Blood Cell Membrane Fatty Acid Research Articles

Clinical laboratory studies in Barth Syndrome

Barth Syndrome is a rare X-linked disorder characterized principally by dilated cardiomyopathy, skeletal myopathy and neutropenia and caused by defects in tafazzin, an enzyme responsible for modifying the acyl chain moieties of cardiolipin. While several comprehensive clinical studies of Barth Syndrome have been published detailing cardiac and hematologic features, descriptions of its biochemical characteristics are limited. To gain a better understanding of the clinical biochemistry of this rare disease, we measured hematologic and biochemical values in a cohort of Barth Syndrome patients. We characterized multiple biochemical parameters, including plasma amino acids, plasma 3-methylglutaconic acid, cholesterol, cholesterol synthetic intermediates, and red blood cell membrane fatty acid profiles in 28 individuals with Barth Syndrome from ages 10months to 30years. We describe a unique biochemical profile for these patients, including decreased plasma arginine levels. We further studied the plasma amino acid profiles, cholesterol, cholesterol synthetic intermediates, and plasma 3-methylglutaconic acid levels in 8 female carriers and showed that they do not share any of the distinct, Barth Syndrome-specific biochemical laboratory abnormalities. Our studies augment and expand the biochemical profiles of individuals with Barth Syndrome, describe a unique biochemical profile for these patients, and provide insight into the possible underlying biochemical pathology in this disorder.

PP47 - The association between red blood cell membrane fatty acids, oxidative stress and inflammatory response after coronary angioplasty

PP47 - The association between red blood cell membrane fatty acids, oxidative stress and inflammatory response after coronary angioplasty

Red Blood Cell Fatty Acid Analysis for Determining Compliance with Omega3 Supplements in Dry Eye Disease Trials

To evaluate pill counts and red blood cell (RBC) membrane fatty acid profiles as measures of compliance with oral omega3 polyunsaturated fatty acids (ω3 PUFAs) and to compare the two techniques. Sixteen dry eye disease subjects were given oral ω3 PUFA or placebo for 3 months. Compliance was measured by pill counts and blood tests at baseline and 3 months. The Wilcoxon signed-rank tests and rank-sum tests were used to compare changes from baseline and the difference between the two groups; Spearman correlation coefficients were used to assess the relationship of pill counts to changes in blood FAs. Pill counts for the ω3 (n=7) and placebo (n=9) groups showed a mean consumption of 4.39 and 4.76 pills per day, respectively. In the ω3 group, the median change from baseline was +1.46% for eicosapentaenoic acid (EPA) (P=0.03), +1.49% for docosahexaenoic acid (DHA) (P=0.08), and -1.91% for arachidonic acids (AA) (P=0.02). In the placebo group, median changes in all measured FAs were small and not statistically significant. The difference in change in FA levels between the two groups was significantly greater for EPA (P=0.01) and AA (P=0.04). The correlations between pill counts and changes in EPA (r=0.36, P=0.43) and DHA (r=0.17, P=0.70) were not strong. RBC FA analysis can be used to measure compliance in the active group and also monitor the placebo group for nonstudy ω3 intake. Low correlation of pill counts with blood levels suggests that pill counts alone may be inaccurate and should be replaced or supplemented with objective measures.

Improved Working Memory but No Effect on Striatal Vesicular Monoamine Transporter Type 2 after Omega-3 Polyunsaturated Fatty Acid Supplementation

