Low Eicosapentaenoic Acid Levels Research Articles

Prognostic Significance of Sarcopenia and Eicosapentaenoic Acid (EPA) Levels in Patients With Unresectable Pancreatic or Biliary Tract Cancer.

This study aimed to investigate the relationship between prechemotherapy blood eicosapentaenoic acid (EPA) levels, sarcopenia, and overall survival in patients with pancreatic and biliary tract cancer undergoing chemotherapy. Forty-five patients with recurrent, non-resected pancreatic or biliary tract cancer undergoing chemotherapy were retrospectively analyzed. The skeletal muscle mass was measured at the third lumbar vertebra. Sarcopenia cut-off values were based on the Japanese Society of Hepatology sarcopenia assessment criteria. Two months after starting chemotherapy, the patients received enteral nutrition containing omega-3 fatty acids. Patients with pancreatic and biliary tract cancers with low pre-treatment blood EPA levels had significantly more intense sarcopenia than those with high EPA levels (p=0.023). Patients with sarcopenia before chemotherapy had significantly lower overall survival than those without sarcopenia. Multivariate analysis revealed blood EPA concentration as an independent prognostic factor (p<0.01). Lumbar muscle volume, a marker of sarcopenia, showed a clear positive correlation with prechemotherapy EPA concentration (p=0.008). In patients administered with enteral nutrition containing omega-3 fatty acids, both EPA concentration and lumbar muscle volume were significantly higher than those prior to intervention, indicating sarcopenia improvement due to the intervention. In patients with recurrent non-resected pancreatic and biliary tract cancer, low blood EPA levels before chemotherapy are associated with sarcopenia and poor prognosis.

Fatty acid profiles reveal dietary variability of a large calanoid copepod Limnocalanus macrurus in the northern Baltic Sea

Eutrophication, climate-induced warming, and salinity fluctuations are altering the fatty acid profiles and the availability of essential polyunsaturated fatty acids (PUFAs) in marine zooplankton communities. Limnocalanus macrurus Sars G.O., 1863 is a large calanoid copepod inhabiting the low-salinity areas in the Baltic Sea, where it is a major source of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) to commercially important fish. L. macrurus is sensitive to warming, eutrophication and hypoxia. As an opportunistic feeder, it is capable of dietary shifts, which affects its fatty acid profiles. Although much studied in boreal lakes, there are only a few studies on the fatty acid profiles of the Baltic Sea populations. This study aimed to compare the fatty acid profiles of L. macrurus in three basins of the Baltic Sea, in relation to the community fatty acids and environmental variables. We collected samples of L. macrurus and filtered plankton community for gas chromatographic fatty acid analyses in August 2021 on R/V Aranda. The nutritional quality of L. macrurus to consumers was lower in the Gulf of Finland (GoF) compared to the Gulf of Bothnia, indicated by the low levels of DHA and EPA, as well as the low n-3/n-6 ratio of PUFAs. The lower ratio of 18:1n-7 to 18:1n-9 implied higher degree of omnivory in GoF. In contrast, a diatom marker 16:1n-7 had high proportion in the Bothnian Bay. High temperatures in GoF may have restricted feeding in the upper water column, possibly forcing a shift towards cyanobacteria or seston-based diet, as interpreted from a high proportion of 18:2n-6 and 18:3n-3. We conclude that the ability of L. macrurus to utilize multiple food sources increases its resilience to environmental change, while the consequences on the nutritional quality may have further cascading effects on the food webs.

Anti-inflammatory and nutritional improvement effects of dietary supplementation combined with fish oil in patients with epithelial cancer.

