Red Blood Cell Eicosapentaenoic Acid Research Articles

Associations of n-3 polyunsaturated fatty acid status and intake with paediatric major depressive disorder in Swiss adolescents: A case-control study

BackgroundObservational studies suggest a link between n-3 polyunsaturated fatty acid (PUFA) intake, n-3 PUFA status, and depression in adults, but studies in adolescents are scarce. This study aimed to determine associations of n-3 PUFA status and intake with paediatric major depressive disorder (pMDD) in Swiss adolescents. MethodsWe conducted a matched case-control study in 95 adolescents diagnosed with pMDD and 95 healthy controls aged 13 to <18 years. We analysed red blood cell (RBC) fatty acid (FA) composition (% of total FA). n-3 PUFA intake was assessed using a focused food frequency questionnaire and depression severity was assessed by the Children's Depression Rating Scale-Revised (CDRS-R). ResultsMean RBC eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were lower in cases than controls (EPA: 0.41 ± 0.11 vs 0.46 ± 0.12, p < 0.001; DHA: 4.07 ± 1.04 vs 4.73 ± 1.04, p < 0.001). Subsequently, the mean RBC n-3 index was lower (4.51 ± 1.10 vs 5.20 ± 1.11, p < 0.001) and the n-6/n-3 PUFA ratio higher (5.51 ± 1.25 vs 4.96 ± 1.08, p < 0.001) in cases than controls. Adolescents with a higher n-3 index had lower odds for depression (OR = 0.49 [95% CI: 0.32–0.71]). In contrast, the n-6/n-3 PUFA ratio was associated with higher odds for depression (OR = 1.58 [95% CI: 1.14–2.25]). Intake of alpha-linolenic acid, EPA and DHA did not differ between cases and controls. ConclusionOur results suggest that a higher RBC n-3 PUFA status during adolescence is associated with a lower risk for pMDD, whereas a higher n-6/n-3 PUFA ratio is associated with a higher risk for pMDD. Differences in n-3 PUFA intake did not explain the observed differences in n-3 PUFA status.

69 The equine blood fatty acid profile and clearance rate of supplemented fatty acids

An optimal equine blood fatty acid (FA) profile has not been defined, nor has a general baseline profile been established. Further, there is little information on the clearance rate of FAs in plasma and red blood cells (RBCs) after supplementation ends. Data from 4 studies were compiled to evaluate the baseline FA profile in horses fed varied diets without FA supplementation for at least 6 mo (n = 68). Sample handling and processing were performed identically in all studies and 24 FAs were quantified using gas chromatography. A subset of data (n = 18) was used to evaluate how eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) affects the FA profile during and after 3 mo of supplementation (4.3–8.7 g EPA+DHA/d). Data were analyzed for mixed-effects. Baseline plasma FA profile included primarily linoleic acid (LA; 49.49% mean; 95% CI [48.32, 50.65]), stearic acid (15.90%; [15.61, 16.19]), palmitic acid (13.99%; [13.59, 14.38]), and oleic acid (10.66%; [10.12, 11.20]). Other FAs included arachidonic acid (AA; 0.94%; [0.87, 1.01]), EPA (0.14%; [0.12, 0.16]), and DHA (0.16%; [0.14, 0.19]). Baseline RBC profile differed slightly, primarily made up of LA (37.47%; [36.76, 38.17]), oleic acid (20.20%; [19.92, 20.47]), stearic acid (17.40%; [17.09, 17.71]), and palmitic acid (14.86%; [14.53, 15.20]). Other FAs included AA (1.23%; [1.18, 1.29]), EPA (0.19%; [0.16, 0.22]),and DHA (0.21%; [0.18, 0.24]). Plasma EPA and DHA increased 277% (0.41%; [0.29, 0.54]; P < 0.001) and 223% (0.56%; [0.40, 0.73]; P < 0.001), respectively, within 1 mo of supplementation and returned to baseline levels (P = 0.98) by 1 mo post-supplementation. RBC EPA and DHA increased 178% (0.37%; [0.29, 0.44]; P < 0.0001) and 102% (0.37%; [0.31, 0.44]; P < 0.0001), respectively, within the first month of supplementation and continued to climb 313% (0.63%; [0.46, 0.79]; P < 0.001) and 197% (0.70%; [0.55, 0.85]; P < 0.001) by the third month, respectively. RBC EPA returned to baseline (P = 0.21) by 3 mo post-supplementation, but RBC DHA had still not returned (P < 0.05). Compared with plasma, RBCs showed gradual changes over time and required significantly more time to appropriately wash out. Additionally, the clearance rate may differ between fatty acids. Plasma values are more commonly reported than values for RBC or other tissues. These data suggest RBC values may be important to consider and that appropriate washout durations from previous FA supplementation may be longer than expected. Further research is needed to evaluate other tissue affected by FA supplementation and how long the FA profile may be altered.

