Erythrocyte Fatty Acid Composition Research Articles

N-3 PUFA supplementation alleviates anxiety symptoms by manipulating erythrocyte fatty acid levels in depression.

Major depressive disorder (MDD) is frequently accompanied by the symptoms of clinical anxiety. Since our previous research has found that n-3 PUFA supplementation alleviates anxiety in MDD, this study was aimed to further explore whether n-3 PUFA supplementation improves anxiety symptoms in depression by directly manipulating fatty acid levels. A secondary analysis of biomarker data (erythrocyte fatty acid composition) collected as part of the randomized clinical trial which investigated the adjunctive effect of n-3 PUFAs was conducted on 72 venlafaxine-treated outpatients with first-diagnosed, drug-naïve depression. All participants with longitudinal biomarker data were included in the association analysis to determine how n-3 PUFA supplementation influences fatty acid composition and alleviates anxiety symptoms in depression. Decreases of the C20:3n6 were found in all participants at both follow-up time points (χ2 = 96.36, p = 0.000). The n-3 index (χ2 = 10.59, p = 0.001), EPA (χ2 = 24.31, p = 0.000), and C22:5n3/C20:5n3 ratio (χ2 = 10.71, p = 0.001) were increased, while C22:4n6 (χ2 = 7.703, p = 0.006) was decreased in n-3 PUFA group compared to the placebo group. The improvement in anxiety symptoms positively correlates with the extent of reduction of C16:0, C18:0, and total fatty acid levels as well as D5 desaturase activity (p < 0.05). These data suggest that the anxiolytic effect exerted by n-3 PUFAs in first-diagnosed, drug-naïve depression is manipulated by erythrocyte fatty acid levels. Saturated fatty acid levels have an important role in predicting the severity of anxiety symptoms.

The associations of fatty acids related dietary patterns with overweight and obesity among Chinese children

BackgroundChildhood overweight and obesity is becoming an emerging face of malnutrition. The aims of this study were to develop fatty acid (FAs) related dietary patterns and explored the associations of FAs related dietary patterns with overweight and obesity among Chinese children.MethodsAn observational study was conducted on 435 children aged 4 to 7 years old in South Central China. Erythrocyte FAs composition was analyzed by gas chromatography-mass spectrometry. Diet was collected by food frequency questionnaires and dietary patterns were evaluated by reduced rank regression. The logistic regression analysis was used to exploring the association of dietary patterns with overweight and obesity.ResultsThe prevalence of overweight, obesity, and overweight or obesity were 6.52, 4.59, and 11.11% in Chinese children, respectively. Twenty five types of FAs were detected in erythrocyte of children and four FAs related dietary patterns were identified. The dietary pattern positively correlated with n-3 PUFAs, but negatively with SFAs,was characterized by high intake of fish, shrimp, crab and shellfish, leaf-off vegetable, nuts, and tubers, which have a significantly decreased overweight risk (OR = 0.580, 95%CI: 0.375 ∼ 0.895, P = 0.014).The pattern positively strong associated with n-6 PUFAs, but negatively strong with n-3 PUFAs, had high intake of snacks, leaf-off vegetable, fresh beans, and coarse cereals, which have a significantly decreased obesity risk (OR = 0.518, 95%CI: 0.325 ∼ 0.827, P = 0.006).ConclusionFour FAs related dietary patterns were identified. The dietary pattern with high intake of fish, shrimp, crab and shellfish decreased overweight risk by increasing n-3 PUFAs, and decreasing SFAs. The dietary pattern with high intake of plant food, decreased obesity risk by providing an balanced n-6/n-3 PUFAs ratio.

Sex differences in erythrocyte fatty acid composition of first-diagnosed, drug-naïve patients with major depressive disorders.

Background: Since depression, sex hormones, and fatty acid status are interrelated, it is important to understand their relationships. In this study, we aimed to investigate sex differences in erythrocyte membrane fatty acid composition among first-diagnosed, drug-naïve patients with major depressive disorders. Methods: The study included 139 individuals with first-diagnosed, drug-naïve depression (male/female = 48/91) and 55 healthy controls (male/female = 24/31). The levels of erythrocyte membrane fatty acids were analyzed to compare the difference between males and females in both patients with depression and healthy controls, as well as to study their correlation with depressive symptoms. Results: In first-diagnosed, drug-naïve patients with major depressive disorders, sex disparities were observed in the levels of erythrocyte saturated fatty acids (SFAs) and n-6 PUFAs (such as C18:0, C20:4n6 and C22:4n6), where higher levels evident in females compared to in males. We found a noteworthy correlation between fatty acid levels and depressive symptoms, in which there is a significant association between female patients and depression but a weaker association between male patients and depression. Conclusion: Our findings demonstrate higher levels of n-6 PUFAs and SFAs in female patients with depression. The relationship between fatty acid composition and depressive symptoms was more prominent in females than males. These findings highlight the significance of considering sex as a crucial and interconnected factor in future investigations and potential adjunctive treatment for mood disorders by targeting fatty acid metabolism.