Studies in rodents indicate that diets deficient in omega-3 polyunsaturated fatty acids (n–3 PUFA) lower dopamine neurotransmission as measured by striatal vesicular monoamine transporter type 2 (VMAT2) density and amphetamine-induced dopamine release. This suggests that dietary supplementation with fish oil might increase VMAT2 availability, enhance dopamine storage and release, and improve dopamine-dependent cognitive functions such as working memory. To investigate this mechanism in humans, positron emission tomography (PET) was used to measure VMAT2 availability pre- and post-supplementation of n–3 PUFA in healthy individuals. Healthy young adult subjects were scanned with PET using [11C]-(+)-α-dihydrotetrabenzine (DTBZ) before and after six months of n–3 PUFA supplementation (Lovaza, 2 g/day containing docosahexaenonic acid, DHA 750 mg/d and eicosapentaenoic acid, EPA 930 mg/d). In addition, subjects underwent a working memory task (n-back) and red blood cell membrane (RBC) fatty acid composition analysis pre- and post-supplementation. RBC analysis showed a significant increase in both DHA and EPA post-supplementation. In contrast, no significant change in [11C]DTBZ binding potential (BPND) in striatum and its subdivisions were observed after supplementation with n–3 PUFA. No correlation was evident between n–3 PUFA induced change in RBC DHA or EPA levels and change in [11C]DTBZ BPND in striatal subdivisions. However, pre-supplementation RBC DHA levels was predictive of baseline performance (i.e., adjusted hit rate, AHR on 3-back) on the n-back task (y = 0.19+0.07, r2 = 0.55, p = 0.009). In addition, subjects AHR performance improved on 3-back post-supplementation (pre 0.65±0.27, post 0.80±0.15, p = 0.04). The correlation between n-back performance, and DHA levels are consistent with reports in which higher DHA levels is related to improved cognitive performance. However, the lack of change in [11C]DBTZ BPND indicates that striatal VMAT2 regulation is not the mechanism of action by which n–3 PUFA improves cognitive performance.

Determinants of the omega-3 index in a Mediterranean population at increased risk for CHD

The omega-3 index, defined as the sum of EPA and DHA in erythrocyte membranes expressed as a percentage of total fatty acids, has been proposed as both a risk marker and risk factor for CHD death. A major determinant of the omega-3 index is EPA+DHA intake, but the impact of other dietary fatty acids has not been investigated. In a cross-sectional study on 198 subjects (102 men and 96 women, mean age 66 years) at high cardiovascular risk living in Spain, the country with low rates of cardiac death despite a high prevalence of cardiovascular risk factors, dietary data were acquired from FFQ and blood cell membrane fatty acid composition was measured by GC. The average consumption of EPA+DHA was 0·9g/d and the mean omega-3 index was 7·1%. In multivariate models, EPA+DHA intake was the main predictor of the omega-3 index but explained only 12% of its variability (P<0·001). No associations with other dietary fatty acids were observed. Although the single most influential determinant of the omega-3 index measured here was the intake of EPA+DHA, it explained little of the former's variability; hence, the effects of other factors (genetic, dietary and lifestyle) remain to be determined. Nevertheless, the high omega-3 index could at least partially explain the paradox of low rates of fatal CHD in Spain despite a high background prevalence of cardiovascular risk factors.

Fish oil-based emulsion for the treatment of parenteral nutrition associated liver disease in an adult patient

Summary Background & aims Reversal of parenteral nutrition associated liver disease with fish oil emulsion (FO) has been reported in infants. We report a similar case in an adult patient. Methods A 58 year-old female on home parenteral nutrition for a short bowel syndrome due to Crohn’s disease, showed a progressive worsening of liver steatosis, and a persistent increase of the plasma liver function tests (LFTs). LFTs, serum alpha-tochopherol, red blood cell membrane fatty acids and liver histology were evaluated before and after an 8 month treatment with FO. Results The patient’s LFT’s improved. There was an increase of the n-3 and a decrease of the n-6 series of fatty acids in erythrocyte membrane. There was an approximate 30% increase in vitamin E status. Before FO, liver histology showed a non-alcoholic steatohepatitis with grade 2 steatosis and inflammation and stage 3 fibrosis. After the treatment, steatosis and inflammation were grade 1, whereas fibrosis remained at stage 3. Conclusions Infusion of FO was associated with consistent changes of cell membrane fatty acid structure and with mild improvement of vitamin E status. A potential role of FO in decreasing liver steatosis and inflammation with no change of liver fibrosis might be suggested.

