Plasma Polyunsaturated Fatty Acids Research Articles

Development and Validation of an LC-MS/MS Method for the Determination of Plasma and Red Blood Cell Omega Fatty Acids: A Useful Diagnostic Tool

Development and Validation of an LC-MS/MS Method for the Determination of Plasma and Red Blood Cell Omega Fatty Acids: A Useful Diagnostic Tool

Higher ratio of plasma omega-6/omega-3 fatty acids is associated with greater risk of all-cause, cancer, and cardiovascular mortality: A population-based cohort study in UK Biobank.

Circulating omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) have been associated with various chronic diseases and mortality, but results are conflicting. Few studies examined the role of omega-6/omega-3 ratio in mortality. We investigated plasma omega-3 and omega-6 PUFAs and their ratio in relation to all-cause and cause-specific mortality in a large prospective cohort, the UK Biobank. Of 85,425 participants who had complete information on circulating PUFAs, 6461 died during follow-up, including 2794 from cancer and 1668 from cardiovascular disease (CVD). Associations were estimated by multivariable Cox proportional hazards regression with adjustment for relevant risk factors. Risk for all three mortality outcomes increased as the ratio of omega-6/omega-3 PUFAs increased (all Ptrend <0.05). Comparing the highest to the lowest quintiles, individuals had 26% (95% CI, 15-38%) higher total mortality, 14% (95% CI, 0-31%) higher cancer mortality, and 31% (95% CI, 10-55%) higher CVD mortality. Moreover, omega-3 and omega-6 PUFAs in plasma were all inversely associated with all-cause, cancer, and CVD mortality, with omega-3 showing stronger effects. Using a population-based cohort in UK Biobank, our study revealed a strong association between the ratio of circulating omega-6/omega-3 PUFAs and the risk of all-cause, cancer, and CVD mortality. Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institute of Health under the award number R35GM143060 (KY). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Higher ratio of plasma omega-6/omega-3 fatty acids is associated with greater risk of all-cause, cancer, and cardiovascular mortality: A population-based cohort study in UK Biobank

Background:Circulating omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) have been associated with various chronic diseases and mortality, but results are conflicting. Few studies examined the role of omega-6/omega-3 ratio in mortality.Methods:We investigated plasma omega-3 and omega-6 PUFAs and their ratio in relation to all-cause and cause-specific mortality in a large prospective cohort, the UK Biobank. Of 85,425 participants who had complete information on circulating PUFAs, 6461 died during follow-up, including 2794 from cancer and 1668 from cardiovascular disease (CVD). Associations were estimated by multivariable Cox proportional hazards regression with adjustment for relevant risk factors.Results:Risk for all three mortality outcomes increased as the ratio of omega-6/omega-3 PUFAs increased (all Ptrend &lt;0.05). Comparing the highest to the lowest quintiles, individuals had 26% (95% CI, 15–38%) higher total mortality, 14% (95% CI, 0–31%) higher cancer mortality, and 31% (95% CI, 10–55%) higher CVD mortality. Moreover, omega-3 and omega-6 PUFAs in plasma were all inversely associated with all-cause, cancer, and CVD mortality, with omega-3 showing stronger effects.Conclusions:Using a population-based cohort in UK Biobank, our study revealed a strong association between the ratio of circulating omega-6/omega-3 PUFAs and the risk of all-cause, cancer, and CVD mortality.Funding:Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institute of Health under the award number R35GM143060 (KY). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Women with Gestational Diabetes Mellitus do not have compromised polyunsaturated fatty acid status