Transgenic Canola Oil Improved Blood Omega-3 Profiles: A Randomized, Placebo-Controlled Trial in Healthy Adults.

Long-chain omega-3 polyunsaturated fatty acids (LC-ω3 PUFA), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), play key roles in physiological functions and disease prevention. The nutrient gap in meeting LC-ω3 intake recommendations in the U.S. and globally can be addressed by alternative sources of LC-ω3. This randomized, placebo-controlled, seamless phase I/II study evaluated the pharmacokinetics, safety, and efficacy of a transgenic LC-ω3-rich canola oil in healthy adults. Participants (n = 33/group) were randomized to receive low-, mid-, or high-dose of the LC-ω3-rich oil (providing 285, 570, or 1,140 mg LC-ω3 PUFA, respectively) or placebo (corn oil). After one dose, plasma ω3 (primary outcome) levels were assessed over a 72 h pharmacokinetic period. Whole blood and red blood cells (RBC) ω3 and serum cardiovascular biomarkers were assessed during a 16-week continuation period with daily supplementation. Compared to low-dose and placebo, high-dose group showed greater DHA AUC0−72h and Cmax. A linear response was observed for DHA and EPA AUC0−72h. Compared to placebo, high- and mid-dose groups showed increased whole blood DHA, EPA, α-linolenic acids (ALA) (high-dose only), omega-3 score, and omega-3 index after 4 weeks, and increased DHA and EPA in RBC after 16 weeks (P < 0.05). No changes in cardiovascular biomarkers were seen. Overall, this LC-ω3-rich oil demonstrated good DHA bioavailability and significantly improved short and long-term blood LC-ω3 profiles. Sixteen weeks of daily supplementation of the LC-ω3-rich oil was safe and well-tolerated.

Twelve Weeks of Additional Fish Intake Improves the Cognition of Cognitively Intact, Resource-Limited Elderly People: A Randomized Control Trial.

Dietary omega 3 polyunsaturated fatty acids (PUFA) may reduce the risk of dementia. Many studies have investigated PUFA supplementation in high-income countries, yet food-based randomized control trials using omega 3 PUFA rich fish in lower to middle income countries, are lacking. To determine the effect on cognition of adding either fish or non-fish foods for twelve weeks to an enhanced diet of cognitively intact, independently living, resource-limited elderly people. Randomized control trial (National Health Trial register: DOH-27-061-6026). Retirement center in urban South Africa. Fifty-seven (74% female, mean age: 72±7 years) elderly participants with cognitive function exceeding 22 on the Mini Mental State Examination were randomized into an intervention (n=31) and control (n=26) group. The usual diets of both groups were enhanced with context-appropriate foods to mimic elements of the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet. The intervention group additionally received canned pilchards and fish spread every week amounting to an additional (theoretical) intake of 2.2g omega 3 PUFA daily. The control group received canned meatballs and texturized soya every week. Cognition was measured twice before and once after the intervention phase using the Cognitive Abilities Screening Instrument (CASI). Adherence was assessed by a study-specific food frequency questionnaire and red blood cell (RBC) PUFA biomarkers. Data were analyzed using a non-parametric analysis of covariance (ANCOVA) with, and without, bootstrap imputation. Participants in the intervention group had a significantly higher post intervention (P=0.036) CASI score than the control group, when the model was fitted with imputation and controlled for baseline scores. Participants in the intervention group also had a significantly higher intake of calculated dietary omega 3 PUFA and higher levels of RBC eicosapentaenoic acid and docosapentaenoic acid content than the control group (P < 0.05). Twelve weeks of fish intake in the context of a modified MIND diet may improve the cognition of cognitively intact, resource-limited elderly people.