Infant formula containing large, milk phospholipid-coated lipid droplets and dairy lipids affects cognitive performance at school age.

Breastfeeding has been positively associated with infant and child neurocognitive development and function. Contributing to this effect may be differences between human milk and infant formula in the milk lipid composition and milk fat globule structure. To evaluate the effects of an infant formula mimicking human milk lipid composition and milk fat globule structure on childhood cognitive performance. In a randomized, controlled trial, healthy term infants received until 4 months of age either a Standard infant formula (n = 108) or a Concept infant formula (n = 115) with large, milk phospholipid coated lipid droplets and containing dairy lipids. A breastfed reference group (n = 88) was included. Erythrocyte fatty acid composition was determined at 3 months of age. Neurocognitive function was assessed as exploratory follow-up outcome at 3, 4, and 5 years of age using the Flanker test, Dimensional Change Card Sort (DCCS) test and Picture Sequence Memory test from the National Institutes of Health Toolbox Cognition Battery. Mann-Whitney U test and Fisher exact test were used to compare groups. Erythrocyte omega-6 to -3 long-chain polyunsaturated fatty acid ratio appeared to be lower in the Concept compared to the Standard group (P = 0.025). At age 5, only the Concept group was comparable to the Breastfed group in the highest reached levels on the Flanker test, and the DCCS computed score was higher in the Concept compared to the Standard group (P = 0.021). These outcomes suggest that exposure to an infant formula mimicking human milk lipid composition and milk fat globule structure positively affects child neurocognitive development. Underlying mechanisms may include a different omega-3 fatty acid status during the first months of life. https://onderzoekmetmensen.nl/en/trial/28614, identifier NTR3683 and NTR5538.

Erythrocyte Membrane Fatty Acid Composition as a Potential Biomarker for Depression.

Major depressive disorders is a chronic and severe psychiatric disorder with poor prognosis and quality of life. Abnormal erythrocyte fatty acid (FA) composition in depressed patients were found in our previous study, but the relationship between erythrocyte membrane FA levels and different severity of depressive and anxiety symptoms remains to be explored. This cross-sectional study included 139 patients with first-diagnosed, drug-naïve depression and 55 healthy controls whose erythrocyte FA composition was analyzed. Patients with depression were divided into severe depression and mild to moderate depression or depression with severe anxiety and mild to moderate anxiety. Then the differences of FA levels among different groups were analyzed. Finally, the receiver operating characteristic curve analysis was applied to identify potential biomarkers in distinguishing the severity of depressive symptoms. Levels of erythrocyte membrane FAs were elevated among patients with severe depression compared with healthy controls or patients with mild to moderate depression of almost all kinds. While C18:1n9t (elaidic acid), C20:3n6 (eicosatrienoic acid), C20:4n6 (arachidonic acid), C22:5n3 (docosapentaenoic acid), total fatty acids (FAs), and total monounsaturated FAs were elevated in patients with severe anxiety compared with patients with mild to moderate anxiety. Furthermore, the level of arachidonic acid, C22:4n6 (docosatetraenoic acid), elaidic acid, and the combination of all 3 were associated with the severity of depressive symptoms. The results suggested that erythrocyte membrane FA levels have the potential to be the biological indicator of clinical characteristics for depression, such as depressive symptoms and anxiety. In the future, more research is needed to explore the causal association between FA metabolism and depression.

