Plasma Plasma Phospholipids Research Articles

Associations of plasma phospholipid cis-vaccenic acid with insulin resistance markers in non-diabetic men with hyperlipidemia

BackgroundThe role of fatty acids (FA) in the pathogenesis of insulin resistance and hyperlipidemia is a subject of intensive research. Several recent works have suggested cis-vaccenic acid (cVA) in plasma lipid compartments, especially in plasma phospholipids (PL) or erythrocyte membranes, could be associated with markers of insulin sensitivity and cardiovascular health. Nevertheless, not all the results of research work testify to these beneficial effects of cVA. Therefore, we decided to investigate the relations of proportion of cVA in plasma PL to markers of insulin resistance in hyperlipidemic men.SubjectsIn 231 men (median age 50) with newly diagnosed hyperlipidemia, we analyzed basic clinical parameters together with FA composition of plasma PL and stratified them according to the content of cVA into upper quartile (Q4) and lower quartile (Q1) groups. We examined also small control group of 50 healthy men.ResultsThe individuals in Q4 differed from Q1 by lower plasma insulin (p < 0.05), HOMA-IR values (p < 0.01), and apolipoprotein B concentrations (p < 0.001), but by the higher total level of nonesterified FA (p < 0.01). Both groups had similar age, anthropometrical, and other lipid parameters. In plasma PL, the Q4 group had lower content of the sum of n-6 polyunsaturated FA, due to decrease of γ-linolenic and dihomo-γ-linolenic acids, whereas the content of monounsaturated FA (mainly oleic and palmitoleic) was in Q4 higher.ConclusionsOur results support hypothesis that plasma PL cVA could be associated with insulin sensitivity in men with hyperlipidemia.

Associations between Fatty Acid Intakes and Plasma Phospholipid Fatty Acid Concentrations in the European Prospective Investigation into Cancer and Nutrition.

The aim of this study is to determine the correlations between dietary fatty acid (FA) intakes and plasma phospholipid (PL) FA levels in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The dietary intake of 60 individual FAs was estimated using centre-specific validated dietary questionnaires. Plasma PL FA concentrations of these FAs were measured in non-fasting venous plasma samples in nested case-control studies within the EPIC cohort (n = 4923, using only non-cases). Spearman rank correlations were calculated to determine associations between FA intakes and plasma PL FA levels. Correlations between FA intakes and circulating levels were low to moderately high (-0.233 and 0.554). Moderate positive correlations were found for total long-chain n-3 poly-unsaturated FA (PUFA) (r = 0.354) with the highest (r = 0.406) for n-3 PUFA docosahexaenoic acid (DHA). Moderate positive correlations were also found for the non-endogenously synthesized trans-FA (r = 0.461 for total trans-FA C16-18; r = 0.479 for industrial trans-FA (elaidic acid)). Our findings indicate that dietary FA intakes might influence the plasma PL FA status to a certain extent for several specific FAs. The stronger positive correlations for health-enhancing long-chain PUFAs and the health-deteriorating trans-FA that are not endogenously produced are valuable for future cancer prevention public health interventions.

Effects of Supplemented Mediterranean Diets on Plasma-Phospholipid Fatty Acid Profiles and Risk of Cardiovascular Disease after 1 Year of Intervention in the PREDIMED Trial.

Plasma fatty acids (FAs) have been associated with cardiovascular disease (CVD) risk. Diet and endogenous metabolism influence the FA profile of the plasma phospholipid (PL) fraction. In the PREDIMED trial, we examined 1-year changes in the FA profile of plasma PL according to a nutritional intervention with Mediterranean diets, either supplemented with extra-virgin olive oil (MedDiet + EVOO) or mixed nuts (MedDiet + nuts), in a high cardiovascular risk population. We also analyzed if 1-year changes in PL FAs were associated with subsequent cardiovascular risk. We included 779 participants in our case-cohort study: 185 incident cases and 594 participants in the subcohort (including 31 overlapping cases). The end point was the incidence of CVD. We measured the FAs of plasma PL at baseline and after 1 year of intervention. MedDiet + EVOO increased C17:0 and C20:3n9 in linear regression models [β coefficientperSD : 0.215 (95% CI, 0.032-0.399) and 0.271 (0.107-0.434), respectively] and decreased 16:1n7 and C22:4n6 [βperSD: -0.239 (95% CI, -0.416 to -0.061) and -0.287 (95% CI, -0.460 to -0.113), respectively] vs the control group. MedDiet + nuts increased C18:3n3 [βperSD: 0.382 (95% CI, 0.225 - 0.539)], C18:2n6 [βper SD: 0.250 (95% CI, 0.073 - 0.428)], C18:0 [βperSD: 0.268 (95% CI, 0.085-0.452)], and C22:0 [βper SD: 0.216 (95% CI, 0.031-0.402)]; and decreased the sum of six n6 FAs [βper SD: -0.147 (95% CI, -0.268 to -0.027)] vs the control group. The 1-year increase in C18:2n6 was inversely associated with the subsequent CVD risk (HRperSD: 0.64 (95% CI, 0.44-0.92)). MedDiet interventions changed n6 FAs and C16:1n7c; other changes were specific for each group: MedDiet + EVOO increased C17:0 and C20:3n9, and MedDiet + Nuts C18:3n3, C18:2n6, C18:0, and C22:0 FAs.