Verbal Memory Performance in Depressed Children and Adolescents: Associations with EPA but Not DHA and Depression Severity.

Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have been described as positively associated with cognitive functioning. Current meta-analyses have identified eicosapentaenoic acid (EPA) as potentially more effective than docosahexaenoic acid (DHA). An especially vulnerable subgroup that might benefit from these beneficial effects are depressed youths. In this study, we examined associations between red blood cell (RBC) DHA and EPA levels and depression severity and verbal memory performance in a sample of 107 moderately (n = 63) and severely (n = 44) depressed youths. The findings showed that youths with high RBC EPA levels had steeper learning curves compared to those with moderate or low RBC EPA levels (Pillai’s Trace = 0.195, p = 0.027, ηp2 = 0.097). No associations between RBC DHA levels or depression severity and verbal memory performance were observed. Our results further confirm previous findings indicating a more important role of EPA compared to DHA in relation to cognitive functioning. Future research should further investigate the differential role of EPA and DHA concerning cognitive functioning in depressed youths. Evidence supporting beneficial supplementation effects could potentially establish a recommendation for a natural and easily accessible intervention for cognitive improvement or remission.

Increased adiposity in children with obesity is associated with low red blood cell omega-3 fatty acid status and inadequate polyunsaturated fatty acid dietary intake.

The association between total dietary fat intake and measures of body fatness in children with obesity remains inconsistent. This study aimed to determine whether dietary long-chain polyunsaturated fatty acids (LCPUFA) and LCPUFA status relate to body composition in children with obesity. Children (n = 63, 9.0 ± 0.2 year, BMI Z-score 3.1 ± 0.2) were divided into tertiles of percentage body fat assessed by dual-energy X-ray absorptiometry. Diet was assessed 3-days food diaries. Fatty acid proportions in red blood cells (RBC) were measured by gas chromatography. Data stratified by sex and Tanner stages were compared with a MIXED model ANOVA. Associations between RBC fatty acid status and dietary intakes were examined with Spearman correlation. Moderate correlations were observed between RBC eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) proportions, dietary EPA and DHA (r = 0.39, P < .05) as well as fish servings (r = 0.33, P < .05). Dietary LCPUFA did not differ among tertiles. Children in tertile 3 had lower RBC α-linolenic acid (-40%) and EPA + DHA (-15%) proportions adjusted for age, Tanner stages and race compared with tertile 1. The lower omega-3 LCPUFA status in children with greater adiposity is consistent with suboptimal intakes of omega-3 LCPUFA and fish in the diet.

Single Nucleotide Polymorphisms in PEMT and MTHFR Genes are Associated with Omega 3 and 6 Fatty Acid Levels in the Red Blood Cells of Children with Obesity.

Polyunsaturated fatty acids (PUFAs) play important roles in health and disease. PUFA levels are influenced by nutrition and genetic factors. The relationship between PUFA composition in red blood cells (RBCs) and genetic variations involved in PUFA metabolism has not been investigated in children with obesity. This study evaluated the association between several genetic variations and PUFA levels in RBCs in children with obesity. One hundred ninety-six children with obesity (101 females, 95 males) were evaluated using anthropometric measurements, dietary intakes, plasma and RBC PUFA quantification, blood biochemistry, and 55 single nucleotide polymorphisms within 14 genes. phosphatidylethanolamine N-methyltransferase (PEMT) rs1109859 and methylenetetrahydrofolate reductase gene (MTHFR) rs4846052 genotypes were associated with PUFA levels in RBCs. PUFA intake did not influence the RBC eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) levels. Higher RBC DHA and EPA levels were observed for PEMT rs1109859 GG and GA genotypes versus the AA genotype. Higher levels of RBC DHA, EPA, arachidonic acid (ARA), and linoleic acid (LA) and were observed for MTHFR rs4846052 TT genotype versus TC and CC genotypes. Genetic variations in PEMT rs1109859 and MTHFR rs4846052 were associated with different PUFA levels in RBC membranes and are estimators for PUFA species in RBCs. Further research is needed to establish whether these genotype-specific alterations are specific to overweight children.