Effect of myostatin gene mutation on erythrocyte osmotic fragility, hematological parameters and fatty acid composition of serum and erythrocyte membranes in piglets

Fatty acid composition of serum and erythrocyte membrane, erythrocyte osmotic fragility and hematological parameters were estimated with the objective of determining effects of the gene mutation in one-week-old MSTN homozygous mutant (KO, MSTN−/−), heterozygous mutant (MSTN−/+) and wild type (WT, MSTN+/+) piglets (n = 4 each). Erythrocyte osmotic fragility, complete blood count (CBC), and fatty acid composition of serum and erythrocyte membrane were determined by flow cytometric analysis, automated hematology analyzer system, and liquid chromatography, respectively. Mean of median corpuscular fragility (MCF) was lower (P < 0.05, 0.001) in KO than MSTN−/+ and WT piglets. KO piglets had decreased (P < 0.05) white blood cell (WBC) count, lymphocyte (LYM) count, platelet (PLT) count, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), red cell distribution width-standard deviation (RDW-SD), red cell distribution width-coefficient volume (RDW-CV), plateletcrit (PCT), mean platelet volume (MPV), platelet distribution width (PDW), platelet-large cell ratio (P-LCR), and an increased red blood cell (RBC) count when compared with MSTN−/+ and WT piglets. The ratios of unsaturated fatty acid (UFA) to saturated fatty acid (SFA) concentrations in serum and erythrocyte membranes of MSTN KO piglets were 2-fold and 4-fold higher compared to WT piglets (P < 0.001), respectively. In conclusion, MSTN KO piglets had a decreased erythrocyte osmotic fragility, and altered hematological profile and fatty acid composition of serum and erythrocyte membranes, as characteristic phenotype.

Abnormal erythrocyte fatty acid composition in first-diagnosed, drug-naïve patients with depression

Background & aimsThe correlation between fatty acids (FAs) and depression is not yet conclusive. This study examined the relationship of FAs composition with the presence and clinical characteristics of first-diagnosed, drug-naïve patients with depression. MethodsA total of 139 first-diagnosed, drug-naïve patients with depression and 55 healthy controls (HCs) were included in the cross-sectional study. The levels of erythrocyte membrane FAs were compared and then the correlation between clinical symptoms and fatty acid levels in depression was investigated. ResultsCompared to HCs, patients with depression had higher C18:1n9t (z = −2.033, p = 0.042), C20:4n6 (z = −2.104, p = 0.035), C20:3n6 (z = −2.104, p = 0.035) and n-6 polyunsaturated fatty acids (PUFAs) (z = −2.127, p = 0.033), whereas the levels of C18:1n9c (z = −3.348, p = 0.001) were significantly lower. Higher C20:3n6, C20:4n6, C18:1n9t and n-6 PUFAs levels were associated with higher severity of depressive and anxiety symptoms in patients with depression, and the correlation remained after adjusting for the related confounding factors (p < 0.05). ConclusionsPatients with first-diagnosed, drug-naïve depression show abnormal erythrocyte fatty acid composition. Trans fatty acids (TFAs) and n-6 PUFAs levels are closely related to clinical characteristics of depression. This study indicated that increased n-6 PUFAs and TFAs are characteristic changes of first-diagnosed, drug-naïve depression.

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The effect of krill oil supplementation on skeletal muscle function and size in older adults: A randomised controlled trial

The aim of this study was to determine the effect of krill oil supplementation, on muscle function and size in healthy older adults. Men and women, aged above 65 years, with a BMI less than 35kg/m2, who participated in less than 1h per week of structured self-reported exercise, were enrolled in the study (NCT04048096) between March 2018 and March 2020. Participants were randomised to either control or krill oil supplements (4g/day) for 6 months in this double blind randomised controlled trial. At baseline, 6 weeks and 6 months, knee extensor maximal torque was measured as the primary outcome of the study. Secondary outcomes measured were grip strength, vastus lateralis muscle thickness, short performance physical battery test, body fat, muscle mass, blood lipids, glucose, insulin, and C-Reactive Protein, neuromuscular (M-Wave, RMS and voluntary activation), and erythrocyte fatty acid composition. A total of 102 men and women were enrolled in the study. Ninety-four participants (krill group (26 women and 23 men) and placebo group (27 women and 18 men)) completed the study (mean (SD): age 71.2 (5.1) years and weight 71.8 (12.3) kg). Six months supplementation with krill oil resulted in, an increase in knee extensor maximal torque, grip strength and vastus lateralis muscle thickness, relative to control (p<0.05). The 6-month treatment effects were 9.3% (95%CI: 2.8, 15.8%), 10.9% (95%CI: 8.3, 13.6%) and 3.5% (95%CI: 2.1, 4.9%) respectively. Increases in erythrocyte fatty acid profile were seen with krill oil for EPA 214% (95%CI: 166, 262%), DHA 36% (95%CI: 24, 48%) and the omega-3 index 61% (95%CI: 49, 73%), relative to control (p<0.05). Krill oil resulted in an increased, relative to control (p<0.05), M-Wave of 17% (95%CI: 12.7, 38.1%) but there was no effect of krill oil on RMS, voluntary activation, or on any other secondary outcomes such as performance of the short performance physical battery test or quality of life. Krill oil supplementation for 6 months results in statistically and clinically significant increases in muscle function and size in healthy older adults. NCT04048096.