Pregnant women who develop pre-eclampsia (PE) and/or intra-uterine growth restriction (IUGR) have reduced polyunsaturated fatty acid (PUFA) status compared to healthy pregnancy(1). It is unknown if pregnant women diagnosed with Gestational Diabetes Mellitus (GDM), and their offspring, also have compromised PUFA status. To determine if women with GDM, and their offspring, have altered PUFA status compared to healthy pregnancy. Pregnant women were recruited from Glasgow Scotland, and Brisbane, Australia from antenatal clinics for this cross sectional study. Third trimester maternal blood samples were collected after an overnight fast and cord blood samples were collected at delivery. Plasma fatty acids were analysed using gas chromatography from women with GDM (n = 37) and healthy pregnancies (n = 27) and their respective offspring (n = 31, from women with GDM, and n = 27 from healthy women). T-tests were used to determine significant differences between maternal with GDM and healthy pregnancy, as well as for their offspring and significance was set at p&lt;0.05. Previously, erythrocyte fatty acids were analysed from women with PE (n = 21), IUGR (n = 13) and healthy pregnancies (n = 86)(1). All results were expressed as mol percent of total fatty acids. There were no differences in maternal plasma arachidonic acid (4.51 ± 1.23 vs. 4.72 ± 0.64, p = 0.39) and plasma EPA &amp; DHA (2.33 ± 0.74 vs 2.69 ± 1.04, p = 0.14) in women with GDM and healthy pregnancies, respectively. There were no differences in fetal plasma arachidonic acid (11.58 ± 2.26 vs. 12.63 ± 1.69, p = 0.08) and plasma EPA &amp; DHA (4.44 ± 1.17 vs. 4.44 ± 1.00, p = 0.89) in offspring from women with GDM and healthy pregnancies, respectively. Women with PE and IUGR had approximately 25% lower erythrocyte EPA &amp; DHA and 35% lower erythrocyte arachidonic acid compared to healthy pregnant(1). Offspring from women with PE and IUGR had approximately 25% lower erythrocyte EPA &amp; DHA and 22% lower erythrocyte arachidonic acid compared to healthy pregnancy(1).Women with PE and IUGR had lower PUFA status likely due to reduced PUFA synthesis(1) and offspring from women with PE and IUGR had reduced PUFA status likely due to ectopic fat in placenta tissue(2). Women with GDM do not have compromised PUFA status suggesting there is no reduced synthesis and transport of PUFA. Offspring from women with GDM do not have reduced PUFA status suggesting there is no problem with PUFA transport across the placenta, unlike offspring from women with PE and/or IUGR. Women with GDM, and their offspring, do not have compromised plasma PUFA status compared to healthy pregnancy.

Longitudinal trajectories of plasma polyunsaturated fatty acids and associations with psychosis-spectrum outcomes in early adulthood

Evidence supports associations between polyunsaturated fatty acids such as docosahexaenoic acid (DHA) and psychosis. However, polyunsaturated fatty acid trajectories in the general population have not been characterized, and associations with psychosis spectrum outcomes in early adulthood are unknown. Plasma omega-6 to omega-3 ratio and DHA (expressed as percentage of total fatty acids) were measured by nuclear magnetic spectroscopy at 7, 15, 17, and 24 years of age in participants of ALSPAC (Avon Longitudinal Study of Parents and Children). Curvilinear growth mixture modeling evaluated body mass index-adjusted trajectories of both measures. Outcomes were assessed at 24 years. Psychotic experiences (PEs), at-risk mental state status, psychotic disorder, and number of PEs were assessed using the Psychosis-Like Symptoms interview (n= 3635; 2247 [61.8%] female). Negative symptoms score was measured using the Community Assessment of Psychic Experiences (n= 3484; 2161 [62.0%] female). Associations were adjusted for sex, ethnicity, parental social class, and cumulative smoking and alcohol use. Relative to stable average, the persistently high omega-6 to omega-3 ratio trajectory was associated with increased odds of PEs and psychotic disorder, but attenuated on adjustment for covariates (PEs adjusted odds ratio [aOR]= 1.63, 95% CI= 0.92-2.89; psychotic disorder aOR= 1.69, 95% CI= 0.71-4.07). This was also the case for persistently low DHA (PEs aOR= 1.42, 95% CI= 0.84-2.37; psychotic disorder aOR= 1.14, 95% CI= 0.49-2.67). Following adjustment, persistently high omega-6 to omega-3 ratio was associated with increased number of PEs (β= 0.41, 95% CI= 0.05-0.78) and negative symptoms score (β= 0.43, 95% CI= 0.14-0.72), as was persistently low DHA (number of PEs β= 0.45, 95% CI= 0.14-0.76; negative symptoms β= 0.35, 95% CI= 0.12-0.58). Optimization of polyunsaturated fatty acid status during development warrants further investigation in relation to psychotic symptoms in early adulthood.