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.

Evaluation of a High Concentrate Omega-3 for Correcting the Omega-3 Fatty Acid Nutritional Deficiency in Non-Alcoholic Fatty Liver Disease (CONDIN).

This randomized controlled trial investigated the safety and efficacy of MF4637, a high concentrate omega-3 fatty acid preparation, in correcting the omega-3 fatty acid nutritional deficiency in non-alcoholic fatty liver disease (NAFLD). The primary end point of the study was set as the change of red blood cell (RBC) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) by MF4637. Whether the omega-3 concentrate could lower liver fat was evaluated in a subset of patients. Furthermore, 176 subjects with NAFLD were randomized to receive the omega-3 concentrate (n = 87) or placebo (n = 89) for 24 weeks, in addition to following standard-of-care dietary guidelines. The omega-3 index, omega-6: omega-3 fatty acid ratio and quantitative measurements of RBC EPA and DHA were determined at baseline and study completion. Magnetic resonance imaging of liver fat was conducted in a subset of patients. Administration of high concentrate omega-3 for 24 weeks significantly increased the omega-3 index and absolute values of RBC EPA and DHA, and decreased the RBC omega-6: omega-3 fatty acid ratio (p < 0.0001). A significant reduction in liver fat content was reported in both groups.

Red Blood Cell Eicosapentaenoic Acid Inversely Relates to MRI-Assessed Carotid Plaque Lipid Core Burden in Elders at High Cardiovascular Risk.

Supplemental marine omega-3 eicosapentaenoic acid (EPA) has an anti-atherosclerotic effect. Clinical research on EPA supplied by the regular diet and atherosclerosis is scarce. In the framework of the PREvención con DIeta MEDiterránea (PREDIMED) trial, we conducted a cross-sectional study in 161 older individuals at high vascular risk grouped into different stages of carotid atherosclerosis severity, including those without ultrasound-detected atheroma plaque (n = 38), with plaques <2.0 mm thick (n = 65), and with plaques ≥2.0 mm (n = 79). The latter were asked to undergo contrast-enhanced 3T magnetic resonance imaging (MRI) and were subsequently grouped into absence (n = 31) or presence (n = 27) of MRI-detectable plaque lipid, a main feature of unstable atheroma plaques. We determined the red blood cell (RBC) proportion of EPA (a valid marker of long-term EPA intake) at enrolment by gas chromatography. In multivariate models, EPA related inversely to MRI-assessed plaque lipid volume, but not to maximum intima-media thickness of internal carotid artery, plaque burden, or MRI-assessed normalized wall index. The inverse association between EPA and plaque lipid content in patients with advanced atherosclerosis supports the notion that this fatty acid might improve cardiovascular health through stabilization of advanced atheroma plaques.

Relationship between the omega-3 index and specialized pro-resolving lipid mediators in patients with peripheral arterial disease taking fish oil supplements

BackgroundOral supplementation with n-3 polyunsaturated fatty acids (PUFA) increases the omega-3 index, a biomarker of red blood cell eicosapentaenoic acid and docosahexaenoic acid, and plasma levels of biosynthesis pathway markers and potent lipid mediators involved in the resolution of inflammation among patients with peripheral arterial disease (PAD). ObjectiveWe aimed to quantify the association between an upstream change in the omega-3 index and downstream changes in lipid mediator production. MethodsWe conducted a secondary analysis of the OMEGA-PAD I Trial, a randomized, placebo controlled trial investigating high-dose n-3 PUFA oral supplementation in PAD patients. Eighty subjects were randomized to either 4.4 g of fish oil or placebo for 1 month. Regression analyses using generalized estimating equation techniques were used to investigate the relationship between changes in the omega-3 index and changes in lipid mediators, pre- and post-intervention. ResultsIn the fish oil group, there was a significant increase in the omega-3 index (5 ± 1% to 9 ± 2%, P < .001) as well as in the plasma levels of several downstream lipid mediator pathway markers of resolution, which are involved with the regulation of leukocyte effector function and host defense. A doubling of the omega-3 index correlated with increases of 2.3-fold in 18-hydroxy-eicosapentaenoic acid (HEPE; P < .0001), 1.7-fold in 15-HEPE (P = .03), 1.9-fold in 5-HEPE (P = .04), and 3.6-fold in 4-hydroxy-docosahexaenoic acid (P < .001). ConclusionAmong subjects with symptomatic PAD who took oral fish oil supplements for 1 month, observed changes in the omega-3 index were strongly associated with increases in downstream mediators in the biochemical pathways of resolution.