The effect of altering n‐6: n‐3 ratio using plant and marine sources of n‐3 fatty acids on biomarkers of bone turnover

While research indicates that the intake of n‐3 polyunsaturated fatty acid (n‐3 PUFA) may have bone health promoting effects, very few human intervention studies have been conducted to date. The aim of this study was to examine whether plant (flaxseed oil, walnuts) and marine sources (microalgae oil) of n‐3 PUFA in the context of low versus high n‐6: n‐3 ratio would influence markers of bone turnover. A randomized cross‐over feeding trial (8‐week periods) in 24 healthy adults was conducted. Subjects consumed eucaloric diets: Control (10:1 n‐6:n‐3 ratio), ALA diet (2:1 n‐6:n‐3 ratio; 8.4g/2400 kcal/d), EPA/DHA diet (0.20/0.72g EPA/DHA per 2400 kcal/d), and Combination diet (8.4g ALA plus 0.20/0.72g EPA/DHA). Under tightly controlled conditions, subjects were fed 3 of the 4 diets for 8 weeks each with a 4–6 week washout between diets. Serum markers of bone turnover [c‐telopeptide (CTX), procollagen Type I N‐terminal propeptide (P1NP) and osteocalcin (OC)] and red blood cell membrane (RBC) fatty acids were analyzed at the end of each diet period. There were no significant changes in serum CTX, P1NP and OC between the diets, but a there was a negative association between age and these bone markers. In conclusion, we did not observe changes in bone markers with either the plant or marine source of n‐3 PUFA in the context of a high (10:1) or low (2:1) n‐6: n‐3 ratio among healthy adults.

Endogenous red blood cell membrane fatty acids and sudden cardiac arrest

Little is known of the associations of endogenous fatty acids with sudden cardiac arrest (SCA). We investigated the associations of SCA with red blood cell membrane fatty acids that are end products of de novo fatty acid synthesis: myristic acid (14:0), palmitic acid (16:0), palmitoleic acid (16:1 n7), vaccenic acid (18:1 n7), stearic acid (18:0), oleic acid (18:1 n9), and a related fatty acid, cis-7 hexadecenoic acid (16:1 n9). We used data from a population-based case-control study where cases, aged 25 to 74 years, were out-of-hospital SCA patients attended by paramedics in Seattle, WA (n = 265). Controls, matched to cases by age, sex, and calendar year, were randomly identified from the community (n = 415). All participants were free of prior clinically diagnosed heart disease. We observed associations of higher red blood cell membrane levels of 16:0, 16:1n-7, 18:1n-7, and 16:1n-9 with higher risk of SCA. In analyses adjusted for traditional SCA risk factors and trans- and n-3 fatty acids, a 1-SD–higher level of 16:0 was associated with 38% higher risk of SCA (odds ratio, 1.38; 95% confidence interval, 1.12-1.70) and a 1-SD–higher level of 16:1n-9 with 88% higher risk (odds ratio, 1.88; 95% confidence interval, 1.27-2.78). Several fatty acids that are end products of fatty acid synthesis are associated with SCA risk. Further work is needed to investigate if conditions that favor de novo fatty acid synthesis, such as high-carbohydrate/low-fat diets, might also increase the risk of SCA.