The present study investigated the effects of dietary supplementation combined with fish oil containing relatively low levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on the inflammatory and nutritional status of patients with epithelial cancer. Fish oil capsules (498 mg EPA and 213 mg DHA) and dietary supplements (100 kcal and 5 g protein) were administered for 8 weeks to 20 patients with cancer and inflammation [C-reactive protein (CRP) ≥0.30 mg/dl]. Blood EPA levels increased significantly after 4 and 8 weeks, while no significant differences were observed in log-transformed (log) CRP levels, which were the major inflammatory indices in these patients. A declining trend was observed at 8 weeks after excluding 2 patients with suspected infection (P=0.06). A significant increase was observed from week 0 to week 8 for log interleukin-6 (IL-6) levels. After excluding the 2 patients with suspected infection, no significant difference was observed when comparing week 0 to week 8 for log IL-6. No deterioration in albumin or pre-albumin levels was observed. These results suggest that although suppression of acute inflammation associated with infection is difficult, intake of relatively low EPA and DHA supplements may be effective for mild chronic inflammation in patients with epithelial cancer without infection. Large-scale randomized clinical trials are required to make the final decision regarding efficacy. The study was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR; 06/07/2018, UMIN000033309).

Association of blood eicosapentaenoic acid levels with intracerebral hemorrhage during the COVID-19 pandemic: preliminary experience from a single-center in Japan

BackgroundThe COVID-19 pandemic has forced lockdowns and declarations of states of emergency, resulting in marked changes to daily life such as dietary habits in many countries. Though serum omega-3 polyunsaturated fatty acids levels have been shown to be useful markers for recurrent vascular events or worse prognosis in cardiovascular diseases and ischemic stroke, the relationship between serum omega-3 PUFA levels and the occurrence of intracerebral hemorrhage has essentially been unknown. We explored the association of serum omega-3 polyunsaturated fatty acids with intracerebral hemorrhage during the COVID-19 pandemic.MethodsParticipants comprised patients admitted to Juntendo University Hospital (Tokyo, Japan) with intracerebral hemorrhage between January 1, 2016 and April 30, 2020. Clinical characteristics including serum omega-3 polyunsaturated fatty acid levels were compared between patients developing intracerebral hemorrhage during the period from January 1, 2016 to February 29, 2020, and the subsequent COVID-19 pandemic period (March 1 to April 30, 2020). Clinical characteristics independently related to intracerebral hemorrhage during the COVID-19 pandemic were analyzed by comparing these two cohorts of intracerebral hemorrhage patients in different periods.ResultsA total of 103 patients (age, 67.0 ± 13.9 years; 67 males) with intracerebral hemorrhage were enrolled. Intracerebral hemorrhage developed in 91 patients before and 12 patients during the COVID-19 pandemic. Monthly averages of intracerebral hemorrhage patients admitted to our hospital during and before the COVID-19 pandemic were 6 and 1.82, respectively. Serum eicosapentaenoic acid levels were significantly lower in intracerebral hemorrhage patients during the COVID-19 pandemic than before (31.87 ± 12.93 μg/ml vs. 63.74 ± 43.29 μg/ml, p = 0.007). Multiple logistic regression analysis showed that, compared to before the COVID-19 pandemic, dyslipidemia (odds ratio 0.163, 95% confidence interval 0.031–0.852; p = 0.032) and eicosapentaenoic acid levels (odds ratio 0.947, 95% confidence interval 0.901–0.994; p = 0.029) were associated with intracerebral hemorrhage during the COVID-19 pandemic.ConclusionsFrom our preliminary results, low eicosapentaenoic acid levels were linked with intracerebral hemorrhage during the COVID-19 pandemic. Low levels of eicosapentaenoic acid might be an endogenous surrogate marker for intracerebral hemorrhage during the COVID-19 pandemic.

