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FADS Polymorphism, Omega-3 Fatty Acids and Diabetes Risk: A Systematic Review.

ABSTRACT: The role of n-3 long chain polyunsaturated fatty acids (LC n-3 PUFA) in reducing the risk of type 2 diabetes (T2DM) is not well established. The synthesis of LC n-3 PUFA requires fatty acid desaturase enzymes, which are encoded by the FADS gene. It is unclear if FADS polymorphism and dietary fatty acid intake can influence plasma or erythrocyte membrane fatty acid profile and thereby the risk of T2DM. Thus, the aim of this systematic review was to assess the current evidence for an effect of FADS polymorphism on T2DM risk and understand its associations with serum/erythrocyte and dietary LC n-3 PUFA. A systematic search was performed using PubMed, Embase, Cochrane and Scopus databases. A total of five studies met the inclusion criteria and were included in the present review. This review identified that FADS polymorphism may alter plasma fatty acid composition and play a protective role in the development of T2DM. Serum and erythrocyte LC n-3 PUFA levels were not associated with risk of T2DM, while dietary intake of LC n-3 PUFA was associated with lower risk of T2DM in one study only. The effect of LC n-3 PUFA consumption on associations between FADS polymorphism and T2DM warrants further investigation.

SUBMITTER: Brayner B

PROVIDER: S-EPMC6024808 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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FADS Polymorphism, Omega-3 Fatty Acids and Diabetes Risk: A Systematic Review.

Brayner Bárbara B Kaur Gunveen G Keske Michelle A MA Livingstone Katherine M KM

Nutrients 20180613 6

The role of n-3 long chain polyunsaturated fatty acids (LC n-3 PUFA) in reducing the risk of type 2 diabetes (T2DM) is not well established. The synthesis of LC n-3 PUFA requires fatty acid desaturase enzymes, which are encoded by the FADS gene. It is unclear if FADS polymorphism and dietary fatty acid intake can influence plasma or erythrocyte membrane fatty acid profile and thereby the risk of T2DM. Thus, the aim of this systematic review was to assess the current evidence ...[more]

PMID: 29899246

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Project description:The relationship between omega-3 polyunsaturated fatty acids (n-3 PUFA) from seafood sources (eicosapentaenoic acid, EPA; docosahexaenoic acid, DHA) or plant sources (alpha-linolenic acid, ALA) and risk of type 2 diabetes mellitus (DM) remains unclear. We systematically searched multiple literature databases through June 2011 to identify prospective studies examining relations of dietary n-3 PUFA, dietary fish and/or seafood, and circulating n-3 PUFA biomarkers with incidence of DM. Data were independently extracted in duplicate by 2 investigators, including multivariate-adjusted relative risk (RR) estimates and corresponding 95 % CI. Generalized least-squares trend estimation was used to assess dose-response relationships, with pooled summary estimates calculated by both fixed-effect and random-effect models. From 288 identified abstracts, 16 studies met inclusion criteria, including 18 separate cohorts comprising 540,184 individuals and 25,670 cases of incident DM. Consumption of fish and/or seafood was not significantly associated with DM (n = 13 studies; RR per 100 g/d = 1·12, 95 % CI = 0·94, 1·34); nor were consumption of EPA+DHA (n = 16 cohorts; RR per 250 mg/d = 1·04, 95 % CI = 0·97, 1·10) nor circulating levels of EPA+DHA biomarkers (n = 5 cohorts; RR per 3 % of total fatty acids = 0·94, 95 % CI = 0·75, 1·17). Both dietary ALA (n = 7 studies; RR per 0·5 g/d = 0·93, 95 % CI = 0·83, 1·04) and circulating ALA biomarker levels (n = 6 studies; RR per 0·1 % of total fatty acid = 0·90, 95 % CI = 0·80, 1·00, P = 0·06) were associated with non-significant trend towards lower risk of DM. Substantial heterogeneity (I²~80 %) was observed among studies of fish/seafood or EPA+DHA and DM; moderate heterogeneity ( < 55 %) was seen for dietary and biomarker ALA and DM. In unadjusted meta-regressions, study location (Asia vs. North America/Europe), mean BMI, and duration of follow-up each modified the association between fish/seafood and EPA+DHA consumption and DM risk (P-interaction ? 0·02 each). We had limited statistical power to determine the independent effect of these sources of heterogeneity due to their high collinearity. The overall pooled findings do not support either major harms or benefits of fish/seafood or EPA+DHA on development of DM, and suggest that ALA may be associated with modestly lower risk. Reasons for potential heterogeneity of effects, which could include true biologic heterogeneity, publication bias, or chance, deserve further investigation.

