Red Blood Cell Eicosapentaenoic Acid Research Articles

U-shaped relationship between tissue docosahexaenoic acid and atrial fibrillation following cardiac surgery

Randomised controlled trials (RCTs) evaluating the effect of fish oil supplementation on postoperative atrial fibrillation (POAF) following cardiac surgery have produced mixed results. In this study, we examined relationships between levels of red blood cell (RBC) n-3 long-chain polyunsaturated fatty acids (LC-PUFAs) and the incidence of POAF. We used combined data (n=355) from RCTs conducted in Australia and Iceland. The primary end point was defined as POAF lasting >10 min in the first 6 days following surgery. The odds ratios (ORs) for POAF were compared between quintiles of preoperative RBC n-3 LC-PUFA levels by multivariable logistic regression. Subjects with RBC docosahexaenoic acid (DHA) in the fourth quintile, comprising a RBC DHA range of 7.0-7.9%, had the lowest incidence of POAF. Subjects in the lowest and highest quintiles had significantly higher risk of developing POAF compared with those in the fourth quintile (OR=2.36: 95% CI; 1.07-5.24 and OR=2.45: 95% CI; 1.16-5.17, respectively). There was no association between RBC eicosapentaenoic acid levels and POAF incidence. The results suggest a 'U-shaped' relationship between RBC DHA levels and POAF incidence. The possibility of increased risk of POAF at high levels of DHA suggests an upper limit for n-3 LC-PUFAs in certain conditions.

Pharmacokinetics of Eicosapentaenoic Acid in Plasma and Red Blood Cells After Multiple Oral Dosing With Icosapent Ethyl in Healthy Subjects.

ObjectiveIcosapent ethyl (IPE) is a prescription form of eicosapentaenoic acid (EPA) ethyl ester. This randomized, open-label study characterized EPA pharmacokinetics.MethodsFour healthy subject groups received IPE for 28 days: three received 2 g/day (1 × 1,000 mg BID, 2 × 1,000 mg QD, or 2 × 500 mg BID); one received 4 g/day (2 × 1,000 mg BID) administered with meals. Blood sampling was before the morning dose on days 1, 14, 26, 28, and at specified intervals during an 18-day pharmacokinetic period. EPA was measured in plasma (total and unesterified) and red blood cells (RBCs) by liquid chromatography/tandem mass spectrometry.ResultsMean plasma total EPA increased from 19 µg/mL to a peak (Cmax) of 366 µg/mL at 5 hours postdosing 4 g/day IPE on Day 28. Mean RBC EPA Cmax after 4 g/day was 89 µg/mL (baseline, 12 µg/mL). Mean steady state (SD) for half-life, clearance, and volume of distribution of total EPA were 79 (47) hours, 757 (283) mL/h, and 82 (56) L, respectively. Steady state for total and unesterified plasma EPA was reached by Day 28, whereas RBC levels were still increasing.ConclusionsEPA pharmacokinetic profile demonstrated a slowly cleared, extensively distributed molecule with dose linearity and comparable exposures with BID and QD regimens.

Consumption of Stearidonic Acid−Rich Oil in Foods Increases Red Blood Cell Eicosapentaenoic Acid