Plasma phospholipid fatty acid profile, estimated desaturase activities and prevalence of the metabolic syndrome in a general population cohort: A cross-sectional study

BACKGROUND: An altered plasma fatty acid (FA) profile and desaturase activities have been associated with several metabolic diseases, including the MetS, but studies in the general populations are lacking, and only few studies have investigated a broad spectrum of FA in plasma phospholipids (PL). OBJECTIVE: We investigated, cross-sectionally, the relationship of the FA profile and desaturase activities in plasma PL with the prevalence of MetS in a general population in The Netherlands. METHODS: Baseline characteristic data from 850 participants (male: 50.2%) aged 38-68 years recruited in the Lifelines cohort study were obtained. The FA profile was determined in fasting plasma PL, and desaturase activities were estimated from product/precursor ratios. The MetS was defined according to International Diabetes Federation. Logistic regressions were used to examine the relation of the FA profile with the prevalence of MetS, and Bonferroni correction was applied to account for multiple testing. RESULTS: 151 participants (17.7%) had the MetS. After adjustment for several confounders and Bonferroni correction, higher tertiles of C18 : 0 (the early precursor of de novo lipogenesis pathway), C18 : 3n6 and C20 : 3n6 (both consistent with a high Δ6 desaturase (D6D) activity), and D6D activity itself were associated with a higher prevalence of MetS, while higher tertiles of C18 : 1n7, C24 : 0, and C24 : 1n9 (very long chain FA) as well as stearoyl-CoA desaturase (SCD)-18 were inversely associated with the MetS. CONCLUSIONS: This study shows that a wide-ranging plasma PL FA profile and estimated desaturase activities were different between adults with and without the MetS in a general representative population and implicates the importance of monitoring individual FAs and desaturase activities as novel modifiable biomarkers for the MetS.

Milk fat globule membrane plus milk fat increase docosahexaenoic acid availability in infant formulas

PurposeMilk fat globule membrane (MFGM) has components with emulsifier properties that could affect the provision of substrates to the brain. We evaluated the effects of MFGM plus milk fat addition to infant formulas on docosahexaenoic acid (DHA) availability and gut development.MethodsIn Experiment 1, suckling piglets were divided into 3 groups: Group L1 (n = 8): fed with a vegetal fat formula with palm oil; L2 (n = 8): canola oil formula and L3 (n = 8): milk fat + canola oil + 1% Lacprodan (3% MFGM of total protein content). In Experiment 2, Group L4 (n = 7): fed with canola oil + 1% Lacprodan (3% MFGM) and Group L5 (n = 5): milk fat + canola oil + 2% Lacprodan (6% MFGM). All formulas contained 0.2% DHA and 0.2% arachidonic acid.ResultsIn Experiment 1, DHA was similar among the groups in both total fatty acids and plasma phospholipids (PL). However, 3% MFGM (L3) increased significantly the proportion of DHA and LC-PUFA n-3 in liver total fatty acids, jejunum, and also in jejunum PL respect to the other formulas. There were no changes in gut histology, cell proliferation, apoptosis, or brain DHA content. In Experiment 2, higher MFGM dose was used. Then, higher DHA was not only found in peripheral tissues of 6% MFGM (L5) piglets but also in plasma PL, while a similar trend was observed in cortex PL (p = 0.123).ConclusionIn conclusion, MFGM plus milk fat may increase DHA availability of infant formulas which could contribute to their beneficial health effects.

