Plasma Omega-3 Polyunsaturated Fatty Acids Research Articles

The value of plasma omega-3 polyunsaturated fatty acids in predicting the response and prognosis of cervical squamous cell carcinoma patients to concurrent chemoradiotherapy.

Background: In recent years, abnormalities in plasma omega-3 polyunsaturated fatty acids (omega-3 PUFAs) have been proven to be related to the risk of cancer, but their prognostic value for cancer is unclear. The purpose of this study was to retrospectively evaluate the response and prognostic significance of plasma omega-3 PUFAs in patients with cervical squamous cell carcinoma (CSCC) treated with concurrent chemoradiotherapy (CCRT). Spearman rank correlation analysis was used to analyze the correlation between omega-3 PUFAs and squamous cell carcinoma antigen (SCC-Ag) levels. Methods: A total of 89 patients with CSCC who underwent CCRT were evaluated retrospectively. Binary logistic regression analysis was used to analyze the independent predictors related to complete response (CR) after CCRT. A Cox proportional hazard model and Kaplan-Meier analysis were utilized to perform survival analysis. Results: According to multivariate logistic regression analyses, a high level of plasma EPA was independently correlated with an increased incidence of CR after CCRT (odds ratio (OR), 0.980; 95% confidence interval (CI), 0.962-0.999, p = 0.038). With a median follow-up of 41.3months, the CSCC patients in the high EPA (≥46.0nmol/mL) group exhibited longer OS and PFS. According to our multivariate analysis, pretreatment plasma EPA level was an independent prognostic factor for PFS in patients with CSCC who underwent CCRT (hazard ratio (HR), 0.263; 95% CI, 0.089-0.782, p = 0.016). However, it was not an independent prognostic factor of OS. Spearman rank correlation analysis revealed was a negative correlation between pretreatment SCC-Ag (pre SCC-Ag) levels and EPA levels (r = -0.305, p = 0.004), and a weak negative correlation between posttreatment SCC-Ag (post SCC-Ag) levels and EPA levels (r = -0.251, p = 0.018). Conclusion: Plasma omega-3 PUFAs are related to the response and survival outcome of patients with CSCC who underwent CCRT. Pretreatment plasma EPA levels may be a promising biomarker for predicting the response and prognosis of patients with CSCC who undergo CCRT. In addition, the pretreatment plasma EPA levels presented a negative correlation with the SCC-Ag levels.

Causal associations of plasma omega-3 polyunsaturated fatty acids with sarcopenia-related traits: a two-sample Mendelian randomization study.

To evaluate the causal effect of plasma omega-3 polyunsaturated fatty acids (PUFAs) on sarcopenia-related traits (lean mass, grip strength and walking pace) utilizing two-sample Mendelian randomization (MR) approach. Based on genome-wide association study (GWAS) summary statistics, we performed two-sample MR applying the inverse variance weighted (IVW) as the primary method, supplemented with four additional sensitivity analyses. Furthermore, multivariable MR (MVMR) was applied to assess these associations independent of alcohol drinking, type 2 diabetes (T2D), triglycerides (TG), estimated glomerular filtration rate (eGFR) and C-reactive protein (CRP). In univariable MR, the IVW analysis suggested no significant causal effect of genetically determined plasma omega-3 PUFAs on fat-free mass (right leg: β = 0.01, 95% CI = -0.02 to 0.05, P = 0.375; left leg: β = 0.01, 95% CI = -0.02 to 0.04, P = 0.446; right arm: β = 0.01, 95% CI = -0.02 to 0.05, P = 0.376; left arm: β = 0.01, 95% CI = -0.02 to 0.04, P = 0.384; trunk:β = 0.02, 95% CI = -0.02 to 0.06, P = 0.283; whole: β = 0.01, 95% CI = -0.03 to 0.04, P = 0.631), grip strength (right hand: β = -0.01, 95% CI = -0.03 to 0.01, P = 0.387; left hand: β = -0.01, 95% CI = -0.02 to 0.01, P = 0.553) and walking pace (β = 0.00, 95% CI = -0.01 to 0.02, P = 0.575), and sensitive analysis generated similar non-significant results. Furthermore, the MVMR revealed no independent causal association. Genetically determined plasma omega-3 PUFAs have no causal effect on sarcopenia-related traits.

