Docosahexaenoic Acid Levels Research Articles

Reduced Cerebrospinal Fluid Levels of Lysophosphatidic Acid Docosahexaenoic Acid in Patients With Major Depressive Disorder and Schizophrenia.

BackgroundLysophosphatidic acid (LPA) is involved in numerous biological processes, including neurodevelopment, chronic inflammation, and immunologic response in the central nervous system. Autotaxin (ATX) is a secreted enzyme that produces LPA from lysophosphatidylcholine (LPC). Previous studies have demonstrated decreased protein levels of ATX in cerebrospinal fluid (CSF) of patients with major depressive disorder (MDD). Based on those studies, the current study investigated the levels of lysophospholipids species including LPA and related metabolic enzymes, in CSF of patients with MDD and schizophrenia (SCZ).MethodsThe levels of lysophospholipids species and related metabolic enzymes were measured with either liquid chromatography-tandem mass spectrometry or enzyme-linked immunosorbent assay. Japanese patients were diagnosed with DSM-IV-TR. CSF was obtained from age- and sex-matched healthy controls (n = 27) and patients with MDD (n = 26) and SCZ (n = 27).ResultsOf all lysophospholipids species, the levels of LPA 22:6 (LPA - docosahexaenoic acid) were significantly lower in patients with MDD and SCZ than in healthy controls. These levels were negatively correlated with several clinical symptomatic scores of MDD, but not those of SCZ. In addition, the levels of LPA 22:6 were significantly correlated with the levels of LPC 22:6 among all 3 groups. On the other hand, the levels of LPA 22:6 were not correlated with ATX activity in patients with MDD and SCZ.ConclusionThe lower levels of LPA 22:6 in patients with MDD and SCZ suggest an abnormality of LPA 22:6 metabolism. In addition, several depressive symptoms in patients with MDD were significantly associated with the lower levels of LPA 22:6, suggesting an involvement of LPA 22:6 in the pathophysiology of MDD.

LPC-DHA/EPA-Enriched Diets Increase Brain DHA and Modulate Behavior in Mice That Express Human APOE4.

Compared with APOE3, APOE4 is associated with greater age-related cognitive decline and higher risk of neurodegenerative disorders. Therefore, development of supplements that target APOE genotype-modulated processes could provide a great benefit for the aging population. Evidence suggests a link between APOE genotype and docosahexaenoic acid (DHA); however, clinical studies with current DHA supplements have produced negative results in dementia. The lack of beneficial effects with current DHA supplements may be related to limited bioavailability, as the optimal form of DHA for brain uptake is lysophosphatidylcholine (LPC)-DHA. We previously developed a method to enrich the LPC-DHA content of krill oil through lipase treatment (LT-krill oil), which resulted in fivefold higher enrichment in brain DHA levels in wild-type mice compared with untreated krill oil. Here, we evaluated the effect of a control diet, diet containing krill oil, or a diet containing LT-krill oil in APOE3- and APOE4-targeted replacement mice (APOE-TR mice; treated from 4 to 12 months of age). We found that DHA levels in the plasma and hippocampus are lower in APOE4-TR mice and that LT-krill oil increased DHA levels in the plasma and hippocampus of both APOE3- and APOE4-TR mice. In APOE4-TR mice, LT-krill oil treatment resulted in higher levels of the synaptic vesicle protein SV2A and improved performance on the novel object recognition test. In conclusion, our data demonstrate that LPC-DHA/EPA-enriched krill oil can increase brain DHA and improve memory-relevant behavior in mice that express APOE4. Therefore, long-term use of LT-krill oil supplements may on some level protect against age-related neurodegeneration.

Potential role of hepatic lipase in the accretion of docosahexaenoic acid (DHA) by the brain

DHA (docosahexaenoic acid) is an essential fatty acid that is required for the normal development and function of the brain. Because of its inability to synthesize adequate amounts of DHA from the precursors, the brain has to acquire DHA from plasma through the blood brain barrier (BBB). Recent studies demonstrated the presence of a transporter at the BBB that specifically transports DHA into the brain in the form of lysophosphatidylcholine (LPC-DHA). However, the mechanism by which LPC-DHA is generated in the plasma is not known. Our previous studies showed that there are at least three different enzymes - lecithin cholesterol acyltransferase (LCAT), endothelial lipase (EL), and hepatic lipase (HL), which can generate LPC-DHA from sn-2 DHA phosphatidylcholine. Here we determined the relative contributions of these enzymes in the delivery of DHA to the brain by measuring the brain DHA levels in the mice deficient in each of these enzymes. The results show that the brain DHA levels of LCAT-deficient mice or EL-deficient mice were not significantly lower than those of their littermates. However, brain DHA was significantly decreased in HL deficient mice (13.5% of total fatty acids) compared to their littermates (17.1%) (p < 0.002), and further decreased to 8.3% of total fatty acids in mice deficient in both HL and EL. These results suggest that HL activity may be the major source for the generation of LPC-DHA in the plasma necessary for transport into the brain, and EL might contribute to this process in the absence of HL.