Maternal erythrocyte fatty acid composition as a predictive marker for pregnancy health.

Pregnancy is accompanied by a surge in demand for fatty acids (FAs) in order to support maternal health, as well as fetal growth and development. Of particular demand is essential for long-chain polyunsaturated FAs. FAs are primarily obtained from dietary sources and are distributed in the body. In comparison with the use of self-reporting approaches, measuring the FA levels within different blood compartments can present a more accurate image of nutritional, and thus tissue, FA composition. Hence, the FA profile of plasma or serum is commonly used for physiological analyses. Nevertheless, plasma and serum FAs are not yet incorporated into cell membranes, and consequently may not be a suitable reflection of the FA status of body tissues. The evaluation of erythrocyte FA levels offers a superior possibility for the following reasons: the biological fluctuation of erythrocyte FA composition is low, phospholipids account for almost all the lipid content of erythrocytes, and the FA profiles of erythrocytes represent those of tissues. Here, we elaborate on whether the status of maternal erythrocyte FAs can serve as a prognostic biomarker for reproductive health and fetomaternal complications, including embryonic and fetoplacental development, gestational length, and preeclampsia. In addition, factors with the potential of altering the maternal erythrocyte FAs such as maternal diet, lifestyle habits, genetics, and body composition are discussed.

Effects of marine-derived and plant-derived omega-3 polyunsaturated fatty acids on erythrocyte fatty acid composition in type 2 diabetic patients

BackgroundDietary fatty acids intake affects the composition of erythrocyte fatty acids, which is strongly correlated with glycolipid metabolism disorders. This study aimed at investigating the different effects of marine-derived and plant-derived omega-3 polyunsaturated fatty acid (n-3 PUFA) on the fatty acids of erythrocytes and glycolipid metabolism in patients with type 2 diabetes mellitus (T2DM).MethodsThe randomized double-blinded trial that was performed on 180 T2DM patients. The participants were randomly assigned to three groups for the six-month intervention. The participants were randomly assigned to three groups for the six-month intervention. The fish oil (FO) group was administered with FO at a dose of 3 g/day containing eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the perilla oil (PO) group was administered with PO at a dose of 3 g/day containing α-linolenic (ALA), the linseed and fish oil (LFO) group was administered with mixed linseed and fish oil at a dose of 3 g/day containing EPA, DHA and ALA. Demographic information were collected and anthropometric indices, glucose and lipid metabolism indexes, erythrocyte fatty acid composition were measured. Statistical analyses were performed using two-way ANOVA.ResultsA total of 150 patients finished the trial, with 52 of them in the FO group, 50 in the PO group and 48 in the LFO group. There were significant effects of time × treatment interaction on fast blood glucose (FBG), insulin, HOMA-IR and C-peptide, TC and triglyceride (TG) levels (P < 0.001). Glucose and C-peptide in PO and LFO groups decreased significantly and serum TG in FO group significantly decreased (P < 0.001) after the intervention. Erythrocyte C22: 5 n-6, ALA, DPA, n-6/n-3 PUFA, AA/EPA levels in the PO group were significantly higher than FO and LFO groups, while EPA, total n-3 PUFA and Omega-3 index were significantly higher in the FO and LFO groups compared to PO group.ConclusionSupplementation with perilla oil decreased FBG while fish oil supplementation decreased the TG level. Marine-based and plant-based n-3 PUFAs exhibit different effects on fatty acid compositions of erythrocytes and regulated glycolipid metabolism.Trial registrationThis trial was recorded under Chinese Clinical Trial Registry Center (NO: ChiCTR-IOR-16008435) on May 28 2016.

Heart Rate Variability and Long Chain n-3 Polyunsaturated Fatty Acids in Chronic Kidney Disease Patients on Haemodialysis: A Cross-Sectional Pilot Study.