Project description:BackgroundFatty acid desaturase 1 (FADS1) and 2 (FADS2) genes code respectively for the enzymes delta-5 and delta-6 desaturases which are rate limiting enzymes in the synthesis of polyunsaturated omega-3 and omega-6 fatty acids (FAs). Omega-3 and-6 FAs as well as conjugated linoleic acid (CLA) are present in bovine milk and have demonstrated positive health effects in humans. Studies in humans have shown significant relationships between genetic variants in FADS1 and 2 genes with plasma and tissue concentrations of omega-3 and-6 FAs. The aim of this study was to evaluate the extent of sequence variations within these two genes in Canadian Holstein cows as well as the association between sequence variants and health promoting FAs in milk.ResultsThirty three SNPs were detected within the studied regions of genes including a synonymous mutation (FADS1-07, rs42187261, 306Tyr > Tyr) in exon 8 of FADS1, a non-synonymous mutation (FADS2-14, rs211580559, 294Ala > Val) within FADS2 exon 7, a splice site SNP (FADS2-05, rs211263660), a 3'UTR SNP (FADS2-23, rs109772589), and another 3'UTR SNP with an effect on a microRNA binding site within FADS2 gene (FADS2-19, rs210169303). Association analyses showed significant relations between three out of seven tested SNPs and several FAs. Significant associations (FDR P < 0.05) were recorded between FADS2-23 (rs109772589) and two omega-6 FAs (dihomogamma linolenic acid [C20:3n6] and arachidonic acid [C20:4n6]), FADS1-07 (rs42187261) and one omega-3 FA (eicosapentaenoic acid, C20:5n3) and tricosanoic acid (C23:0), and one intronic SNP, FADS1-01 (rs136261927) and C20:3n6.ConclusionOur study has demonstrated positive associations between three SNPs within FADS1 and FADS2 genes (a SNP within the 3'UTR, a synonymous SNP and an intronic SNP), with three milk PUFAs of Canadian Holstein cows thus suggesting possible involvement of synonymous and non-coding region variants in FA synthesis. These SNPs may serve as potential genetic markers in breeding programs to increase milk FAs that are of benefit to human health.