Effect of increased levels of dietary α-linolenic acid on the n-3 PUFA bioavailability and oxidative stress in rat.

We investigated the impact of increased alpha-linolenic acid (ALA) dietary levels on its plasma bioavailability and its bioconversion in n-3 long chain poly unsaturated fatty acids during a 60-d kinetics and the oxidative stress potentially associated. Rats were submitted to a normolipidic diet providing 0, 3, 10 and 24% ALA of dietary lipids for 0, 15, 30 and 60 days. The lipid peroxidation and oxidative stress (nitric oxide (NO) contents and catalase (CAT), superoxide dismutase (SOD), gluthation peroxidase (GPx) activities) were studied in the liver and plasma. When the diet was deprived in n-3 PUFAs, ALA, (eicosanoic acid) EPA and docosahexaenoic acid (DHA) levels decreased in all lipid fractions of plasma and in red blood cell (RBC) lipids. The addition of ALA in the diet linearly improves its bioavailability and its bioconversion in EPA (R²=0.98). By providing 10 to 24% ALA in dietary lipids (LA/ALA, 1·6 and 5·5 respectively), ALA and EPA were more broadly packaged in all lipid fractions (triglyceride (TAG), cholesterol ester (CE) and free fatty acids (FFA)) of plasma from 15 to 30 days timeframe. Only 3% ALA was sufficient to promote the maximal bioconversion of ALA in DHA in phospholipid (PL) and TAG fractions. Additionally, the improvement of ALA bioconversion in EPA and DHA did not impact the oxidative stress markers and limiting lipid peroxidation. To conclude, this study demonstrated that in rat, 10% ALA in the lipid diet for 15-30 days promotes its bioavailability and its bioconversion and allowed the greatest levels in plasma and RBCs.

Association between Preoperative Long-Chain Polyunsaturated Fatty Acids and Oxidative Stress Immediately after Total Knee Arthroplasty: A Pilot Study.

Quadriceps muscle atrophy following total knee arthroplasty (TKA) can be caused by tourniquet-induced ischemia–reperfusion (IR) injury, which is often accompanied by oxidative stress and inflammatory responses. n-3 long-chain polyunsaturated fatty acids (LCPUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), exert antioxidant and anti-inflammatory effects against IR injury, whereas n-6 LCPUFAs, particularly arachidonic acid (AA), exhibit pro-inflammatory effects and promote IR injury. This study aimed to examine whether preoperative serum EPA + DHA levels and the (EPA + DHA)/AA ratio are associated with oxidative stress immediately after TKA. Fourteen eligible patients with knee osteoarthritis scheduled for unilateral TKA participated in this study. The levels of serum EPA, DHA, and AA were measured immediately before surgery. Derivatives of reactive oxygen metabolites (d-ROMs) were used as biomarkers for oxidative stress. The preoperative serum EPA + DHA levels and the (EPA + DHA)/AA ratio were found to be significantly negatively correlated with the serum d-ROM levels at 96 h after surgery, and the rate of increase in serum d-ROM levels between baseline and 96 h postoperatively. This study suggested the preoperative serum EPA + DHA levels and the (EPA + DHA)/AA ratio can be negatively associated with oxidative stress immediately after TKA.

Dietary intake and plasma levels of polyunsaturated fatty acids in early-stage Parkinson\u2019s disease

Polyunsaturated fatty acids (PUFA) are important for neuronal function and may contribute to the development of neurodegenerative diseases. Here, we investigated the correlation between dietary intake and plasma concentrations of PUFA and their associations with clinical severity in early-stage Parkinson’s disease (PD). In a case–control study with 38 patients with PD and 33 controls, we assessed dietary intake using food frequency questionnaires and simultaneously measured the plasma levels of five PUFA. No differences were observed in dietary total energy and lipid intake, including PUFA, between patients with PD and controls. However, α-linolenic acid (ALA), linoleic acid (LA), and arachidonic acid (AA) plasma levels were lower in patients with PD. The association between dietary intake and plasma PUFA concentrations was not significant in patients with PD. ALA and LA plasma levels were inversely correlated with motor severity in patients with PD, while docosahexaenoic acid and AA plasma levels were positively correlated with non-motor symptoms after controlling for age and sex.

Eicosanoid profiling in patients with complete form of pachydermoperiostosis carrying SLCO2A1 mutations.