Low heart rate variability (HRV) is independently associated with increased risk of sudden cardiac death (SCD) and all cardiac death in haemodialysis patients. Long chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) may exert anti-arrhythmic effects. This study aimed to investigate relationships between dialysis, sleep and 24 h HRV and LC n-3 PUFA status in patients who have recently commenced haemodialysis. A cross-sectional study was conducted in adults aged 40–80 with chronic kidney disease (CKD) stage 5 (n = 45, mean age 58, SD 9, 20 females and 25 males, 39% with type 2 diabetes). Pre-dialysis blood samples were taken to measure erythrocyte and plasma fatty acid composition (wt % fatty acids). Mean erythrocyte omega-3 index was not associated with HRV following adjustment for age, BMI and use of β-blocker medication. Higher ratios of erythrocyte eicosapentaenoic acid (EPA) to docosahexaenoic acid (DHA) were associated with lower 24 h vagally-mediated beat-to-beat HRV parameters. Higher plasma EPA and docosapentaenoic acid (DPAn-3) were also associated with lower sleep-time and 24 h beat-to-beat variability. In contrast, higher plasma EPA was significantly related to higher overall and longer phase components of 24 h HRV. Further investigation is required to investigate whether patients commencing haemodialysis may have compromised conversion of EPA to DHA, which may impair vagally-mediated regulation of cardiac autonomic function, increasing risk of SCD.

Biomarkers of fatty acid intake are independently associated with preclinical atherosclerosis in individuals with type 1 diabetes.

Information on the association between diet and cardiovascular disease (CVD) in type 1 diabetes (T1D) is scarce. We assessed the association between biomarkers of fatty acid (FA) intake and the presence of carotid plaques (a surrogate marker of future CVD events) in this high-risk population. Cross-sectional study in 167 consecutive T1D patients without CVD and with at least one of the following: ≥ 40years, diabetic nephropathy, or ≥ 10years of T1D duration with another CVD risk factor. The FA profile of erythrocyte membranes was determined by gas chromatography, and the number of carotid plaques (intima-media thickness ≥ 1.5mm) was assessed by ultrasonography. Regression models were constructed adjusting for classical (age, gender, blood pressure, smoking habit, LDL-cholesterol, body mass index and statins) and T1D-specific risk factors (diabetes duration, HbA1c and chronic complications). A total of 58.7% were men (mean age 48.3 ± 10.3years, T1D duration 27.2 ± 10.1years). Sixty-one patients (36.5%) showed carotid plaque. Linoleic acid decreased and all-C18:1trans increased with the number of carotid plaques (none, 1-2, ≥ 3 plaques; p for trend < 0.05). In multivariate regression models, linoleic acid remained inversely associated with the presence of plaque [1% increase of total FAs; OR 0.71 (0.53-0.95), p = 0.021] and ≥ 2 plaques [OR 0.70 (0.51-0.98), p = 0.039]; whereas, all-C18:1trans was positively associated with ≥ 3 plaques (0.1% increase of total FAs; OR 1.51 [1.05-2.16], p = 0.026). Erythrocyte FA composition, as a biomarker of FA intake, was independently associated with preclinical atherosclerosis in T1DM. Our data support the potential role of an unfavorable pattern of fat intake and CVD risk in this population.

Enteral and supplemental parenteral nutrition enriched with omega-3 polyunsaturated fatty acids in intensive care patients – A randomized, controlled, double-blind clinical trial

Enteral nutrition (EN) and parenteral nutrition (PN) enriched with omega-3 polyunsaturated fatty acids (PUFA) have beneficial effects in critical illness. This study aimed to assess the combined effect of EN and supplemental PN enriched with omega-3 PUFA on blood oxygenation in intensive care unit (ICU) patients. Single-center, prospective, randomized, controlled, double-blind, phase III trial conducted from 10/2013 to 11/2017. A total of 100 ICU patients (18-85 years, APACHE II score>15) requiring mechanical ventilation were randomly assigned to received combined EN and PN either with omega-3 PUFA (omega-3 group) or without (control group) for up to 28 days. Primary endpoint: 'change of PaO2/FiO2 from day (D) 1 to D4'. Secondary endpoints: lung function parameters, ICU complications, length of hospital stay, days free of ICU care/ventilation/sedation/catecholamine treatment, mortality, erythrocyte fatty acid composition, inflammatory parameters. Safety parameters: standard laboratory assessment, vital signs, physical examination, SOFA score, adverse events. Combined EN and PN covered energy requirements to more than 80%. Blood oxygenation (ΔPaO2/FiO2 from D1 to D4:-1.3±83.7, n=42, and 13.3±86.1, n=39, in omega-3 and control group, respectively, p=0.7795) and other lung function parameters did not differ between groups but days free of catecholamine treatment were significantly higher in the omega-3 group (~4 days, p=0.0481). On D6, significantly more patients in the omega-3 group tolerated EN alone (51.0% vs. 29.8%, p=0.0342).Eicosapentaenoic acid (EPA) content in erythrocytes was significantly increased in the omega-3 group at last observation compared with the control group (ΔEPA: 0.928±0.808% vs.-0.024±0.190%, p<0.0001). No further significant group differences were detected. Enteral and supplemental PN both enriched with omega-3 PUFA did not improve lung function but allowed earlier weaning from catecholamine treatment and PN. Supplemental PN succeeded to adequately cover energy requirements in critically ill patients. www.clinicaltrials.gov, registration number: NCT01162928.