Project description:ObjectiveTo clarify associations of fish consumption and long chain omega 3 fatty acids with risk of cerebrovascular disease for primary and secondary prevention.DesignSystematic review and meta-analysis.Data sourcesStudies published before September 2012 identified through electronic searches using Medline, Embase, BIOSIS, and Science Citation Index databases.Eligibility criteriaProspective cohort studies and randomised controlled trials reporting on associations of fish consumption and long chain omega 3 fatty acids (based on dietary self report), omega 3 fatty acids biomarkers, or supplementations with cerebrovascular disease (defined as any fatal or non-fatal ischaemic stroke, haemorrhagic stroke, cerebrovascular accident, or transient ischaemic attack). Both primary and secondary prevention studies (comprising participants with or without cardiovascular disease at baseline) were eligible.Results26 prospective cohort studies and 12 randomised controlled trials with aggregate data on 794,000 non-overlapping people and 34,817 cerebrovascular outcomes were included. In cohort studies comparing categories of fish intake the pooled relative risk for cerebrovascular disease for 2-4 servings a week versus ≤ 1 servings a week was 0.94 (95% confidence intervals 0.90 to 0.98) and for ≥ 5 servings a week versus 1 serving a week was 0.88 (0.81 to 0.96). The relative risk for cerebrovascular disease comparing the top thirds of baseline long chain omega 3 fatty acids with the bottom thirds for circulating biomarkers was 1.04 (0.90 to 1.20) and for dietary exposures was 0.90 (0.80 to 1.01). In the randomised controlled trials the relative risk for cerebrovascular disease in the long chain omega 3 supplement compared with the control group in primary prevention trials was 0.98 (0.89 to 1.08) and in secondary prevention trials was 1.17 (0.99 to 1.38). For fish or omega 3 fatty acids the estimates for ischaemic and haemorrhagic cerebrovascular events were broadly similar. Evidence was lacking of heterogeneity and publication bias across studies or within subgroups.ConclusionsAvailable observational data indicate moderate, inverse associations of fish consumption and long chain omega 3 fatty acids with cerebrovascular risk. Long chain omega 3 fatty acids measured as circulating biomarkers in observational studies or supplements in primary and secondary prevention trials were not associated with cerebrovascular disease. The beneficial effect of fish intake on cerebrovascular risk is likely to be mediated through the interplay of a wide range of nutrients abundant in fish.

Project description:BackgroundThe effects of omega-3 fatty acids (FAs), such as eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids, on cardiovascular outcomes are uncertain. We aimed to determine the effectiveness of omega-3 FAs on fatal and non-fatal cardiovascular outcomes and examine the potential variability in EPA vs. EPA+DHA treatment effects.MethodsWe searched EMBASE, PubMed, ClinicalTrials.gov, and Cochrane library databases through June 7, 2021. We performed a meta-analysis of 38 randomized controlled trials of omega-3 FAs, stratified by EPA monotherapy and EPA+DHA therapy. We estimated random-effects rate ratios (RRs) with (95% confidence intervals) and rated the certainty of evidence using GRADE. The key outcomes of interest were cardiovascular mortality, non-fatal cardiovascular outcomes, bleeding, and atrial fibrillation (AF). The protocol was registered in PROSPERO (CRD42021227580).FindingsIn 149,051 participants, omega-3 FA was associated with reducing cardiovascular mortality (RR, 0.93 [0.88-0.98]; p = 0.01), non-fatal myocardial infarction (MI) (RR, 0.87 [0.81-0.93]; p = 0.0001), coronary heart disease events (CHD) (RR, 0.91 [0.87-0.96]; p = 0.0002), major adverse cardiovascular events (MACE) (RR, 0.95 [0.92-0.98]; p = 0.002), and revascularization (RR, 0.91 [0.87-0.95]; p = 0.0001). The meta-analysis showed higher RR reductions with EPA monotherapy (0.82 [0.68-0.99]) than with EPA + DHA (0.94 [0.89-0.99]) for cardiovascular mortality, non-fatal MI (EPA: 0.72 [0.62-0.84]; EPA+DHA: 0.92 [0.85-1.00]), CHD events (EPA: 0.73 [0.62-0.85]; EPA+DHA: 0.94 [0.89-0.99]), as well for MACE and revascularization. Omega-3 FA increased incident AF (RR, 1.26 [1.08-1.48]). EPA monotherapy vs. control was associated with a higher risk of total bleeding (RR: 1.49 [1.20-1.84]) and AF (RR, 1.35 [1.10-1.66]).InterpretationOmega-3 FAs reduced cardiovascular mortality and improved cardiovascular outcomes. The cardiovascular risk reduction was more prominent with EPA monotherapy than with EPA+DHA.FundingNone.

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FADS Polymorphism, Omega-3 Fatty Acids and Diabetes Risk: A Systematic Review.

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FADS Polymorphism, Omega-3 Fatty Acids and Diabetes Risk: A Systematic Review.

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