Pachydermoperiostosis (PDP) is a genetic disease characterized by digital clubbing, periostosis, and pachydermia caused by mutated HPGD or SLCO2A1. Plasma prostaglandin (PG)E2 levels are increased in these patients. However, other eicosanoids have not been quantitated. We aimed to quantitate plasma eicosanoid levels in four patients carrying SLCO2A1 mutations by high-performance liquid chromatography-tandem mass spectrometry. PGE2 level was elevated in all patients; PGD2 and 11β-PGF2 α levels were also increased in some patients, whereas eicosapentaenoic acid, docosahexaenoic acid, and arachidonic acid levels were decreased in all patients. Our data indicate a dysfunctional eicosanoid homeostasis and varied levels of PG in patients with a complete form of PDP carrying SLCO2A1 mutations. PGE2 levels seem to mostly affect the symptoms, with other eicosanoids possibly having a minor effect.

Acyl-CoA synthetase 6 is required for brain docosahexaenoic acid retention and neuroprotection during aging.

The omega-3 fatty acid docosahexaenoic acid (DHA) inversely relates to neurological impairments with aging; however, limited nondietary models manipulating brain DHA have hindered a direct linkage. We discovered that loss of long-chain acyl-CoA synthetase 6 in mice (Acsl6–/–) depletes brain membrane phospholipid DHA levels, independent of diet. Here, Acsl6–/– brains contained lower DHA compared with controls across the life span. The loss of DHA- and increased arachidonate-enriched phospholipids were visualized by MALDI imaging predominantly in neuron-rich regions where single-molecule RNA in situ hybridization localized Acsl6 to neurons. ACSL6 is also astrocytic; however, we found that astrocyte-specific ACSL6 depletion did not alter membrane DHA because astrocytes express a non–DHA-preferring ACSL6 variant. Across the life span, Acsl6–/– mice exhibited hyperlocomotion, impairments in working spatial memory, and increased cholesterol biosynthesis genes. Aging caused Acsl6–/– brains to decrease the expression of membrane, bioenergetic, ribosomal, and synaptic genes and increase the expression of immune response genes. With age, the Acsl6–/– cerebellum became inflamed and gliotic. Together, our findings suggest that ACSL6 promotes membrane DHA enrichment in neurons, but not in astrocytes, and is important for neuronal DHA levels across the life span. The loss of ACSL6 impacts motor function, memory, and age-related neuroinflammation, reflecting the importance of neuronal ACSL6-mediated lipid metabolism across the life span.

Omega-3 Fatty Acids and Vitamin D Decrease Plasma T-Tau, GFAP, and UCH-L1 in Experimental Traumatic Brain Injury.

Traumatic brain injury (TBI) results in neuronal, axonal and glial damage. Interventions targeting neuroinflammation to enhance recovery from TBI are needed. Exercise is known to improve cognitive function in TBI patients. Omega-3 fatty acids and vitamin D reportedly reduce inflammation, and in combination, might improve TBI outcomes. This study examined how an anti-inflammatory diet affected plasma TBI biomarkers, voluntary exercise and behaviors following exposure to mild TBI (mTBI). Adult, male rats were individually housed in cages fitted with running wheels and daily running distance was recorded throughout the study. A modified weight drop method induced mTBI, and during 30 days post-injury, rats were fed diets supplemented with omega-3 fatty acids and vitamin D3 (AIDM diet), or non-supplemented AIN-76A diets (CON diet). Behavioral tests were periodically conducted to assess functional deficits. Plasma levels of Total tau (T-tau), glial fibrillary acidic protein (GFAP), ubiquitin c-terminal hydrolase L1 (UCH-L1) and neurofilament light chain (NF-L) were measured at 48 h, 14 days, and 30 days post-injury. Fatty acid composition of food, plasma, and brain tissues was determined. In rats exposed to mTBI, NF-L levels were significantly elevated at 48 h post-injury (P < 0.005), and decreased to levels seen in uninjured rats by 14 days post-injury. T-tau, GFAP, and UCH-L1 plasma levels did not change at 48 h or 14 days post-injury. However, at 30 days post-injury, T-tau, GFAP and UCH-L1 all significantly increased in rats exposed to mTBI and fed CON diets (P < 0.005), but not in rats fed AIDM diets. Behavioral tests conducted post-injury showed that exercise counteracted cognitive deficits associated with mTBI. The AIDM diets significantly increased docosahexaenoic acid levels in plasma and brain tissue (P < 0.05), and in serum levels of vitamin D (P < 0.05). The temporal response of the four injury biomarkers examined is consistent with studies by others demonstrating acute and chronic neural tissue damage following exposure to TBI. The anti-inflammatory diet significantly altered the temporal profiles of plasma T-tau, GFAP, and UCH-L1 following mTBI. Voluntary exercise protected against mTBI-induced cognitive deficits, but had no impact on plasma levels of neurotrauma biomarkers. Thus, the prophylactic effect of exercise, when combined with an anti-inflammatory diet, may facilitate recovery in patients with mTBI.