Plasma omega-3 polyunsaturated fatty acids and recurrence of endometrial cancer

BackgroundOmega-3 polyunsaturated fatty acids (PUFAs) were proposed to have potential effects against inflammation and cancer. However, results from epidemiology studies remain inconsistent. We aimed to explore the associations of plasma PUFAs with EC recurrence and all-cause mortality.MethodWomen diagnosed with endometrial cancer (EC) between 2008 and 2013 and underwent surgery at Fudan University Shanghai Cancer Center of China were recruited. Survival status was followed up through September 2017. EC recurrence and total cause deaths were identified through medical record and telephone interview. In total, 202 patients with enough plasma samples at time of surgery were included. There were 195 patients who provided baseline plasma and survival information included in the current study. Plasma omega-3 PUFAs were measured by GC-FID. Cox Proportional Hazard model adjusted for potential cofounders was used to estimate HRs and 95% CIs.ResultsMedian follow-up time for patients was 58 months after surgery. A total of 13 recurrences and 11 all-cause deaths, of which, 2 deaths from EC, were identified. Level of plasma EPA was higher in recurrent patients than total patients (0.78% vs 0.51%, P = 0.015). Higher plasma eicosapentaenoic acid (EPA) level trended to have positive association with EC recurrence (P-trend = 0.04), although comparing to the lowest tertile, the highest tertile of EPA level was not significantly associated with increased risk of EC recurrence (HRT3vsT1 = 6.02; 95%CI = 0.7–52.06). The association between total omega-3 PUFA and EC recurrence tended to be stronger among patients with deeper myometrial invasion (OR = 3.41; 95%CI = 1.06–10.95; P-interaction = 0.04).ConclusionsHigher plasma EPA level was significantly associated with EC recurrence. Further studies are warranted to confirm these findings.Trial registrationChiCTR1900025418; Retrospectively registered (26 August 2019); Chinses Clinical Trial Registry.

Genetically Determined Omega-3 Polyunsaturated Fatty Acids and Lung Function: A Mendelian Randomization Analysis

Abstract Objectives Cross-sectional studies have found positive associations of plasma omega-3 polyunsaturated fatty acids (N-3 PUFAs) and lung function parameters, including the forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC). We used Mendelian randomization (MR) to address potential limitations in previous findings, including residual confounding and reverse causality, and improve causal inference for the relationship of N-3 PUFAs on lung function. Methods We instrumented the N-3 PUFAs alpha-linolenic acid (ALA), eicosapentanoic acid (EPA), docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA) with genetic variants in the fatty acid desaturase (FADS1/FADS2) and fatty acid elongase (ELOVL2) genes. We performed two sample MR, using genome-wide association data for N-3 PUFAs in the Cohorts for Heart and Aging Research in Genetic Epidemiology Consortium and for FEV1 and FVC in the UK Biobank. We also performed multivariable MR (MVMR) including linoleic acid (LA), the main dietary N-6 PUFA, to account for shared genetic predictors. We used the Wald's ratio or inverse variance weighted method in all analyses. Results In univariable MR, ALA was negatively associated with FEV1 (−0.27 ± 0.13 SD/% total FA, P = 0.02), while EPA was positively associated with FEV1 (0.05 ± 0.02 SD/% total FA, P = 0.02). The DPA—FEV1 association was similar to EPA (P = 0.05). These results align with the opposing effects of FADS1/2 variants on ALA vs EPA and DPA. DHA was not associated with FEV1 and there were no statistically significant N-3 PUFA—FVC associations. Using GWAS estimates adjusted for correlated N3-PUFAs did not alter these results. In MVMR including LA, the ALA—FEV1 associations were strengthened (P = 0.007), while the EPA—and DPA—FEV1 associations were no longer statistically significant. Conclusions Our analyses suggest that higher ALA has a direct negative effect on lung function, while the positive effects of EPA and DPA may be through the balance of N-3 and N-6 PUFA metabolism. However, interpretation of MVRM findings when modeling metabolic pathways needs further consideration. Funding Sources This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health Training Program (T32) in Translational Nutrition Research at Cornell University.