New light on ω-3 polyunsaturated fatty acids and diabetes debate: a population pharmacokinetic-pharmacodynamic modelling and intake threshold study

Objectiveω-3 polyunsaturated fatty acids (PUFA) are a key modifiable factor in the intervention of type 2 diabetes, yet recommendations for dietary consumption of ω-3 PUFA in type 2 diabetes remain ambiguous and controversial. Here, we revisit the subject in the light of population pharmacokinetic-pharmacodynamic (PPK-PD) modeling and propose a threshold for intake.Research design and methodsPlasma levels of ω-3 PUFA and glycosylated hemoglobin (HbA1c) were measured as pharmacokinetic and pharmacodynamic indicator, respectively. The nonlinear mixed effect analysis was used to construct a PPK-PD model for ω-3 PUFA and to quantify the effects of FADS gene polymorphism, age, liver and kidney function, and other covariables.ResultsData from 161 patients with type 2 diabetes in the community were modeled in a two-compartment model with primary elimination, and HDL was a statistically significant covariate. The simulation results showed that HbA1c showed a dose-dependent decrease of ω-3 PUFA plasma level. A daily intake of ω-3 PUFA at 0.4 g was sufficient to achieve an HbA1c level of 7% in more than 95% of patients.ConclusionsPPK/PD modeling was proposed as a multilevel analytical framework to quantitatively investigate finer aspects of the complex relationship between ω-3 PUFA and type 2 diabetes on genetic and non-genetic influence factors. The results support a beneficial role for ω-3 PUFA in type 2 diabetes and suggested the intake threshold. This new approach may provide insights into the interaction of the two and an understanding of the context in which changes occur.

Plasma Levels of Polyunsaturated Fatty Acids and Adverse Kidney Outcomes

Many studies have reported polyunsaturated fatty acids (PUFA) as significant predictors of cardiovascular disease, but little is known about the relationship between PUFA levels and chronic kidney disease (CKD). This study explored this relationship among individuals with and without CKD. Prospective observational cohort study. 78,950 participants without CKD (cohort 1) and 7,233 participants with CKD (cohort 2) in the UK Biobank Study with PUFA levels measured between 2007 and 2010. Percentage of plasma PUFA, omega-3 fatty acid (FA), omega-6 FA, docosahexaenoic acid (DHA), and linoleic acid relative to total fatty acid. Incident CKD for cohort 1 and incident kidney failure requiring replacement therapy (KFRT) for cohort 2. Cox proportional hazards regression analyses, including a cause-specific competing risk model. In cohort 1, individuals with higher quartiles of plasma PUFA levels had healthier lifestyles and fewer comorbidities. During 841,007 person-years of follow-up (median 11.9 years), incident CKD occurred in 4.5% of participants (incidence rate, 39.1 per 10,000 person-years). For incident CKD in cohort 1, the adjusted cause-specific hazard ratios (HR) (95% CIs) for quartiles 2, 3, and 4 were 0.83 (0.75-0.92), 0.85 (0.76-0.96), 0.71 (0.62-0.82), respectively, compared with quartile 1. This inverse relationship was consistently observed for all PUFA types. In cohort 2, although, total PUFA levels were not associated with KFRT, higher PUFA subtype levels of DHA were associated with a lower risk of KFRT. Observational design and limited generalizability to individuals with higher disease severity; no data on eicosapentaenoic acid. Among individuals without CKD, higher plasma PUFA levels and all four PUFA components were associated with a lower risk of incident CKD. In individuals with CKD, only the omega-3 component of PUFA, DHA, was associated with a lower risk of KFRT.

