Red Blood Cell Polyunsaturated Fatty Acids Research Articles

Red Blood Cell Polyunsaturated Fatty Acid Composition and Mortality Following Breast Cancer: Results From the Women's Healthy Eating and Living (WHEL) Study

Purpose: To examine the associations between red blood cell (RBC) composition of polyunsaturated fatty acids (PUFAs) and mortality among women with breast cancer. Methods: This nested case-control study included 1,104 women from the Women's Healthy Eating and Living Study, a randomized controlled trial of a plant-based dietary change on breast cancer survival. Cases were women who died from any cause (n = 290) from 1995 to 2006. Controls were women who were alive at the end of follow-up matched to cases on age at diagnosis, years since randomization, intervention group, and stage (n = 814). RBC fatty acid composition was measured in blood samples collected at baseline using gas chromatography and included the proportions of four n-3 and seven n-6 PUFAS. We examined each PUFA individually as well as factor analysis-derived factors in association with all-cause and breast cancer-specific mortality using conditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results: In fully-adjusted models, all-cause mortality ORs were elevated among women with PUFAs >median (versus ≤ median) for alpha-linolenic acid (ALA, C18:3n3; OR = 1.56; 95% CI = 1.14–2.14) and for linolenic acid (LnA, C18:2n6, OR = 1.54; 95% CI = 1.15–2.07), and breast cancer-specific mortality ORs were elevated for LnA (OR = 1.72, 95% CI = 1.24–2.38) and gamma-linolenic acid (GLA, C18:3n6; OR = 1.40; 95% CI = 0.97–2.00). Factor 1 [arachidonic acid, C20:4n6; adrenic acid, C22:4n6; and docosapentaenoic acid, C22:5n6] scores >median (versus ≤median) were associated with lower odds of all-cause (OR = 0.72; 95% CI = 0.53–0.98) and breast cancer-specific (OR = 0.67; 95% CI = 0.47–0.94) mortality, and Factor 4 [ALA and GLA] scores >median (versus ≤median) were associated with increased odds of breast cancer-specific mortality (OR = 1.42; 95% CI = 1.01–2.01). Additionally, 1-SD increase in Factor 4 scores were associated with ORs of 1.22 (95% CI = 1.04–1.42) for all-cause mortality and 1.24 (95% CI = 1.05–1.47) for breast cancer-specific mortality. Conclusions: RBC PUFA composition profiles are associated with all-cause and breast cancer-specific mortality risk among women with breast cancer.

A prospective analysis of red blood cell membrane polyunsaturated fatty acid levels and risk of non-Hodgkin lymphoma

Published studies report inconsistent associations of polyunsaturated fatty acid (PUFA) intake with non-Hodgkin lymphoma (NHL) risk. We conducted a nested case-control study in Nurses’ Health Study and Health Professionals Follow-Up Study participants to evaluate a hypothesis of inverse association of pre-diagnosis red blood cell (RBC) membrane PUFA levels with risk of NHL endpoints. We confirmed 583 NHL cases and matched 583 controls by cohort/sex, age, race and blood draw date/time. We estimated odds ratios (OR) and 95% confidence intervals (CI) for risk of NHL endpoints using logistic regression. RBC PUFA levels were not associated with all NHL risk; cis 20:2n-6 was associated with follicular lymphoma risk (OR [95% CI] per one standard deviation increase: 1.35 [1.03–1.77]), and the omega-6/omega-3 PUFA ratio was associated with diffuse large B-cell lymphoma risk (2.33 [1.23–4.43]). Overall, PUFA did not demonstrate a role in NHL etiology; the two unexpected positive associations lack clear biologic explanations.

Red blood cell fatty acids and age-related macular degeneration in postmenopausal women.

