Dataset Information

Circulating long-chain n-3 polyunsaturated fatty acid and incidence of stroke: a meta-analysis of prospective cohort studies.

ABSTRACT: Circulating long-chain (LC) n-3 polyunsaturated fatty acid (PUFA) can provide objective measures that reflect both dietary consumption and relevant biological processes. Nevertheless, prospective cohort studies on circulating LC n-3 PUFA in relation to incidence of stroke have yielded inconsistent results. We therefore conducted a meta-analysis to quantitatively evaluate the association.A total of 2,836 stroke events occurred among 20,460 individuals aged 35-79 yr from 10 prospective cohort studies. Circulating LC n-3 PUFA was significantly associated with reduced risk of stroke (RR: 0.86; 95% CI: 0.76, 0.98; I2 = 0.00%), especially 22:5n-3 (RR: 0.74; 95% CI: 0.60, 0.92) and 22:6n-3 (RR: 0.78; 95% CI: 0.65, 0.94). The associations were more pronounced with ischemic stroke (RR: 0.81; 95% CI: 0.68, 0.96), but not with hemorrhagic stroke (RR: 0.95; 95% CI: 0.60, 1.49). A 1% increment of 22:5n-3 and 22:6n-3 proportions in circulating blood was associated with 25% (RR: 0.75; 95% CI: 0.64, 0.87) and 11% (RR: 0.89; 95% CI: 0.83, 0.95) reduced risk of stroke, respectively.Pertinent studies were identified from Cochrane Library, PubMed and EMBASE database through June 2017. Multivariate-adjusted risk ratios (RRs) with 95% confidence interval (CI) for incident stroke when comparing the top with the bottom tertiles of baseline LC n-3 PUFA proportions in blood were pooled using a random-effect model.Circulating LC n-3 PUFAs were linearly associated with reduced risk of stroke, especially 22:5n-3 and 22:6n-3. Such findings highlight the importance of circulating LC n-3 PUFA in the development of ischemic stroke.

SUBMITTER: Yang B

PROVIDER: S-EPMC5663554 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Circulating long-chain n-3 polyunsaturated fatty acid and incidence of stroke: a meta-analysis of prospective cohort studies.

Yang Bo B Ren Xiao-Li XL Huang Hong H Guo Xiao-Juan XJ Ma Ai-Guo AG Li Duo D

Oncotarget 20170725 48

<h4>Background</h4>Circulating long-chain (LC) n-3 polyunsaturated fatty acid (PUFA) can provide objective measures that reflect both dietary consumption and relevant biological processes. Nevertheless, prospective cohort studies on circulating LC n-3 PUFA in relation to incidence of stroke have yielded inconsistent results. We therefore conducted a meta-analysis to quantitatively evaluate the association.<h4>Results</h4>A total of 2,836 stroke events occurred among 20,460 individuals aged 35-79 ...[more]

PMID: 29137382

Similar Datasets

Project description:Higher circulating polyunsaturated fatty acids (PUFAs), especially omega-3 fatty acids, have been linked to a better prognosis in patients of coronavirus disease 2019 (COVID-19). However, the effects and causality of pre-infection PUFA levels remain unclear. This study aimed to investigate the observational and causal associations of circulating PUFAs with COVID-19 susceptibility and severity. We first performed a prospective cohort study in UK Biobank, with 20,626 controls who were tested negative and 4,101 COVID-19 patients, including 970 hospitalized ones. Plasma PUFAs at baseline (blood samples collected from 2007 to 2010) were measured by nuclear magnetic resonance, including total PUFAs, omega-3 PUFAs, omega-6 PUFAs, docosahexaenoic acid (DHA), linoleic acid (LA), and the omega-6/omega-3 ratio. Moreover, going beyond UK Biobank, we leveraged summary statistics from existing genome-wide association studies to perform bidirectional two-sample Mendelian randomization (MR) analyses to examine the causal associations of eight individual PUFAs, measured in either plasma or red blood cells, with COVID-19 susceptibility and severity. In the observational association analysis of each PUFA measure separately, total, omega-3, and omega-6 PUFAs, DHA, and LA were associated with a lower risk of severe COVID-19. Omega-3 PUFAs and DHA were also associated with a lower risk of testing positive for COVID-19. The omega-6/omega-3 ratio was positively associated with risks of both susceptibility and severity. When omega-6, omega-3, and their ratio are jointly analyzed, only omega-3 PUFAs remained significantly and inversely associated with both susceptibility and severity. The forward MR analysis indicated that docosapentaenoic acid (DPA-n3) and arachidonic acid (AA) might be causally associated with a lower risk of severe COVID-19, with OR (95% CI) per one SD increase in the plasma level as 0.89 (0.81, 0.99) and 0.96 (0.94, 0.99), respectively. The reverse MR analysis did not support any causal effect of COVID-19 on PUFAs. Our observational analysis supported that higher circulating omega-3 PUFAs, especially DHA, may lower the susceptibility to and alleviate the severity of COVID-19. Our MR analysis further supported causal associations of DPA-n3 and AA with a lower risk of severe COVID-19.