High linoleic acid levels in red blood cells predict a poor response to neoadjuvant chemotherapy in human epidermal growth factor receptor type 2-positive breast cancer patients

ObjectivePolyunsaturated fatty acids are categorized as ω-3 or ⍵-6. Previous studies demonstrate that breast cancers display a high expression of fatty acid synthase and high fatty acid levels. Our study sought to determine if changes in plasma or red blood cell membrane fatty acid levels were associated with the response to preoperative (neoadjuvant) chemotherapy in non-metastatic breast cancer patients. MethodsOur prospective study assessed fatty acid levels in plasma and red blood cell membrane. Response to neoadjuvant chemotherapy was evaluated by the presence or absence of pathologic complete response and/or residual cancer burden. ResultsA total of 28 patients were included. First, patients who achieved pathologic complete response had significantly higher neutrophil-to-lymphocyte ratio versus no pathologic complete response (P = 0.003). Second, total red blood cell membrane polyunsaturated fatty acids were higher in the absence of pathologic complete response (P = 0.0028). Third, total red blood cell membrane ⍵-6 polyunsaturated fatty acids were also higher in no pathologic complete response (P < 0.01). Among ⍵-6 polyunsaturated fatty acids, red blood cell membrane linoleic acid was higher in the absence of pathologic complete response (P < 0.01). Notably, plasma polyunsaturated fatty acid, ⍵-6, and linoleic acid levels did not have significant differences. A multivariate analysis confirmed red blood cell membrane linoleic acid was associated with no pathologic complete response; this was further confirmed by receiver operating characteristic analysis (specificity = 92.3%, sensitivity = 76.9%, and area under the curve = 0.855). ConclusionsPending further validation, red blood cell membrane linoleic acid might serve as a predictor biomarker of poorer response to neoadjuvant chemotherapy in non-metastatic human epidermal growth factor receptor type 2–positive breast cancer. Measuring fatty acids in red blood cell membrane could offer a convenient, minimally invasive strategy to identifying patients more likely to respond or those with chemoresistance.

Association between plasma polyunsaturated fatty acids and depressive among US adults.

Depression is associated with greater functional impairment and high societal costs than many other mental disorders. Research on the association between plasma polyunsaturated fatty acids (PUFAs) levels and depression have yielded inconsistent results. To evaluate whether plasma n-3 and n-6 PUFAs levels are associated with depression in American adults. A cross-sectional study included 2053 adults (aged ≥20 y) in the National Health and Nutrition Examination Survey (NHANES), 2011-2012. The level of plasma n-3 and n-6 PUFAs were obtained for analysis. Self-reported Patient Health Questionnaire-9 (PHQ-9) was used to identify the depression status. Binary logistic regression analysis was performed to evaluate the association between quartiles of plasma n-3 and n-6 PUFAs and depression after adjustments for confounders. The study of 2053 respondents over 20 years of age with a weighted depression prevalence of 7.29% comprised 1,043 men (weighted proportion, 49.13%) and 1,010 women (weighted, 50.87%), with a weighted mean (SE) age of 47.58 (0.67) years. Significantly increased risks of depression over non-depression were observed in the third quartiles (OR = 1.65, 95% CI = 1.05-2.62) for arachidonic acid (AA; 20:4n-6); the third quartiles (OR = 2.20, 95% CI = 1.20-4.05) for docosatetraenoic acid (DTA; 22:4n-6); the third (OR = 2.33, 95% CI = 1.34-4.07), and highest quartiles (OR = 1.83, 95% CI = 1.03-3.26) for docosapentaenoic acid (DPAn-6; 22:5n-6); and the third (OR = 2.18, 95% CI = 1.18-4.03) and highest quartiles (OR = 2.47, 95% CI = 1.31-4.68) for docosapentaenoic acid (DPAn-3; 22:5n-3); the second (OR = 2.13, 95% CI = 1.24-3.66), third (OR = 2.40, 95% CI = 1.28-4.50), and highest quartiles (OR = 2.24, 95% CI = 1.08-4.69) for AA/docosahexaenoic acid (DHA; 22:6n-3) ratio compared with the lowest quartile after adjusting for confounding factors. Higher plasma levels of AA, DTA, DPAn-6, DPAn-3 PUFAs, and AA/DHA ratio may be potential risk factors for depression in US adults.

Higher Plasma Omega-3 Levels are Associated With Improved Exacerbation Risk and Respiratory-Specific Quality of Life in COPD.

