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Background: Intake of polyunsaturated fatty acids (PUFA) may affect mortality following breast cancer; however, epidemiological studies have relied on the self-reported assessment of PUFA intake. Herein, we examined the associations between red blood cell (RBC) PUFAs and mortality., Methods: This nested case-control study included 1,104 women from the Women's Healthy Eating and Living study, a multistate randomized controlled trial. Cases (n = 290) comprised women who died from 1995 to 2006. Matched controls (n = 814) comprised women who were alive at the end of follow-up. PUFAs were measured in baseline RBC samples and included four ω-3 and seven ω-6 PUFAs. We examined each PUFA individually and principal components factor analysis (PCFA)-derived scores in association with all-cause mortality (ACM) and breast cancer-specific mortality (BCM) using conditional logistic regression to estimate ORs and 95% confidence intervals (CIs)., Results: In fully adjusted models, ACM ORs were elevated among women with PUFAs above the median  (>median) versus at the median or below (≤median) for α-linolenic acid (ALA; OR = 1.63, 95% CI, 1.18-2.24) and linolenic acid (LA; OR = 1.56, 95% CI, 1.16-2.09). BCM ORs were elevated for ALA (OR = 1.83, 95% CI, 1.27-2.63), LA (OR = 1.70, 95% CI, 1.23-2.37), and γ-linolenic acid (GLA; OR = 1.50, 95% CI, 1.04-2.16). PCFA Factor 1 (arachidonic acid-adrenic acid-docosapentaenoic acid) scores above the median (vs. ≤median) were associated with lower odds of ACM (OR = 0.71, 95% CI, 0.52-0.97) and BCM (OR = 0.69, 95% CI, 0.49-0.97). PCFA Factor 4 (ALA/GLA) scores above the median (vs. ≤median) were associated with increased odds of BCM (OR = 1.47, 95% CI, 1.04-2.09)., Conclusions: RBC ALA, LA, and GLA may be prognostic indicators among breast cancer survivors., Impact: These results are important for understanding the associations between a biomarker of PUFA intake and mortality among BC survivors., (©2024 American Association for Cancer Research.)

Background : Mixed lipid emulsions (LE) containing fish oil present several advantages compared to the sole soybean oil LE, but little is known about the safety of essential fatty acids (EFA) profile in paediatric patients on long-term Parenteral Nutrition (PN). Aim of the study : to assess glycerophosfolipid polyunsaturated fatty acids (PUFA) levels on plasma and red blood cell (RBC) membrane of children on long term PN with composite LE containing fish oil (SMOF), and to compare it with a group receiving olive oil LE (Clinoleic ® ) and to the reference range for age, previously determined on a group of healthy children. Results : A total of 38 patients were enrolled, median age 5.56 (0.9-21.86) years, 15 receiving Clinoleic ® , 23 receiving SMOF. Patients on SMOF showed significantly higher levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), lower levels of arachidonic acid (ARA) and Mead acid (MEAD)/ARA ratio in plasma and RBC compared with patients on Clinoleic ® and with healthy children. Triene:tetraene (T:T) ratio of both groups of patients did not differ from that of healthy children-median plasma (MEAD/ARA: 0.01, interquartile rage (IQR) 0.01, p = 0.61 and 0.02, IQR 0.02, p = 0.6 in SMOF and Clinoleic ® patients, respectively), and was considerably lower than Holman index (>0.21). SMOF patients showed no statistically significant differences in growth parameters compared with Clinoleic ® patients. Patients of both groups showed stiffness class F0-F1 of liver stiffness measure (LSM) 5.6 (IQR 0.85) in SMOF patients and 5.3 (IQR 0.90) in Clinoleic ® patients, p = 0.58), indicating absence of liver fibrosis. Conclusions : Fatty acids, measured as concentrations (mg/L), revealed specific PUFA profile of PN patients and could be an accurate method to evaluate nutritional status and eventually to detect essential fatty acid deficiency (EFAD). SMOF patients showed significantly higher EPA, DHA and lower ARA concentrations compared to Clinoleic ® patients. Both LEs showed similar hepatic evolution and growth.

Objective: To examine the association of erythrocyte n-6 polyunsaturated fatty acid (PUFA) biomarkers with incident type 2 diabetes and explore the potential role of gut microbiota in the association., Research Design and Methods: We evaluated 2,731 participants without type 2 diabetes recruited between 2008 and 2013 in the Guangzhou Nutrition and Health Study (Guangzhou, China). Case subjects with type 2 diabetes were identified with clinical and biochemical information collected at follow-up visits. Using stool samples collected during the follow-up in the subset ( n = 1,591), 16S rRNA profiling was conducted. Using multivariable-adjusted Poisson or linear regression, we examined associations of erythrocyte n-6 PUFA biomarkers with incident type 2 diabetes and diversity and composition of gut microbiota., Results: Over 6.2 years of follow-up, 276 case subjects with type 2 diabetes were identified (risk 0.10). Higher levels of erythrocyte γ-linolenic acid (GLA), but not linoleic or arachidonic acid, were associated with higher type 2 diabetes incidence. Comparing the top to the bottom quartile groups of GLA levels, relative risk was 1.72 (95% CI 1.21, 2.44) adjusted for potential confounders. Baseline GLA was inversely associated with gut microbial richness and diversity (α-diversity, both P < 0.05) during follow-up and significantly associated with microbiota β-diversity ( P = 0.002). α-Diversity acted as a potential mediator in the association between GLA and type 2 diabetes ( P < 0.05). Seven genera ( Butyrivibrio , Blautia , Oscillospira , Odoribacter , S24-7 other , Rikenellaceae other , and Clostridiales other ) were enriched in quartile 1 of GLA and in participants without type 2 diabetes., Conclusions: Relative concentrations of erythrocyte GLA were positively associated with incident type 2 diabetes in a Chinese population and also with gut microbial profiles. These results highlight that gut microbiota may play an important role linking n-6 PUFA metabolism and type 2 diabetes etiology., (© 2020 by the American Diabetes Association.)

The purpose of this research was to explore various allometric scaling models for dietary nutrients to improve translational validity between preclinical experimental rodent models and humans, focusing on polyunsaturated fats. Currently, there is no authoritative document that provides standardized guidelines for which dietary designs can be based on to improve translational fidelity between species. This paper reviews the challenges of using a rodent model, the major allometric scaling models, the use of these mathematical models to extrapolate human equivalent doses, and then tests one of these models using data generated in mice, with comparisons of data generated in human clinical trials. Mice were fed diets containing micro- and macronutrient compositions that approximated the US diet based on energy distribution and were then supplemented with increasing levels of various n-3 and n-6 polyunsaturated fatty acids at human equivalent doses. Changes in plasma and erythrocyte fatty acid phospholipid compositions were determined and compared to corresponding data generated in humans. Our findings suggest that basing lipid composition on percent of energy may result in comparable outcomes between mice and humans and that extrapolation of non-energy producing nutrients between species might be done using differences in energy needs (based on food intake)., Competing Interests: Declarations of Competing Interest None, (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The interest in the amount of polyunsaturated fatty acids (PUFA) in the umbilical cord blood (UCB) is increasing, but the stability of erythrocyte PUFA in these samples during storage and washing of the erythrocytes has not been directly evaluated. The purpose of this study was to analyze the effect of the lapse of time on the fatty acid (FA) content from UCB sample collection and maintained at 4 °C (0-12 h) until erythrocyte separation and washing. Palmitic acid (16:0), stearic acid (18:0), 18:1n-7/n-9, linoleic acid (18:2n-6), arachidonic acid (20:4n-6), 22:4n-6, eicosapentaenoic acid (20:5n-3), docosapentaenoic acid (22:5n-3), and docosahexaenoic acid (22:6n-3) together accounted for 87% of the FA profile in the umbilical vein erythrocytes. No difference was observed in the concentration of any of the FA studied, nor in the sum of saturated fatty acids (SFA), PUFA, or LC-PUFA in umbilical erythrocytes obtained at delivery and stored up to 12 h before the separation of erythrocytes. However, if a washing step was included in the processing of the erythrocytes, a decrease in the concentration of 16:0, 18:0, 18:3n-3, 20:4n-6, 22:4n-6, total SFA, PUFA, LC-PUFA, and n-6 LC-PUFA was evidenced, compared to unwashed erythrocytes. The FA concentration in umbilical cord erythrocytes did not change between samples stored from 0 to 12 h until erythrocyte separation. Erythrocyte washing before storage decreased the concentration of significant individual and total SFA, PUFA, and LC-PUFA. These results should be considered when planning the collection of UCB samples for the study of fatty acid concentration due to the nonscheduled timing of deliveries., (© 2020 AOCS.)