Project description:BackgroundHigher circulating polyunsaturated fatty acids (PUFAs), especially omega-3 ones, have been linked to a better prognosis in patients of coronavirus disease 2019 (COVID-19). However, the effects and causality of pre-infection PUFA levels remain unclear.ObjectiveTo investigate the observational and causal associations of circulating PUFAs with COVID-19 susceptibility and severity.DesignWe first performed a prospective cohort study in UK Biobank, with 20,626 controls who were tested negative and 4,101 COVID-19 patients, including 970 hospitalized ones. Plasma PUFAs at baseline were measured by nuclear magnetic resonance, including total PUFAs, omega-3 PUFAs, omega-6 PUFAs, docosahexaenoic acid (DHA), linoleic acid (LA), and the omega-6/omega-3 ratio. Moreover, bidirectional two-sample Mendelian randomization (MR) analyses were performed to examine the causal associations of eight individual PUFAs, measured in either plasma or red blood cells, with COVID-19 susceptibility and severity using summary statistics from existing genome-wide association studies.ResultsIn the observational association analysis, total PUFAs, omega-3 PUFAs, omega-6 PUFAs, DHA, and LA were associated with a lower risk of severe COVID-19. Omega-3 PUFAs and DHA were also associated with a lower risk of testing positive for COVID-19. The omega-6/omega-3 ratio was positively associated with risks of both susceptibility and severity. The forward MR analysis indicated that arachidonic acid (AA) and docosapentaenoic acid (DPA-n3) might be causally associated with a lower risk of severe COVID-19, with OR (95% CI) per one SD increase in the plasma level as 0.96 (0.94, 0.99) and 0.89 (0.81, 0.99), respectively. The reverse MR analysis did not support any causal effect of COVID-19 on PUFAs.ConclusionsOur observational analysis supported that higher circulating PUFAs, either omega-3 or omega-6, are protective against severe COVID-19, while omega-3 PUFAs, especially DHA, were also associated with reducing COVID-19 susceptibility. Our MR analysis further supported causal associations of AA and DPA-n3 with a lower risk of severe COVID-19.

Project description:Background Habitual intake of long-chain omega-3 fatty acids, especially eicosapentaenoic and docosahexaenoic acid (EPA+DHA) from fish, has been associated with a lower risk of fatal coronary heart disease (CHD) in population-based studies. Whether that is also the case for patients with CHD is not yet clear. We studied the associations of dietary and circulating EPA+DHA and alpha-linolenic acid, a plant-derived omega-3 fatty acids, with long-term mortality risk after myocardial infarction. Methods and Results We analyzed data from 4067 Dutch patients with prior myocardial infarction aged 60 to 80 years (79% men, 86% on statins) enrolled in the Alpha Omega Cohort from 2002 to 2006 (baseline) and followed through 2018. Baseline intake of fish and omega-3 fatty acids were assessed through a validated 203-item food frequency questionnaire and circulating omega-3 fatty acids were assessed in plasma cholesteryl esters. Hazard ratios (HRs) with 95% CIs were obtained from Cox regression analyses. During a median follow-up period of 12 years, 1877 deaths occurred, of which 515 were from CHD and 834 from cardiovascular diseases. Dietary intake of EPA+DHA was significantly inversely associated with only CHD mortality (HR, 0.69 [0.52-0.90] for >200 versus ≤50 mg/d; HR, 0.92 [0.86-0.98] per 100 mg/d). Similar results were obtained for fish consumption (HRCHD, 0.74 [0.53-1.03] for >40 versus ≤5 g/d; Ptrend: 0.031). Circulating EPA+DHA was inversely associated with CHD mortality (HR, 0.71 [0.53-0.94] for >2.52% versus ≤1.29%; 0.85 [0.77-0.95] per 1-SD) and also with cardiovascular diseases and all-cause mortality. Dietary and circulating alpha-linolenic acid were not significantly associated with mortality end points. Conclusions In a cohort of Dutch patients with prior myocardial infarction, higher dietary and circulating EPA+DHA and fish intake were consistently associated with a lower CHD mortality risk. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03192410.