Circulating de novo lipogenesis fatty acids and all-cause mortality in a prospective Dutch population cohort

Circulating fatty acids (FA) from de novo lipogenesis (DNL) are associated with all-cause mortality in individuals with elevated CVD risk. However, compared to FA early in the DNL synthetic pathway, cis-vaccenic acid, one of the FA distal in the DNL synthetic pathway, has rarely been studied in a general population cohort. We hypothesized that circulating cis-vaccenic acid is more strongly related to all-cause mortality than other circulating DNL-related FA. The primary and secondary objectives of this study were to investigate the prospective associations of plasma levels of cis-vaccenic acid and other DNL-related FA with all-cause mortality in a general population, respectively. We included 850 participants (mean ± SD age 53±15 years) from the Dutch Lifelines cohort study. Circulating levels of palmitic (C16:0), palmitoleic (C16:1n7), cis-vaccenic (cis-C18:1n7), stearic (C18:0), oleic acid (C18:1n9) in plasma phospholipids (PL) and triglycerides (TG) were measured by gas chromatography. The associations of circulating cis-C18:1n7 and other DNL-related FA with all-cause mortality were assessed using Cox regression analyses. During a median follow-up of 9.3 (IQR: 5.4-10.8) years, 34 (4.0%) participants had died. In plasma PL, a 1-SD increase in cis-C18:1n7 was associated with an increased risk of all-cause mortality in univariate and multivariate models (p<0.02 for all), with a HR [95% CI] of 1.60 [1.13-2.25] after adjustment for age and sex. Circulating plasma PL cis-C18:1n7 was associated with a higher risk for all-cause mortality. More studies are needed in different cohorts to verify and validate our results.

The assessment of plasma fatty acid profiles in newly diagnosed treatment-naive paediatric Crohn's disease.

Fatty acid (FA) profiles as potentially relevant components of Crohn's disease (CD) have been insufficiently analysed. We sought to explore the plasma profiles of n-3 and n-6 polyunsa-turated fatty acids (PUFAs) in newly diagnosed untreated active CD. We included 26 consecutive CD pediatric patients (<19 years) and 14 healthy controls (HCs). Disease characteristics, including inflammatory markers, dietary histories, and the Pediatric Crohn's Disease Activity Index (PCDAI), were obtained. The profiles of plasma FAs in plasma lipid classes were analysed by gas chromatography with FID detection of methyl esters. The erythrocyte sedimentation rate, C-reactive protein level and fecal calprotectin level (all p<0.001) were significantly higher in CD patients than in HCs. Most changes were observed in plasma phospholipids (PLs), such as a higher content of n-3 and changes in n-6 long-chain PUFAs in the CD group. The CD group had a lower ratio of n-6/n-3 PUFAs in PLs (p<0.001) and triacylglycerols (TAGs) (p<0.01). Correlations of the FA content in plasma PLs with disease activity scores of CD were also observed, which were positive for the sum of monounsaturated fatty acids (MUFAs) as well as oleic acid (18:1n-9) (both p<0.05). The metabolism of PUFAs is significantly altered even in treatment-naive newly diagnosed active pediatric CD, and the content of major FAs in PLs correlates with disease activity and inflammatory markers, thus probably contributing to the still unclear early disease pathogenesis.

Effects of plasma fatty acids and desaturase activity on metabolic syndrome in a general population

Abstract Background Altered plasma fatty acid (FA) profile and desaturase activities have been associated with several metabolic disease, including MetS. However, their relations have rarely been studied among general population, and no study have included the FA profile in plasma phospholipids (PL) and triglycerides (TG) separately. We investigated the relationship of the FA profile and desaturase activities in plasma PL and TG with MetS, and investigated if there were new characteristics of altered FA profile that could be related to MetS status in a general population. Methods Baseline characteristic data from 850 participants (Male: 50.2%) aged 38-68 years who were recruited in the Lifelines Cohort study in the Netherlands were obtained. Individual FA profile was determined in fasting plasma PL and TG, and desaturase activities were estimated from product/precursor ratios. MetS was defined according to International Diabetes Federation in 2006. Logistic regression and odds ratios (OR) were used to examine these relations with the prevalence of MetS, and possible moderation effect of gender in these relation was also investigated. Results There was 102 people (12%) who had MetS. After adjustment for several confounders, higher tertiles of PL C18:3 n-6, C18:0, C20:3 n-6, Δ6 desaturase (D6D), and TG C14:0, C16:0, C20:0 were associated with an increasing prevalence of MetS, while higher tertiles of PL C18:1 n-7, C24:1 n-9, C20:0, C24:0, Δ5 desaturase (D5D), stearoyl-CoA desaturase (SCD-18), and TG C24:0, C18:2 n-6, C20:4 n-6, C24:1 n-9, C20:5 n-3, C22:5 n-3, C22:6 n-3, D5D were inversely associated with MetS. Meanwhile, men seemed to be more vulnerable to MetS when having an altered or unfavorable FA profile in both plasma PL and TG. Conclusions It is important to increase w-3 and w-6 essential fatty acids intake and decrease saturated fatty acids intake, and monitoring the D5D, D6D, and SCD-18 desaturases as additional fatty acids biomarkers is of equal importance. Key messages This study have added the evidence that an altered fatty acids profile was associated with metabolic syndrome (MetS) in a general population. The altered fatty acids profile that was associated with metabolic syndrome differed in plasma PL and TG, which requires further study.

