA) and total very long chain n3-PUFA (3.3 vs. 2.0, g/100 g FA) than lambs born to ewes fed the control diet. Conclusion: The ewes supplemented with fishmeal supplementation showed a positive response with the enrichment of docosahexaenoic acid, eicosapentaenoic acid and total very long chain n3-PUFA in plasma during gestation and these fatty acids were transferred to the fetus as well.

Nutritional intervention with fish oil provides a benefit over standard of care for weight and skeletal muscle mass in patients with nonsmall cell lung cancer receiving chemotherapy

Involuntary weight loss is a major contributor to mortality and morbidity in patients with advanced cancer. Nutritional intervention with fish oil (FO)-derived eicosapentaenoic acid (EPA) may prevent deterioration of body composition. This study compared intervention with FO with standard of care (SOC; no intervention) with regard to weight, skeletal muscle, and adipose tissue in newly referred patients with nonsmall cell lung cancer from the time of initiation to completion of first-line chemotherapy. Forty patients completed the study; there were 16 in the FO group (dose of 2.2 g of EPA/day) and 24 patients in the SOC group. Skeletal muscle and adipose tissue were measured using computed tomography images. Blood was collected and weight was recorded at baseline and throughout chemotherapy. Patients in the SOC group experienced an average weight loss of 2.3 ± 0.9 kg whereas patients receiving FO maintained their weight (0.5 ± 1.0 kg) (P = .05). Patients with the greatest increase in plasma EPA concentration after FO supplementation were found to have the greatest gains in muscle (r(2) = 0.55; P = .01). Approximately 69% of patients in the FO group gained or maintained muscle mass. Comparatively, only 29% of patients in the SOC group maintained muscle mass, and overall the SOC group lost 1 kg of muscle. No difference in total adipose tissue was observed between the 2 groups. Nutritional intervention with 2.2 g of FO per day appears to provide a benefit over SOC, resulting in the maintenance of weight and muscle mass during chemotherapy.

Relationships between Plasma Fatty Acid Composition and Coronary Artery Disease

The Japan EPA Lipid Intervention Study (JELIS) was the first prospective randomized clinical trial to demonstrate prevention of coronary events by pure eicosapentaenoic acid (EPA). The aim of this study was to examine the relationships between various plasma fatty acid concentrations and the risk of coronary events in JELIS participants. In 15,534 participants, we calculated the hazard ratio for major coronary events (sudden cardiac death, fatal or nonfatal myocardial infarction, unstable angina pectoris, and angioplasty/stenting or coronary artery bypass grafting) relative to the on-treatment average level of plasma fatty acids with the Cox proportional hazard model. As a result of EPA intervention, the plasma EPA concentration increased, but the docosahexaenoic acid (DHA) concentration did not. The other fatty acids measured decreased slightly. The higher plasma level of EPA (hazard ratio=0.83, p=0.049, in all participants and hazard ratio=0.71, p=0.018, in the EPA intervention group), but not of DHA, was inversely associated with the risk of major coronary events. The associations between other fatty acids and the risk of major coronary events were not significant. In all JELIS participants, the risk of major coronary events was significantly decreased (20%) in the group with high (150 µg/mL or more) on-treatment plasma EPA concentration compared with that in the low (less than 87 µg/mL) group. The risk of coronary artery disease is influenced by variations in plasma fatty acid composition. Among n-3 polyunsaturated fatty acids, EPA and DHA exhibited differences in the correlation with the risk of major coronary events.