BackgroundConsumption of soybean oil enriched with stearidonic acid was previously shown to increase eicosapentaenoic acid (EPA) in red blood cells (RBC). ObjectiveThis study was designed to evaluate the effect of stearidonic acid oil used as a food ingredient in baked products and beverages on the RBC fatty acid profile. DesignThis was a randomized, double-blind, controlled, parallel-arm study. ParticipantsHealthy men and women 21 to 65 years of age were included. InterventionParticipants consumed either negative control (1.5 g/day high-oleic sunflower ethyl ester oil softgel capsules+foods containing 7 g/day high-oleic sunflower oil), positive control (1.5 g/day EPA oil ethyl ester softgel capsules+foods containing 7 g/day high-oleic sunflower oil), or active (1.5 g/day high-oleic sunflower ethyl ester oil softgel capsules+foods containing 7 g/day stearidonic acid soybean oil) for 12 weeks. Main outcome measuresRBC membrane fatty acid profile (at weeks 0, 2, 4, 6, 8, 10, and 12); fasting serum lipids (weeks −2, 0, 6, 10, and 12); and fasting plasma glucose and insulin (weeks −2, 0, 10, and 12) were assessed. Statistical analyses performedA repeated measures analysis of covariance was used for continuous variables, and pair-wise comparisons between treatments were adjusted using a step-down Bonferroni method. Fisher’s exact or χ2 tests were used for categorical data. ResultsRBC %EPA throughout the 12-week study were significantly different between all groups. Means at 12 weeks were 0.50%±0.03%, 2.17%±0.21%, and 0.85%±0.05% for control, EPA, and stearidonic acid, respectively. Other efficacy outcome measures were not significantly different among treatment groups. ConclusionsConsumption of stearidonic acid-enriched soybean oil incorporated into common foods increased RBC %EPA in healthy men and women. Stearidonic acid soybean oil, a sustainable and accessible source of long-chain n-3, can effectively be used to increase EPA in RBC.

Comparative effects of an acute dose of fish oil on omega-3 fatty acid levels in red blood cells versus plasma: Implications for clinical utility

Omega-3 fatty acid (n-3 FA) biostatus can be estimated with red blood cell (RBC) membranes or plasma. The matrix that exhibits the lower within-person variability and is less affected by an acute dose of n-3 FA is preferred in clinical practice. We compared the acute effects of a large dose of n-3 FA on RBC and plasma levels of eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA). Healthy volunteers (n = 20) were given 4 capsules containing 3.6 g of n-3 FA with a standardized breakfast. Blood samples were drawn at 0, 2, 4, 6, 8, and 24 hours. The EPA + DHA content of RBC membranes and plasma (the latter expressed as a percentage of total FA and as a concentration) were determined. General linear mixed models were used to analyze the mean response profiles in FA changes over time for plasma and RBCs. At 6 hours after load, the plasma concentration of EPA + DHA had increased by 47% (95% confidence interval [CI], 24% to 73%) and the plasma EPA + DHA percentage of total FA by 19% (95% CI, 4.7% to 36%). The RBC EPA + DHA percentage of composition was unchanged [-0.6% (95% CI, -2.6% to 1.5%)]. At 24 hours, the change in both of the plasma EPA + DHA markers was 10-fold greater than that in RBCs. An acute dose of n-3 FA (eg, a meal of oily fish or fish oil supplements) taken within a day before a doctor's visit can elevate levels of EPA + DHA in plasma, whether expressed as a percentage or a concentration, but not in RBC membranes. Similar to hemoglobin A1c, which is not affected by an acute glycemic deviation, RBCs provide a more reliable estimate of a patient's chronic EPA + DHA status than does plasma.

Erythrocyte omega-3 fatty acids increase and linoleic acid decreases with age: Observations from 160,000 patients

BackgroundThe fatty acid (FA) composition of the red blood cell (RBC) has been reported to provide prognostic information regarding risk for coronary heart disease (CHD). In particular, the Omega-3 Index (RBC eicosapentaenoic acid+docosahexaenoic acid, EPA+DHA) has been shown to be independently and inversely related to risk for sudden cardiac death and for acute coronary syndromes. Higher linoleic acid (n-6) and lower trans FA levels have also been associated with improved CHD outcomes. Accordingly, the RBC FA panel has recently been introduced in routine clinical laboratory testing. ObjectiveThe purpose of this study was to define age- and gender-based norms for RBC FA levels. MethodsRBC FA profiles from about 160,000 patients (48% from males, 52% from females) were measured at Health Diagnostic Laboratory. These data were used to create age decade and gender-specific norms (percentiles). FA values were expressed as a percent of total identified FA. ResultsCompared to men, women generally had higher C18 trans levels, and between the ages of 10–29 years, they had DHA and lower EPA levels. Among the major FA classes, saturated (41% of total) and trans (∼0.85%) fats did not vary appreciably by age, whereas monounsaturated fats tended to rise slightly. Of the two major n-6 polyunsaturates, arachidonic and linoleic acids, the former was unchanged across decades (16.4% abundance) whereas the latter decreased by about 2 percentage points (13.0–11.1%). The overall median Omega-3 Index was 4.5%, and across the decades it increased by about 1.5 percentage points. The Omega-3 Index and linoleic acid stabilized after age 70. ConclusionWhereas RBC saturated, mono- and polyunsaturated FA levels are generally stable across the lifespan, there is a shift in the composition of the latter, with an increase in the Omega-3 Index and a decrease in linoleic acid. Higher DHA and lower EPA levels in younger women is consistent with enhanced conversion of EPA to DHA during the early reproductive years. The availability of RBC FA norms will facilitate research into the relationships between altered FA status and human disease, and will help physicians evaluate the n-3 FA status of their patients.