Association of omega-3 levels and sleep in US adults, National Health and Nutrition Examination Survey, 2011-2012

ObjectiveTo determine associations between serum long-chain (LC) omega-3 fatty acid levels and sleep parameters among adults (N = 1314) in NHANES 2011-2012. MethodsRegression analyses accounting for the complex-survey design were used to assess associations between serum LC omega-3 fatty acid levels, sleep duration, difficulty falling sleeping and sleep disorder. ResultsOverall, 48.6% were male, the mean age was 47.2 years, 5% reported very short sleep, 29% short sleep, 63% normal sleep and 3% long sleep. The sum of LC omega-3 fatty acid levels was lower among adults with short versus normal sleep, although differences were attenuated with adjustment for sociodemographic factors. Relative to normal sleep, adults with very short sleep had lower levels of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and sum of LC omega-3 fatty acids. Differences remained significant (p < .05 for all) with adjustment for sociodemographic factors. No associations were observed with difficulty falling sleeping or sleep disorder. ConclusionOur results suggest that omega-3 fatty acid levels are associated with healthy sleep duration, although, interventions are needed to clarify causality.

Association between Sarcopenia and Omega-3 Polyunsaturated Fatty Acid in Patients with Hepatocellular Carcinoma.

Introduction: This study aimed to validate whether preoperative sarcopenia can predict long-term outcomes in patients with hepatocellular carcinoma (HCC) and identify the associations between sarcopenia and polyunsaturated fatty acids (PUFAs). Methods: This large, retrospective study included 353 patients who underwent hepatic resection for HCC and preoperative computed tomography scans. Skeletal muscle mass was measured at the third lumbar vertebrae. The cutoff value for sarcopenia followed the Japan Society of Hepatology’s assessment criteria for sarcopenia. Results: Ninety-three patients (26.3%) with preoperative sarcopenia were enrolled. These patients had a significantly lower body mass index (p < 0.0001) and serum albumin level (p = 0.0070) as well as a higher rate of advanced-stage cancer (p = 0.0062) than those without sarcopenia. Patients with sarcopenia had significantly shorter overall survival than the other patients before (p = 0.0001) and after (p = 0.0415) propensity score matching. The sarcopenia group was significantly associated with low levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which were categorized based on omega-3 PUFAs, compared with those in the non-sarcopenia group (p = 0.0030 and p = 0.0135). Conclusions: We demonstrated an association between sarcopenia and the long-term prognosis in patients with HCC. Low EPA and DHA levels were associated with preoperative sarcopenia. Further prospective studies are needed to investigate whether nutritional support using omega-3 PUFAs can prevent and manage skeletal muscle mass depletion.

Warming Decreases Bioconversion of Polyunsaturated Fatty Acids in Chironomid Larvae Maintained on Cyanobacterium Microcystis.

Cyanobacteria dominance and warming have been suggested to decrease the production of polyunsaturated fatty acids (PUFA) in freshwater ecosystems. Physiological adaptations of poikilothermic animals to higher temperatures may further decrease PUFA levels in aquatic food webs. We conducted diet manipulation experiments to investigate the combined effects of dietary PUFA and warming on the proportions of eicosapentaenoic acid (EPA) and arachidonic acid (ARA) in Chironomus riparius. The experimental diet consisted of a nontoxic cyanobacterium Microcystis, which contained C20 PUFA: 20:3n-3, 20:4n-3, and 20:3n-6, but no EPA or ARA. Additionally, we used TetraMin® fish flakes as a control treatment. A temperature increase from 20 °C to 25 °C decreased the proportion of n-3 C20 PUFA and the n-3/n-6 ratio in Microcystis. Diet manipulation experiments indicated that Chironomus desaturated dietary C20 precursors to EPA and ARA, but warming decreased this bioconversion and resulted in lower levels of EPA and ARA in Chironomus. Warming did not alter the proportions of EPA and ARA in Chironomus larvae if these PUFA were readily available in the diet (TetraMin® control treatment). In conclusion, warming and cyanobacteria dominance may decrease the production and trophic transfer of physiologically important PUFA in freshwaters by (1) decreasing the n-3/n-6 ratio and the abundance of n-3 C20 precursors in Microcystis, and (2) decreasing the bioconversion of n-3 and n-6 C20 precursors to EPA and ARA in chironomids. These changes may have cascading effects throughout the food web and decrease the content of EPA in fish, potentially affecting its availability to humans.