Differences in Sensorimotor Development Among U.S. Infants Receiving Breastmilk and/or Formula in the First 6-Months From the PediaTrac™ Project

ObjectivesAchieving sensorimotor (SEM) milestones is one measure of early infant brain development promoted through higher docosahexaenoic acid (DHA) levels. Both breastmilk and formula contain DHA, with a global level of 0.32% in breastmilk and many formula brands. However, a 2017 study of Midwestern U.S. mothers found significantly lower breastmilk DHA levels. It was thus hypothesized that infants fed formula would have higher SEM scores. The objective of this study was to measure differences in SEM development between infants fed breastmilk, formula, or a combination in participants of the PediaTrac™ Project. PediaTrac is a web-based measure providing longitudinal, real time, multidomain data on infant and toddler growth and development at time periods corresponding to well child visits. MethodsUsing PediaTrac, data were collected from 548 caregiver-infant dyads across multiple Midwestern sites. Caregivers reported the primary nutrition source as breastfeeding, formula or combination. Their responses to gross and fine motor function questions were used to create a SEM composite, Percent of Maximum Possible (POMP) score at newborn (NB), 2-, 4- and 6-months. Data were analyzed via ANOVA and Tukey test using SPSS. ResultsInfants fed formula had statistically higher mean SEM scores at NB (M = 0.618Formula, M = 0.590Breast, p = 0.017), 2- (M = 0.706Formula, M = 0.680Breast, p = 0.006) and 6-months (M = 0.727Formula, M = 0.696Breast, p = 0.014) compared to breastfed infants. Mean SEM scores of combination fed infants were higher than breastfed infants at 2- (M = 0.701Combination, M = 0.680Breast, p = 0.184), 4- (M = 0.684Combination, M = 0.673Breast, p = 0.573) and 6-months (M = 0.704Combination, M = 0.696Breast, p = 0.895), despite no significant differences between scores. ConclusionsFormula fed infants showed consistently higher SEM scores than breastfed infants in the first 6-months. These findings contradict previous research, indicating a need for further investigation into variables contributing to these discrepancies such as maternal breastmilk DHA concentrations, socioeconomic factors, site specific confounds, accuracy of parent reports of motor development, etc. Funding SourcesEunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health. EMU College of Health & Human Services Research Support Award.

The effect of docosahexaenoic acid on predicting the survival of patients with idiopathic pulmonary arterial hypertension.

BackgroundAbnormal lipid metabolism has been reported in patients with idiopathic pulmonary arterial hypertension (IPAH); however, the prognostic value of plasma free fatty acids (FFAs) for these patients is unclear. The present study aimed to determine whether FFA can play a role in predicting the survival of patients with IPAH.MethodsA total of 69 blood samples from patients with IPAH were subjected to liquid chromatography-mass spectrometry (LC-MS). According to the classification criteria for pulmonary hypertension in the European Society of Cardiology (ESC) guidelines, patients were divided into low-risk, intermediate-risk, and high-risk groups. The FFA expression levels of patients in the three groups were compared, and the indicators with significant differences were selected. Cox regression analysis was performed to examine the associations between survival and different factors. Receiver operator characteristic (ROC) curves were used to assess the predictive effect of plasma lipids in assessing patients’ risk of morbidity, including area under the curve (AUC), sensitivity, specificity and the best cutoff value. Kaplan-Meier curves were used to predict survival.ResultsA total of 24 FFA molecules were detected in the patients with IPAH. Among them, FFA (20:4), FFA (20:5), FFA (22:5), FFA (22:6), FFA (24:0) and FFA (30:4) showed significant differences between the low-risk and the intermediate-risk or high-risk patients with IPAH. These six FFAs were significantly correlated with hemodynamic parameters. FFA (22:6), named docosahexaenoic acid (DHA), displayed significant negative correlations with World Health Organization functional classification (WHO FC), mean right atrial pressure (mRAP), and pulmonary vascular resistance (PVR), and significant positive correlations with 6-minute walking distance (6MWD) and cardiac index (CI). Cox regression analyses demonstrated that total bilirubin (TBIL) and DHA were independent risk factors for survival of IPAH. Receiver operating characteristic curve analysis revealed that DHA had a cut-off value of 77.55, which had a sensitivity of 96.7% and a specificity of 62.5% for predicting survival. Kaplan-Meier curve analysis showed that a lower level of DHA predicted a poor outcome in patients with IPAH.ConclusionsOur study suggested that FFA levels were correlated with disease severity. Lower levels of DHA predict poor survival in patients with IPAH.