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).

Altered Indices of Fatty Acid Elongases ELOVL6, ELOVL5, and ELOVL2 Activities in Patients with Impaired Fasting Glycemia

Background: Dysregulation of fatty acids (FA) seems to participate in the pathogenesis of disorders such as metabolic syndrome (MetS), cardiovascular diseases, or some cancers. Activities of enzymes FA desaturases and elongases [elongation of very long-chain fatty acid (ELOVL)] significantly influence FA profile in different body compartments. Although the impact of activities of desaturases on cardiometabolic diseases was broadly studied, relatively little attention was devoted to the role of elongases. Methods: Case-control study was carried out in 36 patients (18 men/18 women) with impaired fasting glycemia (IFG) without MetS and 36 age and gender-matched healthy controls. FA profiles in plasma phospholipids (PL) were assessed using gas chromatograph-flame ionization detector and indices of desaturase and elongase activities were calculated. Results: In the IFG group, we observed decreased estimated activities of ELOVL2 and ELOVL5, whereas higher estimated activities of elongase ELOVL6 were noted. IFG group was also characterized by altered composition of plasma PL FA, above all by lower percentage of cis-vaccenic acid (cVA; 18:1n-7) and of total polyunsaturated FA n-6, especially linoleic acid, and by higher proportion of stearic acid and gamma-linolenic acid. Concurrently, elevated estimated activities of desaturases delta-9-desaturase (D9D), D6D were found. Conclusions: Lower estimated activities of ELOVL2 and ELOVL5 with lowered proportion of PL cVA could be associated with disturbances of glucose homeostasis development and their corresponding indices could serve as biomarkers of such risk.

Marine n-3 fatty acid consumption in a Norwegian renal transplant cohort: Comparison of a food frequency questionnaire with plasma phospholipid marine n-3 levels.

High levels of plasma marine n-3 fatty acids (n-3FAs) are associated with improved patient and graft survival in renal transplant recipients (RTRs). The aim of this study was to evaluate the utility of a new food frequency questionnaire (FFQ) to estimate marine n-3FA consumption in future epidemiological research. We developed an FFQ with a simple design of 10 questions to assess intake of marine sources of n-3FAs. RTRs included in the recent ORENTRA trial (n = 132) completed the study FFQ at the baseline visit eight weeks after engraftment and at the end of study visit one year post-transplant. We measured the reference biomarker plasma phospholipid (PL) marine n-3FA levels by gas chromatography at the same time points to evaluate association and degree of agreement between FFQ based marine n-3FA consumption estimates and the biomarker. The median plasma PL marine n-3FA level was 6.0 weight percentage (wt)% (interquartile range [IQR] 4.7 to 7.3) at baseline and 6.3 wt% (IQR 4.8 to 7.4) at end of study. Median FFQ based marine n-3FA consumption estimates were 22.8 g/month (IQR 13.0 to 34.0) at baseline and 20.3 g/month (IQR 14.5 to 32.3) at end of study. FFQ based marine n-3FA consumption estimates showed a moderate correlation with plasma PL marine n-3FA levels at baseline (Spearman's correlation coefficient rs = 0.43, p<0.001) and a stronger correlation at end of study (rs = 0.62, p<0.001). Bland Altman plots showed a reasonable degree of agreement between the two methods at both time points. Marine n-3FA consumption estimates based on the FFQ showed a moderate correlation with the reference biomarker plasma PL marine n-3FA levels. The FFQ might be useful in epidemiological studies where resources are limited.