Associations Between Erythrocyte Membrane Fatty Acid Compositions and Biomarkers of Vascular Health in Adults With Type 1 Diabetes With and Without Insulin Resistance: A Cross-Sectional Analysis

ObjectivesThe aim of this study was to assess the relationship between specific erythrocyte fatty acid levels and vascular health in type 1 diabetes (T1D) with and without insulin resistance (IR). MethodsWe analyzed baseline pretreatment data in a subset of 23 patients with T1D from a previously published randomized controlled trial consisting of comprehensive erythrocyte-derived fatty acid profiles and a panel of inflammation-associated endothelial markers. Estimated glucose disposal rate was used to identify and categorize patients with IR. We utilized principal component analysis (PCA) to cluster vascular biomarkers to compute a single “vascular signal” and utilized univariate linear regression models to investigate the association with IR and fatty acid profiles. ResultsSubjects with IR displayed significantly higher levels of linoleic acid (p=0.001), lower levels of eicosapentaenoic acid (EPA) (p<0.001), lower levels of omega-3 polyunsaturated fatty acid (n-3PUFA) (p<0.006) and an increased omega-6 (n-6)PUFA:n-3PUFA ratio (p=0.001). IR was associated with significantly higher linoleic acid levels, total n-6PUFA and an increased ratio of n-6PUFA:n-3PUFA, and negatively associated with arachidonic acid and EPA levels, total saturated fatty acid and total n-3PUFA. The PCA-derived vascular biomarker cluster was positively associated with linoleic acid and n-6PUFA:n-3PUFA ratio, and inversely associated with EPA. ConclusionsSpecific erythrocyte membrane fatty acid compositions are associated with impaired vascular health and IR in adults with T1D. These findings suggest that IR and risk of associated complications may be influenced by specific fatty acid profiles, and thus potentially modified by the selective targeting of dietary fatty acids.

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.

Fatty Acid Composition and Digestive Enzyme Activities of Rainbow Trout in Response to Dietary Docosahexaenoic Acid (DHA) and Eicosapentaenoic Acid (EPA) During Salinity Acclimation

This physiological study aimed to evaluate the effects of dietary docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on the fatty acid composition and digestive enzyme activities of rainbow trout (Oncorhynchus mykiss) during salinity acclimation. Rainbow trout with an average initial weight of 90.61 g ±9.25 g were fed diets with the quantities of DHA and EPA equaling to 0.54%, 0.95%, 1.40% and 1.79% (abbreviated as DE-0.54, DE-0.95, DE-1.40, and DE-1.79, respectively) for eight weeks, after which the gastric and intestinal fatty acids composition were analyzed. Subsequently, the fish underwent salinity acclimation. On days 1, 4, 7, and 14 after the freshwater was replaced by seawater and at the end of the 8-week period, gastric and intestinal digestive enzyme activities were determined. The results showed that the gastric and intestinal DHA and EPA contents of the fish were positively correlated to their dietary DHA and EPA levels. Low dietary DHA and EPA levels inhibited the protease activity of rainbow trout. Fish in the DE-0.54 group increased the lipase activity to enhance the utilization of lipids maybe due to the inadequate essential fatty acids for fish in this group. Hence, rainbow trout in the DE-0.54 group failed to maintain suitable activities of digestive enzymes after salinity acclimation. Therefore, a diet with minimum 0.95% DHA and EPA levels is necessary for rainbow trout during salinity acclimation.

Journal Digest: High-Dose Omega-3; Dabigatran; Youth With OCD; Diazepam’s Activity; Lavender

Journal Digest: High-Dose Omega-3; Dabigatran; Youth With OCD; Diazepam’s Activity; Lavender

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.