Incorporation of eicosapentaenoic and docosahexaenoic acids into lipid pools when given as supplements providing doses equivalent to typical intakes of oily fish

Background: Estimation of the intake of oily fish at a population level is difficult. The measurement of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in biological samples may provide a useful biomarker of intake.Objective: We identified the most appropriate biomarkers for the assessment of habitual oily fish intake and changes in intake by elucidating the dose- and time-dependent response of EPA and DHA incorporation into various biological samples that represent roles in fatty acid transport, function, and storage.Design: This was a double-blind, randomized, controlled intervention trial in 204 men and women that lasted 12 mo. EPA and DHA capsules were provided in a manner to reflect sporadic consumption of oily fish (ie, 1, 2, or 4 times/wk). EPA and DHA were assessed at 9 time points over 12 mo in 9 sample types (red blood cells, mononuclear cells, platelets, buccal cells, adipose tissue, plasma phosphatidylcholine, triglycerides, cholesteryl esters, and nonesterified fatty acids).Results: A dose response (P < 0.05) was observed for EPA and DHA in all pools except for red blood cell EPA (P = 0.057). EPA and DHA measures in plasma phosphatidylcholine and platelets were best for the discrimination between different intakes (P < 0.0001). The rate of incorporation varied between sample types, with the time to maximal incorporation ranging from days (plasma phosphatidylcholine) to months (mononuclear cells) to >12 mo (adipose tissue).Conclusions: Plasma phosphatidylcholine EPA plus DHA was identified as the most suitable biomarker of acute changes in EPA and DHA intake, and platelet and mononuclear cell EPA plus DHA were the most suitable biomarkers of habitual intake. This trial was registered at Current Controlled Trials (www.controlled-trials.com) as ISRCTN48398526.

Effects of two different dietary sources of long chain omega-3, highly unsaturated fatty acids on incorporation into the plasma, red blood cell, and skeletal muscle in horses1

The objective of this study was to examine the effects of different sources of dietary omega-3 (n-3) fatty acid supplementation on plasma, red blood cell, and skeletal muscle fatty acid compositions in horses. Twenty-one mares were blocked by age, BW, and BCS and assigned to 1 of 3 dietary treatments with 7 mares per treatment. Dietary treatments were: 1) control or no fatty acid supplement (CON), 2) 38 g of n-3 long chain, highly unsaturated fatty acid (LCHUFA) supplement/d provided by algae and fish oil (MARINE) containing alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and docosapentaenoic acid (DPA), and 3) 38 g of n-3 LCHUFA supplement/d provided by a flaxseed meal (FLAX) containing ALA. Each supplement was added to a basal diet consisting of hay and barley and was fed for 90 d. Blood samples and muscle middle gluteal biopsies were taken at d 0, 30, 60 and 90 of supplementation. Plasma, red blood cell and skeletal muscle fatty acid profiles were determined via gas chromatography. Plasma linoleic acid (LA) and ALA were at least 10 and 60% less (P < 0.01), respectively, in the MARINE compared with the FLAX and CON groups. Plasma EPA and DHA were only detected in the MARINE group, and EPA increased 40% (P < 0.001) from d 30 to 60, and DHA 19% (P < 0.01) from d 30 to 90. Red blood cell LA and ALA were not different among treatments. Red blood cell EPA and DHA were only detected in the MARINE group, where EPA increased 38% (P < 0.01) from d 30 to 60, and DHA increased 56% (P < 0.001) between d 30 and 90. Skeletal muscle LA was at least 17% less (P < 0.001) in the MARINE group compared with the other treatments. Skeletal muscle ALA was 15% less (P = 0.03) in the MARINE group compared with FLAX and CON groups. Skeletal muscle EPA was at least 25% greater (P < 0.001) in MARINE group compared with other treatments and increased (P < 0.001) by 71% from d 30 to 60. Skeletal muscle DHA was at least 57% greater (P < 0.001) in the MARINE group compared with other groups and increased (P < 0.001) by 40% between d 30 and 90. As far as the authors are aware, this is the first study to demonstrate that dietary fatty acid supplementation will affect muscle fatty acid composition in horses. Incorporation of n-3 LCHUFA into blood and muscle depends directly on dietary supply of specific fatty acids.