Influence of genetic variants in FADS2 and ELOVL2 genes on BMI and PUFAs homeostasis in children and adolescents with obesity.

Several studies identified genetic variants in FADS and ELOVL2 genes associated with obesity-related conditions, such as alterations in blood lipid parameters and insulin homeostasis. The aim of this cross-sectional study was to determine whether FADS and ELOVL2 genetic variants were associated with obesity and adiposity, besides dyslipidaemia and insulin resistance, in a large sample of obese children and adolescents. One thousand six hundred and forty-nine obese children underwent physical examination, anthropometry, fasting blood tests measuring plasma glucose, lipid and liver profile. Two genetic variants were genotyped: rs2236212 in ELOVL2 gene and rs1535 in FADS2, for the gene cluster FADS. In a subgroup of obese children (n = 105), erythrocyte fatty acid composition was measured. Generalized linear models were used to assess association between genotypes and variables. A positive association between zBMI and the minor allele of rs2236212 (p = 0.028), the major allele of rs1535 (p = 0.046) and the genetic score (p = 0.008), created by summing up both risk alleles, were found. The estimation of enzymatic activity revealed that minor alleles were associated significantly with a reduction of the enzymatic activity of elongase and desaturase (p = 0.048 and p = 0.0001, respectively). Common variants in the FADS2 and ELOVL2 genes were associated with BMI in a large population of obese Italian children. These SNPs were associated with alterations in LC-PUFAs homeostasis, not accompanied by modifications of plasma lipids or HOMA-IR. These findings provide additional support to the genetics accounting for BMI interindividual variability and the molecular basis of obesity.

Omega-3 polyunsaturated fatty acid supplementation versus placebo on vascular health, glycaemic control, and metabolic parameters in people with type 1 diabetes: a randomised controlled preliminary trial

BackgroundThe role of omega-3 polyunsaturated fatty acids (n-3PUFA), and the potential impact of n-3PUFA supplementation, in the treatment and management of type 1 diabetes (T1D) remains unclear and controversial. Therefore, this study aimed to examine the efficacy of daily high-dose-bolus n-3PUFA supplementation on vascular health, glycaemic control, and metabolic parameters in subjects with T1D.MethodsTwenty-seven adults with T1D were recruited to a 6-month randomised, double-blind, placebo-controlled trial. Subjects received either 3.3 g/day of encapsulated n-3PUFA or encapsulated 3.0 g/day corn oil placebo (PLA) for 6-months, with follow-up at 9-months after 3-month washout. Erythrocyte fatty acid composition was determined via gas chromatography. Endpoints included inflammation-associated endothelial biomarkers (vascular cell adhesion molecule-1 [VCAM-1], intercellular adhesion molecule-1 [ICAM-1], E-selectin, P-selectin, pentraxin-3, vascular endothelial growth factor [VEGF]), and their mediator tumor necrosis factor alpha [TNFα] analysed via immunoassay, vascular structure (carotid intima-media thickness [CIMT]) and function (brachial artery flow mediated dilation [FMD]) determined via ultrasound technique, blood pressure, glycosylated haemoglobin (HbA1c), fasting plasma glucose (FPG), and postprandial metabolism.ResultsTwenty subjects completed the trial in full. In the n-3PUFA group, the mean ± SD baseline n-3PUFA index of 4.93 ± 0.94% increased to 7.67 ± 1.86% (P < 0.001) after 3-months, and 8.29 ± 1.45% (P < 0.001) after 6-months. Total exposure to n-3PUFA over the 6-months (area under the curve) was 14.27 ± 3.05% per month under n-3PUFA, and 9.11 ± 2.74% per month under PLA (P < 0.001). VCAM-1, ICAM-1, E-selectin, P-selectin, pentraxin-3, VEGF, TNFα, CIMT, FMD, blood pressure, HbA1c, FPG, and postprandial metabolism did not differ between or within groups after treatment (P > 0.05).ConclusionsThis study indicates that daily high-dose-bolus of n-3PUFA supplementation for 6-months does not improve vascular health, glucose homeostasis, or metabolic parameters in subjects with T1D. The findings from this preliminary RCT do not support the use of therapeutic n-3PUFA supplementation in the treatment and management of T1D and its associated complications.Trial Registration ISRCTN, ISRCTN40811115. Registered 27 June 2017, http://www.isrctn.com/ISRCTN40811115.