Omega-3 polyunsaturated fatty acids (PUFAs) have been associated with systemic anti-inflammatory responses. Dietary intake of omega-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) has also been associated with lower chronic obstructive pulmonary disease (COPD) morbidity using self-report food frequency questionnaires. The objective of this study was to investigate the relationship between measured PUFA intake using plasma EPA+DHA levels and COPD morbidity. Former smokers with moderate-to-severe COPD living in low-income communities were enrolled in a 6-month prospective cohort study. Participants completed standardized questionnaires, spirometry, and plasma samples at 3-month intervals. Total plasma PUFAs were analyzed using gas chromatography/mass spectrometry for DHA and EPA concentrations. Linear or logistic mixed model regression was used to evaluate EPA+DHA's and COPD morbidity's association, accounting for demographics, lung function, pack years, comorbidities, and neighborhood poverty. A total of 133 plasma EPA+DHA samples from 57 participants were available. Participants exhibited average plasma EPA and DHA levels of 14.7±7.3µg/mL and 40.2±17.2µg/mL, respectively, across the 3 clinic visits. Each standard deviation increase in EPA+DHA levels was associated with 2.7 points lower St George's Respiratory Questionnaire score (95% confidence interval [CI] -5.2, -0.2) and lower odds of moderate exacerbation (odds ratio 0.4; 95% CI 0.2, 0.9), but lacked significant association with the COPD Assessment Test score (95% CI -2.4, 0.8), modified Medical Research Council dyspnea scale (95% CI -02, 0.2), or severe exacerbations (95% CI 0.3, 1.4). Plasma EPA+DHA levels are associated with better respiratory-specific quality of life and lower odds of moderate exacerbations in patients with moderate-to-severe COPD. Further research is warranted to investigate the efficacy of an omega-3 dietary intervention in the management of COPD morbidities.

Cholesterol is more readily oxidized than phospholipid linoleates in cell membranes to produce cholesterol hydroperoxides

Cholesterol is an essential component of cell membranes and serves as an important precursor of steroidal hormones and bile acids, but elevated levels of cholesterol and its oxidation products have been accepted as a risk factor for maintenance of health. The free and ester forms of cholesterol and fatty acids are the two major biological lipids. The aim of this hypothesis paper is to address the long-standing dogma that cholesterol is less susceptible to free radical peroxidation than polyunsaturated fatty acids (PUFAs). It has been observed that cholesterol is peroxidized much slower than PUFAs in plasma but that, contrary to expectations from chemical reactivity toward peroxyl radicals, cholesterol appears to be more readily autoxidized than linoleates in cell membranes. The levels of oxidation products of cholesterol and linoleates observed in humans support this notion. It is speculated that this discrepancy is ascribed to the fact that cholesterol and phospholipids bearing PUFAs are localized apart in raft and non-raft domains of cell membranes respectively and that the antioxidant vitamin E distributed predominantly in the non-raft domains cannot suppress the oxidation of cholesterol lying in raft domains which are relatively deficient in antioxidant.

Sex differences in the association between plasma polyunsaturated fatty acids levels and moderate-to-severe plaque psoriasis severity: a cross-sectional and longitudinal study