Supplementing Docosahexaenoic Acid and Arachidonic Acid During Suckling Period Is Beneficial for Developing Tolerance to Egg Protein in Allergy Prone Brown Norway Rats

ObjectivesWe aimed to study the effect of supplementing arachidonic acid (ARA) and docosahexaenoic acid (DHA) during suckling (through Suckling Diet, SD) and weaning (through weaning diet, WD) on oral tolerance (OT) development in allergy susceptible Brown Norway rats. MethodsDams were assigned to consume either ARA+DHA (0.4% ARA, 0.8% DHA w/w total fat) SD or control SD (0% ARA, DHA) for 21d during the pups’ suckling period. At 21d, pups from each SD group were randomized to receive ARA + DHA WD (0.5% ARA, 0.5% DHA w/w total fat) or control WD (0% ARA, DHA) until 8wk. Between 21–25 d, pups from each of the 4 diet groups were randomized to receive ovalbumin (Ova, 3 mg) or a placebo (8% sucrose) for OT induction. At 7 wk, pups received an Ova + alum injection IP to induce systemic immunization. In necropsy, plasma was collected and splenocytes were isolated to determine immune cell types and ex-vivo cytokine production to phorbol myristate acetate + ionomycin (PMAi). ResultsAlthough higher DHA levels in dams’ breastmilk were seen with ARA+DHA SD, this SD effect was not seen in the 8wk pups. At 8wks, ARA+DHA WD resulted in significantly higher DHA level in (1.5x) plasma phospholipids (PL) and (2x) splenocytes. ARA composition in pups’ plasma and splenocytes PL was not different among SD and WD groups. OT development was confirmed by a significantly lower plasma level of Ova-IgG1 and Ova-IgE in Ova OT groups. Further, SD ARA+DHA supplementation also had 30% lower plasma Ova-IgG1 than control SD (P = 0.02) but the SD had no effect on production of IL2, IL4, IL10, IFNg, TNFα and IL13 by PMAi stimulated splenocytes. However, pups from Ova group that received ARA+DHA SD and control WD produced more TGFβ than control for SD and WD (P = 0.05). Pups from sucrose OT groups, when supplemented with ARA+DHA SD had 50% higher T regulatory cells (CD3+CD4+CD25+FoxP3+, Tregs) than controls SD in spleen. In pups that received control SD groups, the Ova group had lower activated T helper (CD3+CD4+CD28+) than sucrose, however, when pups received ARA+DHA SD, OT effect was absent. ConclusionsARA and DHA in WD increased DHA status without affecting ARA status in plasma. ARA and DHA provided in SD was beneficial for OT development shown by lowered ova-IgG1, which may be due to higher Tregs and TGFβ produced by splenocytes in brown Norway offspring. Funding SourcesNSERC, AGES-ALES (Patel).

Omega-3 Fatty Acids and Vitamin D Decrease Plasma T-tau, GFAP, and UCH-L1 in Experimental Traumatic Brain Injury

ObjectivesTraumatic brain injury (TBI) results in neuronal, axonal and glial damage. Interventions targeting neuroinflammation to enhance recovery from TBI are needed. Exercise is known to improve cognitive function in TBI patients. Omega-3 fatty acids and vitamin D reportedly reduce inflammation, and in combination, might improve TBI outcomes. This study examined how an anti-inflammatory diet affected plasma TBI biomarkers, voluntary exercise and behavior following exposure to mild TBI (mTBI). MethodsAdult, male rats were individually housed in cages fitted with voluntary running wheels and daily running distance was recorded during the study. A modified weight drop method induced mTBI, and during 30 days post-injury, rats were fed diets supplemented with omega-3 fatty acids and vitamin D3 (AIDM diet), or non-supplemented AIN-76A diets (CON diet). Behavioral tests were periodically conducted to assess functional deficits. Plasma levels of Total tau (T-tau), glial fibrillary acidic protein (GFAP), ubiquitin c-terminal hydrolase L1 (UCH-L1) and neurofilament light chain (NF-L) were measured at 48 h, 14 d and 30 d post-injury. Fatty acid composition of food, plasma and brain tissues was determined. ResultsIn rats exposed to mTBI, NF-L levels were significantly elevated at 48 h post-injury (P < 0.005), and decreased to levels seen in uninjured rats by 14 d post-injury. T-tau, GFAP and UCH-L1 plasma levels did not change at 48 h or 14 d post-injury. However, at 30 d post-injury, T-tau, GFAP and UCH-L1 all significantly increased in rats exposed to mTBI and fed CON diets (P < 0.005), but not in rats fed AIDM diets. Behavioral tests conducted post-injury showed that exercise counteracted cognitive deficits associated with mTBI. The AIDM diets significantly increased docosahexaenoic acid levels in plasma and brain tissue (P < 0.05), and in serum levels of vitamin D (P < 0.05). ConclusionsThe anti-inflammatory diet significantly altered the temporal profiles of plasma T-tau, GFAP and UCH-L1 following mTBI. Voluntary running exercise protected against mTBI-induced cognitive deficits, but had no impact on plasma levels of neurotrauma biomarkers. Thus the prophylactic effect of exercise, when combined with an anti-inflammatory diet, may facilitate recovery in patients with mTBI. Funding SourcesU.S. Army MRDC.