Effects of oily fish intake on cognitive and socioemotional function in healthy 8–9-year-old children: the FiSK Junior randomized trial

Long-chain n-3 PUFAs (n-3 LCPUFAs) accrete in the brain during childhood and affect brain development. Randomized trials in children show inconsistent effects of n-3 LCPUFAs on cognitive and socioemotional function, and few have investigated effects of fish per se. We aimed to investigate the effects of oily fish consumption on overall and domain-specific cognitive and socioemotional scores and explore sex differences. Healthy 8-9-y-old children (n=199) were randomly allocated to receive ∼300 g/wk oily fish or poultry (control) for 12±2 wk. At baseline and endpoint, we assessed attention, processing speed, executive functions, memory, emotions, and behavior with a large battery of tests and questionnaires and analyzed erythrocyte fatty acid composition. One hundred and ninety-seven (99%) children completed the trial. Children in the fish group consumed 375 (25th-75th percentile: 325-426) g/wk oily fish resulting in 2.3 (95% CI: 1.9, 2.6) fatty acid percentage points higher erythrocyte n-3 LCPUFA than in the poultry group. The overall cognitive performance score tended to improve by 0.17 (95% CI: -0.01, 0.35) points in children who received fish compared with poultry, supported by n-3 LCPUFA dose dependency. This was driven mainly by fewer errors [-1.9 (95% CI: -3.4, -0.3)] in an attention task and improved cognitive flexibility measured as faster reaction time [-51 ms (95% CI: -94, -7 ms)] in a complex relative to a simple task ("mixing cost"). The fish intervention furthermore reduced parent-rated Strength and Difficulties Questionnaire total difficulties by -0.89 (95% CI: -1.60, -0.18) points mainly due to a -0.63 (95% CI: -1.11, -0.16) points reduction in internalizing problems that was reflected in tendency to a decrease in the overall socioemotional problems score of -0.13 (95% CI: -0.26, 0.01) points. The overall effects were similar in boys and girls. Oily fish dose-dependently improved cognitive function, especially attention and cognitive flexibility, and reduced socioemotional problems. The results support the importance of n-3 LCPUFAs for optimal brain function and fish intake recommendations in children.The trial was registered at www.clinicaltrials.gov as NCT02809508.

Erythrocyte Levels of n-3 Polyunsaturated Fatty Acids and the Risk of Frailty: The Korean Frailty and Aging Cohort Study

Abstract Objectives Inflammation is a major risk factor for frailty, and n-3 polyunsaturated fatty acids (PUFA) are well known as an anti-inflammatory agent. The purpose of present study was to investigate the hypothesis that the higher erythrocyte levels of long-chain n-3 PUFA were associated with lower odds of frailty and frailty criterion in community-dwelling older people. Methods Cross-sectional analysis from the data of the Korean Frailty and Aging Cohort Study, a total of 1435 older people aged 70–84 years were included in the analysis. Sex- and age-stratified community residents, drawn in urban and rural regions nationwide, were eligible for participation in the study. All participants were categorized as frail and non-frail according to the Cardiovascular Health Study index, and analyzed for erythrocyte fatty acid composition by gas chromatography. The erythrocyte levels of PUFA were expressed as a % of total erythrocyte PUFAs. Results After adjusting for confounding factors, the risk of frailty was negatively associated with the erythrocyte levels of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and Omega-3 Index, but positively associated with erythrocyte levels of arachidonic acid/EPA ratio. Consistently, the frailty score was negatively correlated with erythrocyte levels of EPA, DHA, and Omega-3 Index, but positively correlated with erythrocyte levels of arachidonic acid/EPA ratio. In addition, for each frailty criterion, the risk of slow walking speed, low handgrip strength, exhaustion, and low physical activity were negatively associated with erythrocyte levels of n-3 PUFA. Conclusions The present study showed that the risk of frailty and frailty criteria were significantly associated with lower erythrocyte levels of long-chain n-3 PUFAs, suggesting that lower erythrocyte levels of long-chain n-3 PUFAs could be a marker for the risk of frailty. Funding Sources This research was supported by a grant of the Korea Health Technology R&amp;D Project through the Korean Health Industry Development Institute (KHIDI) funded by the Ministry of Health and Welfare, Republic of Korea (grant No. HI15C3153), and the National Research Foundation (NRF) of Korea grant funded by the Korea government (NRF-2018R1A2B6002486).