Measurement of red blood cell eicosapentaenoic acid (EPA) levels in a randomised trial of EPA in patients with colorectal cancer liver metastases

We investigated red blood cell (RBC) PUFA profiles, and the predictive value of RBC EPA content for tumour EPA exposure and clinical outcomes, in the EMT study, a randomised trial of EPA in patients awaiting colorectal cancer (CRC) liver metastasis surgery (Cockbain et al., 2014) [8]. There was a significant increase in RBC EPA in the EPA group (n=43; median intervention 30 days; mean absolute 1.26[±0.14]% increase; P<0.001), but not in the placebo arm (n=45). EPA incorporation varied widely in EPA users and was not explained by treatment duration or compliance. There was little evidence of ‘contamination’ in the placebo group. The EPA level predicted tumour EPA content (r=0.36; P=0.03). Participants with post-treatment EPA≥1.22% (n=49) had improved OS compared with EPA <1.22% (n=29; HR 0.42[95%CI 0.16–0.95]). RBC EPA content should be evaluated as a biomarker of tumour exposure and clinical outcomes in future EPA trials in CRC patients.

Genetic Polymorphisms are Associated with Body Burden of Metals, Persistent Organic Pollutants (POPs) and Omega-3 Fatty Acids Levels among Inuit in the Canadian Arctic

Introduction: Fish and marine mammals are dietary staples for Inuit residing in the Canadian Arctic. This diet is a source of both nutrients [docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA)] and toxicants [mercury (Hg), dichlorodiphenyldichloroethylene (DDE), and polychlorinated biphenyls (PCBs)]. Exposures to cadmium (Cd) and lead (Pb) and genetic variability in toxicant and nutrient metabolism further impact Inuit health. We hypothesize that single nucleotide polymorphisms (SNPs) underline inter-individual differences in biomarker concentrations of toxicants and omega-3 fatty acids. Methods: During the 2007-2008 International Polar Year Inuit Health Survey, 362 adults were recruited from the Inuvialuit Settlement Region (ISR) of Canada. Hg, Cd, and Pb were quantified in whole blood, DDE and PCB-153 in plasma, and DHA and EPA in red blood cells. Polymorphisms relevant to toxicant or lipid metabolism were genotyped in 280 participants with biomarker data. ANOVA and linear regressions were used for statistical analysis. Results: Biomarker levels for Hg, Cd, Pb, DDE, and PCB 153 varied by genotype for 11, 7, 9, 8, or 6 SNPs, respectively (p&lt;0.05, ANOVA). DHA and EPA levels differed by genotype of 12 and 9 SNPs, respectively. Following Bonferroni correction, genotype-biomarker relationships remaining significant were: rs1056836 with Cd, rs1042838 with Cd and DDE, rs180040 and rs4671393 with DHA and EPA, and rs11644094 with DHA. When linear regression was used to assess the association between SNPs and Hg or Cd biomarker concentrations adjusting for reported sources of exposure, 16 and 24 SNPs had significant (p&lt;0.05) main effects and/or gene-exposure source interactions for Hg and Cd. Conclusion: Polymorphisms can influence biomarker levels of toxicants as well as omega-3 fatty acids. Consideration of gene-environment relationships may improve the ability to assess the health risks and benefits of the Inuit diet.