High-dose eicosapentaenoic acid (EPA) improves attention and vigilance in children and adolescents with attention deficit hyperactivity disorder (ADHD) and low endogenous EPA levels

No studies have examined the relationship between endogenous polyunsaturated fatty acids (PUFAs) levels and treatment response to PUFAs. We conducted a 12-week, double-blind, placebo-controlled trial comparing the effects of high-dose eicosapentaenoic acid (EPA, 1.2 g) and placebo on cognitive function (continuous performance test) in n = 92 youth (age 6–18-years-old) with Attention Deficit Hyperactivity Disorder (ADHD). Blood erythrocytes PUFAs were measured before and after treatment, to examine the effects of baseline endogenous EPA levels on treatment response and the effects of EPA treatment on PUFAs levels. Secondary measures included other ADHD symptoms, emotional symptoms, and levels of plasma high-sensitivity c-reactive protein (hs-CRP) and brain-derived neurotrophic factor (BDNF). Overall, EPA group improved more than placebo group on focused attention (variability, Effect size (ES) = 0.38, p = 0.041); moreover, within youth with the lowest baseline endogenous EPA levels, EPA group improved more than placebo group in another measure of focused attention (hit reaction time, HRT, ES = 0.89, p = 0.015) and in vigilance (HRT interstimulus interval changes, HRTISIC, ES = 0.83, p = 0.036). Interestingly, EPA group improved less than placebo group in impulsivity (commission errors), both overall and in youth with the highest baseline EPA levels, who also showed less improvement in other ADHD and emotional symptoms. EPA increased blood erythrocytes EPA by 1.6-fold but not DHA levels, and did not affect hs-CRP and BDNF plasma levels. In conclusion, EPA treatment improves cognitive symptoms in ADHD youth, especially if they have a low baseline endogenous EPA level, while youth with high EPA levels may be negatively affected by this treatment.

Altered polyunsaturated fatty acid levels in relation to proinflammatory cytokines, fatty acid desaturase genotype, and diet in bipolar disorder

Inflammation and altered polyunsaturated fatty acid (PUFA) levels have been implicated in bipolar disorder (BD). A recent genome-wide association study identified a locus in the fatty acid desaturase (FADS) gene cluster conferring susceptibility to BD. In this study, we examined PUFA levels in patients with BD in relation to proinflammatory cytokines, FADS genotype, and dietary habits. We enrolled 83 patients with BD and 217 healthy controls who underwent plasma PUFA measurement. A subsample of 65 patients and 90 controls underwent plasma interleukin (IL)-6 and tumor necrosis factor alpha (TNFα) measurement, and three FADS single nucleotide polymorphisms (SNPs) were genotyped. Information on fish consumption was obtained by a self-reported diet history questionnaire. In comparing PUFA levels between patients and controls, significant differences were found for all 7 PUFAs tested. Specifically, n-3 eicosapentaenoic acid (EPA) level was decreased, and n-6 arachidonic acid level was increased in the patients (p < 0.0001 for both). Plasma IL-6 and TNFα levels were both significantly increased in the patients. Plasma EPA level was negatively correlated with IL-6 and TNFα levels. The FADS genotype, which was associated with increased n-6 PUFA levels, was also associated with marked elevation in TNFα levels. Less frequent fish intake was associated with low EPA and high IL-6 level. Taken together, our results provide strong evidence for altered plasma PUFA and proinflammatory cytokine levels in patients with BD. Furthermore, FADS genotype and fish consumption may contribute not only to altered PUFA levels but also to inflammation in BD.

Interaction between dietary fatty acids and genotype on immune response in Atlantic salmon (Salmo salar) after vaccination: A transcriptome study.