To evaluate the relationship between red blood cell (RBC) polyunsaturated fatty acid (PUFA) levels, and dietary PUFA and fish intake, with prevalent and incident age-related macular degeneration (AMD) in a US cohort of postmenopausal women. This analysis included 1456 postmenopausal women from the Women's Health Initiative (WHI) Clinical Trials. RBC PUFAs were measured from fasting serum samples collected at WHI baseline. Dietary PUFAs and fish intake were assessed via food frequency questionnaires at baseline. There were 240 women who had prevalent AMD and 138 who self-reported AMD development over 9.5years. Adjusted odds ratios and 95% confidence intervals were estimated for prevalent AMD by RBC PUFA levels, dietary PUFA intake, and frequency of fish consumption. Adjusted hazard ratios and 95% confidence intervals were estimated for incident AMD. A p-for-trend was estimated for continuous measures of dietary PUFA and fish intake. No significant association was found between prevalent or incident AMD and RBC docosahexaenoic acid (DHA) + eicosapentaenoic acid (EPA), EPA, DHA, alpha-linolenic acid (ALA), linoleic acid (LA), or arachidonic acid (AA). A positive association was found between dietary intake of AA and odds of prevalent AMD (p-for-trend for continuous AA intake = 0.02) and between intake of LA/ALA and incident AMD (p-for-trend for continuous ratio of LA/ALA intake = 0.03). No statistically significant associations were found between AMD and dietary intake of PUFAs or fish. RBC PUFAs were not associated with AMD in this cohort. Overall, dietary analyses of PUFAs supported this, excepting dietary AA intake and intake of LA in proportion to ALA of which there were trends of increased risk.

Plasma and Red Blood Cell PUFAs in Home Parenteral Nutrition Paediatric Patients-Effects of Lipid Emulsions.

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.

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.

Predictors of change in omega-3 index with fish oil supplementation in peripheral artery disease

BackgroundThe omega-3 index represents the red blood cell (RBC) content of two major long-chain n-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid, and docosahexaenoic acid. We sought to determine factors associated with a favorable response to fish oil treatment and to characterize changes in RBC PUFAs associated with fish oil supplementation. MethodsThis study was a secondary analysis of the OMEGA-PAD I trial, a randomized, double-blinded, placebo-controlled trial investigating short-duration, high-dose n-3 PUFA oral supplementation on endothelial function and inflammation in subjects with peripheral arterial disease. Patients with mild to severe claudication received either 4.4 g of fish oil providing 2.6 g of eicosapentaenoic acid and 1.8 g of docosahexaenoic acid daily (n = 40) or placebo capsules (n = 40) for 1 mo. The RBC fatty acid content was measured by gas chromatography and expressed as a percent of total fatty acids. The change in omega-3 index was calculated as the difference between pre- and post-supplementation in the fish oil and placebo groups. Univariate analysis identified predictors of change in omega-3 index, with these variables included in our multivariable model. ResultsIn the fish oil group, there was an increase in the omega-3 index (5.1± 1.3% to 9.0± 1.8%; P < 0.0001), whereas there was no change in the control group. Factors associated with a favorable response (i.e., greater than the median change of 4.06%) included a lower body mass index and higher concentrations of low-density lipoproteins. Other demographic and/or lifestyle factors such as age, race, or smoking status were unrelated to the response. Oral n-3 PUFA supplementation also decreased the n-6 PUFA content in RBCs. ConclusionsShort-term, high-dose n-3 PUFA supplementation increases the omega-3 index to a greater extent in patients with a lower body mass index and higher total and low-density lipoprotein cholesterol levels.

Polyunsaturated Fatty Acid (PUFA) Status in Pregnant Women: Associations with Sleep Quality, Inflammation, and Length of Gestation.

Mechanistic pathways linking maternal polyunsaturated fatty acid (PUFA) status with gestational length are poorly delineated. This study examined whether inflammation and sleep quality serve as mediators, focusing on the antiinflammatory ω-3 docosahexaenoic acid (DHA; 22:6n3) and proinflammatory ω-6 arachidonic acid (AA; 20:4n6). Pregnant women (n = 135) provided a blood sample and completed the Pittsburgh Sleep Quality Index (PSQI) at 20–27 weeks gestation. Red blood cell (RBC) fatty acid levels were determined by gas chromatography and serum inflammatory markers [interleukin (IL)-6, IL-8, tumor necrosis factor-α, IL-1β, and C-reactive protein] by electrochemiluminescence using high sensitivity kits. Both higher serum IL-8 (95% CI = 0.10,3.84) and poor sleep (95% CI = 0.03,0.28) served as significant mediators linking lower DHA:AA ratios with shorter gestation. Further, a serial mediation model moving from the DHA:AA ratio → sleep → IL-8 → length of gestation was statistically significant (95% CI = 0.02, 0.79). These relationships remained after adjusting for depressive symptoms, age, BMI, income, race, and smoking. No interactions with race were observed in relation to length of gestation as a continuous variable. However, a significant interaction between race and the DHA:AA ratio in predicting preterm birth was observed (p = 0.049); among African Americans only, odds of preterm birth decreased as DHA:AA increased (p = 0.048). These data support a role for both inflammatory pathways and sleep quality in linking less optimal RBC PUFA status with shorter gestation in African American and European American women and suggest that African-Americans have greater risk for preterm birth in the context of a low DHA:AA ratio.