Icosapent ethyl: Eicosapentaenoic acid concentration and triglyceride-lowering effects across clinical studies

Icosapent ethyl is a high-purity prescription form of eicosapentaenoic acid (EPA) ethyl ester approved at a dose of 4g/day as an adjunct to diet to reduce triglyceride (TG) levels in adult patients with severe (≥500mg/dL) hypertriglyceridemia. This post-hoc exploratory analysis examined the relationship of icosapent ethyl dose with EPA concentrations in plasma and red blood cells (RBCs) across 3 clinical studies—a phase 1 pharmacokinetic study in healthy adult volunteers and 2 pivotal phase 3 studies (MARINE and ANCHOR) in adult patients with hypertriglyceridemia—and examined the relationship between EPA levels and TG-lowering effects in MARINE and ANCHOR. In all 3 studies, icosapent ethyl produced dose-dependent increases in the concentrations of EPA in plasma and RBCs. In both MARINE and ANCHOR, these dose-dependent EPA increases correlated with the degree of TG level lowering (all P<0.01). In patients with high TG levels (≥200mg/dL) and treated with icosapent ethyl 4g/day, the end-of-treatment plasma and RBC EPA concentrations were >170μg/mL and>70μg/mL, respectively. These studies support icosapent ethyl as producing predictable dose-dependent pharmacokinetics/pharmacodynamics, with TG level lowering dependent upon icosapent ethyl dose and EPA concentrations in plasma and RBCs.

Prevalence of unexplained anaemia in Inuit men and Inuit post-menopausal women in Northern Labrador: International Polar Year Inuit Health Survey.

To identify correlates of hemoglobin (Hb) and anaemia unexplained by iron deficiency (UA) in Canadian Inuit adults. A cross-sectional survey assessed diet, demographic information, anthropometry, fasting Hb, ferritin, soluble transferrin receptor (on a subset), high-sensitivity C-reactive protein (hs-CRP) in serum, red blood cell (RBC) fatty acid composition, blood lead, and antibodies to Helicobacter pylori in non-pregnant, Inuit adults (n = 2550), ≥18 years of age from randomly selected households in 36 Inuit communities in Inuvialuit Settlement Region, Nunavut Territory and Nunatsiavut of Northern Labrador, Canada. Hb concentrations were lower and UA prevalence higher in Inuit men after 50 years of age. Rate of anaemia was constant among Inuit women but changed from primarily iron deficiency anaemia pre-menopause, to primarily UA in post-menopause. Low education levels and hs-CRP were associated with increased risk of UA. For Inuit men, % RBC eicosapentaenoic acid (EPA) and elevated blood lead were also associated with increased risk of UA. Frequency of traditional food intake was positively associated with Hb. Age patterns and regional variation of anaemia suggest that ethnicity-related physiological differences cannot explain anaemia prevalence for Inuit. High RBC EPA status, inflammation and infections, and lower education levels may contribute to the prevalence of anaemia in this population, which is not related to iron status. Thus, traditional lifestyle may protect Inuit from nutritional anaemia but contribute to lower Hb through environmental exposures. The clinical significance of UA for older Inuit adults requires further investigation, as the prevalence represents a moderate public health problem.

Krill oil reduces plasma triacylglycerol level and improves related lipoprotein particle concentration, fatty acid composition and redox status in healthy young adults - a pilot study