Plasma long-chain omega-3 polyunsaturated fatty acids and macular pigment in subjects with family history of age-related macular degeneration: the Limpia Study.

In numerous epidemiological studies, omega-3 polyunsaturated fatty acids (PUFAs) have been associated with a decreased risk of age-related macular degeneration (AMD). Beyond their structural, functional and neuroprotective roles, omega-3 PUFAs may favour the retinal accumulation of lutein and zeaxanthin and thus increase macular pigment optical density (MPOD). We examined the associations of MPOD with plasma omega-3 PUFAs in subjects with family history of AMD. The Limpia study is a double-blind, placebo-controlled, prospective randomized clinical trial performed in 120 subjects. Subjects with at least one parent treated for neovascular AMD, aged 40-70, with a best corrected visual acuity (BCVA) >20/25, free of late AMD and other major eye conditions and with no use of supplement containing lutein or zeaxanthin the preceding year were recruited in Bordeaux and Dijon, France. At baseline, MPOD within 1° of eccentricity was measured by modified Heidelberg retinal analyser (Heidelberg, Germany) and plasma omega-3 PUFAs by gas chromatography. Medical history and lifestyle data were collected from a standardized questionnaire. Associations of MPOD with plasma omega-3 PUFAs were assessed at the baseline examination, using mixed linear models adjusted for age, gender, centre, body mass index, smoking, plasma high-density lipoprotein (HDL) cholesterol and lutein+zeaxanthin. After multivariate adjustment, high MPOD was significantly associated with higher level of plasma docosapentaenoic acid (DPA) (β=0.029, 95% CI: 0.003, 0.055; p=0.03). Plasma alpha linolenic, eicosapentaenoic and docosahexaenoic acids were not significantly associated with MPOD. In the Limpia study, high MPOD within 1° was significantly associated with higher plasma levels of omega-3 DPA.

Maternal fish consumption, fatty acid levels and angiogenic factors: The Generation R Study

IntroductionAngiogenic factors, such as placental growth factor (PlGF) and soluble Flt-1 (sFlt-1), are key regulators of placental vascular development. Evidence from in vitro studies indicates that fatty acids can affect angiogenesis. We investigated the associations of maternal fish consumption and fatty acids levels with angiogenic factors during pregnancy, and in cord blood in a large population-based prospective cohort. MethodsFirst trimester fish consumption was assessed among 3134 pregnant women using a food-frequency questionnaire. Plasma fatty acid levels were measured in second trimester. Plasma PlGF and sFlt-1 were measured in first and second trimester and in cord blood. Associations of fish consumption or fatty acid levels with angiogenic factors were assessed by multivariable linear regression analyses. ResultsThere were no consistent associations of total fish or lean fish consumption with levels of PlGF, sFlt-1, or sFlt-1/PlGF ratio. Neither fatty fish nor shellfish were associated with angiogenic factors. Plasma omega-3 polyunsaturated fatty acids, which are the main type of fatty acids in fish, were inconsistently associated with angiogenic factors in second trimester and cord blood. Yet, higher levels of arachidonic acid, an omega-6 polyunsaturated fatty acid, were associated with lower levels of PlGF and sFlt-1. DiscussionWe found no consistent associations of fish consumption or fatty acids levels with angiogenic factors in a population with low fish consumption. Studies including populations with higher fish consumption are required to fully grasp the potential effects of maternal fish consumption on placental angiogenesis.