Effect on red blood cell membrane fatty acids of diets enriched with different sources of n‐3 fatty acids in healthy adults

BackgroundConsumption of n‐3 fatty acids from algal‐oil supplements and plant sources produce health benefits, which may be dependent on the incorporation of eicosapentaenoic acid (EPA) and docosahexanoic acid (DHA) into cell membranes.Aim and MethodsTo determine if plant sources (flaxseed oil and walnuts) of á‐linolenic acid (ALA) produce similar change in red blood cell (RBC) membrane fatty acids as algal‐oil (EPA/DHA) supplements, we performed a randomized cross‐over study (3 8‐week study periods) in 24 healthy adults (15 women, 9 men; mean±SE age 42±2.7 years; BMI 25.4±0.9 kg/m2). Under controlled feeding conditions, subjects consumed eucaloric lacto‐ovo vegetarian diets [Control, ALA (6‐7g/2400 kcal/d), EPA/DHA (0.20/0.72g EPA/DHA per 2400 kcal/d), and Combination (ALA + EPA/DHA)]. Fasting EPA and DHA levels were measured at baseline and at week 8 for the 3 study periods. Mixed model analyses were performed.ResultsIncreased EPA levels were observed in the RBC membrane with consumption of the EPA/DHA (41%, p&lt;0.0001), ALA (54%, p=0.0064) and Combination (101%, p&lt;0.0001) diets. DHA levels increased with consumption of the EPA/DHA (49%, p&lt;0.0001) and Combination (36%, p=0.0025) diets.ConclusionN‐3 fatty acids from algal‐oil and plant sources produce similar increases in RBC membrane EPA levels; however DHA levels increased only in the algal‐oil containing diets.

Familial aggregation of red blood cell membrane fatty acid composition: the Kibbutzim Family Study

The fatty acid composition of membranes plays an important role in health and diseases. Whether genetic factors play a role in interindividual variability in membrane fatty acid levels has received limited attention. Using variance decomposition methods, we estimated the heritability of red blood cell (RBC) membrane fatty acids in an unselected population sample of 80 families (205 male and 212 female subjects) living in kibbutz settlements in Israel. Fatty acid levels were measured by gas chromatography. We estimated that polygenes explained 40% to 70% of the sex- and age-adjusted interindividual variability in all RBC fatty acids: saturated, monounsaturated, and polyunsaturated. The heritability estimates remained very similar after further adjustment for smoking, alcohol consumption, physical activity, lipoproteins, body mass index, waist to hip ratio, education, and religiosity. In bivariate genetic analyses, we observed positive genetic correlations for the fatty acid pairs 20:4n6-22:6n3 and 20:5n3-22:6n3, and negative genetic correlations for the pairs 16:0-20:4n6, 16:0-22:6n3, 18:1n9-20:3n6, 18:2n6-20:4n6, 18:2n6-24:0, and 20:3n6-20:4n6, suggesting that shared effects of the same sets of loci account for 12% to 30% of the additive genetic variance in these pairs of fatty acids. This study suggests a considerable polygenic component for all RBC membrane fatty acids and provides evidence that shared genetic effects account for the additive genetic variance in various fatty acid pairs. Future studies are needed to map the genes underlying the interindividual variation in these inherited phenotypes.

Effect of omega‐3 fatty acid suplementation on Omega‐3 Index and red blood cell (RBC) membrane fatty acid composition

Omega‐3 fatty acids (n‐3 FA) have been shown from epidemiological studies and clinical trials to lower incidence of cardiovascular disease (CVD) in patients with pre‐existing CVD as well as in healthy individuals. In randomized secondary prevention trials fish or fish oil have been shown to lower total and coronary heart disease (CHD) mortality at intakes of about 1 g/day. The Omega‐3 Index (EPA + DHA expressed as % of total FA) has been proposed as a physiologically relevant, modifiable, independent and graded risk factor for death from CHD. RBC membrane FA composition correlates well with biomarkers of n‐3 FA including serum EPA and DHA, whole blood EPA, DPA and DHA and FA composition of cardiac tissue. The present dietary intervention study investigates the effect of a fish‐oil based, n‐3 FA supplement on Omega‐3 Index and RBC membrane FA composition. Thirty healthy men and women consumed a supplement providing 1070 mg total n‐3 FA (460 mg DHA, 480 mg EPA, and 80 mg other n‐3 FA) daily for 4 wks. At the end of this period there was a significant 24% increase (p&lt;0.01) in the Omega‐3 Index (Fig.1). While there were no significant changes in % linoleic, gamma linoleic, and alpha linolenic acid; EPA, DPA and DHA significantly (p&lt;0.01) increased compared to baseline values (0.76% versus 1.4%, 2.30% versus 2.58% and 5.49% versus 6.60% respectively), and % arachidonic acid significantly decreased (19.58% versus 18.83%, p&lt;0.05). This study shows that RBC membrane FA composition and so Omega‐3 Index can change in a short time using a fish‐oil based supplement.