BackgroundPsoriasis is a chronic inflammatory skin disease with metabolic abnormalities serving as important contributors for pathogenesis and progression. Polyunsaturated fatty acids (PUFAs) have been found to be associated with human diseases, including psoriasis. However, differences and controversies exist regarding their content and roles.MethodsPlasma PUFAs concentrations were measured in 296 patients with moderate-to-severe plaque psoriasis from the Shanghai Psoriasis Effectiveness Evaluation CoHort. Disease severity was assessed using Clinician-Reported Outcomes (ClinROs), including Psoriasis Area and Severity Index (PASI), Body Surface Area (BSA) and Physician Global Assessment (PGA), as well as Patient-Reported Outcomes (PROs), including Patient Global Assessment (PtGA) and Dermatology Life Quality Index (DLQI). Multivariate generalized linear regression models (GLMs), subgroup and interaction analysis, and restricted cubic spline were used to estimate the cross-sectional associations between PUFAs concentrations and disease severity. Longitudinal assessments of PASI scores and PASI response were conducted at a 12-week follow-up. Associations between baseline plasma PUFAs levels and prospective PASI scores or PASI response were assessed using multivariate GLMs or logistic regression models.ResultsMales suffered severer psoriasis and presented lower plasma docosahexaenoic acid (DHA) and arachidonic acid (ARA) levels compared to females. Among males, plasma eicosadienoic acid (EDA) level was positively associated with PASI, BSA and PGA scores, while total Omega-3 PUFAs and/or eicosapentaenoic acid (EPA) levels exhibited non-linear associations with PASI and/or BSA scores. α-Linolenic acid (ALA) was negatively, whereas ARA was positively, associated with DLQI scores. In females, Omega-3 PUFAs, including EPA, DHA, and total Omega-3 PUFAs, showed inverse associations with PASI and BSA scores. Longitudinally, plasma total Omega-6 PUFAs were positively associated with the likelihood of achieving PASI 100 at 12 weeks in males. In females, concentrations of dohomo-γ-linolenic acid were prospectively associated with an increase in PASI scores, and DHA was associated with the likelihood of achieving PASI 75 and PASI 90 decline.ConclusionsSex differences cross-sectionally exist in disease severity and plasma PUFAs levels. The association between PUFAs and psoriasis severity also varies cross-sectionally and longitudinally between males and females. Sex differences should be considered when studying the function and clinical application of PUFAs in psoriasis.

Abstract 15927: Polyunsaturated Fatty Acid Levels and Their Relationship With Peak Exercise Measures in HFpEF

Background: Polyunsaturated fatty acids (PUFAs) regulate the inflammatory cascade and have been implicated in potential pathologic and therapeutic roles in heart failure with preserved LVEF (HFpEF). The purpose of this study was to explore the relationship between plasma levels of omega-3 (ω-3) fatty acids and invasive hemodynamic profiles characteristic of early HFpEF. Methods: In a single-center referral cohort undergoing evaluation for exertional dyspnea and suspected HFpEF, we assayed ω-3 concentrations in plasma by liquid chromatography. We derived an ω-3 score by summing Z-scores of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). Linear regression was used to relate plasma ω -3 levels to simultaneously collected physiologic data from cardiopulmonary exercise testing (CPET) with invasive catheterization. Results: 588 patients (52% female, age 62 ± 12 years, BMI 30 ± 6 kg/m 2 , peak oxygen uptake (VO 2 ) 15.5 ± 5.1 mL/min/kg [76 ± 20% predicted], NTproBNP 118 [33 - 405] pg/mL) were studied. Median ω -3 concentrations were 72 [46 - 107] pg/mL for EPA and 315 [225 - 457] pg/mL for DHA. Female sex and increased age were associated with higher levels of ω-3 fatty acids ( Table , p=0.03). After adjustment for age, sex, and BMI, a higher ω-3 score was associated with greater exercise capacity measured by peak VO 2 (p&lt;0.001) and peak workload (p&lt;0.001) along with an increase in peak exercise peripheral O 2 extraction (CavO 2 ; p &lt; 0.001). Notably, increased ω-3 score was associated with lower supine pulmonary capillary wedge pressure (PCWP; p=0.03), PCWP to cardiac output (CO) slope during exercise (p = 0.009), and NTproBNP (p &lt; 0.001). Conclusion: These data demonstrate that circulating ω-3 fatty acid levels are associated with exercise capacity and both central cardiac and peripheral function in HFpEF. Further studies are needed to unravel the relationship between modulation of plasma PUFAs and rest and exercise hemodynamic profiles of HFpEF.