Low levels of plasma omega 3-polyunsaturated fatty acids are associated with cerebral small vessel diseases in acute ischemic stroke patients

Cerebral small vessel diseases (SVDs) are related to stroke or cognitive dysfunction. n-3-polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) represent possible disease-modifying factors for cardiovascular disease or dementia. Our hypothesis was that a low proportion of plasma FAs would be associated with cerebral SVDs. We prospectively enrolled 220 patients with a first-episode cerebral infarction within 7days after symptom onset. The composition of plasma FAs was analyzed by gas chromatography methods. The presence and burden of cerebral microbleeds (CMBs), high-grade white matter changes (HWCs), high-grade perivascular spaces (HPVSs), and asymptomatic lacunar infarctions (ALIs) were investigated. The mean proportion (±SD) was 2.0 ± 0.7 for EPA, 8.9 ± 1.5 for DHA, and 12.0 ± 2.1 for ∑ n-3-PUFAs. In total, 46 (20.9%) patients had CMBs, 64 (29.1 %) had HWCs, 57 (25.9%) had HPVSs, and 65 (29.5%) had ALIs. In univariate analyses, CMBs, HWCs, and HPVSs were each negatively correlated with the proportion of EPA, DHA, and ∑ n-3-PUFAs. In the multivariate analysis, a lower proportion of EPA, DHA and ∑ n-3-PUFAs was associated with the presence of CMBs, HWCs and HPVS, but not ALIs. Total SVDs score was inversely correlated with the proportion of EPA, DHA and ∑ n-3-PUFAs. Overall, we found an association between low proportions of plasma n-3-PUFAs and cerebral SVDs pathologies. Further studies are needed to explore the association and potential therapeutic role of FAs in cerebral SVDs.

Plasma Omega-3 Polyunsaturated Fatty Acids and Survival in Patients with Chronic Heart Failure and Major Depressive Disorder

The omega-3 fatty acid (FA) concentration is low in patients with coronary heart disease (CHD). Supplement of omega-3 FA improves cardiovascular outcomes in patients with CHD and heart failure (HF). However, plasma omega-3 FA and its role for prognosis in HF patients have not been examined previously. In this study, we explore the prognostic value of omega-3 polyunsaturated FA in HF patients with major depressive disorder (MDD). Plasma was obtained from HF patients with MDD who participated in the Sertraline Against Depression and Heart Disease in Chronic Heart Failure trial. FA methyl esters were analyzed by the method of a flame ionization detector. Weight percent is the unit of the omega compounds. The primary outcome was survival which was analyzed using Cox proportional hazards regression modeling. A total of 109 depressed HF patients had adequate volume for completion of the FA assays. Plasma total omega-3 (hazard ratio [HR] 0.65, 95% confidence interval [CI] 0.43-0.98) and EPA_(0.1 unit) (HR 0.73, 95% CI 0.56-0.96) were significantly associated with survival of patients with HF and co-morbid MDD. The results suggest that low plasma omega-3 FA is a significant factor for reduced survival in HF patients with MDD.

Dietary Perilla Seed Oil Supplement Increases Plasma Omega-3 Polyunsaturated Fatty Acids and Ameliorates Immunoglobulin A Nephropathy in High Immunoglobulin A Strain of ddY Mice

Background/Aims: The beneficial effects of omega-3 polyunsaturated fatty acids (n–3 PUFA) in the treatment of immunoglobulin A nephropathy (IgAN) have been reported. Perilla frutescens (Linn.) Britton var. frutescens is grown in Eastern Asia and its seed (perilla seed) is rich in α-linolenic acid, an n–3 PUFA. We investigated the antinephritic effects of perilla seed oil in a mouse model of IgAN. Methods: Ten-week-old high IgA ddY mice were fed diets containing either perilla seed oil (PS group) or corn oil (C group, control). After 20 weeks, we compared body weight, blood pressure, serum creatinine levels, IgA levels, fatty acid composition, urinary protein excretion, mesangial matrix expansion, and glomerular transforming growth factor-β₁ mRNA expression between groups. Results: Serum n–3 PUFA levels were higher in the PS group than the C group (p < 0.001). Blood urea nitrogen levels were lower (p = 0.0246) and urinary protein excretion was reduced (p = 0.0198) in the PS group. Mesangial matrix expansion (p = 0.0063) and glomerular transforming growth factor-β₁ mRNA expression (p = 0.0291) were suppressed in the PS group. No significant differences between groups were found in body weight, blood pressure, serum IgA, and creatinine levels. Conclusions: Dietary perilla seed oil supplement could suppress the progression of IgAN.