Assessment of erythrocyte phospholipid fatty acid composition as a biomarker for dietary MUFA, PUFA or saturated fatty acid intake in a controlled cross-over intervention trial

BackgroundDietary intervention trials rely on self-reported measures of intake for assessment of energy and macronutrient composition. Dietary fat intake is of particular interest due to strong associations with pathophysiology. In epidemiological trials phospholipid fatty acid composition may reflect composition of habitual diet, although strong correlations have been identified only for essential polyunsaturated fatty acids (PUFAs). Preliminary evidence shows that saturated fatty acids (SFA) C15:0 and C17:0 may be acceptable biomarkers. This study measured changes in erythrocyte membrane fatty acids during a period of strictly controlled fat feeding to investigate their use as a short-term marker of compliance, particularly for intake of SFAs.ResultsThis was a randomised cross-over trial in which diet was provided and strictly controlled. 20 healthy, male subjects were given a 40 energy % (en%) fat diet, high in saturated (high-SFA, 20 en%) or unsaturated (high-USFA, 24 en%) fatty acids for 2 periods of 3 weeks. Subjects were residential during intervention with all food and beverages provided. Dietary composition was verified by direct chemical analysis. Blood samples were collected on days 1,7,14, 21 and analysed for red blood cell (RBC) membrane fatty acid composition. Pearson correlation showed RBC fatty acid composition to mimic dietary composition by 3 weeks, but the relationships were weak. Of the SFAs only RBC C16:0 decreased in response to decreased dietary content on high-USFA treatment (ANOVA, diet, P < 0.05). Of the USFAs, higher levels of C18:1 MUFA, C20:4 and C22:6 long chain PUFA on high-USFA diet lead to higher C18:1, C20:4 and C22:6 within RBCs (ANOVA, time*diet, P < 0.05). Pearson's correlation was significant between dietary and RBC fatty acids during the 21d dietary manipulation for C18:1, and C20:5, C22:6 only (P < 0.05).ConclusionRBC membrane fatty acids cannot reliably be used as an independent measure of compliance for dietary SFA intake in short-term studies. The MUFA oleic acid and PUFAs EPA and DHA may be more useful as markers of compliance during short term intervention trials.

Effects of omega-3 fatty acid on platelet serotonin responsivity in patients with schizophrenia

Studies suggest that the omega-3 fatty acid supplementation may be beneficial in reducing symptom severity in schizophrenia. The mechanism(s) underlying the clinical effect is not known. Serotonin (5-HT) has been implicated in the pathophysiology of schizophrenia and in the mechanism of some antipsychotic agents. 5-HT receptors are known to be modified by omega-3 fatty acids. We examined whether supplementation with the omega-3 fatty acid eicosapentaenoic acid (EPA)-modified 5-HT amplified ADP-induced platelet aggregation in patients with schizophrenia. Two grams of ethyl-EPA was administered daily for 6 months supplementally to ongoing antipsychotic treatment in 12 patients with chronic schizophrenia, using an open-label design. Red blood cell membrane fatty acids and platelet functions (platelet aggregation and dense granule secretion) were monitored at baseline, 1-, 3- and 6-months. The EPA levels were elevated more than five-fold in RBC membranes of all patients after 3 months supplementation, indicating a high degree of compliance. Consistent with previous reports, there was inhibition of ADP-induced platelet aggregation by EPA supplementation. Moreover, EPA markedly enhanced the 5-HT responsivity as measured by the magnitude of 5-HT amplification on ADP-induced platelet aggregation. Previously, we have demonstrated a significant inverse correlation between 5-HT responsivity and psychosis severity in unmedicated patients with schizophrenia. Taken together, the present data support the notion that EPA may be mediating its therapeutic effects in schizophrenia via modulation of the 5-HT 2 receptor complex.