Red blood cell omega-3 fatty acid levels and markers of accelerated brain aging

Higher dietary intake and circulating levels of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) have been related to a reduced risk for dementia, but the pathways underlying this association remain unclear. We examined the cross-sectional relation of red blood cell (RBC) fatty acid levels to subclinical imaging and cognitive markers of dementia risk in a middle-aged to elderly community-based cohort. We related RBC DHA and EPA levels in dementia-free Framingham Study participants (n = 1575; 854 women, age 67 ± 9 years) to performance on cognitive tests and to volumetric brain MRI, with serial adjustments for age, sex, and education (model A, primary model), additionally for APOE ε4 and plasma homocysteine (model B), and also for physical activity and body mass index (model C), or for traditional vascular risk factors (model D). Participants with RBC DHA levels in the lowest quartile (Q1) when compared to others (Q2-4) had lower total brain and greater white matter hyperintensity volumes (for model A: β ± SE = -0.49 ± 0.19; p = 0.009, and 0.12 ± 0.06; p = 0.049, respectively) with persistence of the association with total brain volume in multivariable analyses. Participants with lower DHA and ω-3 index (RBC DHA+EPA) levels (Q1 vs. Q2-4) also had lower scores on tests of visual memory (β ± SE = -0.47 ± 0.18; p = 0.008), executive function (β ± SE = -0.07 ± 0.03; p = 0.004), and abstract thinking (β ± SE = -0.52 ± 0.18; p = 0.004) in model A, the results remaining significant in all models. Lower RBC DHA levels are associated with smaller brain volumes and a "vascular" pattern of cognitive impairment even in persons free of clinical dementia.

Effects of duration of treatment and dosage of eicosapentaenoic acid and stearidonic acid on red blood cell eicosapentaenoic acid content

Objective The purpose of this randomized, controlled, parallel group study was to characterize the relationships between dosages of stearidonic acid (SDA) and eicosapentaenoic acid (EPA), and incorporation of EPA into red blood cell (RBC) membranes over time. Methods Healthy subjects ( n=131) received capsules with placebo (safflower oil), SDA (0.43, 1.3, 2.6, or 5.2 g/d) or EPA (0.44, 1.3, or 2.7 g/d) for 12 weeks. RBC fatty acids were analyzed biweekly. Results RBC %EPA increased in all EPA and SDA groups ( p<0.02 vs. control) except the 0.43 g/d SDA group ( p=0.187). For theoretical intakes of EPA of 0.25, 0.5, and 0.89 g/d, the amounts of SDA needed to achieve equivalent RBC EPA enrichment were 0.61, 1.89, and 5.32 g/d (conversion efficiencies of 41%, 26%, and 17%), respectively. Conclusions SDA increased RBC %EPA in a dosage and time-dependent manner at intakes as low as 1.3 g/d.