Feeding a Bioactive Oil Enriched in Stearidonic Acid during Early Life Influences Immune System Maturation in Neonatal Sprague-Dawley Rats

Long-chain n-3 PUFAs (LCPUFAs) improve immune development and reduce atopic disease risk in infants. Stearidonic acid (SDA) can be a substrate for biosynthesis of n-3 LCPUFAs. We aimed to determine the effect of feeding an SDA-enriched diet during suckling and weaning on offspring immunity and ability to develop oral tolerance (OT). Pregnant Sprague-Dawley rats were randomly assigned to consume either SDA (3g SDA/100g fat) or a control (no SDA) diet, 5 d before parturition and through lactation (21 d). For the OT treatment, 10-d-old pups were fed ovalbumin (Ova; 200 μL of 8mg/mL) or placebo daily for 5 d. At 21 d, pups (both sexes) were weaned to their respective maternal diet until 6 wk of age or killed. Systemic immunization was induced using Ova (in 3-wk-old pups) or Ova+adjuvant (in 6-wk-old pups). The effect of suckling diet (in 3-wk-old pups) or weaning diet (in 6-wk-old pups) and OT treatment on immune function (main outcome) in spleen and blood was compared using 2-factor ANOVA. An SDA-enriched maternal diet, compared with the control diet, resulted in higher plasma phospholipid (PL) EPA (15 times higher), docosapentaenoic acid (DPA; 3 times higher), and DHA (1.3 times higher) content in 3-wk-old pups, accompanied by higher B-cell function [plasma ovalbumin-specific IgG1 (Ova-IgG1), 2 times higher] ( P<0.05). Compared with pups fed a control diet, the splenocytes from these pups had more (23%) helper T (Th) cells (CD3+CD4+) and activated (12%) Th cells (CD4+CD28+) (P<0.02) than controls. At 6 wk, the SDA group had 30% more CD4+CD25+splenocytes, and when stimulated ex vivo with LPS, produced less inflammatory IL-6 (50%) and TNF-α (30%) and more immunoregulatory IL-10 (45%) cytokines (P<0.05) than the control group. The Ova-exposed group had less (30%) plasma Ova-IgG1 than the placebo group. Splenocytes and plasma PLs from the 6-wk-old SDA group had more EPA (2x) and DPA (3.5x) (P<0.05), but not DHA, than the control group. Feeding SDA during lactation and weaning altered immune responses in directions believed to be beneficial.

Increasing the proportion of plasma MUFA, as a result of dietary intervention, is associated with a modest improvement in insulin sensitivity.

The effect of modifying dietary fatty acid (FA) composition on insulin sensitivity remains unclear. We aimed to investigate whether changes in plasma phospholipid (PL) FA composition, as a result of dietary intervention, correspond with changes in insulin sensitivity. The RISCK study was a 6-month randomised controlled dietary intervention study, which assessed the effect of modifying dietary fat and the glycaemic index (GI) of carbohydrates on insulin sensitivity. Total NEFA levels, fasting plasma PL FA profiles and an insulin sensitivity index (Si), derived from intravenous glucose tolerance minimal-model analysis, were available from 533 participants, all at elevated risk of type 2 diabetes. Bivariate correlations between changes in saturated PL FA (SFA), MUFA (as a percentage of total plasma NEFA) and changes in Si were assessed according to treatment group. Age, sex, ethnicity, percentage change in body mass and change in dietary GI were controlled for. Increasing total NEFA concentration was associated with worsening Si (r -0·152; P = 0·001). In the high-MUFA/low-GI diet group, change in PL-MUFA was positively and independently associated with change in Si (r 0·297; P = 0·002). Among MUFA, change in oleic acid (18 : 1) was most strongly correlated with change in Si (r 0·266; P = 0·005), as was change in minor FA 24 : 1 (r 0·244; P = 0·011) and 17 : 1 (r 0·196; P = 0·042). In the high-SFA/high-GI group, change in SFA concentration was not significantly associated with change in Si. In conclusion, increases in the proportion of plasma PL-MUFA following a high-MUFA dietary intervention were associated with improvements in insulin sensitivity.