Reduced Red Blood Cell Membrane Essential Polyunsaturated Fatty Acids in First Episode Schizophrenia at Neuroleptic-Naive Baseline

There is emerging evidence in schizophrenia of membrane abnormalities, primarily reductions in the essential omega-3 and omega-6 series of polyunsaturated fatty acids (PUFA). Because previous studies have largely been in chronic patients, it is not known whether these membrane abnormalities also occur early in illness. In the present study, red blood cell membrane fatty acid levels were determined by capillary gas chromatography from 24 neuroleptic-naive patients with first episode schizophrenia or schizoaffective disorder and 31 age-matched normal controls. Relative to normal subjects, patients had significant reductions in total PUFA (-13%) but not in monounsaturated or saturated fatty acids. Specifically, significant reductions were found in arachidonic acid (-18%), docosapentaenoic acid (-36%), and docosahexaenoic acid (-26%) concentrations. These reductions were not related to age, gender, smoking status, or cotinine levels. These results confirm previous findings of membrane deficits in schizophrenia and show that significant PUFA reductions occur early in the illness, prior to initiation of treatment, raising the possibility that these deficits are trait related. The findings also suggest that membrane fatty acid losses are quite specific to the highly unsaturated fatty acids.

Correlations between peripheral polyunsaturated fatty acid content and in vivo membrane phospholipid metabolites

Background There is evidence for membrane abnormalities in schizophrenia. It is unclear whether the observed membrane deficits in peripheral cells parallel central membrane phospholipid metabolism. To address this question we examined the relations between red blood cell polyunsaturated fatty acids and brain phospholipid metabolites from different regions of interest in schizophrenia and healthy subjects. Methods Red blood cell membrane fatty acids were measured by capillary gas chromatography and in vivo brain phospholipid metabolite levels were measured using a multi-voxel 31P Magnetic Resonance Spectroscopy technique on 11 first-episode, neuroleptic-naïve schizophrenic subjects and 11 normal control subjects. Results Both the total polyunsaturated fatty acids and the individual 20:4(n-6) contents were significantly correlated with the freely-mobile phosphomonoester [PME(s-τ c)] levels ( r = .5643, p = .0062 and r = .6729, p = .0006, respectively). The 18:2(n-6) polyunsaturated fatty acids content correlated positively with freely-mobile phosphodiester [PDE(s-τ c)] levels ( r = .5573, p = .0071). The above correlations were present in the combined right and left prefrontal region of the brain, while other regions including the basal ganglia, occipital, inferior parietal, superior temporal and centrum semiovale yielded no significant correlations. Conclusions Our preliminary data support the association between the decreased red blood cell membrane phospholipid polyunsaturated fatty acids content and the decreased building blocks [PME(s-τ c)] and breakdown products [PDE(s-τ c)] of membrane phospholipids in the prefrontal region of first-episode, neuroleptic-naïve schizophrenic subjects.

Procyanidins from Vitis vinifera seeds: in vivo effects on oxidative stress.