Plasma polyunsaturated fatty acids and mental disorders in adolescence and early adulthood: 2 cross-sectional and longitudinal associations in a general population cohort

Abstract Polyunsaturated fatty acids (PUFAs) may be pertinent to the development of mental disorders, for example 28 via modulation of inflammation and synaptogenesis. We wished to examine cross-sectional and longitudinal 29 associations between PUFAs and mental disorders in a large cohort of young people. Participants in the 30 Avon Longitudinal Study of Parents and Children were interviewed and provided blood samples at two 31 sampling periods when approximately 17 and 24 years old. Plasma PUFA measures (total omega-6 [n-6], 32 total omega-3 [n-3], n-6:n-3 ratio and docosahexaenoic acid [DHA] percentage of total fatty acids) were 33 assessed using nuclear magnetic resonance spectroscopy. Cross-sectional and longitudinal associations 34 between standardised PUFA measures and three mental disorders (psychotic disorder, moderate/severe 35 depressive disorder and generalised anxiety disorder [GAD]) were measured by logistic regression, adjusting 36 for age, sex, body mass index and cigarette smoking. There was little evidence of cross-sectional 37 associations between PUFA measures and mental disorders at age 17. At age 24, the n-6:n-3 ratio was 38 positively associated with psychotic disorder, depressive disorder and GAD, while DHA was inversely 39 associated with psychotic disorder. In longitudinal analyses, there was evidence of an inverse association 40 between DHA at age 17 and incident psychotic disorder at age 24 (adjusted odds ratio 0.44, 95% confidence 41 interval 0.22 - 0.87) with little such evidence for depressive disorder or GAD. There was little evidence for 42 associations between change in PUFA measures from 17 to 24 years and incident mental disorders at 24 43 years. These findings provide support for associations between PUFAs and mental disorders in early 44 adulthood, and in particular, for DHA in adolescence in relation to prevention of psychosis.

Omega-3 Polyunsaturated Fatty Acid Levels in Maternal and Cord Plasma Are Associated with Maternal Socioeconomic Status.

Omega-3 (n-3) polyunsaturated fatty acids (PUFAs) play a crucial role in fetal growth and neurodevelopment, while omega-6 (n-6) PUFAs have been associated with adverse pregnancy outcomes. Previous studies have demonstrated that socioeconomic status (SES) influences dietary intake of n-3 and n-6 PUFAs, but few studies have evaluated the association between maternal and cord plasma biomarkers of PUFAs and socioeconomic markers. An IRB-approved study enrolled mother-infant pairs (n = 55) at the time of delivery. Maternal and cord plasma PUFA concentrations were analyzed using gas chromatography. Markers of SES were obtained from validated surveys and maternal medical records. Mann-Whitney U tests and linear regression models were utilized for statistical analysis. Maternal eicosapentaenoic acid (EPA) (p = 0.02), cord EPA (p = 0.04), and total cord n-3 PUFA concentrations (p = 0.04) were significantly higher in college-educated mothers vs. mothers with less than a college education after adjustment for relevant confounders. Insurance type and household income were not significantly associated with n-3 or n-6 PUFA plasma concentrations after adjustment. Our findings suggest that mothers with lower educational status may be at risk of lower plasma concentrations of n-3 PUFAs at delivery, which could confer increased susceptibility to adverse pregnancy and birth outcomes.

Direct Comparison of 18 Carbon n–3 and n–6 Fatty Acids at Equal Levels in an Oil Blend on Tissue Enrichment of Long-Chain Polyunsaturated Fatty Acid in Broiler Chickens

BackgroundOmega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFAs) are of interest because of their health effects. However, most experiments use natural oils and are confounded by PUFA concentrations and other fatty acids (FAs) that impact biosynthesis of the very long-chain derivatives (VLC). ObjectivesTo directly compare the effect of 18 C n-3 or n-6 FA fed at similar rates on their elongation and desaturation to VLC PUFA and their incorporation into tissues. MethodsOil blends that substituted ∼23% points of stearidonic acid (SDA) with alpha-linolenic acid (ALA), gamma-linolenic acid (GLA), or linoleic acid (LA) while minimizing differences in other FA were prepared. COBB500 broilers were fed the oil blends at 1.25% of the diet from day 14–35 age. ResultsThere was greater enrichment of VLC PUFA in breast, thigh, liver, and plasma when diets were supplemented with high-SDA and high-GLA oil blends than high-ALA and high-LA oil blends. The efficiency of VLCn-3 PUFA synthesis from SDA and ALA was lower than the efficiency of VLCn-6 PUFA synthesis from GLA and LA, suggesting that the elongation and desaturation enzymes more efficiently utilized n-6 substrates. The efficiency of biotransformation of SDA to VLCn-3 PUFA was greater than that of high-ALA, and synthesis of VLCn-6 PUFA from GLA was higher than that of high-LA in breast, thigh, liver, and plasma. There were minimal effects on tissue-saturated and monounsaturated FA. ConclusionsThe high-SDA and high-GLA oil blends efficiently enriched tissues with their VLC-PUFA more than high-ALA and high-LA treatments.