An accurate and specific gas chromatography-mass spectrometry (GC-MS) method was optimized to quantify specific polyunsaturated fatty acids (PUFAs) in plasma and in erythrocyte membranes for clinical purposes. The developed and fully-validated method showed optimal linearity in addition to adequate results in terms of accuracy, intra-day and inter-day precision. By adopting the Matrix-Corrected Calibration approach on all the biological matrices tested, both the constant and the proportional errors of the developed analytical methodology were considered to assure that the method was not affected by matrix bias. Moreover, a pilot study involving patients in parental nutrition with two different compositions of the administered fat emulsion was performed. The comparison of results obtained in these patients with a group of healthy subjects (i.e. control population) showed significant differences in the collected values of PUFAs in both plasma and erythrocyte membranes, thus providing evidence that the described GC-MS method could be employed as a simple tool for fast and accurate PUFAs analysis aimed at optimizing parenteral nutrition protocols., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: People living with human immunodeficiency virus infection and acquired immune deficiency syndrome (HIV/AIDS) (PLWH) are at an increased risk of cardiovascular disease. Diet-related factors may contribute. The aim of this pilot study was to determine, in PLWH, the relationship between atherosclerosis assessed by carotid intima-media thickness (CIMT) and (A) plasma antioxidant micronutrients and oxidative stress or (B) red blood cell polyunsaturated fatty acids (RBC PUFA), particularly long chain omega-3 polyunsaturated fatty acids (n-3 PUFA)., Methods: (A) In a cross-sectional study, subjects had CIMT evaluated by high resolution carotid artery ultrasound. Plasma was collected for vitamin C, measured by spectrophotometry; and alpha- and gamma-tocopherol, retinol, and malondialdehyde-a marker of oxidative stress-using high pressure liquid chromatography and fluorescence spectrophotometry. (B) In a prospective cohort study, other subjects had RBC PUFA measured at baseline, using gas chromatography, and CIMT assessed at baseline and repeated after 2 years. Clinical data was also collected., Results: (A) 91 PLWH participated. Only alpha- and gamma-tocopherol levels were positively correlated with CIMT. In a multivariate analysis, age and systolic blood pressure were significantly associated with CIMT with gamma-tocopherol near significance ( p = 0.053). (B) 69 PLWH participated. At baseline, docosahexaenoic acid (n-3 PUFA) and the ratio of docosahexaenoic acid to arachidonic acid (n-6 PUFA) were significantly and negatively correlated with CIMT. However, a multivariate analysis failed to detect a significant relationship either at baseline or 2 years after., Conclusion: In addition to age and systolic blood pressure, atherosclerosis assessed by CIMT might be associated with higher serum gamma-tocopherol levels. There was a non-significant association between CIMT and RBC n-3 PUFA or the ratio of n-3 to n-6 PUFA.

Background: N-3 polyunsaturated fatty acids (n-3 PUFA) may have multiple beneficial effects on the outcome of pregnancy, maternal health and child development. The present study introduced the protocol of a birth cohort study to examine the beneficial effects of n-3 PUFA status in pregnant Japanese women as an adjunct study of the Japan Environment and Children's Study (JECS)., Methods: The JECS participants in the coastal areas of Miyagi Prefecture were further invited to participate in this adjunct study, and 1,878 pregnant women were enrolled prior to delivery. Their n-3 PUFA status was evaluated with fatty acid profiles in erythrocytes of maternal blood collected from 1,623 mothers at 24-30 weeks of gestation and cord blood from 1,505 deliveries., Results: The baseline results, including comprehensive data on the fatty acid status and determinants affecting the PUFA status, were analyzed. In stepwise multivariate analyses, the cord blood docosahexaenoic acid (DHA) level was found to be significantly influenced by the DHA level in maternal blood, the child's sex, and the gestational period. The maternal DHA level was influenced by fish intake, maternal age, and the prepregnancy body mass index. While cord blood eicosapentaenoic acid (EPA) was influenced by maternal EPA, fish intake, and season at birth, additional factors such as maternal education, household income, and smoking habits affected the maternal EPA content., Conclusion: Further studies are warranted to clarify the nutritional impacts of n-3 PUFA in pregnant Japanese women of the cohort study.

In vitro, mono- and polyunsaturated fatty acids (FAs) may decrease the binding affinity of vitamin D metabolites for vitamin D-binding protein, which in turn may influence their bioavailability. FAs incorporated as phospholipids in erythrocyte (ery-) cell membranes reflect dietary intake. The purpose of this study was to investigate ery-FA composition in relation to markers for vitamin D. In healthy females (age 22.6 ± 2.0 years) total 25(OH)D was measured by LC-MS/MS (n = 78), free 25(OH)D with ELISA (n = 64 of 78), and bioavailable 25(OH)D was calculated. Analysis of ery-FA composition was by gas chromatography (n = 56 of 78). A strong correlation between total 25(OH)D and free 25(OH)D was seen (r = .66, p < .001), and between total-25(OH)D and bioavailable 25(OH)D (r = .68, p < .001). No correlations between 25(OH)D fractions and specific fatty acids were found, and in particular, no associations with mono- and poly-unsaturated FA compositions. All 25(OH)D fractions were correlated with leptin (total 25(OH)D (r = -.33, p < .003); bioavailable 25(OH)D (r = -.47, p < .001); free 25(OH)D (r = -.44, p < .001). Associations were found between PTH and total 25(OH)D (r = -.35, p = .002) and weaker between bioavailable 25(OH)D (r = -.35, p = .040) and free 25(OH)D (r = -.28, p = .079). All fractions of 25(OH)D appear to correlate in a similar way to PTH, BMI and body fat (leptin). No association was found between ery-FA composition and free/bioavailable 25(OH)D. It is unlikely that FAs are a strong uncoupling factor of DBP-bound 25(OH)D.

Background: The prognostic value of circulating polyunsaturated fatty acid (PUFA) levels is unclear., Objectives: To determine the associations between red blood cell (RBC) PUFA levels and risk for death., Methods: This prospective cohort study included 6501 women aged 65 to 80 years who participated in the Women's Health Initiative Memory Study (enrolment began 1996). RBC PUFA levels were measured at baseline and expressed as a percent of total RBC PUFAs. PUFAs of primary interest were the n-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and their sum (the Omega-3 Index). PUFAs of secondary interest included the 2 major n-6 PUFAs, linoleic acid and arachidonic acid, and the PUFA factor score (a calculated variable including 6 PUFAs that accounts for their intercorrelations). The primary outcome was total mortality through August 2014., Results: After a median of 14.9 years of follow-up, 1851 women (28.5%) had died. RBC levels of EPA and DHA were higher in the survivors (P < .002 for each). In the fully adjusted models, the hazard ratios (99% confidence intervals) for mortality associated with a 1 standard deviation PUFA increase for total mortality were 0.92 (0.85, 0.98) for the Omega-3 Index, 0.89 (0.82, 0.96) for EPA, 0.93 (0.87, 1.0) for DHA, and 0.76 (0.64, 0.90) for the PUFA factor score. There were no significant associations of alpha-linolenic acid, arachidonic acid or linoleic acid with total mortality., Conclusions: Higher RBC levels of marine n-3 PUFAs were associated with reduced risk for all-cause mortality. These findings support the beneficial relationship between the Omega-3 Index and health outcomes., (Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Introduction: Polyunsaturated fatty acids (PUFA) are metabolized in a complex network of elongation, desaturation and beta oxidation., Material and Methods: The short (1 and 3 wk), and long term (6 and 12 wk) effect of 1076mg/d docosahexaenoic acid (DHA, free of eicosapentaenoic acid (EPA)) on (absolute) PUFA concentrations in plasma and red blood cells (RBC) of 12 healthy men (mean age 25.1±1.5 years) was investigated., Results: RBC DHA concentrations significantly (p<0.001) increased from 28±1.6µg/mL to 38±2.0µg/mL (wk 1), 52±3.3µg/mL (wk 3), 68±2.6µg/mL (wk 6), and 79±3.5µg/mL (wk 12). Arachidonic acid (AA) concentrations declined in response to DHA treatment, while the effect was more pronounced in plasma (wk 0: 183±9.9µg/mL, wk 12: 139±8.0µg/mL, -24%, p<0.001) compared to RBC (wk 0: 130±3.7µg/mL, wk 12: 108±4.0µg/mL, -16%, p=0.001). Furthermore, an increase of EPA concentrations in plasma (wk 0: 15±1.5µg/mL, wk 1:19±1.6µg/mL, wk 3: 27±2.3µg/mL, wk 6: 23±1.2µg/mL, wk 12: 25±1.7µg/mL, p<0.001) and RBC (wk 0: 4.7±0.33µg/mL, wk 1: 6.7±1.3µg/mL, wk 3: 8.0±0.66µg/mL, wk 6: 6.9±0.44µg/mL, wk 12: 6.7±0.45µg/mL, n.s.) was observed suggesting a retroconversion of DHA to EPA., Conclusion: Based on PUFA concentrations we showed that DHA supplementation results in increased EPA levels, whereas it is not known if this impacts the formation of EPA-derived lipid mediators. Furthermore, shifts in the entire PUFA pattern after supplementation of EPA or DHA should be taken into account when discussing differential physiological effects of EPA and DHA., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Numerous clinical trials examining the use of omega-3 long chain polyunsaturated fatty acids (n-3 LCPUFAs) on various health outcomes have been conducted, and fish oil remains one of the most widely used nutritional supplements. More recently, studies have begun to utilize the omega-3 index, defined as the sum of EPA+DHA in red blood cells (RBCs), as both a biomarker of n-3 LCPUFA exposure and a potential risk factor for coronary heart disease (CHD). Considerably less research evaluates whether RBC phospholipid fatty acids reflect the phospholipid fatty acid composition of other tissues across increasing intakes of n-3 LCPUFAs. We fed mice diets containing increasing amounts of EPA+DHA, equivalent to current recommendations by the American Heart Association on a percent of energy basis, and analyzed the phospholipid fatty acid composition of various tissues in relation to RBCs. We observed that RBCs, heart, muscle, spleen, lung, and adipose tissues all respond to dietary supplementation with EPA+DHA with increasing n-3 LCPUFA and decreasing n-6 LCPUFA levels. Furthermore, the n-3 LCPUFA profiles of all measured tissues had strong (r>0.7) and significant (p<0.001) correlations to RBCs. Interestingly, we also observed changes in saturated fatty acid (SFA) and monounsaturated fatty acid (MUFA) levels across various tissues in response to increased EPA+DHA intakes despite there being no change in dietary SFA and MUFA. Specifically, there were increases in RBC SFA and spleen MUFA and decreases in heart MUFA. These demonstrate that the RBC, including the omega-3 index, may serve as a marker for the relative levels of n-3 and n-6 LCPUFAs in phospholipids of certain tissues., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objective: Epidemiologic and clinical studies have suggested that hormone therapy (HT) and n-3 polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), exert antidepressant effects through regulation of the serotonergic pathway. The present study was conducted to evaluate the hypothesis that erythrocyte levels of n-3 PUFAs and depression were negatively associated in postmenopausal women, particularly those using HT., Methods: A total of 214 postmenopausal women were divided into groups defined by depression and HT status. Depression was defined as a Beck Depression Inventory score of at least 14, and the types and durations of HT were obtained from medical records., Results: Erythrocyte levels of EPA, docosapentaenoic acid (DPA), DHA, omega-3 index (sum of EPA + DHA), total n-3 PUFA, and arachidonic acid were significantly higher in women using HT than in those not using HT. There were significant negative correlations between depression and erythrocyte levels of alpha-linolenic acid (r = -0.310), DPA (r = -0.272), DHA (r = -0.209), and total n-3 PUFA (r = -0.234) in women using HT. Multivariate-adjusted logistic regression analysis also showed that depression was negatively associated with the erythrocyte levels of alpha-linolenic acid (P for trend = 0.018), DPA (P for trend = 0.014), and DHA (P for trend = 0.036), only in women using HT., Conclusions: Negative associations between erythrocyte levels of n-3 PUFAs and depression were found in Korean postmenopausal women using HT but not in those not using HT, suggesting a synergistic effect of HT and n-3 PUFAs on depression.

Background: Patients with phenylketonuria have been reported to be deficient in long-chain polyunsaturated fatty acids (LCPUFAs). It has been postulated that good compliance with the dietary regimen negatively influences LCPUFA status., Methods: In 36 patients with phenylketonuria and 18 age-matched healthy control subjects LCPUFA-levels in plasma phospholipids and cholesteryl esters, erythrocyte phosphatidylcholine and phosphatidylethanolamine were evaluated., Results: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) levels did not differ significantly between patients and control subjects in plasma and erythrocyte fractions. There was a significant negative correlation between SDS (standard deviation) scores of DHA-levels in erythrocyte parameters from the respective age-matched control group and patients' concurrent and long-term phenylalanine levels for erythrocyte phosphatidylethanolamine and erythrocyte phosphatidylcholine. Patients with lower (higher) phenylalanine levels had positive (negative) DHA-SDS., Conclusion: In contrast to previous reports we did not find lower LCPUFA-levels in patients with phenylketonuria compared to age-matched healthy control subjects. Good dietary control was associated with better LCPUFA status., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objectives: Dietary deficiency in polyunsaturated fatty acids (PUFAs), including the omega-3 fatty acids eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3), and excesses in omega-6 fatty acids, including linoleic acid (LA; 18:2n-6) and arachidonic acid (AA; 20:4n-6), may be associated with the pathophysiology of bipolar disorder. In an effort to provide clarification regarding the relationship between PUFA biostatus and bipolar disorder, this meta-analysis investigated studies comparing erythrocyte (red blood cell) membrane PUFA composition in patients with bipolar disorder and healthy controls., Methods: A meta-analysis was performed on case-control studies comparing erythrocyte PUFA (EPA, DHA, LA and AA) levels in patients with bipolar I disorder and healthy controls. Standardized effect sizes were calculated and combined using a random effects model., Results: Six eligible case-control studies comprising n = 118 bipolar I patients and n = 147 healthy controls were included in the analysis. Compared with healthy controls, patients with bipolar I disorder exhibited robust erythrocyte DHA deficits (p = 0.0008) and there was a trend for lower EPA (p = 0.086). There were no significant differences in LA (p = 0.42) or AA (p = 0.64)., Conclusions: Bipolar I disorder is associated with robust erythrocyte DHA deficits. These findings add to a growing body of evidence implicating omega-3 PUFA deficiency in the pathophysiology of bipolar disorder., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: Evidence of an association between n-3 polyunsaturated fatty acids (PUFAs) and metabolic syndrome (MS) is limited and inconsistent. We investigated the association between n-3 PUFAs in erythrocytes and the presence of MS in Chinese adults., Methods: The levels of α-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) in erythrocytes were measured using gas chromatography in 3072 participants (900 men and 2172 women) aged 30-75 years from Guangzhou, China. Cardiometabolic factors were determined, and MS was defined using the updated Adult Treatment Panel III criteria. Other covariates were collected via interviewer-administered questionnaires., Results: After adjusting for age and other confounders, higher levels of marine-derived n-3 PUFAs, including EPA, DPA, and DHA, were associated with a lower presence of metabolic syndrome in both men and women. The odds ratios (95 % confidence interval) for MS obtained by comparing extreme quartiles were 0.55 (0.35-0.88) (EPA), 0.54 (0.34-0.87) (DPA), 0.45 (0.27-0.73) (DHA), and 0.52 (0.32-0.84) (total n-3 PUFAs) in men (p trend <0.05 for all results); and 0.74 (0.56-0.99) (EPA), 0.73 (0.55-0.98) (DPA), 0.75 (0.56-1.02) (DHA), and 0.71 (0.53-0.96) (total n-3 PUFAs) in women, respectively. No significant association of ALA with MS was observed (p trend > 0.05)., Conclusion: Higher levels of total n-3 PUFAs, EPA, DPA, and DHA, but not of ALA, in erythrocyte membranes are associated with a lower presence of metabolic syndrome in Chinese adults.

Background/objectives: We examined the prevalence of elevated plasma high-sensitivity C-reactive protein (hs-CRP) concentrations and associations with red blood cell (RBC) long-chain n-3 polyunsaturated fatty acids (LCn-3PUFA) in the James Bay Cree population from the province of Quebec (Canada)., Subjects/methods: A total of 744 Cree adults (18-91 years) from seven communities of Eastern James Bay were included in these cross-sectional analyses. Associations between RBC LCn-3PUFA and proinflammatory markers (hs-CRP, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α)) were assessed by using multivariate general linear models with adjustment for sex, age and waist circumference. An arbitrary inflammation score was defined based on the sum of the quartiles of hs-CRP, IL-6 and TNF-α concentrations (range=3-12)., Results: Elevated hs-CRP concentrations (>3 mg/l) were present in 46.9% (95% confidence interval (CI) 43.3-50.5) of the James Bay Cree population. RBC docosapentaenoic acid (DPAn-3; C22:5n-3) was inversely associated with hs-CRP, TNF-α and the inflammation score (all P trend<0.02), whereas eicosapentaenoic acid (C20:5n-3) and docosahexaenoic acid (C22:6n-3) in RBC were not associated with inflammation (all P trend>0.18). Among participants with RBC DPAn-3 levels above the median of the population, odds ratio of having an elevated inflammation score (≥9) was 0.67 (95% CI, 0.48-0.93) compared with participants below the median., Conclusions: RESULTS indicate that low-grade systemic inflammation is highly prevalent and that higher RBC DPAn-3 levels are associated with a lower risk of systemic inflammation in the James Bay Cree population.

Background & Aims: The importance of route of administration of omega-3 (n-3) polyunsaturated fatty acids (PUFA) (oral vs intravenous (iv)) is not clear. We determined the relative concentrations of fatty acids in plasma phosphatidylcholine (PC), red blood cells (RBC), white blood cells (WBC) and several tissues after short-term oral or iv administration of soybean oil (SO) or fish oil (FO)., Methods: Wistar rats (n = 6/group) received saline, FO, or SO by gavage or saline, FO based-lipid emulsion (FLE), or SO based-lipid emulsion (SLE) iv. The oils were provided at 0.2 g/kg/day for three consecutive days. The animals were sacrificed 24 h after the last administration, blood was collected for plasma, WBC and RBC separation and tissues removed. Fatty acids were analysed by gas chromatography., Results: FO resulted in higher eicosapentaenoic acid (EPA) in plasma PC and liver than the control. FLE resulted in higher EPA, docosahexaenoic acid (DHA) and total n-3 PUFA in plasma PC, WBC and liver than both the control and SLE groups. EPA, DHA and total n-3 PUFA were higher in the heart with FLE compared with SLE. Individual and total n-3 PUFA were higher in plasma PC, WBC, liver and heart with FLE than with FO given by gavage., Conclusion: Short-term iv administration of n-3 PUFA appears to be more effective at increasing EPA and DHA status in plasma, WBC, liver and heart than oral administration. This might be important for rapid treatment with n-3 PUFA., (Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Purpose: Despite the detailed knowledge of the absorption and incorporation of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) into plasma lipids and red blood cells (RBC) in humans, very little is known about docosapentaenoic acid (DPA, 22:5 n-3). The aim of this study was to investigate the uptake and incorporation of pure DPA and EPA into human plasma and RBC lipids., Methods: Ten female participants received 8 g of pure DPA or pure EPA in randomized crossover double-blinded manner over a 7-day period. The placebo treatment was olive oil. Blood samples were collected at days zero, four and seven, following which the plasma and RBC were separated and used for the analysis of fatty acids., Results: Supplementation with DPA significantly increased the proportions of DPA in the plasma phospholipids (PL) (by twofold) and triacylglycerol (TAG) fractions (by 2.3-fold, day 4). DPA supplementation also significantly increased the proportions of EPA in TAG (by 3.1-fold, day 4) and cholesterol ester (CE) fractions (by 2.0-fold, day 7) and of DHA in TAG fraction (by 3.1-fold, day 4). DPA proportions in RBC PL did not change following supplementation. Supplementation with EPA significantly increased the proportion of EPA in the plasma CE and PL fractions, (both by 2.7-fold, day 4 and day 7) and in the RBC PL (by 1.9-fold, day 4 and day 7). EPA supplementation did not alter the proportions of DPA or DHA in any lipid fraction. These results showed that within day 4 of supplementation, DPA and EPA demonstrated different and specific incorporation patterns., Conclusion: The results of this short-term study suggest that DPA may act as a reservoir of the major long-chain n-3 fatty acids (LC n-3 PUFA) in humans.

Aim: In previous animal studies, we confirmed that linoleic acid (LNA) enhanced colon carcinogenesis, whereas eicosapentaenoic acid (EPA) had protective effects in azoxymethane-induced colon tumorigenesis. In regard to the protective effects of marine n-3 polyunsaturated fatty acids (PUFAs) on colorectal cancer however, evidence from epidemiological studies is inconsistent., Materials and Methods: In the present study we investigated the fatty acid composition in plasma, red blood cells (RBCs) and adipose tissue from Japanese patients with colorectal cancer, or benign disease., Results: Sixty-one patients with histologically-confirmed colorectal cancer and 42 patients with non-malignant disease were recruited for this study. The fatty acid composition of the total phospholipid (PL) fraction of plasma and washed RBCs was determined by gas chromatography. The fatty acid composition of the triacylglycerol (TAG) fraction of subcutaneous adipose tissue was determined in a similar manner. The EPA proportion in the plasma and RBC PL fractions was significantly lower in patients with cancer than in the controls (p<0.05). Similarly, the LNA proportion in the RBC PL fraction was lower in patients with cancer, but no changes were found in the plasma PL fraction. Arachidonic acid was the only PUFA in the adipose TAG fraction that exhibited significant differences, with higher levels in the patients with cancer than in the controls., Conclusion: Our findings suggest that patients with cancer have abnormalities in PUFAs in the plasma PL, erythrocyte PL, and adipose TAG fractions. Further investigation is needed to clarify the differences in the results between the various fractions.

Little is known about nonpathological facial skin problems at present. The aim of the present study was to investigate the relationships among facial skin conditions, mood, and the fatty acid composition of red blood cells (RBCs) in women. One hundred and thirty-two apparently healthy Japanese women aged between 20 and 60 years were recruited. Facial skin conditions were analyzed using a Robo Skin Analyzer, and the RBC fatty acid composition was also determined. Questionnaires concerning mood were administered. Forehead pigmentation was more mood-dependent (in 20s group) and less arachidonic acid (AA)-dependent (in all participants) than that in other areas of the face. Actually there was no correlation in pigmentation between the forehead and other areas of the face when adjusted for age, smoking, and drinking. Skin conditions were adversely correlated with a negative mood. α-Linolenic acid concentrations were negatively correlated with negative mood scores. Pigmentation characteristics in the forehead were independent from other areas of the face. Negative mood and AA were adversely correlated with skin conditions.

Background: Polyunsaturated fatty acids (PUFAs) are bimodally distributed in acute schizophrenia, suggesting two endophenotypes. We intended to characterize these endophenotypes clinically. Our a priori hypothesis was that low PUFA patients have more negative symptoms., Patients and Methods: Patients (aged 18-39) with schizophrenia, schizoaffective or schizophreniform disorders were recruited at hospital admission during an acute episode. The baseline Positive and Negative Syndrome Scale, vital signs and biochemical variables were measured in 97 patients with available RBC PUFA levels. Adjustment for multiple testing was not performed., Results: The median Negative Subscale score was higher (p=0.04) in the low PUFA (25 points, n=30) than in the high PUFA group (19 points, n=67). Among 95 patients with measurements of serum triglycerides, hypertriglyceridaemia was more prevalent (p=0.009) among low PUFA patients (66%) than high PUFA patients (36%). PUFA modified the effect of antipsychotics on triglycerides (p=0.046). Serum glucose and mean corpuscular haemoglobin were higher (p=0.03, 0.001, respectively) in low PUFA than in high PUFA patients. Low PUFA men were heavier (p=0.04) than high PUFA men., Conclusions: During an acute episode of schizophrenia, patients with low RBC PUFA have more negative symptoms and more metabolic and haematological abnormalities than those with high PUFA. This indicates that PUFA levels define two clinically distinct endophenotypes of the disorder., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Experimental studies have suggested different effects of various fats on blood pressure. However, epidemiologic evidence of these relations remains limited and inconsistent. We therefore assessed the association of fatty acid (FA) composition in erythrocyte membranes with the risk of hypertension. We selected 516 cases of incident hypertension and 516 matched controls during 12.9 y of follow-up in the Women's Health Study. Erythrocyte FA was measured in baseline bloods using GC. After controlling matching factors and lifestyle factors, erythrocyte SFA showed a positive association, whereas total cis PUFA, cis (n-3) PUFA, and the ratio of PUFA:SFA (PS ratio) showed an inverse association with the risk of hypertension. The multivariable RR of hypertension across the increasing quartiles of erythrocyte FA subtypes were 1.00, 1.19, 1.44, and 1.76 for total SFA; 1.00, 0.84, 0.88, and 0.56 for total cis PUFA; 1.00, 0.87, 0.66, and 0.65 for cis (n-3) PUFA; and 1.00, 0.99, 0.70, and 0.51 for the PS ratio. After further adjusting for obesity-related metabolic factors, these associations were attenuated and remained significant only for the PS ratio. cis MUFA, cis (n-6) PUFA, and trans unsaturated FA in erythrocyte membranes were not associated with the risk of hypertension. Our study showed that FA composition in erythrocyte membranes is associated with the risk of hypertension in middle-aged and older women. However, after controlling for obesity-related metabolic factors, the associations remained significant only for the PS ratio.

Unlabelled: Based on the biochemical composition of erythrocyte membrane and asymmetric distribution of phospholipids, proteins, and cholesterol, FT-IR spectroscopy can monitor the distribution and interaction pattern of membrane constituents., Material and Methods: The study series included 21 clinically healthy subjects aged between 20 and 60 years. Complete blood counts were performed and the serum biochemical compounds (cholesterol, triglycerides, total protein, glucose) were determined., Results and Discussions: The parameters that can be assessed by erythrocyte FT-IR in relation with the biochemical factors that may influence membrane fluidity are: degree of fatty acids unsaturation, saturated fatty acids/unsaturated fatty acids ratio, cholesterol/phospholipids ratio, and phospholipids/protein ratio. Based on the obtained results, in the assessment of membrane status the following vibration modes were selected as spectral parameters: vibration associated valence bond (=CH), asymmetric valence CH2 groups, modes associated with P=O bond and amine bands I and II specific for proteins. Other parameters, such as v(C-O) specific to glucose, may provide additional information on glucose metabolic status., Conclusions: By correlating biochemical markers with these spectral parameters information on red cell membrane status, status that may reflect different pathological processes, can be obtained.

Background: Blood and tissue long-chain polyunsaturated fatty acid (LC-PUFA) amounts, which have been associated with early development and lifelong health, depend on dietary intake and endogenous conversion of precursor fatty acids (FAs) by the enzymes Δ⁵-desaturase and Δ⁶-desaturase. Polymorphisms in the desaturase encoding genes FADS1 and FADS2 have been associated with several n-6 (omega-6) and n-3 (omega-3) FAs and especially with arachidonic acid (AA) amounts. Associations with docosahexaenoic acid (DHA), which is considered particularly important for brain and retina development, are hardly existent., Objective: We explored the relation between FADS gene cluster polymorphisms and red blood cell (RBC) FA amounts in > 4000 pregnant women participating in the Avon Longitudinal Study of Parents and Children., Design: Linear regression analysis of 17 single nucleotide polymorphisms (SNPs) in the FADS gene cluster was conducted with RBC phospholipid FAs from 6711 samples from 4457 women obtained throughout pregnancy (mean ± SD gestational age: 26.8 ± 8.2 wk)., Results: Independent of dietary effects, the minor alleles were consistently positively associated with precursor FAs and negatively associated with LC-PUFAs and product:substrate ratios of the n-6 (AA:linoleic acid ratio) and n-3 (eicosapentaenoic acid:α-linolenic acid ratio) pathways. In contrast to previous studies, we also showed significant inverse associations with DHA. Similar but weaker associations were shown for the FADS3 SNP rs174455., Conclusions: FADS genotypes influence DHA amounts in maternal RBC phospholipids and might affect the child's DHA supply during pregnancy. It is highly likely that a gene product of FADS3 has a desaturating activity.

Objectives: Previous data have indicated that the erythrocyte membrane may be the preferred sample type for assessing long-chain polyunsaturated fatty acid (LCPUFA) contents in cardiac and cerebral membranes. In this epidemiological study, we examined whether plasma phospholipids can be used for accurate biological monitoring of the LCPUFA state or whether analysis of erythrocyte membrane phospholipids is indispensable., Methods: (1) The analysis of LCPUFA contents in erythrocyte membrane phospholipids was conducted at baseline and after 1 and 3 days at 4°C, and 21 days at -40°C, after blood drawing, and the changes in LCPUFA content were examined. (2) The LCPUFA compositions of plasma and erythrocyte phospholipids in 133 young women (18-30 years old) were examined and the relationships between the sample type and the levels of LCPUFAs were determined., Results: Eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and DHA/arachidonic acid (AA) and (EPA+DHA)/AA ratios in erythrocyte membrane phospholipids after 21 days of blood drawing significantly decreased compared with the corresponding baseline data. Regarding AA, EPA and DHA, a significant positive correlation was shown between levels of erythrocyte membrane phospholipids and plasma phospholipids (AA, r=0.364; EPA, r=0.709; DHA, r=0.653). The predictive value of plasma phospholipids for determining the highest concentration quartile in erythrocyte phospholipids was better in EPA (70%) than in DHA (55%) and AA (42%)., Conclusions: The measurement of LCPUFA content in erythrocyte membrane phospholipids is necessary for accurate biological monitoring. We also found that LCPUFA in erythrocyte membrane phospholipids is stable in cold storage (4°C) for 3 days after blood drawing.

Arachidonic acid (ARA) is considered to be a minor contributor to the diet. Previous reports regarding the effect of ARA supplementation on the composition of long-chain polyunsaturated fatty acids (LCPUFA) in the blood of humans are extremely limited. In the present study, we conducted a crossover double-blind, placebo-control study. Twenty-three young Japanese women consumed one capsule containing triacylglycerol enriched with 80 mg ARA, equivalent to the amount in one egg, daily for 3 weeks. Blood samples were drawn before and after treatment periods, and the compositions of the LCPUFA in blood lipid fractions were measured. The supplementation of ARA increased the composition of ARA, but did not decrease the composition of n-3LCPUFA in erythrocyte phospholipids and plasma phospholipids, esterified cholesterol, and triacylglycerol. We found that dietary ARA increased the ARA level in all lipid fractions of the blood, even at a very low dose., ((c) 2010 Elsevier Ltd. All rights reserved.)

Background: There is evidence that the impact of environmental factors on insulin sensitivity is modified by the presence of family history of diabetes., Aim: To compare the association between the erythrocyte phospholipid fatty acid composition (a biomarker of dietary fatty acids) and insulin sensitivity in daughters of Type 2 diabetic patients with the corresponding association in women without family history of diabetes., Material/subjects and Methods: Eighteen offspring of Type 2 diabetic patients [age 30+/-6.5 yr; body mass index (BMI) 22.2+/-2.5 kg/m2; body fat 31.8+/-5.1%] and 18 matched women (age 30.1+/-6.8 yr; BMI 22.2+/-1.8 kg/m2; body fat 32.2+/-6.0%) participated in the study., Results: Insulin Sensitivity Index (ISI)-Matsuda tended to be lower (p=0.06) in the Offspring than the control group. Weight proportions of erythrocyte phospholipid saturated (SFA), polyunsaturated (PUFA), and monounsaturated fatty acids (MUFA) were similar between the two groups. In the offspring, erythrocyte total SFA were negatively correlated with ISI-Matsuda [r=-0.47, p<0.05), ISI(gly)-Belfiore (r=-0.52, p<0.05) and ISI(ffa)-Belfiore (r=-0.53, p<0.05)], whereas total PUFA were positively correlated with insulin sensitivity [ISI-Matsuda, r=0.46, p<0.05; ISI(gly)-Belfiore, r=0.53, p<0.05; ISI(ffa)-Belfiore, r=0.54, p<0.05]. No significant correlations were observed in the control group., Conclusions: The associations between erythrocyte fatty acid composition and insulin sensitivity are distinct between daughters of Type 2 diabetic patients and women without family history of diabetes.

Aim: We assessed levels of polyunsaturated fatty acid (PUFA) in serum and red blood cells (RBCs) among groups stratified by generation and its clinical significance in Japanese subjects living in an urban area., Methods: We enrolled 200 apparently healthy Japanese (126 males, mean age: 50.3+/-9.2 years) living in an urban area. Levels of PUFA, including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (AA), and dihomo-gamma-linolenic acid (DGLA) in serum and RBCs were measured for each generation (G1 <35y, G2 35y-<45y, G3 45y-<55y, G4 55y-<65y, G5>or=65y)., Results: No significant differences in EPA, DHA, AA, or EPA/AA were observed between males and females. After dividing into generations, stepwise increases in EPA and DHA, but not DGLA or AA, were observed in serum (all p<0.0001). EPA/AA ratios were stepwisely increased in serum (mean: G1:0.26, G2:0.29, G3:0.43, G4:0.58, G5:0.68, p<0.0001) and RBCs (mean: G1:0.10, G2:0.09, G3:0.15, G4:0.20, G5:0.23, p<0.0001). Positive correlations of EPA (r=0.83), DHA (r=0.55), DGLA (r=0.54), AA (r=0.29), and EPA/AA (r=0.91) were demonstrated between serum and RBCs. In addition, a significant positive correlation between EPA/AA ratios and insulin sensitivity as well as a negative correlation between those ratios and insulin resistance were observed in subjects with metabolic syndrome., Conclusion: Low levels of EPA/AA, which were associated with insulin resistance, were demonstrated in young Japanese adults living in an urban area.

Prior clinical studies suggest that chronic treatment with atypical antipsychotic medications increase erythrocyte and postmortem prefrontal cortex (PFC) omega-3 fatty acid composition in patients with schizophrenia (SZ). However, because human tissue phospholipid omega-3 fatty acid composition is potentially influenced by multiple extraneous variables, definitive evaluation of this putative mechanism of action requires an animal model. In the present study, we determined the effects of chronic treatment with the atypical antipsychotic risperidone (RISP, 3.0 mg/kg/d) on erythrocyte and PFC omega-3 fatty acid composition in rats maintained on a diet with or without the dietary omega-3 fatty acid precursor, alpha-linolenic acid (ALA, 18:3n-3). Chronic RISP treatment resulted in therapeutically-relevant plasma RISP and 9-OH-RISP concentrations (18+/-2.6 ng/ml), and significantly increased erythrocyte docosahexaenoic acid (DHA, 22:6n-3, +22%, p=0.0003) and docosapentaenoic acid (22:5n-3, +18%, p=0.01) composition, and increased PFC DHA composition (+7%, p=0.03) in rats maintained on the ALA+ diet. In contrast, chronic RISP did not alter erythrocyte or PFC omega-3 fatty acid composition in rats maintained on the ALA- diet. Chronic RISP treatment did not alter erythrocyte or PFC arachidonic acid (AA, 20:4n-6) composition. These data suggest that chronic RISP treatment significantly augments ALA-DHA biosynthesis, and preferentially increases peripheral and central membrane omega-3 fatty acid composition. Augmented omega-3 fatty acid biosynthesis and membrane composition represents a novel mechanism of action that may contribute in part to the efficacy of RISP in the treatment of SZ.

Background: Whereas dietary intake of long-chain n-3 fatty acids has been associated with risk of nonfatal myocardial infarction (MI), few studies have examined the relation for blood concentrations., Objective: We aimed to investigate the effect of long-chain n-3 fatty acids in blood on the risk of nonfatal MI., Design: Baseline blood samples were collected from 32 826 participants of the Nurses' Health Study in 1989-1990, among whom 146 incident cases of nonfatal MI were ascertained during 6 y of follow-up and matched with 288 controls., Results: After multivariate adjustment, the relative risks (95% CI) comparing the highest with the lowest quartiles in plasma were 0.23 (0.09, 0.55; P for trend = 0.001) for eicosapentaenoic acid (EPA), 0.40 (0.20, 0.82; P for trend = 0.004) for docosapentaenoic acid (DPA), and 0.46 (0.18, 1.16; P for trend = 0.07) for docosahexaenoic acid (DHA). The associations for these fatty acids in erythrocytes were generally weaker and nonsignificant. In contrast to EPA and DHA, blood concentrations of DPA were not correlated with dietary consumption of n-3 fatty acids. Higher plasma concentrations of EPA, DPA, and DHA were associated with higher plasma concentrations of HDL cholesterol and lower concentrations of triacylglycerol and inflammatory markers., Conclusions: Higher plasma concentrations of EPA and DPA are associated with a lower risk of nonfatal MI among women. These findings may partly reflect dietary consumption but, particularly for DPA, may indicate important risk differences based on metabolism of long-chain n-3 fatty acids.

Depression is a common problem among patients with multiple sclerosis (MS). Previous research has shown differences between MS patients and controls in the levels of certain fatty acids, and differences in many of these same fatty acids have also been reported in psychiatric patients with major depression. The current study sought to determine whether fatty acid levels in MS patients might be associated with depression. Fatty acids were measured in red blood cells (RBCs) for 38 patients with relapsing-remitting MS and 33 healthy controls who also completed 3-day dietary records and depression questionnaires. Levels of certain omega-3 and omega-6 fatty acids were lower and levels of certain monounsaturated and saturated fatty acids were higher in the MS patients. These differences were generally of medium effect size and occurred despite the fact that no differences were found between the two groups in dietary intake of any fatty acids. However, neither RBC nor dietary fatty acid levels were related to depression in the MS sample.

Background: Different fatty acids may vary in their effect on the metabolic syndrome (MetS). We tested whether fatty acid classes measured in erythrocytes are associated with the MetS or its components., Methods: Included were men [n = 497; mean (SD) age, 49 (16) years] and women [n = 539; age, 48 (16) years] from 187 families in a National Heart, Lung, and Blood Institute (NHLBI) family study of the Genetics of Lipid-Lowering Drugs and Diet Network (GOLDN) conducted in Utah and Minnesota. We used gas chromatography to measure erythrocyte fatty acids and obtained data on potential confounding variables from interviewer-administered questionnaires., Results: The prevalence of the MetS as defined by the updated Adult Treatment Panel III criteria was 36.8% in Utah and 39.6% in Minnesota (P >0.05). In a multivariate model that included 4 fatty acid classes, covariates, and pedigree as a random effect, the odds ratios (95% confidence interval) for the MetS in the 1st, 2nd, 3rd, and 4th quartile of polyunsaturated fatty acids were 1.00, 0.72 (0.47-1.10), 0.67 (0.43-1.05), and 0.39 (0.24-0.64), respectively (P for trend = 0.0002). For the corresponding quartiles of saturated fatty acids, the odds ratios were 1.00, 1.19 (0.77-1.84), 1.48 (0.94-2.34), and 1.63 (1.01-2.63), respectively (P for trend = 0.03). Unlike n6 fatty acids, which showed an inverse association (P <0.05) with MetS, n3, trans, and monounsaturated fatty acids were not associated with the MetS (P >0.05). We observed significant correlations (P <0.05) between fatty acid classes, insulin, and components of the MetS., Conclusions: Polyunsaturated fats are inversely associated with the MetS, whereas saturated fatty acids are positively associated with the MetS, probably through their effect on lipids, adiposity, insulin, and blood pressure.

Variable levels of essential polyunsaturated fatty acids (EPUFAs) reported in schizophrenia are likely due to differences in age, sex, ethnicity, diet, life style and treatments. The present study examined the EPUFAs levels in plasma, RBC and CSF in never-medicated first-episode psychotic patients and normal controls matched for ethnicity, diet and life style. The plasma EPUFAs levels were similar in both groups. Among the EPUFAs enriched in the brain, predominantly docosahexaenoic acid (DHA) levels were lower in RBC (p=<0.01) whereas higher in CSF (p=<0.01) in male>female patients. This altered DHA metabolism may provide clues for neuropathology and treatment of schizophrenia.

Lipid peroxidation has gained renewed attention with increasing evidence showing its biological role in producing toxic compounds and cellular signaling mediators. The assessment of lipid peroxidation levels in vivo is difficult partly because lipids are oxidized by different oxidants by different mechanisms to give versatile types of products, which may undergo metabolism and secondary reactions. In the present study, total hydroxyoctadecadienoic acids (tHODE) and 7alpha- and 7beta-hydroxycholesterol (t7-OHCh) from 44 healthy human subjects were assessed as biomarkers after reduction with sodium borohydride followed by saponification with potassium hydroxide comparing with the prevailing standard 8-isoprostaglandin F(2alpha) (t8-iso-PGF(2alpha)). The average concentrations of tHODE, total 8-isoprostaglandin F(2alpha) (t8-iso-PGF(2alpha)), t7alpha-OHCh, and t7beta-OHCh were 203, 0.727, 87.1, and 156 nmol/l plasma and 1,917, 12.8, 1,372, and 3,854 nmol/l packed erythrocytes, respectively. The ratios of tHODE and t7-OHCh to the parent substrates were 194 and 3,519 micromol tHODE/mol linoleates and 40.9 and 686 micromol t7-OHCh/mol cholesterol in plasma and erythrocytes, respectively. It was found that (1) t7-OHCh in blood was unexpectedly high, as high as or even higher than tHODE, (2) the amounts of tHODE was more than 100 fold higher than t8-iso-PGF(2alpha) (3) the level of lipid oxidation products in erythrocytes was higher than that in plasma, and (4) lipid peroxidation products level tended to increase while antioxidant level decrease with age. These products may be used as potential biomarker for assessment of lipid peroxidation and oxidative stress in vivo.

Background: The role of individual fatty acids in the development and progression of breast cancer is unclear. Although in vitro and animal experiments have supported an inverse association between intake of long chain n-3 fatty acids [primarily eicosapentaenoic acid (EPA) and docosahexaenoic acid] and breast cancer risk, findings from population studies are inconsistent. Recent studies have also shown associations between the ratio of saturated to monounsaturated fatty acids (SI) and breast cancer risk. The SI reflects the activity of several genes involved in lipid metabolism, including fatty acid synthase and steroyl coenzyme-A desaturase, that have been shown to be overexpressed in breast cancer., Objective: The purpose of this analysis was to determine the association between erythrocyte fatty acid concentrations and breast cancer risk among women participating in a randomized trial of breast self-examination in Shanghai, China., Design: We conducted a case-control study. Erythrocyte fatty acid concentrations were determined in specimens from 322 women with histologically confirmed breast cancer and 1030 frequency age-matched control women., Results: We report a significant direct association among palmitic, gamma-linolenic, palmitoleic, and vaccenic acids and risk of breast cancer. Total n-3 fatty acids, EPA, and the SI for palmitic to palmitoleic acid were associated with significantly lower risk of breast cancer., Conclusion: Our results support a protective effect of n-3 fatty acids on breast cancer risk and provide additional evidence for the importance of evaluating the ratio of fatty acids when evaluating diet and breast cancer risk.

Atopy is a growing problem for Korean children. Since eicosapentaenoic acid is a precursor of less active inflammatory eicosanoids, n-3 polyunsaturated fatty acids (PUFA) may have a protective effect on atopy. This study was undertaken to determine whether n-3 PUFA in red blood cells (RBC) is lower in atopic than in non-atopic preschoolers. Three hundred and eight Korean children aged 4-6 years were enrolled. Total RBC fatty acid composition was measured by gas chromatography. The prevalence of atopic dermatitis, allergic rhinitis, or asthma was 29%. Total RBC n-3 PUFA were lower in preschoolers with atopy than controls (9.8 +/- 1.2 vs. 11.4 +/- 1.6%; P<0.05), while n-6 PUFA (33.0 +/- 1.4 vs. 32.2 +/- 1.0%; P<0.05) and n-6/n-3 PUFA ratio (3.4 +/- 0.6 vs. 2.8 +/- 0.5; P<0.05) were greater. The following factors were also associated with an increase in atopy: higher saturated fatty acids (39.6 +/- 1.4 vs. 40.6 +/- 1.9; P<0.05) and arachidonic acid (15.3 +/- 1.6 vs. 16.0 +/- 2.9; P<0.05), and lower total PUFA (43.8 +/- 0.7 vs. 42.8 +/- 1.4; P<0.05) and omega-3 index (EPA + DHA; 9.1 +/- 0.8 vs. 7.8 +/- 0.5; P<0.05) in RBC. Maternal history of atopy was a significant (P<0.05) risk factor, while lactation was not. The results suggest that a reduced content of n-3 PUFA in the RBC membrane could play a role in early children atopy.

Insulin resistance is a major factor in the pathogenesis of type 2 diabetes mellitus (T2DM) and is related to the fatty acid profile of the plasma membranes. The purpose of the present study was to investigate fatty acid composition and cholesterol content of cell membranes in patients with type 2 diabetes and, thus, to evaluate the possible factors leading to the alteration of plasma membrane fluidity. The study was performed in 20 healthy control subjects and 32 patients with type 2 diabetes. The fatty acid profiles and cholesterol content of the erythrocyte (RBC) and leukocyte (WBC) membranes were determined by a gas chromatographic method. When one considers the membrane constituents increasing fluidity and the ones decreasing it, the diabetics had a membrane composition decreasing fluidity compared to controls. On the other hand, when compared to control subjects, type 2 diabetic patients showed a significantly higher proportion of C16:0 components in erythrocyte and leukocyte membranes and plasma samples (25.4+/-3.1% vs. 31.1+/-4%; 23.3+/-2.4% vs. 29.3+/-5.2%; 27.6+/-3.9% vs. 34.5+/-5.7%; p<0.005, p<0.01 and p<0.005, respectively). Our results suggest that the ratio of saturated:unsaturated fatty acids changes in plasma and cell membranes of patients with type 2 diabetes. This situation may cause, at least in part, RBC-WBC function abnormalities and insulin resistance because of inconvenient membrane fluidity.

Objective: This case-control study was conducted in Lima, Peru, from June 1997 through January 1998 to assess whether alteration in maternal erythrocyte omega-3 (n-3) and omega-6 (n-6) fatty acids was associated with increased risk of preeclampsia., Methods: A total of 99 preeclampsia and 100 normotensive pregnant women were included. Maternal erythrocyte n-3 and n-6 fatty acids were determined using capillary gas chromatography/mass spectrometry and expressed as micromolar (mM) concentrations. We employed logistic regression procedures to estimate odds ratios (ORs) and 95% confidence intervals (CIs)., Result: n-3 fatty acids were consistently lower in preeclampsia cases than controls. After adjusting for confounders, the corresponding ORs for preeclampsia across decreasing quartiles of sum of long-chain n-3 fatty acids were 1.0, 3.3, 2.4, and 3.3, respectively (P=0.07 for trend). A similar pattern was observed for eicosapentenoic acid (20:5n-3, EPA) and docosahexenoic acid (22:6n-3, DHA). There was no clear evidence of an association between arachidonic acid (20:4n-6, AA) and preeclampsia risk, the ORs in successively lower quartiles were 1.0, 1.1, 1.0, and 1.5 (P=0.48 for trend). A similar pattern was seen for the sum of long-chain n-6 fatty acids., Conclusion: In Peruvian women, low erythrocyte n-3 fatty acids appeared to be associated with an increased risk of preeclampsia.

There have been conflicting reports regarding the effectiveness of dietary nucleotides (NT) to regulate tissue desaturases and hence stimulate accumulation of both n-6 and n-3 long-chain polyunsaturated fatty acids (LCPUFA). The aim of this study was to examine the effect of NT-supplemented cow's milk-based formula on erythrocyte phospholipid FA status in a large randomized controlled trial involving a well-nourished infant population born at term. Formula-fed infants were allocated to control formula with an innate level of NT at 10 mg/L (n = 102), or formula fortified with NT at 34 mg/L (n = 98). A parallel group of breastfed infants was included as a reference. Peripheral blood samples were collected by venipuncture at 7 mon of age and erythrocyte phospholipid FA determined by capillary GC. Erythrocyte LCPUFA levels did not differ between the NT-supplemented and control formula groups and were reduced in both groups compared with breastfed infants. We conclude that there is no induction of LCPUFA accumulation in erythrocyte phospholipids of term, formula-fed infants following 7 mon of NT supplementation.

Background: Epidemiologic studies show that low fish intake is a risk factor of suicidality; however, there are no case-control studies investigating suicide attempt risk and tissue n-3 fatty acid levels., Methods: We recruited 100 suicide-attempt cases and another 100 control patients injured by accidents who were admitted to three hospitals affiliated with Dalian Medical University in Dalian, China. Case and control subjects were matched for age, gender, and smoking status. Those who were inebriated at the time of hospitalization were excluded. Blood was sampled immediately after admission to a hospital. Washed red blood cells (RBCs) were obtained, and the fatty acid composition of the total RBC phospholipid fraction was analyzed by gas chromatography., Results: Eicosapentaenoic acid (EPA) levels in RBC in the case subjects were significantly lower than those of the control subjects (.74 +/-.52% vs. 1.06 +/-.62%, p <.0001). When the highest and lowest quartiles of EPA in RBC were compared, the odds ratios of suicide attempt was.12 in the highest quartile (95% confidence interval:.04-.36, p for trend =.0001) after adjustment for possible confounding factors, Conclusions: Our findings suggest that low n-3 fatty acid levels in tissues were a risk factor of suicide attempt. Further studies including intervention with fish oil are warranted.

Aim: The aim of the present study was to determine how the fatty acid composition of plasma and erythrocyte phospholipids is influenced by the diabetic condition and by dietary or glibenclamide treatment in type 2 diabetes., Methods: The fatty acid composition of plasma and erythrocyte phospholipids is assessed in 3 nonobese groups of Cuban diabetics with comparable age and BMI: 13 newly diagnosed, 15 on diet alone and 15 on diet/glibenclamide. Thirteen healthy individuals were used as controls. Fasting serum glucose, insulin and glycosylated hemoglobin and dietary fat intake were assessed., Results: In plasma phospholipids, significant lower values were found for 14:0, 15:0 and 17:0 in newly diagnosed patients than in controls. In red blood cell phospholipids, 14:1, 20:0 and 24:1 of newly diagnosed patients were significantly lower than of controls, and 16:1omega7 and 18:4omega3 were significantly higher. The different treatments had an effect on 18:0, 18:1t, 20:0 and total trans fatty acids in erythrocyte, but not in plasma phospholipids., Conclusions: Changes in plasma phospholipid fatty acids found in type 2 diabetics may be due to an 'adapted' dietary pattern, whereas those in erythrocyte phospholipids may be attributed to effects of the disease itself and may be susceptible to normalization by diet or glibenclamide., (Copyright (c) 2004 S. Karger AG, Basel.)

The fatty acid components of the plasma triglycerides and the phospholipid fractions of the red blood cells of a captive group of two African (Loxodonta africana) and four Asian (Elephas maximus) elephants were investigated. All the animals received the same diet of hay, fruits and vegetables, and concentrates. A comparison with data from free-ranging African elephants or Asian work-camp elephants showed that the captive elephants had lower proportions of polyunsaturated fatty acids (PUFAs), and for several lipid fractions a higher n-6:n-3 ratio, than their counterparts in the wild or under the more natural, in terms of diet, work-camp conditions. The difference in PUFA content was smaller in the African than in the Asian elephants. The captive Asian elephants tended to have lower levels of n-3 and total unsaturated fatty acids in their red blood cells than the captive African elephants.

Background: Being devoid of both nuclei and mitochondria, mature human erythrocytes provide an opportunity to study membrane structure and function outwith the restrictions of genetic control. With its unique rapid increase in vascularisation, pregnancy is considered the most opportune period in which to investigate blood rheology., Methods: Maternal and fetal (cord) bloods were retained at delivery from 32 (25 singleton and seven twin) normal pregnancies at two maternity hospitals in the Glasgow area over a nine month period. Erythrocyte fatty acid compositions were assessed by mass spectroscopy, and corresponding membrane deformabilities measured by ultrafiltration through a membrane of 5 micro m diameter pore size, to mimic placental microcirculation., Results: Significant direct correlations (Spearman rank) were found between erythrocyte membrane omega-3 docosahexaenoic acid concentrations and corresponding deformabilities in maternal and cord blood from both singleton and twin pregnancies, whereas greater omega-6 arachidonic acid content was associated with increased maternal membrane rigidity. Membrane concentrations of omega-3 fatty acids only correlated strongly both within and between maternal and cord bloods. Mean cord erythrocyte docosahexaenoic acid concentration was higher than maternal in singletons but lower in twins. When maternal erythrocyte concentrations exceeded about 7% (of total fatty acids), resistance to erythrocyte flow was virtually eliminated., Conclusions: It may be that a greater maternal intake of docosahexaenoic acid should be encouraged in some pregnancies for optimal tissue perfusion. Fetal demand for docosahexaenoic acid may not be entirely satisfied in multiple pregnancies.

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., (Copyright 2002 Elsevier Science Ltd.)

Fatty acid distribution was investigated in ethnically and economically homogenous Korean mothers (n = 40) and neonates. Venous blood, maternal before delivery and cord, was obtained. Choline (CPG) and ethanolamine (EPG) phosphoglycerides and sphingomyelin (SM) were assayed. Mean arachidonic acid (AA) level was higher in plasma CPG and SM (p < 0.0001), and red cell CPG (p < 0.0001), EPG (p < 0.0001) and SM (p = 0.005) of the neonates. Similarly, the neonates had higher proportions of docosahexaenoic acid (DHA) in plasma CPG (p < 0.0001) and red cell CPG (p = 0.001) and EPG (p = 0.036). In contrast, linoleic and alpha-linolenic acids were significantly higher in maternal blood. Mead acid was elevated in plasma CPG (p < 0.0001) and red cell CPG and EPG (p < 0.0001) of the neonates. Consistent with data from high-fat-intake populations, our subjects, whose traditional diet is low in fat, exhibited maternal-fetal gradient in AA and DHA in plasma and red cell phospholipids. This may be due to an imbalance between supply and maternal and fetal requirements, and/or a physiological response to pregnancy. Prenatal nutritional constraint is associated with impaired development and a risk of chronic diseases in adults. AA and DHA are vital nutrients. Hence, there is a need to investigate whether the discrepancy between maternal and neonatal AA and DHA is a manifestation of nutritional insufficiency.

The objective of this study was to examine compositional and quantitative changes in fatty acids of plasma components and red blood cell phospholipids (PL) immediately following and during recovery from burn injury. Subjects (n = 10) with >10% total body surface area burn had blood drawn at specific timepoints (0 to >50 d) following burn injury. Fatty acid composition of red blood cell PL and plasma PL, cholesteryl esters (CE), and triglycerides was determined using gas-liquid chromatography after separating each fraction from extracted lipids by thin-layer chromatography. Total plasma PL and CE in burn patients were lower than in healthy control subjects with reduced 20:4n-6, n-6, and n-3 fatty acids and higher levels of monounsaturated and saturated fatty acids early after burn. CE levels remained half that of healthy control values up to 50 d post-burn. Red blood cell PL had decreased 20:4n-6 content and profiles similar to that of an essential fatty acid deficiency early after burn. These results suggest an impairment in lipoprotein and polyunsaturated fatty acid metabolism in the early post-burn period. Lower levels of 20:4n-6 and n-3 fatty acids in every plasma fraction suggest increased use of these fatty acids for wound healing and immune function following burn injury. Further work is needed to determine the ability of burn patients to utilize essential fatty acids in order to design nutritional intervention that promotes wound healing and immunological functions consistent with recovery in these patients.

Objective: Healthy foetal and infant development is dependent on an adequate maternal supply of essential and polyunsaturated fatty acids (PUFA). While there are published data on the fatty acid status of pregnant women, there are few on the status of non-pregnant women of reproductive age. The aims of this study were to test the hypotheses that the fatty acid status of non-pregnant women is affected by socio-economic status and anthropometric, behavioural and obstetric factors., Design: Observational study, Methods: One-hundred and thirty-five women of child-bearing age (mean 29.8 y, s.d. 6.92) were invited to provide a blood sample and to answer a questionnaire, of whom 114 were included in the study. Plasma and red cell total fatty acids were measured as their methyl esters by gas chromatography mass spectrometry., Results: On multivariate analyses, use of hormonal contraception was independently associated with lower plasma polyunsaturated fatty acids (difference between means -2.76, 95% confidence interval (-4.64, -0.88), P=0.0034), whereas cigarette smoking was associated with higher red cell oleic acid (0.74 (0.18, 1.29), P=0.0094). Fish intake was associated with higher red cell total n-3 fatty acids (0.62 (0.27, 0.85), P=0.0014)., Conclusions: We have reported data on the range of the fatty acids of plasma and red blood cells (RBC) total lipids of 114 healthy women of reproductive age. These data provide further information on how socio-economic, anthropometric, behavioural and obstetric factors may be relevant to female and nutrition and health., Sponsorship: University of Glasgow.

Several studies have suggested that the oxidative modification of low-density lipoprotein (LDL) could play a key role in the early stages of atherosclerosis. The susceptibility of LDL to oxidation has been found to be greater in patients with coronary heart disease. Familial hypercholesterolaemia (FH) is a powerful clinical model in which to study the predictive role of LDL in atherogenesis. LDL-apheresis is a treatment that is able to decrease lipid levels in plasma. This study was aimed at investigating the reducing capacity of erythrocytes and the in vitro susceptibility to oxidation of LDL isolated from patients with homozygous, heterozygous and double-heterozygous FH, who were treated fortnightly with LDL-apheresis or left untreated. In 14 FH patients, at baseline and after a cycle of treatment, the susceptibility of LDL to oxidative modification was analysed by studying the kinetics of conjugate diene formation. Plasma hydroperoxides, polyunsaturated fatty acid content, LDL electrophoretic mobility on agarose, the titre of auto-antibodies against oxidized LDL and serum paraoxonase activity were also measured. Furthermore, in order to evaluate a potential relationship between LDL oxidation and redox status, erythrocyte GSH and ATP levels were determined in FH patients treated regularly or never treated previously by LDL-apheresis. Unlike in the control group, the oxidative status of LDL in all FH patients was modified by LDL-apheresis, as revealed by the higher negative charge and the increase in levels of hydroperoxides and antibodies against oxidized LDL in the plasma. Our findings suggest both an acute effect and a long-term effect of LDL-apheresis in FH patients treated with dextran sulphate cellulose apheresis. The acute effect of LDL-apheresis on the susceptibility to oxidation of plasma and LDL was demonstrated by significant decreases in plasma hydroperoxide content, total LDL concentration and polyunsaturated fatty acid content. The increased resistance of LDL to oxidation was shown by prolongation of the lag time (P<0.05) in samples after a single cycle of treatment. The long-term effect of LDL-apheresis was demonstrated by the comparable values for lag phases (obtained from the kinetics of conjugate diene formation) in patients under active treatment and controls. Compared with healthy controls and untreated patients, the erythrocyte GSH content was significantly higher (P

Aim: To assess the modifications of the main fatty acids (FA) in plasma and red blood cells during pregnancy., Methods: A longitudinal study of 36 normal pregnant women was carried out with 3 cut-off points: first trimester, second trimester and third trimester. 14 FA in plasma and erythrocyte phospholipids were measured using capillary gas chromatography. Measurements were expressed in percentages and in absolute values., Results: In plasma there was a significant increase in the proportion of saturated FA and a decrease in the proportion of long chain polyunsaturated fatty acids (PUFA) both in the omega 6 (omega 6) and omega 3 (omega 3) series. On the other hand, in erythrocyte phospholipids there was a decrease in the proportion of eicosapentaenoic acid and an increase in that of docosahexaenoic acid. In the omega 6 series, dihomo-gamma-linolenic acid increased, whereas the omega 6 docosapentaenoic acid decreased., Conclusion: There was a significant decrease in the proportion of omega 3 PUFA in plasma from the first to the third trimester. Thus, it is suggested that the omega 3 PUFA intake during pregnancy should be increased in the last trimester.