A pivotal matter to aquaculture is the sourcing of sustainable resources as ingredients to aquafeeds. Levels of plant delivered oils as source of fatty acids (FA) in aquafeeds have reached around 70% resulting in reduced levels of long-chain omega-3 polyunsaturated fatty acids (LC n-3 PUFA), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), in salmon fillet composition. EPA and DHA can modulate inflammation and immune response, so it is crucial to understand how fish immune response is affected by low LC n-3 PUFA diet and if this diet can have a detrimental effect on vaccine response. Atlantic salmon (Salmo salar) can produce EPA/DHA from α-linolenic acid (ALA) and this endogenous capacity can be explored to develop families with higher tolerance to low LC n-3 PUFA diets. Here we analyze innate and adaptive immune response in Atlantic salmon to a commercial vaccine after being fed low levels of EPA and DHA, and we also compare three strains of salmon selected by their endogenous capacity of synthesizing LC- n-3 PUFA. A total of 2,890 differentially expressed genes (DEGs) were identified (p-value adjusted < 0.1) when comparing vaccinated fish against control non-vaccinated. Gene ontology (GO) and KEGG analysis with 442 up/downregulated genes revealed that most DEGs were both related to immune response as well as part of important immune related pathways, as “Toll-like receptor” and “Cytokine-Cytokine interaction”. Adaptive response was also addressed by measuring antigen specific IgM, and titers were significantly higher than in the pre-immune fish at 62 days post-immunization. However, diet and strain had no/little effect on vaccine-specific IgM or innate immune responses. Atlantic salmon therefore display robustness in its response to vaccination even when feed low levels of LC n-3 PUFA.

Eicosanoid Metabolites Associated with Type-1 Interferon Production from Plasmacytoid Dendritic Cells Stimulated with Toll-like Receptors (P19-012-19)

ObjectivesCommon among several autoimmune diseases is a prominent interferon (IFN) signature caused by aberrant IFN-α production from plasmacytoid dendritic cells (pDC). This uncontrolled response occurs when pDCs are activated through endosomal toll-like receptors (TLR). Within the endosomal compartment, TLR 7/8 and 9 are stimulated through nuclear immune complexes. The objective of this work was to determine the eicosanoids associated with IFN-α production upon TLR stimulation of murine bone marrow derived dendritic cells. MethodsFemale C57BL/6Ncrl mouse bone marrow was cultured in FLT3-ligand (FMS-like tyrosine kinase 3) for 8 days to generate dendritic cell subsets. On day 8, TLR ligands were added. Supernatant was analyzed for eicosanoids by liquid chromatography- mass spectrometry and cell pellets were analyzed for phospholipid fatty acid content by gas chromatography- mass spectrometry and IFN-α by ELISA. ResultsMurine pDCs stimulated with TLR 7 ligand Poly U (GU-rich ssRNA40) and TLR 3 ligand Poly I: C (polyinosinic-polycytidylic acid) produced no observable IFN-α production. Upon stimulation with TLR 9 ligand ODN1585 CpG and TLR 8 ligand R848 (resiquimod), IFN-α was significantly increased with both TLR agonists as compared to unstimulated no target samples. Targeted lipidomics analysis of eicosanoids showed that in cultures stimulated with TLR8 ligand and TLR9 ligand, pro-inflammatory eicosanoid production of prostaglandin E2 and leukotriene B4 were increased. Phospholipid analysis revealed high levels of arachidonic acid and low eicosapentaenoic acid levels within the phospholipid membranes. ConclusionsUnderstanding the role of fatty acids associated with IFN-α production in pDCs may provide therapeutic and mechanistic targets for autoimmune diseases with an IFN signature. Funding SourcesFunding for this project was provided by university internal funds.

Low Levels of Branched Chain Amino Acids, Eicosapentaenoic Acid and Micronutrients Are Associated with Low Muscle Mass, Strength and Function in Community-Dwelling Older Adults.