Relation Between Red Blood Cell Omega-3 Fatty Acid Index and Bleeding During Acute Myocardial Infarction

Omega-3 fatty acids have multiple cardiovascular benefits but may also inhibit platelet aggregation and increase bleeding risk. If this platelet inhibition is clinically meaningful, patients with the highest omega-3 indexes (red blood cell eicosapentaenoic acid plus docosahexaenoic acid), which reflect long-term omega-3 fatty acid intake, should be at the risk for bleeding. In this study, 1,523 patients from 24 United States centers who had their omega-3 indexes assessed at the time of acute myocardial infarction were studied. The rates of serious bleeding (Thrombolysis In Myocardial Infarction [TIMI] major or minor) and mild to moderate bleeding (TIMI minimal) were identified in patients with low (<4%), intermediate (4% to 8%), and high (>8%) omega-3 indices. There were no differences in bleeding across omega-3 index categories. After multivariate adjustment, there remained no association between the omega-3 index and either serious (per 2% increase, relative risk 1.03, 95% confidence interval 0.90 to 1.19) or mild to moderate bleeding (per 2% increase, relative risk 1.02, 95% confidence interval 0.85 to 1.23). In conclusion, no relation was found between the omega-3 index and bleeding in this large, multicenter cohort of patients with acute myocardial infarction, suggesting that concerns about bleeding should not preclude the use of omega-3 supplements or increased fish consumption when clinically indicated.

Effect of Dietary Fish Oil on Atrial Fibrillation After Cardiac Surgery

An open-label study reported that ingestion of a fish oil concentrate decreased the incidence of atrial fibrillation (AF) after coronary artery bypass grafting (CABG) surgery. However, a general cardiac surgery population involves valve and CABG surgeries. We undertook a double-blinded randomized controlled trial to examine the effectiveness of fish oil supplementation on the incidence of postsurgical AF after CABG and valve procedures. The primary end point was incidence of AF in the first 6 days after surgery. Two hundred patients were randomized to receive fish oil (providing 4.6 g/day of long-chain ω-3 fatty acids) or a control oil starting 3 weeks before surgery; 194 subjects completed the study, with 47 of 97 subjects in the control group and 36 of 97 subjects in the fish oil group developing AF (odds ratio 0.63, 95% confidence interval [CI] 0.35 to 1.11). There was a nonstatistically significant delay in time to onset of AF in the fish oil group (hazard ratio 0.66, 95% CI 0.43 to 1.01). There was a significant decrease in mean length of stay in the intensive care unit in the fish oil group (ratio of means 0.71, 95% CI 0.56 to 0.90). In conclusion, in a mixed cardiac surgery population, supplementation with dietary fish oil did not result in a significant decrease in the incidence of postsurgical AF. However, there was a significant decrease in time spent in the intensive care unit.

Effects of Fish Oil Supplementation on Markers of the Metabolic Syndrome

To investigate whether fish oil affects cardiovascular risk factors during the adolescent growth spurt. A total of 78 boys age 13-15 years with a mean body fat percentage of 30%+/-9% were randomly assigned to consume fish oil (providing 1.5 g of n-3 long-chain polyunsaturated fatty acid/day) or vegetable oil (control) for 16 weeks. The oils were included in bread. After the intervention, the red blood cell (RBC) content of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were 1.2%+/-0.5% and 6.7%+/-1.6%, respectively, in the those receiving fish oil (FO group), compared with 0.6%+/-0.3% and 4.1%+/-0.9% in the control group. Systolic blood pressure (SBP) was 3.8+/-1.4 mm Hg lower (P<.006) and diastolic blood pressure (DBP) was 2.6+/-1.1 mm Hg lower (P<.01) in the FO group compared with the control group. Plasma triacylglycerol (TAG) concentration and insulin sensitivity were unaffected by either of the treatments. Plasma high-density lipoprotein (HDL) and non-HDL cholesterol were increased by 5% and 7%, respectively, in the FO group, and by 2% and 0% in the control group (P<.01-.02). The changes in RBC EPA content were inversely correlated with the changes in SBP and DBP and directly correlated with the increases in HDL cholesterol and non-HDL cholesterol concentrations. No association was seen between RBC EPA and plasma TAG concentration or insulin sensitivity. Fish oil improves BP in normotensive and normolipidemic slightly overweight adolescent boys.