Variation in biomarker levels of metals, persistent organic pollutants, and omega-3 fatty acids in association with genetic polymorphisms among Inuit in Nunavik, Canada

BackgroundBiomarker measures of contaminant exposure and nutrient status can help increase understanding of the risks and benefits associated with the consumption of traditional foods by Inuit. While gene-environment and gene-nutrient interactions may help explain variations in biomarker measures, the role of genetic polymorphisms is largely understudied especially for vulnerable sub-populations. ObjectiveThe aim of this study was to characterize the relationship between single nucleotide polymorphisms (SNPs) in key genes and blood concentrations of environmental chemicals and nutrients among Inuit. MethodsBlood samples from 665 individuals who participated in the Qanuippitaa Survey (Nunavik, Canada) in 2004 were analyzed for toxicants and nutrients. DNA was extracted and 140 SNPs in classes relevant to the toxicokinetics and/or toxicodynamics of the target contaminants and nutrients, and/or are involved in cardiovascular health and lipid metabolism were genotyped using the Sequenom iPLEX Gold platform. ResultsGeometric means (μg/L) of mercury (Hg), cadmium (Cd), lead (Pb), DDE, PCB-153, and selenium (Se) were 11.1, 2.8, 39.9, 2.9, 1.1 and 301.2, respectively. Red blood cell membrane levels of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) were 5.1%/total fatty acid (TFA) and 1.3%/TFA respectively. Out of 106 SNPs which met our inclusion criteria, biomarker levels for Hg, Cd, Pb, DDE, PCB-153, DHA, and EPA differed (p < 0.05) by genotype for 20, 13, 12, 19, 21, 9 and 8 SNPs, respectively. Following Bonferroni correction (p < 0.0005), only 9 SNPs remained significant (rs2274976 in MTHFR, rs174602 in FADS2, rs7115739 and rs74771917 in FADS3, rs713041 in GPX4, rs2306283 and rs4149056 in SLCO1B1, rs1885301 in ABCC2/MRP2, and rs4244285 in CYP2C19; 5 associated with Hg, 2 with Pb, 2 with DDE, 4 with PCB-153, 1 with DHA). ConclusionsThe findings suggest that polymorphisms in environmentally-responsive genes can influence biomarker levels of key toxicants and nutrients. While there are no immediate clinical or public health implications of these findings, we believe that such gene-environment and gene-nutrient studies provide a foundation that will inform and provide direction to future studies.

Ikan teri Engraulis encrasicolus berpotensi sebagai pangan fungsional

Anchovy Engraulis encrasicolus is a good prospect to be developed in the future, maybe it can be used for hyperlipidemia diet. This study, therefore, aims to measure and assess the content of EPA (eikosapentaenoat acid) and DHA (docosahexaenoic acid).from Anchovy Engraulis encrasicolus oil extract. The samples were obtained from the city of Kendari in Southeast Sulawesi, Indonesia. It was processed and manufactured at the Halu Oleo University in Pharmacy Laboratory. Furthermore, the extraction process utilized the Soxhlet method, while measuring and analyzing the content of EPA and DHA using UV/Vis Spectropometric. It was found that 25 mg of Anchovy Engraulis encrasicolus oil produced DHA levels of 145,5 mg/g (14,5%) and EPA levels of 97,15 mg/g (7,71%). Anchovy Engraulis encrasicolus is a potential for functional food used to provide protection against diseases associated with metabolic disorders and diet hyperlipidemia.

Omega-3 polyunsaturated fatty acid intake and plasma fatty acids of school going Indian children - a cross-sectional study