Abstract P034: Circulating Odd-Chain Fatty Acids in Relation to Intake of Dairy and Fiber in Post-Myocardial Infarction Patients

Background: Odd-chain fatty acids (OCFA) pentadecanoic (15:0) and heptadecanoic acid (17:0) are considered to reflect dairy intakes in studies on cardiometabolic outcomes. A recent randomized controlled trial on dietary fiber showed that circulating proportions of these OCFA may also be related to fiber intake, which may result from fermentation by gut microbes. Objective: To examine the associations between circulating OCFA and dairy and fiber intake in patients with a history of myocardial infarction. Methods: We performed cross-sectional analyses in a subsample of 896 Dutch post-MI patients of the Alpha Omega Cohort. Proportions of OCFA (as % of total fatty acids) were measured in plasma phospholipids (PL) and cholesterol esters (CE). Dietary intakes (g/d) were assessed using a 203-item validated food frequency questionnaire. Spearman correlations ( r ) were computed between circulating OCFA in PL and CE and intakes of total dairy, types of dairy products, dietary fiber and total meat. Results: Patients were on average 69 years old, 78% was male and 89% used statins. Dairy intake was predominantly from milk and yogurt. PL 15:0 was positively correlated with total dairy intake ( r =0.16, p&lt;0.001; Table 1), especially yogurt. PL 15:0 was not correlated with dietary fiber ( r =0.01, p=0.75). For CE 15:0, correlations were similar. PL 17:0 was positively correlated with total dairy ( r =0.15, p&lt;0.001), but also with dietary fiber ( r =0.13, p&lt;0.001). For CE 17:0 similar correlations were observed, although somewhat weaker (dairy: r =0.10, p=0.003; fiber: r =0.09, p=0.009). OCFA were not significantly correlated with meat intake. Conclusions: Plasma PL 15:0 and CE 15:0 were related to dairy and not to fiber intake. PL 17:0 and CE 17:0 were equally related to dairy and fiber intake. Cardiometabolic health benefits attributed to biomarkers of dairy intake, especially 17:0, may be (partly) attributable to fiber intake. Further research is needed into endogenous OCFA synthesis as a result of fermentation of dietary fiber by gut microbes.

F24. OMEGA-6 PUFA METABOLISM DISTURBED IN PHOSPHO- AND SPHINGOLIPIDS IN NEUROLEPTIC-NAïVE FIRST-EPISODE SCHIZOPHRENIA PATIENTS – A FATTY ACID PROFILING STUDY IN FIVE LIPID FRACTIONS

BackgroundAlterations of polyunsaturated fatty acid (PUFA) levels are a well-replicated finding in schizophrenia research. There is however a controversy about the origin of this abnormality and its importance in the pathogenesis of schizophrenic illness. To investigate the influence of nutrition, in this study we investigate different aspects of fatty acid metabolization in a cohort of neuroleptic naïve first-episode schizophrenia patients (FEP) and a group of healthy controls (HC) matched for age and gender.MethodsIn 33 FEP (25.8 ± 4.8y, male 60.6% 20/33) and 32 HC (24.9 ± 4.6y, male 53.1% 17/32) fatty acid profile was investigated by gas chromatography in blood plasma lipids of the triacylglycerol (TAG) fraction (closely related to fat consumption within recent days, rich in SFA, MUFA (~50%), and LA (C18:2n6)), the cholesterol ester (CE) fraction (dependent on fat consumption within recent days, rich in LA (C18:2n6)(~51%), SFA and PUFA), and the plasma phospholipid (PL) fraction (reflecting fat consumption of the last weeks to month, rich in SFA (~50%), AA (~7%), and LA (C18:2n6). In erythrocyte membranes (sensitive to fat consumption within weeks to month), fatty acid profile was investigated in phospholipids of the phosphoethanolamin (PE) fraction (rich in PUFA (~45%), AA (C20:4n6) and SFA) and of the sphingomyelin (SM) fraction (rich in long chain SFA (>70%) and MUFA (including NA C24:1c15). Psychopathology was assessed using the PANSS, BPRS-E and SCL-90-R ratings. Statistical analysis included multi- and univariate ANOVA, non-parametric tests and correlation analysis.ResultsIn the plasma PL fraction and in the lipid fractions of erythrocyte membranes (PE, SM) that are less influenced by recent nutrition, patients showed generally reduced omega-6 PUFA levels, particularly in terms of AA in the SM fraction. While PUFA of the PL and PE fraction were positively correlated in HC, this was not the case in the FEP group.DiscussionOur results support the previous finding of a general omega-6 PUFA deficit in FEP. The decrease points towards an endogenous regulation deficit that is independent of recent nutrition, might affect the metabolism of grey and white matter structural components, and could cause alterations of AA downstream functions. While correlation analysis in HC strongly suggests that nutrition and supplementation have the potential to influence PUFA availability, inner transport and metabolization pathways seem to be disturbed in FEP.