Effects of a Mediterranean‐style, low‐glycemic‐load diet on red blood cell omega‐3 index and fatty acid profile in women with metabolic syndrome

We evaluated effects of a 12‐week Mediterranean‐style, low‐glycemic‐load diet (MLGD), alone or combined with a phytosterol‐soy based medical food (PSS) on red blood cell (RBC) fatty acids (FAs) and other coronary risk factors in women with metabolic syndrome (MetS). Subjects (BMI 25–45 kg/m2, LDL≥100 mg/dL, and triglycerides≥150 mg/dL) were randomly assigned to MLGD+PSS (n=8) or MLGD alone (n=9). Analysis is presented on combined groups. RBC eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) levels (omega‐3 index) increased (3.7% to 4.6%; P&lt;0.001) due to increased DHA (3.3% to 4.1%; P&lt;0.0005); EPA did not change. Total trans FAs decreased (P&lt;0.05). Intakes of saturated FAs, n‐6 polyunsaturated FAs, and trans FAs decreased (all p&lt;0.005). Monounsaturated FA intake increased (P &lt; 0.001), but omega‐3 FA intake did not change. The change in the omega‐3 index was inversely correlated with changes in LDL (r = −0.678, P&lt;0.01), apolipoprotein B (r = −0.586, P&lt;0.05), and intracellular (r= −0.829, P&lt;0.0005) and vascular adhesion molecules (r= −0.757, P&lt;0.005). MLGD, with or without PSS, increased the omega‐3 index despite no increase in dietary DHA. These data suggest that favorable changes in membrane FA composition can be achieved without altering omega‐3 FA intakes and correlate with coronary risk factor reduction, including inflammatory markers. Supported by MetaProteomics, LLC.

Associations of very high intakes of eicosapentaenoic and docosahexaenoic acids with biomarkers of chronic disease risk among Yup’ik Eskimos

Few studies have examined the associations of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) with biomarkers of chronic disease risk in populations with high intakes. We examined the associations of red blood cell (RBC) EPA and DHA, as percentages of total fatty acids, with biomarkers of chronic disease risk across a wide range of EPA and DHA intakes. In a cross-sectional study of 357 Yup'ik Eskimos, generalized additive models were used to plot covariate-adjusted associations of EPA and DHA with chronic disease biomarkers. Linear regression models were used to test for the statistical significance of these associations. Means (5th-95th percentiles) for RBC EPA and DHA were 2.8% (0.5-5.9%) and 6.8% (3.3-9.0%), respectively. Associations of EPA and DHA were inverse and linear for triglycerides (beta +/- SE = -0.10 +/- 0.01 and -0.05 +/- 0.01, respectively) and positive and linear for HDL cholesterol (beta +/- SE = 2.0 +/- 0.5 and 0.9 +/- 0.6, respectively) and apolipoprotein A-I (beta +/- SE = 2.6 +/- 0.8 and 1.7 +/- 0.8, respectively). Positive linear associations of DHA with LDL and total cholesterol (beta +/- SE = 7.5 +/- 1.4 and 6.80 +/- 1.57, respectively) were observed; for EPA, these associations were nonlinear and restricted to concentrations approximately <5% of total fatty acids. Associations of EPA and DHA with C-reactive protein were inverse and nonlinear: for EPA, the association appeared stronger at concentrations approximately >3% of total fatty acids; for DHA, it was observed only at concentrations approximately >7% of total fatty acids. Increasing EPA and DHA intakes to amounts well above those consumed by the general US population may have strong beneficial effects on chronic disease risk.

Relation between stable isotope ratios in human red blood cells and hair: implications for using the nitrogen isotope ratio of hair as a biomarker of eicosapentaenoic acid and docosahexaenoic acid

BackgroundThe nitrogen isotope ratio (expressed as δ15N) of red blood cells (RBCs) is highly correlated with the RBC long-chain ω−3 (n–3) fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in Yup’ik Eskimos. Because δ15N can also be measured in hair samples, it could provide a noninvasive, retrospective biomarker for EPA and DHA intakes. ObjectivesWe investigated the agreement between δ15N in hair and RBCs and then evaluated the relations between hair δ15N and RBC EPA and DHA. We also assessed the agreement in carbon isotope ratios (δ13C) between hair and RBCs, because δ13C has been proposed as a dietary biomarker in other populations. DesignWe assessed relations between hair and RBC δ15N and δ13C in a community-based sample of 144 Yup’ik Eskimos and examined the correlations between δ15N and RBC EPA and DHA in a subset of these participants (n = 44). ResultsWe showed a 1:1 relation with good agreement between hair and RBC δ15N (r = 0.91) and δ13C (r = 0.87). Hair isotope ratios were greater than RBC ratios by 1.5‰ for δ15N and by 2.3‰ for δ13C. There were strong correlations between hair δ15N and RBC EPA and DHA (r = 0.83 and 0.84, respectively). ConclusionsThese results support the use of hair δ15N values as a biomarker of EPA and DHA intakes. Because hair collection is noninvasive and the samples require no special processing, studies of EPA and DHA intakes in large populations could use biomarkers rather than self-reports to assess these fatty acids.