BackgroundLipid abnormalities, enhanced inflammation and oxidative stress seem to represent a vicious circle in atherogenesis, and therapeutic options directed against these processes seems like a reasonable approach in the management of atherosclerotic disorders. Krill oil (RIMFROST Sublime®) is a phospholipid-rich oil with eicosapentaenoic acid (EPA): docosahexaenoic acid (DHA) ratio of 1.8:1. In this pilot study we determined if krill oil could favourable affect plasma lipid parameters and parameters involved in the initiation and progression of atherosclerosis.MethodsThe study was conducted as a 28 days intervention study examining effect-parameters of dietary supplementation with krill oil (832.5 mg EPA and DHA per day). 17 healthy volunteers in the age group 18–36 (mean age 23 ± 4 years) participated. Plasma lipids, lipoprotein particle sizes, fatty acid composition in plasma and red blood cells (RBCs), plasma cytokines, antioxidant capacity, acylcarntines, carnitine, choline, betaine, and trimethylamine-N-oxide (TMAO) were measured before and after supplementation.ResultsPlasma triacylglycerol (TAG) and large very-low density lipoprotein (VLDL) & chylomicron particle concentrations decreased after 28 days of krill oil intake. A significant reduction in the TAG/HDL cholesterol resulted. Krill oil supplementation decreased n-6/n-3 polyunsaturated fatty acids (PUFA) ratio both in plasma and RBCs. This was due to increased EPA, DHA and docosapentaenoic acid (DPA) and reduced amount of arachidonic acid (AA). The increase of n-3 fatty acids and wt % of EPA and DHA in RBC was of smaller magnitude than found in plasma. Krill oil intake increased the antioxidant capacity, double bond index (DBI) and the fatty acid anti-inflammatory index. The plasma atherogenicity index remained constant whereas the thrombogenicity index decreased. Plasma choline, betaine and the carnitine precursor, γ-butyrobetaine were increased after krill oil supplementation whereas the TMAO and carnitine concentrations remained unchanged.ConclusionKrill oil consumption is considered health beneficial as it decreases cardiovascular disease risk parameters through effects on plasma TAGs, lipoprotein particles, fatty acid profile, redox status and possible inflammation. Noteworthy, no adverse effects on plasma levels of TMAO and carnitine were found.

Validation of fatty acid intakes estimated by a food frequency questionnaire using erythrocyte fatty acid profiling in the Montreal Heart Institute Biobank.

To improve the prevention, treatment and risk prediction of cardiovascular diseases, genetic markers and gene-diet interactions are currently being investigated. The Montreal Heart Institute (MHI) Biobank is suitable for such studies because of its large sample size (currently, n = 17 000), the availability of biospecimens, and the collection of data on dietary intakes of saturated (SFAs) and n-3 and n-6 polyunsaturated (PUFAs) fatty acids estimated from a 14-item food frequency questionnaire (FFQ). We tested the validity of the FFQ by correlating dietary intakes of these fatty acids with their red blood cell (RBC) content in MHI Biobank participants. Seventy-five men and 75 women were selected from the Biobank. We successfully obtained RBC fatty acids for 142 subjects using gas chromatography coupled to mass spectrometry. Spearman correlation coefficients were used to test whether SFA scores and daily intakes (g day(-1)) of n-3 and n-6 PUFAs correlate with their RBC content. Based on covariate-adjusted analyses, intakes of n-3 PUFAs from vegetable sources were significantly correlated with RBC α-linolenic acid levels (ρ = 0.23, P = 0.007), whereas n-3 PUFA intakes from marine sources correlated significantly with RBC eicosapentaenoic acid (ρ = 0.29, P = 0.0008) and docosahexaenoic acid (ρ = 0.41, P = 9.2 × 10(-7)) levels. Intakes of n-6 PUFAs from vegetable sources correlated with RBC linoleic acid (ρ = 0.18, P = 0.04). SFA scores were not correlated with RBC total SFAs. The MHI Biobank 14-item FFQ can appropriately estimate daily intakes of n-3 PUFAs from vegetable and marine sources, as well as vegetable n-6 PUFAs, which enables the possibility of using these data in future studies.

The role of FADS1/2 polymorphisms on cardiometabolic markers and fatty acid profiles in young adults consuming fish oil supplements.