Abstract P227: Circulating and Dietary Linoleic Acid and Prevalent Diabetes in Post-Myocardial Infarction Patients

Background: Circulating linoleic acid 18:2n-6 (LA) has been considered to reflect LA intake, but its utility as a dietary biomarker could be affected by metabolism. Objective: To study the associations of plasma and dietary LA with T2D prevalence in drug-treated patients with a history of myocardial infarction (MI). Methods: Cross-sectional analysis of baseline data in 4,072 Dutch post-MI patients of the Alpha Omega Cohort. Circulating LA (as % of total fatty acids) was assessed in plasma cholesterol esters (CE) in the total cohort and in plasma phospholipids (PL) in a random subset of 833 patients. LA intake was assessed by a 203-item validated food frequency questionnaire. Prevalence ratios of T2D and associations with metabolic parameters were estimated in plasma and dietary LA quintiles using multivariable generalized linear models adjusted for demographic, lifestyle and dietary factors. Results: Patients were on average 69 years old, 79% was male and 77% were overweight or obese. Most patients used statins (86%), antihypertensive drugs (90%) and antiplatelet drugs (84%). A total of 813 patients (20%) had T2D. Mean LA intake (±SD) was 5.7±2.2 energy%, and circulating LA was 49.9±5.0% in CE and 18.7±3.0% in PL. Spearman’s correlations of dietary LA with circulating LA in CE and PL were 0.16 and 0.10, respectively. Higher plasma LA, but not dietary LA, was significantly associated with a lower diabetes prevalence (Table 1). BMI (β= -0.07, p&lt;0.001), log non-fasting triglycerides (β= -0.01, p&lt;0.001), log non-fasting glucose (β= -0.01, p&lt;0.001), and log alcohol intake (β= -0.03, p&lt;0.001) were significantly associated with circulating LA in plasma CE. Similar associations were found for LA in plasma PL. Dietary LA was not significantly associated with T2D prevalence and metabolic parameters (all p&gt;0.05). Conclusions: Circulating LA may reflect both LA intake and metabolic state in drug-treated post-MI patients. This bears restrictions for its use as a biomarker of dietary LA intake in epidemiological studies.

Higher Lipophilic Index Indicates Higher Risk of Coronary Heart Disease in Postmenopausal Women

Fatty acids (FAs) are essential components of cell membranes and play an integral role in membrane fluidity. The lipophilic index [LI, defined as the sum of the products between FA levels and melting points (°C), divided by the total amount of FA: [Formula: see text]] is thought to reflect membrane and lipoprotein fluidity and may be associated with the risk of coronary heart disease (CHD). Therefore, we examined the associations of dietary and plasma phospholipid (PL) LI with CHD risk among postmenopausal women. We determined dietary LI for the cohort with completed baseline food frequency questionnaires and free of prevalent cardiovascular diseases in the Women's Health Initiative (WHI) observational study (N=85,563). We additionally determined plasma PL LI in a matched case-control study (N=2428) nested within the WHI observational cohort study. Cox proportional hazard regression and multivariable conditional logistic regression were used to calculate HRs/ORs for CHD risk between quartiles of LI after adjusting for potential sources of confounding and selection bias. Higher dietary LI in the cohort study and plasma PL LI in the case-control study were significantly associated with increased risk of CHD: HR=1.18 (95% CI 1.07-1.31, P for trend <0.01) and OR=1.76 (95% CI 1.33-2.33, P for trend <0.01) comparing extreme quartiles and adjusting for potential confounders. These associations still persisted after adjusting for the polyunsaturated to saturated fat ratio. Our study indicated that higher LI based on either dietary or plasma measurements, representing higher FA lipophilicity, was associated with elevated risk of CHD among postmenopausal women.

Conversion ratios of n-3 fatty acids between plasma and erythrocytes: a systematic review and meta-regression.