Red blood cell δ15N: a novel biomarker of dietary eicosapentaenoic acid and docosahexaenoic acid intake

Background: The long-chain omega-3 (n–3) fatty acids derived from fish, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are associated with a reduced risk of cardiovascular disease and other chronic diseases. Study of the associations between EPA and DHA intake and disease requires a valid biomarker of dietary intake; however, the direct measurement of tissue fatty acid concentrations is expensive and time consuming.Objective: Because the nitrogen stable isotope ratio (15N/14N, expressed as δ15N) is elevated in fish, we investigated whether δ15N is a valid alternative biomarker of EPA and DHA intake.Design: We examined the relation between red blood cell (RBC) δ15N and RBC EPA and DHA in a community-based sample of 496 Yup’ik Eskimos with widely varying intake of n–3 fatty acids. We also assessed the correlation between δ15N and dietary EPA and DHA intake based on 24-h dietary recalls and 3-d food records completed by a subset of 221 participants.Results: RBC δ15N was strongly correlated with RBC EPA and DHA (r = 0.83 and 0.75, respectively). These correlations differed only modestly by sex and age class. RBC δ15N also correlated with dietary EPA and DHA intake (r = 0.47 and 0.46, respectively) and did not differ by sex and age.Conclusions: The results strongly support the validity of RBC δ15N as a biomarker of EPA and DHA intake. Because the analysis of RBC δ15N is rapid and inexpensive, this method could facilitate wide-scale assessment of EPA and DHA intake in clinical and epidemiologic studies.

Reduced mania and depression in juvenile bipolar disorder associated with long-chain ω-3 polyunsaturated fatty acid supplementation

Long-chain omega-3 polyunsaturated fatty acid (LCn-3PUFA) supplementation may improve symptoms of depression in children and bipolar disorder (BD) in adults. No studies have examined the effectiveness of LCn-3PUFA supplementation in the treatment of mania and depression in juvenile BD (JBD) when given as an adjunct to standard pharmacological treatment. Eighteen children and adolescents with JBD received supplements containing 360 mg per day eicosapentaenoic acid (EPA) and 1560 mg per day docosahexaenoic acid (DHA) for 6 weeks in an open-label study. Intake and fasting red blood cell (RBC) LCn-3PUFA, mania, depression and global function were assessed before and after supplementation. RBC EPA and DHA were significantly higher following supplementation. Clinician ratings of mania and depression were significantly lower and global functioning significantly higher after supplementation. Parent ratings of internalizing and externalizing behaviours were also significantly lower following supplementation. A larger randomized controlled trial appears warranted in this participant population.

Alcohol consumption and n–3 polyunsaturated fatty acids in healthy men and women from 3 European populations