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are omega-3 (n-3) fatty acids (FAs) known to influence cardiometabolic markers of health. Evidence suggests that single nucleotide polymorphisms (SNPs) in the fatty acid desaturase 1 and 2 (FADS1/2) gene cluster may influence an individual’s response to n-3 FAs. This study examined the impact of a moderate daily dose of EPA and DHA fish oil supplements on cardiometabolic markers, FA levels in serum and red blood cells (RBC), and whether these endpoints were influenced by SNPs in FADS1/2. Young adults consumed fish oil supplements (1.8 g total EPA/DHA per day) for 12 weeks followed by an 8-week washout period. Serum and RBC FA profiles were analyzed every two weeks by gas chromatography. Two SNPs were genotyped: rs174537 in FADS1 and rs174576 in FADS2. Participants had significantly reduced levels of blood triglycerides (−13%) and glucose (–11%) by week 12; however, these benefits were lost during the washout period. EPA and DHA levels increased significantly in serum (+250% and +51%, respectively) and RBCs (+132% and +18%, respectively) within the first two weeks of supplementation and remained elevated throughout the 12-week period. EPA and DHA levels in RBCs only (not serum) remained significantly elevated (+37% and +24%, respectively) after the washout period. Minor allele carriers for both SNPs experienced greater increases in RBC EPA levels during supplementation; suggesting that genetic variation at this locus can influence an individual’s response to fish oil supplements.

Higher RBC EPA + DHA corresponds with larger total brain and hippocampal volumes

To test whether red blood cell (RBC) levels of marine omega-3 fatty acids measured in the Women's Health Initiative Memory Study were related to MRI brain volumes measured 8 years later. RBC eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and MRI brain volumes were assessed in 1,111 postmenopausal women from the Women's Health Initiative Memory Study. The endpoints were total brain volume and anatomical regions. Linear mixed models included multiple imputations of fatty acids and were adjusted for hormone therapy, time since randomization, demographics, intracranial volume, and cardiovascular disease risk factors. In fully adjusted models, a 1 SD greater RBC EPA + DHA (omega-3 index) level was correlated with 2.1 cm(3) larger brain volume (p = 0.048). DHA was marginally correlated (p = 0.063) with total brain volume while EPA was less so (p = 0.11). There were no correlations between ischemic lesion volumes and EPA, DHA, or EPA + DHA. A 1 SD greater omega-3 index was correlated with greater hippocampal volume (50 mm(3), p = 0.036) in fully adjusted models. Comparing the fourth quartile vs the first quartile of the omega-3 index confirmed greater hippocampal volume (159 mm(3), p = 0.034). A higher omega-3 index was correlated with larger total normal brain volume and hippocampal volume in postmenopausal women measured 8 years later. While normal aging results in overall brain atrophy, lower omega-3 index may signal increased risk of hippocampal atrophy. Future studies should examine whether maintaining higher RBC EPA + DHA levels slows the rate of hippocampal or overall brain atrophy.

Long-chain n-3 polyunsaturated fatty acid dietary recommendations are moderately efficient in optimizing their status in healthy middle-aged subjects with low fish consumption: a cross-over study

Several dietary recommendations have been made for marine n-3 polyunsaturated fatty acid (PUFA) intake; however, the effectiveness of these fatty acids has not been thoroughly examined. The aim of this study was to investigate whether public-aimed dietary recommendations for long-chain n-3 PUFA from oily fish or fish oil supplements are efficient in optimizing their status in red blood cells (RBCs) and platelets of healthy middle-aged subjects with low customary fish consumption. In a randomized, cross-over trial conducted over an 8-week period and separated by a 6-month washout period, 33 participants received an oily fish (salmon), providing 274 mg eicosapentaenoic acid (EPA) + 671 mg docosahexaenoic acid (DHA) per day, or a commercial fish oil supplement, providing 396 mg EPA + 250 mg DHA per day. Blood samples were collected before and after each intervention period, and RBCs and platelets were used for analysis of fatty acids. After 8 weeks, there were significant increases in EPA and DHA content in RBCs and platelets with both salmon and fish oil capsules. The increase in EPA in both RBCs and platelets was higher with capsules, whereas the increase in DHA in both RBCs and platelets was higher with salmon. In spite of the quantitative and qualitative differences between n-3 fatty acid profiles in salmon and the fish oil supplement, the overall incorporation of these fatty acids into RBCs and platelets did not differ in our short-term study (P > .05). The sum of EPA + DHA significantly increased in both compartments following dietary recommendations for oily fish and fish oil supplements intake in middle-aged healthy subjects with low baseline long-chain n-3 PUFA status, although targeted values with optimal cardioprotective effect of more than 8% were not achieved.