Long-chain omega-3 polyunsaturated fatty acids (PUFA) such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) play an essential role in cognitive and behavioural changes among school going children. This study delineates the dietary omega-3 PUFA [alpha-Linolenic acid (ALA), DHA, and EPA] intake and plasma fatty acids levels among school-going children. This is a cross-sectional study purely observational in nature, wherein 625 apparently healthy boys and girls aged between 7 and 13 years were selected from five different schools of Hyderabad. Dietary information on omega-3 PUFA (ALA, DHA, and EPA) intake was collected using a food frequency questionnaire. Plasma fatty acid concentrations were measured in 34% of sub-sample using standard gas chromatography. The study revealed that the average dietary intakes of omega-3 PUFA, ALA, DHA, and EPA were 55.46, 15.82, 35.59, 4.06 mg/day, respectively. There was a significant difference in mean DHA intake among gender and age group [girls (38.64±1.45 mg/day), boys (31.80±1.38 mg/day) p < 0.001] and [7–10 years (31.75±1.38 mg/day), 11–13 years (38.07±1.40 mg/day) p < 0.01]. The mean plasma DHA and DPA levels of overall subjects were 0.98 nmol% and 0.18nmol% respectively which was comparable among different gender, age and BMI-for age groups. There was a positive correlation between dietary DHA intake and plasma DHA level [ρ=0.376 (p < 0.001)]. The current study demonstrated that the omega-3 PUFA intake in school going children was less and reinforces the importance of increasing the omega-3 PUFA intake through diet and supplements.

Association Between Achieved ω-3 Fatty Acid Levels and Major Adverse Cardiovascular Outcomes in Patients With High Cardiovascular Risk

In patients treated with ω-3 fatty acids, it remains uncertain whether achieved levels of eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) are associated with cardiovascular outcomes. To determine the association between plasma levels of EPA and DHA and cardiovascular outcomes in a trial of ω-3 fatty acids compared with corn oil placebo. A double-blind, multicenter trial enrolled patients at high cardiovascular risk with elevated triglyceride levels and low levels of high-density lipoprotein cholesterol at 675 centers (enrollment from October 30, 2014, to June 14, 2017; study termination January 8, 2020; last visit May 14, 2020). Participants were randomized to receive 4 g daily of ω-3 carboxylic acid (CA) or an inert comparator, corn oil. The primary prespecified end point was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina requiring hospitalization. The primary outcome measure was the hazard ratio, adjusted for baseline characteristics, for patients treated with the ω-3 CA compared with corn oil for the top tertile of achieved EPA and DHA plasma levels 12 months after randomization. Of the 13 078 total participants, 6539 (50%) were randomized to receive ω-3 CA and 6539 (50%) randomized to corn oil. ω-3 Fatty acid levels were available at both baseline and 12 months after randomization in 10 382 participants (5175 ω-3 CA patients [49.8%] and 5207 corn oil-treated patients [50.2%]; mean [SD] age, 62.5 [8.9] years, 3588 [34.6%] were women, 9025 [86.9%] were White, and 7285 [70.2%] had type 2 diabetes). The median plasma levels at 12 months in ω-3 CA patients were 89 μg/mL (interquartile range [IQR], 46-131 μg/mL) for EPA and 91 μg/mL (IQR, 71-114 μg/mL) for DHA with top tertile levels of 151 μg/mL (IQR, 132-181 μg/mL) and 118 μg/mL (IQR, 102-143 μg/mL), respectively. Compared with corn oil, the adjusted hazard ratios for the highest tertile of achieved plasma levels were 0.98 (95% CI, 0.83-1.16; P = .81) for EPA, and 1.02 (95% CI, 0.86-1.20; P = .85 for DHA. Sensitivity analyses based on changes in plasma and red blood cell levels of EPA and DHA and primary and secondary prevention subgroups showed similar results. Among patients treated with ω-3 CA, the highest achieved tertiles of EPA and DHA were associated with neither benefit nor harm in patients at high cardiovascular risk. ClinicalTrials.gov Identifier: NCT02104817.

The effect of omega-3 polyunsaturated fatty acids in prevention of postoperative atrial fibrillation development in patients undergoing coronary artery bypass graft surgery

Abstract Funding Acknowledgements Type of funding sources: None. Purpose. To estimate the effect of omega-3 polyunsaturated fatty acids (PUFAs) in prevention of postoperative atrial fibrillation (POAF) in patients with coronary artery disease undergoing coronary artery bypass graft (CABG) surgery. Methods. Studied were 306 patients who underwent CABG. All the patients were divided into two groups depending on the prescription of omega-3 PUFAs in the pre- and postoperative period by randomization method: 1 group comprised 158 patients without PUFAs (82.7% men, median age 63.0 (57.0;67.0) years, 2 group - 148 patients with PUFAs (89.3% men, median age 60.0 (57.0;64.0) years). PUFAs were prescribed 2000 mg daily starting with 5 days before CABG and 1000 mg daily after CABG for 21 days. In all the patients, we studied interleukin (IL)-6, IL-8, IL-10, NT-proBNP, troponin, superoxide dismutase (SOD), malondialdehyde (MDA), glutathione and omega-3 index. Results. During the observation period POAF occurred in 29.7% patients of group 1, and in 16.9% patients of group 2 (p = 0.009). In postoperative period patients of group 1 had median IL-6 level 39.3% higher (p = 0.001) and median IL-10 level - 20.2% higher (p = 0.01) comparing with group 2. In patients of group 2 we found SOD median level 78.9% lower (р&amp;lt;0.0001) and MDA median level 33.8% lower compared to the patients of group 1 (р=0.03). In postoperative period in group 2 the median level of docosahexaenoic acid was 55% higher (p = 0.03), and omega-3 index - 43.4% higher (h = 0.04) compared with group 1. Conclusion. We found that patients with PUFAs had less activation of inflammation and oxidative stress after CABG than patients without PUFAs. The patients with PUFAs also had increased levels of docosahexaenoic acids and omega-3 index compared to the patients without PUFAs. We also found a significant decrease of the prevalence of POAF after CABG in patients with PUFAs.