BackgroundBecause high dietary and blood n–3 (omega-3) fatty acids (FAs) are protective against coronary heart disease and sudden cardiac death, the alcohol-associated increase in blood n–3 FAs could be considered an original mechanism of alcohol’s cardioprotective effect. ObjectiveOur objective was to assess whether alcohol consumption is associated with concentrations of very-long-chain “marine” (eg, fish oil) n–3 FAs both in plasma and in red blood cell membranes. DesignIn the framework of the IMMIDIET (Dietary Habit Profile in European Communities with Different Risk of Myocardial Infarction: the Impact of Migration as a Model of Gene-Environment Interaction) Project, 1604 subjects (802 women-men pairs), aged 26–65 y, were enrolled in Italy, Belgium, and England. A 1-y-recall food-frequency questionnaire was used to evaluate dietary intake. ResultsIn fully adjusted multivariate analyses, alcohol intake was positively associated with plasma eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and EPA + DHA concentrations (P < 0.0001, P = 0.036, and P = 0.002, respectively) in women and with EPA and the EPA + DHA index in red blood cells (P < 0.0001 and P = 0.037, respectively). In men, only plasma and red blood cell EPA concentrations were associated with alcohol intake (P = 0.003 and P = 0.004, respectively). Stratified analyses showed an association between alcohol and both plasma and red cell EPA (P = 0.008 and P = 0.002, respectively), DHA (P = 0.014 and P = 0.008, respectively), and the EPA + DHA index (P = 0.010 and P = 0.006, respectively) in wine drinkers, whereas no association was found in those who drink beer and spirits. ConclusionsAlcohol intake was associated with higher plasma and red blood cell concentrations of marine n–3 FAs. Components of wine other than alcohol (polyphenols) might exert these effects. Part of the alcohol-induced cardioprotection may be mediated through increased marine n–3 FAs.

Clinical Investigation: Determinants of Blood Cell Omega-3 Fatty Acid Content

BACKGROUND: Although red blood cell eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) content (the Omega-3 Index) predicts cardiovascular death, the factors determining the Index are unknown. METHODS: In 704 outpatients, we undertook an investigation of the clinical determinants of the Index. RESULTS: Factors associated with the Index in decreasing order were: EPA+DHA supplement use, fish consumption frequency, triglyceride level, age, high cholesterol history, and smoking. These factors explained 59% of Index variability, with capsules/fish intake together accounting for 47%. The Index increased by 13% (p< 0.0001) for each serving level increase in fish intake and EPA+DHA supplementation correlated with a 58% increase (p< 0.0001) regardless of background fish intake (p=0.25; test for interaction). A 100 mg/dL decrease in serum triglycerides was associated with a 15% higher (p<0.0001) Index. CONCLUSIONS: The intake of EPA+DHA-rich foods and supplements principally determined the Omega-3 Index, but explained only about half of the variability.

Omega‐3 PUFA plasma and red blood cell status in chronic hemodialysis patients

Omega-3 (n-3) polyunsaturated fatty acid (PUFA) levels have been inversely associated with cardiovascular (CVD) mortality. Chronic hemodialysis patients (HP), who suffer from extremely high rates of CVD, may be at risk for inadequate n-3 consumption. This study was designed to determine n-3 status in a hemodialysis population by comparing their PUFA levels to those of a healthy control group. Fasting plasma and red blood cell (RBC) fatty acid levels were measured in 75 HP and 25 control subjects (CS). The HP were more likely to have diabetes mellitus (43% vs. 20%), hypertension (91% vs. 36%), and less formal education. CS had significantly higher levels of plasma eicosapentaenoic acid (EPA) (mean wt % ± SD) (0.42 ± 0.13 vs. 0.35 ± 0.32, p<0.001), docosahexaenoic acid (DHA) (1.51 ± 0.36 vs. 1.33 ± 0.38, p=0.03), long chain (LC) (2.44 ± 0.50 vs. 2.11 ± 0.56, p=0.005) and total (3.12 ± 0.49 vs. 2.76 ± 0.58, p=0.007)) n-3 levels. Though RBC EPA levels were not significantly different, HP had higher DHA levels (4.65 ± 0.92 vs. 3.16 ± 1.15, p<0.0001), LC (7.32 ± 1.05 vs. 5.07 ± 1.73, p<0.0001) and total n-3 (7.61 ± 1.21 vs. 5.20 ± 1.75, p<0.001). Plasma findings suggest that short-term fish consumption was greater in CS. The fact that RBC DHA levels and LC n-3 PUFA were higher in HP (while EPA levels were not different) raises the possibility that the uremic milieu upregulates the Sprecher pathway or reduces DHA retroconversion to EPA. The relatively modest amount of fish oil-associated n-3 PUFA (i.e. EPA + DHA) in HP suggest they may benefit from fish oil supplementation. This research was supported by the National Kidney Foundation of Indiana, Inc.