Sarcopenia, the age-related decrease in muscle mass and function can result in adverse health outcomes and subsequent loss of independence. Inadequate nutrition is an important contributor to the aetiology of sarcopenia, and dietary strategies are studied to prevent or delay this geriatric syndrome. The present study investigated whether there is an association between biochemical nutrient status markers, muscle parameters and sarcopenia in community-dwelling older adults. Data from the cross-sectional Maastricht Sarcopenia study (MaSS) were used, in which skeletal muscle index (SMI), 4 meter gait speed, 5 times chair stand and handgrip strength were assessed among older adults (n=227). Sarcopenia was defined following the algorithm of the European Working Group on Sarcopenia in Older People. Fasted blood samples were analyses on amino acids levels, RBC phospholipid profile, 25-hydroxyvitamin D (25(OH)D), α-tocopherol, magnesium and homocysteine were determined in fasted blood levels. Generalized linear modelling and logistic regression were used for data analysis. Lower blood levels of essential amino acids (EAA), total branched-chain amino acids (BCAA) and leucine were associated with lower SMI (P<0.001), strength (P<0.001) and longer time to complete the chair stand (P<0.05), whereas no association was found for total amino acids (TAA). Lower levels of eicosapentaenoic acid (EPA), 25(OH)D and homocysteine were associated with lower muscle parameter values (P<0.05). No significant associations were found for SFA, MUFA, PUFA, n-3 and n-6 fatty acids, docosahexaenoic acid (DHA), α-tocopherol-cholesterol ratio and magnesium. Sarcopenia was more frequent among those with lower levels of leucine, BCAA, EAA, EPA, 25(OH)D and higher levels of homocysteine (P<0.05). Age and BMI were identified as relevant covariates. A robust association was only found for lower gait speed and lower 25(OH)D levels. Compromised muscle parameters are associated with low blood values of specific amino acids, fatty acids, vitamin D and high homocysteine.

Association of Decreased Docosahexaenoic Acid Level After Statin Therapy and Low Eicosapentaenoic Acid Level with In-Stent Restenosis in Patients with Acute Coronary Syndrome.

Aim: It is speculated that statin therapy modulates the synthesis of polyunsaturated fatty acids (PUFA), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). However, the data available on the effects of statin therapy on the serum levels of PUFA and the subsequent impact on in-stent restenosis (ISR) in patients with acute coronary syndrome (ACS) are limited.Methods: A total of 120 ACS patients who received emergent coronary stent implantation, follow-up coronary angiography to evaluate ISR, and new statin therapy were enrolled. We measured the serum levels of the PUFA and lipids at the onset of ACS and at the follow-up coronary angiography.Results: The follow-up coronary angiography revealed 38 ISR cases. New statin therapy significantly reduced the serum levels of DHA and low-density lipoprotein cholesterol (LDL-C), while it did not affect EPA level. Single regression analysis revealed that a decreased serum level of LDL-C was associated with decreased DHA level. The multiple logistic regression analysis revealed that the decreased DHA level after statin therapy and low serum level of EPA on admission were determinants of prevalence of ISR.Conclusion: Statin therapy decreased the serum level of DHA with a parallel reduction in LDL-C level in patients with ACS. Decreased DHA level after statin therapy and low EPA level on admission are risk factors for ISR, indicating that in patients with ACS, decreased serum levels of DHA may be a residual target for the prevention of ISR.

F25. NEURAPRO REVISITED: INCREASES IN LONG-CHAIN OMEGA-3 FATTY ACIDS IMPROVE FUNCTIONAL AND SYMPTOMATIC OUTCOMES IN ULTRAHIGH RISK PATIENTS