Acyl‐CoA synthetase 6 is required for brain docosahexaenoic acid retention and neuroprotection during aging

The omega-3 fatty acid docosahexaenoic acid (DHA) inversely relates to neurological impairments with aging. However, limited non-dietary in vivo models specifically depleting brain DHA have limited direct linkage of DHA to neurological aging processes. We discovered that loss of long-chain acyl-CoA synthetase 6 (ACSL6) depletes brain membrane phospholipid DHA levels. Here, the effects of membrane phospholipid DHA depletion on behavioral and neurological outcomes across the natural progression of aging in control and Acsl6 knockout mice (Acsl6-/-) were determined. Across the lifespan, Acsl6-/- brains contained lower DHA compared to controls. The loss of DHA-enriched and increased arachidonic acid-enriched phospholipids was visualized by MALDI imaging, predominantly in neuronal rich regions where robust Acsl6 gene expression localized by smFISH to neurons across the brain, including pyramidal, Purkinje, and within the cerebellar granular layer. ACSL6 was also found in astrocytes; however, astrocyte-specific loss of ACSL6 did not regulate membrane DHA, a phenomenon attributed to astrocyte-specific expression of alternative-exon ACSL6 variants that do not prefer DHA as substrate. Total ACSL6 knockout mice exhibited hyperlocomotion across the lifespan, early-onset impairments in working spatial memory, and increased expression of cholesterol biosynthesis genes. In response to aging, cerebellar neuroinflammation and gliosis developed. Neuroinflammation was not accompanied by major alterations of lipid mediators but was preceded by decreased expression of synaptic proteins. Together our findings suggest that ACSL6 is enriched in neurons to promote membrane DHA enrichment, is important for brain DHA levels across the lifespan, protects against disordered motor function, memory, and age-related neuroinflammation reflecting the importance of DHA, and its metabolism by ACSL6, early in life and in age-related neuroprotection.

ADIPOR1 deficiency-induced suppression of retinal ELOVL2 and docosahexaenoic acid levels during photoreceptor degeneration and visual loss

Lipid metabolism-related gene mutations can cause retinitis pigmentosa, a currently untreatable blinding disease resulting from progressive neurodegeneration of the retina. Here, we demonstrated the influence of adiponectin receptor 1 (ADIPOR1) deficiency in retinal neurodegeneration using Adipor1 knockout (KO) mice. Adipor1 mRNA was observed to be expressed in photoreceptors, predominately within the photoreceptor inner segment (PIS), and increased after birth during the development of the photoreceptor outer segments (POSs) where photons are received by the visual pigment, rhodopsin. At 3 weeks of age, visual function impairment, specifically photoreceptor dysfunction, as recorded by electroretinography (ERG), was evident in homozygous, but not heterozygous, Adipor1 KO mice. However, although photoreceptor loss was evident at 3 weeks of age and progressed until 10 weeks, the level of visual dysfunction was already substantial by 3 weeks, after which it was retained until 10 weeks of age. The rhodopsin mRNA levels had already decreased at 3 weeks, suggesting that reduced rhodopsin may have contributed to early visual loss. Moreover, inflammation and oxidative stress were induced in homozygous KO retinas. Prior to observation of photoreceptor loss via optical microscopy, electron microscopy revealed that POSs were present; however, they were misaligned and their lipid composition, including docosahexaenoic acid (DHA), which is critical in forming POSs, was impaired in the retina. Importantly, the expression of Elovl2, an elongase of very long chain fatty acids expressed in the PIS, was significantly reduced, and lipogenic genes, which are induced under conditions of reduced endogenous DHA synthesis, were increased in homozygous KO mice. The causal relationship between ADIPOR1 deficiency and Elovl2 repression, together with upregulation of lipogenic genes, was confirmed in vitro. Therefore, ADIPOR1 in the retina appears to be indispensable for ELOVL2 induction, which is likely required to supply sufficient DHA for appropriate photoreceptor function and survival.