Early-onset coronary atherosclerosis in patients with low levels of omega-3 fatty acids.

Coronary artery calcification (CAC) can reliably predict cardiovascular events. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are thought to inhibit vascular calcification on a cellular level and in animal models, however, the correlation in humans is controversial. In symptomatic patients, CAC was quantified according to Agatstons' method using non-contrast coronary CT. We assessed the association of EPA and DHA with early-onset coronary atherosclerosis, defined as presence of CAC above the 75th Agatston-Score (AS) percentile in sex adjusted age categories. Erythrocyte fatty acid composition was analyzed with a standardized methodology. The percentage of EPA and DHA in relation to all fatty acids present in the erythrocyte membrane is regarded the Omega-3 Index®. Among 71 patients, 51 were below and 20 were above the 75th AS-percentile. No differences were seen in age, gender, cardiovascular risk factors, and relevant medication. In univariable analysis, significantly lower values for EPA (0.77%[0.63; 0.97] vs. 0.93%[0.72; 1.21]; p = 0.045), DHA (4.90%[4.12; 5.57] vs. 5.50%[4.58; 6.52]; p = 0.038) and the Omega-3 Index (5.73%[4.75; 6.35] vs. 6.22%[5.46; 7.71]; p = 0.034) were seen in patients above the 75th AS-percentile. All other fatty acids showed no significant differences. In multivariable analysis, the Omega-3 Index showed a significant inverse association with early onset of CAC (OR: 0.533 (95%CI: 0.303-0.938; p = 0.029)), independent of age, gender, statin use, and creatinine level (all p > 0.05). Low levels of EPA and DHA (Omega-3 Index) are associated with early-onset coronary atherosclerosis. This finding needs to be validated in larger cohorts and might help understand the beneficial cardiovascular effects of omega-3 fatty acids.

Breast milk and erythrocyte fatty acid composition of lactating women residing in a peri‑urban South African township

Data on breast milk fatty acid (FA) composition in South African lactating women in relation to their FA status, as well as on potential compositional changes within feed, are limited.The aim of this study was to assess the FA composition of breast milk sampled at three time points within feed, and to determine associations with red blood cell (RBC) total phospholipid FA levels in lactating South African mothers of 2–4-month-old breastfed infants.FA composition (% total FAs) was analyzed in RBC total phospholipids, and in fore-, mid-feed and hind-milk samples of lactating mothers (n = 100) of Black African descent living in a peri‑urban township.The mean age of the lactating women was 27.8 ± 6.8 years. Geometric mean (95% CI) breast milk SFA, MUFA and PUFA contents were 37.7 (37.3,38.1), 28.5 (27.9, 28.8), and 23.5 (23.2, 24.5)%, respectively. Breast milk DHA and AA contents were 0.25 (0.24, 3.71) and 0.81 (0.79, 0.83)%, respectively, in fore-, mid- and hind-milk combined. Maternal RBC EPA, DHA and AA levels were 0.37 (0.34, 0.40), 3.8 (3.6, 4.0) and 15.4 (14.8, 16.1)%, respectively. Women who reported to consume fish often (n = 3) had significantly higher RBC EPA levels than women who consumed fish sometimes (n = 56), never (n = 14) or rarely (n = 19). Breast milk DHA positively correlated with maternal RBC DHA, while no correlations were found between breast milk AA and maternal RBC AA. Breast milk ALA and DHA contents were significantly higher in mid-feed [ALA= 0.8 (0.2, 0.2), DHA=0.3 (0.2, 0.3)] and hind-milk [ALA=0.8 (0.8, 0.9), DHA=0.3 (0.3, 0.3)] than foremilk [ALA=0.8 (0.7, 0.9), DHA=0.2 (0.2, 0.3)]. In contrast, LA and AA contents remained constant within feed.In this sample of peri‑urban South African lactating mothers, breast milk was low in DHA and high in AA compared to global means. Breast milk DHA was associated with maternal RBC status, while breast milk AA was not. We further showed that breast milk ALA and DHA increased, while LA and AA remained unchanged within feed. This suggests that n-3 PUFA maybe preferentially transferred to breast milk within feed through biomagnification.