The purpose of this study was to evaluate the effect of supplementation with procyanidins from Vitis vinifera on markers of oxidative stress. Ten healthy volunteers received a daily dose of 110 mg of procyanidins for 30 days. Fasting venous blood samples were taken before and at the end of the supplementation period and after 7 days of wash-out. The total antioxidant activity and the plasma concentrations of alpha-tocopherol were not modified. Conversely, the levels of alpha-tocopherol in red blood cell membranes increased significantly from 1.8 +/- 0.1 to 2.8 +/- 0.2 mg/g. Similarly, the lymphocyte oxidized DNA [8-oxo-7,8-dihydro-2'-deoxyguanosine/2'-deoxyguanosine ratio] was reduced from 7.23 +/- 2.47 to 2.34 +/- 0.51, and the red blood cell membrane fatty acid composition shifted to a higher level of polyunsaturated fatty acids. On the basis of these results, it may be suggested that dietary procyanidins exert their antioxidant protection in vivo by sparing liposoluble vitamin E and reducing DNA oxidative damage.

Red blood cell fatty acid profile of chronic renal failure patients receiving maintenance haemodialysis treatment

The fatty acid profile of chronic renal failure (CRF) patients on maintenance haemodialysis treatment (MHT) is abnormal and results point towards an essential fatty acid (EFA) deficiency. However, controversies still exist as to which of the essential fatty acids (EFAs) or EFA-products are decreased. In this study, the results of a comprehensive analysis of the fatty acids, performed on the red blood cells of 14 CRF patients on MHT, are presented. The red blood cell membrane fatty acids determined in this study include a range of saturated fatty acids (SFAs), mono-unsaturated fatty acids (MUFAs) and poly-unsaturated fatty acids (PUFAs). Results confirmed the suggested presence of an essential fatty acid deficiency in CRF patients on MHT. It showed the total content of the n-6 fatty acids (31.66±3.21 vs 34.67±2.05), as well as the total content of the PUFAs (37.22±4.08 vs 40.93±2.35), to be significantly decreased. The total MUFA content was, in contrast, significantly increased (16.87±0.91 vs 15.49±1.18). The EFA deficiency profile seen in this study points towards that of a chronic inflammatory condition. This is borne out by the fact that all three precursors of the eicosanoids—the mediators of various inflammatory and immune responses—were reduced in the presence of an increase in MUFAs as well as SFAs. The possibility of the fatty acid profile of CRF patients on MHT being that of a chronic inflammatory condition is supported by the fact that continuous complement-dependent and complement-independent immune activation, due to bio-incompatibility between blood cells and the dialysis membranes, is known to occur during the dialysis process.

Supplementation with a combination of ω-3 fatty acids and antioxidants (vitamins E and C) improves the outcome of schizophrenia

Reduced levels of membrane essential polyunsaturated fatty acids (EPUFAs), namely, arachidonic acid (AA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acids (DHAs), and their association with psychopathology have been consistently reported in both chronic-medicated schizophrenic patients as well as in never-medicated patients soon after the first episode of psychosis. Past supplementation studies with either ω-6 or ω-3 or both EPUFAs generally in chronic-medicated-older patients have reported varying degrees of therapeutic effects, and have suggested that supplementation with primarily ω-3 EPUFAs (EPA>DHA) may be preferable. We report the supplementation with a mixture of EPA/DHA (180:120 mg) and antioxidants (vitamin E/C, 400 IU:500 mg) orally morning and evening to schizophrenic patients ( N=33) for 4 months. The red blood cell (RBC) membrane fatty acid levels, plasma lipid peroxides and clinical measures were carried out by established procedures at pretreatment, posttreatment and after 4 months of postsupplementation period to determine the stability of treatment effects within patients. Levels of fatty acids and lipid peroxides were compared with their levels in normal controls (NC) ( N=45). Posttreatment levels of RBC EPUFAs were significantly higher than pretreatment levels as well as levels in normal controls without any significant increase in plasma peroxides. Concomitantly, there was significant reduction in psychopathology based on reduction in individual total scores for brief psychiatric rating scale (BPRS) and positive and negative syndrome scale (PANSS), general psychopathology-PANSS and increase in Henrich's Quality of Life (QOL) Scale. The EPUFA levels returned to pretreatment levels after 4 months of supplementation washout. However, the clinical improvement was significantly retained. Future studies need be done in placebo-controlled trials and also with a comparison group supplemented with fatty acids alone in a larger number of patients, both chronic as well as never medicated, and for a longer duration of treatment while the dietary intake is monitored. This may establish the EPUFA supplementation a very effective treatment to improve the outcome for an extended period of time.