As biomarkers of dietary intake or disease risk factor, n-3 fatty acid (FA) can be measured in plasma phospholipids (PL), total lipids (TL) or erythrocytes. However, the numeric relationships between n-3 FA in these lipid pools are not clear. Our goal was to derive conversion ratios for plasma and erythrocyte n-3 FA. Potential studies were identified through systematic literature search in PubMed, Embase and the Cochrane Library of Systematic reviews (1950 to October 2014). In all, fifty-six studies reporting n-3 in healthy individuals were included, of which thirty-four articles reported plasma PL and erythrocytes, and twenty-two reported plasma TL and erythrocytes. Meta-regressions were performed to quantify the ratio between plasma and erythrocyte n-3 FA weight percentages, controlling for covariates including age, sex and study design. The conversion ratios from plasma PL to erythrocytes for EPA, DHA, DPA and total n-3 PUFA are 0·75, 1·16, 2·32 and 1·22; the corresponding conversion ratios from plasma TL to erythrocytes are 1·00, 2·10, 3·85 and 2·08, respectively. The conversion ratios were validated using reported values from the literature and measured data from fifty individuals. The relative error of the predicted results were within 10 % of the mean reported values except for EPA, and the individual measured data except for DPA, in plasma TL. The conversion ratios between plasma PL and erythrocytes were more stable compared with plasma TL. Such conversion ratios will be useful for nutritionists or public health professionals to assess FA profiles of different populations using data collected with different methodologies.

Abstract P012: Associations Between Plasma Phospholipid and Cholesterol Ester Fatty Acids and Reproducibility During 10-year Follow-up of Elderly Individuals: A Population Based Study

Background: Fatty acid (FA) composition in different blood compartments is used as biomarkers of dietary fat quality, but it is unclear how FA compositions differ between compartments and which biomarker is most appropriate for epidemiological studies. Furthermore, as most cohorts use single FA measurements to reflect long-term intake, reproducibility data of plasma FAs are clearly warranted. Objective: To investigate inter-correlations of FA compositions in plasma phospholipids (PP) and cholesterol esters (CE), and to evaluate 10-y reproducibility of FA composition in plasma CE. Methods: Baseline FA composition of PP and CE was assessed in a population-based cohort of 70-year-old Swedes (n=940), and in a subsample (n=539), FA was additionally measured in CE during follow-up at ages 75 and 80 y. FA in PP and CE was measured by gas chromatography. Spearman’s rank correlation coefficients were calculated between proportions of individual FA measured in plasma PP and CE collected at age 70 y. Plasma CE compositions at ages 70, 75, and 80 y were utilized to assess 10-year reproducibility by calculating intraclass correlation coefficients (ICC) in one-way random-effect models. Results: Strong correlations between PP and CC were observed for most FA, with the only exceptions palmitic acid and stearic acid (Table). Fair to good reproducibility was observed for most FA, and was greatest for palmitoleic acid (ICC [95% CI] = 0.72 [0.69-0.76]) and all n-6 polyunsaturated FA (ICC=0.64-0.68). Poor reproducibility was only observed for α-linoleic acid, pentadecanoic acid, and stearic acid, with ICC (95% CI) 0.19 (0.14-0.25), 0.22 (0.17-0.28), and 0.23 (0.18-0.29), respectively. Conclusions: Overall, FA levels measured in plasma PP and CE correlates strongly, suggesting that FA composition in these compartments generally can be used interchangeably as biomarkers in epidemiological studies. Overall good reproducibility of FA levels in CE indicates that single a measurement can reliably estimate average levels over a 10-y period.

Associations between a fatty acid desaturase gene polymorphism and blood arachidonic acid compositions in Japanese elderly

We investigated whether the single nucleotide polymorphism rs174547 (T/C) of the fatty acid desaturase-1 gene, FADS1, is associated with changes in erythrocyte membrane and plasma phospholipid (PL) long-chain polyunsaturated fatty acid (LCPUFA) composition in elderly Japanese participants (n=124; 65 years or older; self-feeding and oral intake). The rs174547 C-allele carriers had significantly lower arachidonic acid (ARA; n-6 PUFA) and higher linoleic acid (LA, n-6 PUFA precursor) levels in erythrocyte membrane and plasma PL (15% and 6% ARA reduction, respectively, per C-allele), suggesting a low LA to ARA conversion rate in erythrocyte membrane and plasma PL of C-allele carriers. α-linolenic acid (n-3 PUFA precursor) levels were higher in the plasma PL of C-allele carriers, whereas levels of the n-3 LCPUFAs eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) were unchanged in erythrocyte membrane and plasma PL. Thus, rs174547 genotypes were significantly associated with different ARA compositions of the blood of elderly Japanese.