Project description:Docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (ARA, 20:4n-6) are the major long chain polyunsaturated fatty acids (LCPUFA) of the central nervous system. We examined the alterations in transcriptional profiles in neonate baboon cerebral cortex brain tissue using high-density Affymetrix oligonucleotide arrays ("U133 plus 2.0"). Twelve neonates were divided into 3 groups: Control (C, no DHA-ARA); 1× LCPUFA (L, 0.33%DHA-0.67%ARA); 3× LCPUFA (L3, 1.00%DHA-0.67%ARA). Significance analysis (P < 0.05) of a total of >54,000 probe sets (ps) identified changes in expression levels of 1108 ps, representing 2.05% of the total ps on the oligoarray, with most ps showing <2-fold change. Comparing L and C, 534 ps were upregulated with supplementation, and 574 ps were downregulated. For the L3/C comparisons, 666 ps were upregulated and 442 ps were downregulated. Characterization of differentially regulated genes by gene ontology assign them to diverse biological functions, notably lipid metabolism, ion channel and transport, G-protein and signal transduction, development, visual perception, membrane function, apoptosis, cytoskeleton, peptidases, cell cycle, stress response, kinases and phosphatases, transcription regulation, receptors, and ubiquitin, with about 400 transcripts having no defined function. Of differentially expressed genes involved in lipid metabolism, PLA2G6, a phospholipase recently associated with infantile neuroaxonal dystrophy, was downregulated in both LCPUFA groups. ELOVL5, a PUFA elongase, was the only enzyme in the LCPUFA biosynthetic pathway that was differentially expressed. Mitochondrial fatty acid carrier, CPT2, was among several genes associated with mitochondrial fatty acid oxidation to be downregulated, while the mitochondrial proton carrier, UCP2, was upregulated. PUFA-regulated receptor, Retinoic acid receptor alpha (RARA) was repressed in both groups, while HNF4A, a PUFA regulated factor, was downregulated in L3/C. Genes involved in neural development, TIMM8A, NRG1, SEMA3D and NUMB, were upregulated while HES1 and SIM1 showed decreased expression. LUM, EML2, TIMP3 and TTC8 which have roles in visual perception were upregulated and TIA1, a silencer of COX2 gene translation is upregulated in L3/C. Ingenuity network analysis identified a top network associated with nervous system development and function with EGFR as the outstanding interaction partner. In this network EGFR interacts with genes involved in neural or visual perception, TIMP3, NRG1, ADAM17, EDG7 and FGF7. Quantitative real time-PCR analysis on selected genes confirmed the array results. The L and L3 groups have DHA and ARA content within the ranges observed in human and baboon breastmilk, and thus these data indicate that LCPUFA concentrations within the normal range of human breastmilk induce global changes in gene expression across numerous functions including transcripts involved in neural development, visual perception, etc. Keywords: dietary dose response

Dataset Information

Circulating long-chain n-3 polyunsaturated fatty acid and incidence of stroke: a meta-analysis of prospective cohort studies.

Publications

Circulating long-chain n-3 polyunsaturated fatty acid and incidence of stroke: a meta-analysis of prospective cohort studies.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets