Blood Cell Polyunsaturated Fatty Acids Research Articles

Red Blood Cell Polyunsaturated Fatty Acids and Mortality Following Breast Cancer.

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. 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). 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). RBC ALA, LA, and GLA may be prognostic indicators among breast cancer survivors. These results are important for understanding the associations between a biomarker of PUFA intake and mortality among BC survivors.

Red Blood Cell Polyunsaturated Fatty Acids and Vascular Diseases: A Mendelian Randomization Study

Abstract Objectives To evaluate the causal association of omega-3 and omega-6 polyunsaturated fatty acids (PUFAs), as measured in red blood cells (RBC), with cardiovascular disease (CVD), cerebrovascular disease (CBVD), and peripheral vascular disease (PVD). Methods Applying a two-sample Mendelian Randomization approach, we first developed genetic instruments for RBC-PUFAs by utilizing summary statistics from previous genome-wide association study in the Framingham Heart Study. We then evaluated the association of these instrumental variables with CVD, CBVD, PVD, and their subtypes in the UK Biobank cohort. Results Strong evidence of causal association with at least one RBC-PUFAs was observed for the overall risk of PVD and three of its subtypes (aortic aneurysm and dissection, arterial embolism and thrombosis, and other PVDs), but only for two CVD subtypes (hypertensive heart disease, and chronic ischemic heart disease) and for two CBVD subtypes (stroke, and cerebral infarction). Based on their effects on all examined diseases, RBC-PUFAs clustered into two groups: a protective group with alpha-Linolenic acid (ALA), linoleic acid (LA), eicosadienoic acid (EDA), and dihomo-gamma-linolenic acid (DGLA); and the other risk group with docosapentaenoic acid (DPA), gamma-linolenic acid (GLA), arachidonic acid (AA), and adrenic acid (AdrA). PUFAs in the protective group are protective, while those in the risk group are risk-increasing, for all diseases with significant associations except for hypertensive heart diseases. In the metabolic pathway converting short-chain PUFAs into long-chain ones, the protective group is mapped to precursors of desaturases, while the risk group corresponds to their products. Conclusions Genetically regulated RBC-PUFAs are associated with the risk of PVD, and subtypes of PVD, CVD, and CBVD. Funding Sources University of Georgia Research Foundation.

Relationships between Atherosclerosis and Plasma Antioxidant Micronutrients or Red Blood Cell Polyunsaturated Fatty Acids in People Living with HIV.

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.

Red blood cell polyunsaturated fatty acids and mortality in the Women's Health Initiative Memory Study

The prognostic value of circulating polyunsaturated fatty acid (PUFA) levels is unclear. To determine the associations between red blood cell (RBC) PUFA levels and risk fordeath. This prospective cohort study included 6501 women aged 65 to 80years 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 August2014. After a median of 14.9years 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. 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.

Abstract P1-09-30: Relationship of dietary and red blood cell polyunsaturated fatty acids to inflammatory markers in breast cancer survivors taking aromatase inhibitors

Abstract Introduction: A large body of literature supports modulation of inflammation by polyunsaturated fatty acids (PUFA). Inflammation may play a role in the painful joint symptoms commonly experienced by breast cancer survivors taking aromatase inhibitors (AI). AI-induced joint symptoms negatively impact drug adherence and quality of life in many breast cancer survivors. N-3 PUFAs, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have anti-inflammatory effects; in contrast, excess very long chain n-6 PUFAs may promote peripheral and joint inflammation. We hypothesized that breast cancer survivors with greater EPA+DHA or n-3/n-6 PUFA in their diet would have decreased inflammation and be less likely to develop AI-induced joint symptoms. Materials and methods: This is a secondary analysis of PUFA intake self-reported from food frequency questionnaires and red blood cell (RBC) PUFA data from a randomized placebo-controlled pilot study comparing n-3 PUFA supplementation vs placebo in 44 postmenopausal women with breast cancer initiating first line adjuvant AIs. Primary outcomes were feasibility and tolerability; secondary outcomes were differences in clinical symptoms and inflammatory markers. Participants were randomized to 4.8 g/day DHA+EPA vs matched placebo for 24 weeks (wks). Serial peripheral blood samples were drawn for RBC PUFA levels and inflammatory cytokines (IL-6, TNFα-R2 and IL-17). Clinical symptoms were assessed by the Brief Pain Inventory short form (BPI-SF), FACTB-ES, and Stanford Health Assessment -Disability Index (HAS) at 12 and 24 wks. Compliance and toxicity were evaluated monthly. Results: Median age of all 44 women enrolled and randomized was 60 years (range 43-76); breast cancer stage I (n=29), II (n=10), III (n=5); prior taxane (n=15, 34%).Baseline mean dietary intakes of n-3 PUFAs were: total n-3 PUFAs = 1.43 ± 0.86 g/d; EPA = 0.05 ± 0.05g/d; and DHA = 0.10 ± 0.11 g/d. There was a trend toward lower TNFα-R2 with higher dietary intake of EPA (p=0.09) and DHA (p=0.10). Baseline mean RBC EPA+DHA (n-3 Index) was 4.36% and the RBC n-3/n-6 ratio was 0.20. RBC total n-3 PUFAs were similar at baseline between n-3 treatment and placebo groups (6.6 ± 1.6%, 7.2 ±1.9%, p=0.20). RBC PUFAs were not predictive of baseline IL-6 or IL-17. However, the baseline RBC n-3 Index trended toward an inverse relationship with TNFα-R2 (r = -0.23, p 0.14) Mean dietary intake of n-3 PUFAs did not change over 24 wks for the 30 women with complete FFQ data and blood samples: total n-3 = 1.38 ± 0.70 g/d; EPA = 0.06 ± 0.07 g/d; and DHA = 0.13 ± 0.14 g/d. Dietary EPA and DHA were significantly associated with lower TNFα-R2 (r = -0.40, p=0.02 for both) at 24 wks. RBC total n-3 PUFAs were significantly higher in the n-3 treatment vs placebo group at wk 24 (6.5%±1.0% vs 15.0%±3.3%, p&amp;lt;0.001). RBC EPA+DHA and RBC n-3/n-6 ratio were not predictive of inflammatory cytokines at 24 wks. Conclusions: There was a trend toward lower TNFα-R2 in breast cancer survivors with higher dietary and RBC EPA and DHA before starting AIs, but only dietary intake of EPA and DHA was significantly related to lower TNFα-R2 after 24 wks of AI therapy. Citation Format: Tonya S Orchard, Xueliang Pan, Joanne Lester, Amanda Logan, Charles L Shapiro, Rebecca D Jackson, Martha A Belury, Lisa Yee, Maryam B Lustberg. Relationship of dietary and red blood cell polyunsaturated fatty acids to inflammatory markers in breast cancer survivors taking aromatase inhibitors [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-09-30.

Fish oil and multivitamin supplementation reduces oxidative stress but not inflammation in healthy older adults: A randomised controlled trial

The effects of daily fish oil supplementation, with and without multivitamins, on biochemical markers of health were examined. Healthy adults (N = 160) were randomised to receive 3 g of salmon oil with a multivitamin, 6 g of salmon oil with a multivitamin, 6 g of salmon oil in isolation or placebo in a double-blind fashion on a daily basis for 16 weeks. Relative to placebo, both 6 g salmon oil groups displayed significantly lower F2-isoprostane levels at endpoint. Increases in red blood cell polyunsaturated fatty acids correlated with reductions in F2-isoprostanes. Treatment had no effect on inflammatory cytokines, C-reactive protein, fibrinogen, cholesterol or triacylglycerol.

Bimodal Distribution of Polyunsaturated Fatty Acids in Schizophrenia Suggests Two Endophenotypes of the Disorder

There is conflicting evidence of whether polyunsaturated fatty acids (PUFA) in red blood cells are bimodally distributed in schizophrenia. The purpose of this study was to examine the distribution of PUFA, as well as its links to plausible causal factors. A 16-week cohort study and a case-control study as part of a randomized controlled trial. Ninety-nine patients with DSM-IV schizophrenia, schizoaffective disorder, or schizophreniform disorder, aged 18 to 39, were consecutively included at admission to psychiatric departments of nine Norwegian hospitals. Fatty acids were measured in 97 of these patients and in 20 healthy control subjects. The primary outcome measure was the bimodality test statistic T, assessed by a χ(2) test of the likelihood of one or two normal distributions of PUFA. At baseline, levels of polyunsaturated fatty acids were highly significantly bimodally distributed among patients. One third of patients constituted a group (low PUFA) who had PUFA levels at one fifth (p < .001) of those in high PUFA patients and healthy control subjects, which did not differ. Bimodality was mainly accounted for by docosahexaenoic acid and arachidonic acid. Bimodality was confirmed after 16 weeks. α-tocopherol was a robust predictor of PUFA at both occasions. Desaturase and elongase indexes differed between PUFA groups. Smoking, gender, antipsychotic medication, and dietary factors did not explain the bimodal distribution. Red blood cell PUFA were bimodally distributed among acutely ill patients with schizophrenia and schizoaffective disorder. Endogenous deficiencies of redox regulation or synthesis of long-chain PUFA in the low PUFA group may explain our findings.

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.

Oxidative stress during acute respiratory exacerbations in cystic fibrosis

BACKGROUNDPatients with cystic fibrosis experience chronic systemic oxidative stress. This is coupled with chronic inflammation of the lung involving bronchial polymorphonuclear neutrophil accumulation and activation. We hypothesised that, during periods...