Altered mucosal and plasma polyunsaturated fatty acids, oxylipins, and endocannabinoids profiles in Crohn’s disease

Selected mucosal and plasma polyunsaturated fatty acids (PUFAs) and related oxylipins and endocannabinoids were determined in 28 Crohn’s disease (CD) patients and 39 controls. Fasting blood and colonic biopsies were collected in all participants, during a disease flare for the patients. Thirty-two lipid mediators including PUFAs, oxylipins, and endocannabinoids were assessed by LC-MS/MS. The pattern of lipid mediators in CD patients is characterized by an increase in arachidonic acid-derived oxylipins and endocannabinoids and a decrease in n-3 PUFAs and related endocannabinoids. A model combining increased 6-epi-lipoxin A4 and 2-arachidonyl glycerol with decreased docoasapentaenoic acid in plasma fairly discriminates patients from controls and may represent a lipidomic signature for CD flare. The study findings suggest that lipid mediators are involved in CD pathophysiology and may serve as biomarkers for disease flare. Further research is required to confirm the role of these bioactive lipids and test their therapeutic potential in CD.

Phospholipid Fatty Acid Profiles of Plasma and Erythrocyte Membranes in Dogs Fed with Commercial Granulated Food

Abstract Intake of long-chain n-3 polyunsaturated fatty acids (PUFA) benefits human and animal health. Our study aimed to analyze the long-chain n-3 PUFA content of two types of food and their effect on plasma and erythrocyte phospholipids of Belgian Shepherd dogs. A total of 10 dogs were fed commercial granulated food (Food 1), and another 10 were provided commercial Premium granulated food of high quality (Food 2). All the analyses were performed using gas-liquid chromatography. Our results showed that Food 1 contained more n-3 PUFA than Food 2, which was reflected in higher n-3 PUFA in plasma and erythrocyte phospholipids. Because long-chain n-3 PUFA in phospholipids are precursors for antioxidative molecules, further studies should investigate the effects of the analyzed commercial granulated food rich in n-3 on oxidative stress parameters in dogs.

Altered profile of plasma phospholipids in woman with recurrent pregnancy loss and recurrent implantation failure treated with lipid emulsion therapy.

Recurrent Pregnancy Loss (RPL) and Recurrent Implantation Failure (RIF) are highly heterogeneous condition and many of the mechanisms involved still require elucidation. The aim was to analyze the lipidomic profile in plasma of women with RPL and RIF before and after receiving the Lipid Emulsion Therapy (LET) containing 10% fish oil (SMOFlipid® 20%). This study included twenty-six women with RPL or RIF from immunological or inflammatory causes, with elevated natural killer cell levels and divided into a Pregnancy Loss or a Live Birth group according to the outcome. The women received intravenous LET and sample collecting was done before the first, third and fifth dose of LET in the pregnant women. Ultra-performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-QTOF MS) and multivariate statistical methods were performed to evaluate the profile of phospholipids present in the women's plasma. An increase of phosphatidylcholines (PC) 40:8 and 36:5 levels with predominance of n6 polyunsaturated fatty acids (PUFA) was observed in plasma lipids of the Pregnancy Loss Group compared to Live Birth Group. We also observed an increase in the relative abundance of n3 PUFA-PC species (42:10 and 36:6) and LysoPC 15:0 with the long term use of LET. The greater availability of n3 PUFA in plasma of the pregnant women stemming from LET use can be considered advantageous regarding the alteration of the phospholipid profile and its postulated anti-inflammatory and immunomodulatory role.

Plasma Polyunsaturated Fatty Acid Levels in Patients with Chronic Kidney Disease on Dialysis

Plasma Polyunsaturated Fatty Acid Levels in Patients with Chronic Kidney Disease on Dialysis