BackgroundThe NEURAPRO multicentre randomised controlled trial (RCT) of long-chain polyunsaturated omega-3 fatty acids (ω-3 PUFAs) (‘fish oil’) in combination with high-quality psychosocial intervention (cognitive behavioural case management [CBCM]) vs. placebo in combination with CBCM in young people at ultrahigh risk (UHR) of psychosis showed that the group allocated to fish oil had no clinical benefits over the placebo group. However, a limitation of the trial was that adherence with the study medication was relatively low. Furthermore, although RCTs are placed at the top of the evidence hierarchy, this methodology has limitations in fish oil RCTs, since the test agent is not only present in the intervention group, but ω-3 fats are present in the diet and in the tissues of all participants. A biomarker analysis of ω-3 changes during the trial can ultimately determine the efficacy of ω-3 supplementation in this trial.MethodsThe NEURAPRO study was conducted from March 2010 to September 2014, in 10 specialized early psychosis treatment services in Australia, Asia, and Europe. In this study of 304 young people at UHR for psychotic disorders, 153 (50.3%) were allocated to ω-3 PUFAs and 151 (49.7%) to placebo. In all, 139 (45.7%) were male; mean (SD) age was 19.1 (4.6) years. The primary outcome was transition to psychosis assessed with the Comprehensive Assessment of the At-Risk Mental State. Secondary outcomes were levels of psychopathology and functioning assessed by the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Negative Symptoms (SANS), the Montgomery Asberg Depression Rating Scale (MADRS), the Young Mania Rating Scale (YMRS), the Social and Occupational Functioning Assessment Scale (SOFAS), and the Global Functioning: Social and Role scales). Levels of ω-3 PUFAs in fish oil, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (amongst other fatty acids) were measured as percentage of total fatty acids in erythrocytes at baseline and at month 6 (end-of-intervention). We examined changes in cell membrane levels of EPA and DHA, as measures of ω-3 intake independent of source. Data were analysed as a single cohort. Cox proportional hazards models and linear regression analyses were used to examine relationships between the ω-3 index (EPA+DHA) with clinical outcomes at month 6 and 12.ResultsWhen analysed as a single cohort, no association was observed between the ω-3 index and transition to psychosis at any follow-up time point but increase of the ω-3 index was found significantly related with most of the functional and symptomatic measures at month 6 and 12, in linear regression models adjusting for relevant baseline factors (i.e., functioning, psychopathology, ω-3 index and smoking). The models revealed consistent results, with low functioning or high psychopathology at baseline, low levels of ω-3s at baseline and increase of the ω-3 index independently predicting clinical improvements at in this sample.DiscussionIn contrast to our RCT analysis, this study using biomarkers shows that increase in erythrocyte ω-3 PUFAs may improve clinical outcomes of UHR patients. The results also imply that people with low DHA and EPA levels may benefit more from supplementation with fish oil. The analysis also highlights shortcomings of the RCT design in situations when the tested intervention is available outside the study.

The Clinical Significance of Low Serum Arachidonic Acid in Sepsis Patients with Hypoalbuminemia.

Objectives Fatty acids (FAs) have various roles in pro-inflammatory and anti-inflammatory functions. Hypoalbuminemia is often observed in sepsis patients. An imbalance among these compounds formed from FAs caused by hypoalbuminemia may be related to increased mortality in sepsis patients. The purpose of this study was to investigate the correlations between serum albumin and FAs in sepsis and the outcome. Methods This study was an observational investigation. The clinical and laboratory data of sepsis patients were recorded and the Sequential Organ Failure Assessment (SOFA) score was calculated at admission. The serum arachidonic acid (AA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and dihomo-gamma-linolenic acid (DHLA) levels were also measured as FAs. The body mass index (BMI) was used to determine the general nutrition status. Results Two hundred sepsis patients were enrolled during the study period. No significant correlations were observed between the BMI and the SOFA score or the serum albumin level at admission. The FA levels of the non-survivors were significantly lower, but there were no significant differences in the EPA/AA levels of the survivors and non-survivors. A low serum albumin level was closely related to low AA (p<0.0001), EPA (p<0.0001), DHA (p=0.0003), and DHLA levels (p<0.0001). A multiple logistic-regression analysis revealed that a high SOFA score [adjusted odds ratio, 1.19; 95% confidence interval (CI), 1.02-1.39, p=0.026] and low AA (adjusted odds ratio, 0.98; 95% CI, 0.978-0.994, p=0.041) were associated with a poor outcome. Conclusion A lower AA level was an important determinant of the outcome of patients with sepsis. These findings are consistent with the findings of previous studies, which reported that hypoalbuminemia might alter the AA metabolism in sepsis patients.