Abstract 285: Rapid Change In Red Blood Cell PUFA Composition With High-dose Fish Oil Supplementation In Patients With Peripheral Artery Disease (PAD).

Introduction: Current guidelines recommend a diet rich in fish or n-3 polyunsaturated fatty acid (PUFA) supplementation in patients with cardiovascular disease including PAD. The omega-3 index represents the red blood cell (RBC) content of the two major long-chain n-3 PUFA, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) with less within-patient variation compared to plasma levels of n-3 PUFA. We aimed to quantify the change in the omega-3 index with high-dose n-3 PUFA supplementation in a PAD cohort. Methods: This study was a secondary analysis of the OMEGA-PAD I Trial (NCT01310270), a randomized, double-blinded, placebo-controlled trial addressing the hypothesis that short-duration, high-dose n-3 PUFA oral supplementation improves endothelial function and inflammation in subjects with PAD. Eighty patients with stable claudication received 4.4g of fish oil (2.6g of EPA + 1.8g of DHA) daily (n=40) or placebo capsules (n=40) for 1 month. The RBC fatty acids (FA) content was measured by gas chromatography (OmegaQuant Analytics, Sioux Falls, SD) and expressed as a percent of total FA. Results: There was no difference in baseline PUFA content between the two groups. There was a shift in the n-6:n-3 ratio in RBC from 5 ± 1 to 3 ± 1 (p&lt;0.0001) and the omega-3 index increased from 5 ± 1 to 9 ± 2 (p&lt;0.0001) in the fish but not in the placebo group (Table). There was a significant increase in EPA, DHA, and n-3 docosapentaenoic acid and a significant decrease in all n-6 PUFA content of RBC in the fish oil but not in the placebo group. Following treatment, there was also a significant reduction in plasma triglycerides (-34 ± 46, p&lt;0.001) in the fish oil group. The change in triglycerides was significantly correlated with the change in omega-3 index (p=0.03). Conclusions: High-dose fish oil supplementation increases the omega-3 index and reduces n-6 PUFA levels. The implications of these changes for patients with PAD will continue to be investigated in a follow-up trial (OMEGA-PAD II).

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.

Evaluation of Red Blood Cell Lipoperoxidation in Hemodialysed Patients during Erythropoietin Therapy Supplemented or Not with Iron

To investigate the effects of erythropoietin (rHuEPO) therapy supplemented or not with iron on hemolysis in hemodialysed patients (HD) we evaluated lipoperoxidation (LPO) by assaying (i) the red blood cell (RBC) antioxidant enzymatic system including superoxide dismutase (SOD), glutathione peroxidase, and catalase (Cat), (ii) RBC polyunsaturated fatty acids (PUFA) and (iii) malondialdehyde (MDA). Group 1 included 12 HD patients, group 2 had 7 HD patients with iron supplementation, group 3 comprised 12 HD patients with rHuEPO therapy and group 4 included 9 HD patients with both iron and rHuEPO therapies. No LPO was found in group 1 as regards MDA and PUFA levels. However, SOD and Cat activities were significantly elevated as compared to controls (p < 0.001). In the second group, a significant decrease in PUFA percentage was observed, particularly in 20:4(n-6) and 22:4(n-6) (the main ones involved in LPO) as compared to the other groups, whereas total MDA level was higher than that of the other groups. Similarly a decreased SOD activity was observed as compared to group 1 (p < 0.001), indicating its inactivation subsequent to an hyperproduction of reactive oxygen species through iron injection. In groups 3 and 4 no change was observed in MDA levels or PUFA percentages indicating no LPO. However, marked differences were observed in the enzymatic defense system. Particularly in group 3, SOD and Cat activities decreased when compared to group 1 (p < 0.001) whereas the association of erythropoietin and iron (group 4) increased the three enzymatic activities (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)