Substrates for hypothalamic PGE2 synthesis are not decreased in cholestatic rats.

We have recently described impaired IL-1 beta-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis in cholestatic rats and have implicated defective IL-1 beta-mediated hypothalamic generation of PGE2 in this finding. Since patients with obstructive cholestasis have decreased levels of PGE2 precursor fatty acids in their red blood cell membranes (arachidonic acid) we speculated that a similar deficiency of membrane prostaglandin percursor fatty acids in the hypothalamus of cholestatic rats may contribute to the defective cytokine-mediated PGE2 generation we have previously described. Therefore, in this study we determined red blood cell and hypothalamic membrane fatty acid composition in rats with obstructive cholestasis due to bile duct resection and in non-cholestatic sham resected controls 5 days after operation. To do this red blood cell membrane and hypothalamic membrane fatty acids were extracted, methyl esterified and quantified by gas liquid chromatography. Similar to results found in patients with obstructive cholestasis, bile duct resected rats had significantly reduced levels of red blood cell membrane arachidonic acid compared to levels in sham resected controls (p < or = 0.02). However, bile duct resected and sham resected rats had similar levels of hypothalamic membrane arachidonic acid. Therefore, these results suggest that the impaired IL-1 beta-induced HPA axis activation in cholestatic rats cannot be explained by lower hypothalamic membrane levels of the PGE2 substrate arachidonic acid in these animals. Furthermore, our results suggest that the brain in cholestasis appears to be protected from membrane fatty acid composition alterations which are seen outside the blood-brain-barrier.

Dietary intake and cell membrane levels of long-chain n-3 polyunsaturated fatty acids and the risk of primary cardiac arrest.

To assess whether the dietary intake of long-chain n-3 polyunsaturated fatty acids from seafood, assessed both directly and indirectly through a biomarker, is associated with a reduced risk of primary cardiac arrest. Population-based case-control study. Seattle and suburban King County, Washington. A total of 334 case patients with primary cardiac arrest, aged 25 to 74 years, attended by paramedics during 1988 to 1994 and 493 population-based control cases and controls, matched for age and sex, randomly identified from the community. All cases and controls were free of prior clinical heart disease, major comorbidity, and use of fish oil supplements. MEASURES OF EXPOSURE: Spouses of case patients and control subjects were interviewed to quantify dietary n-3 polyunsaturated fatty acid intake from seafood during the prior month and other clinical characteristics. Blood specimens from 82 cases (collected in the field) and 108 controls were analyzed to determine red blood cell membrane fatty acid composition, a biomarker of dietary n-3 polyunsaturated fatty acid intake. Compared with no dietary intake of eicosapentaenoic acid (C20:5n-3) and docosahexaenoic acid (C22:6n-3), an intake of 5.5 g of n-3 fatty acids per month (the mean of the third quartile and the equivalent of one fatty fish meal per week) was associated with a 50% reduction in the risk of primary cardiac arrest (odds ratio [OR], 0.5; 95% confidence interval [CI], 0.4 to 0.8), after adjustment for potential confounding factors. Compared with a red blood cell membrane n-3 polyunsaturated fatty acid level of 3.3% of total fatty acids (the mean of the lowest quartile), a red blood cell n-3 polyunsaturated fatty acid level of 5.0% of total fatty acids (the mean of the third quartile) was associated with a 70% reduction in the risk of primary cardiac arrest (OR, 0.3; 95% CI, 0.2 to 0.6). Dietary intake of n-3 polyunsaturated fatty acids from seafood is associated with a reduced risk of primary cardiac arrest.