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1.
Br J Nutr ; 120(1): 23-32, 2018 07.
Article in English | MEDLINE | ID: mdl-29729672

ABSTRACT

n-3 Fatty acids are associated with better cardiovascular and cognitive health. However, the concentration of EPA, DPA and DHA in different plasma lipid pools differs and factors influencing this heterogeneity are poorly understood. Our aim was to evaluate the association of oily fish intake, sex, age, BMI and APOE genotype with concentrations of EPA, DPA and DHA in plasma phosphatidylcholine (PC), NEFA, cholesteryl esters (CE) and TAG. Healthy adults (148 male, 158 female, age 20-71 years) were recruited according to APOE genotype, sex and age. The fatty acid composition was determined by GC. Oily fish intake was positively associated with EPA in PC, CE and TAG, DPA in TAG, and DHA in all fractions (P≤0·008). There was a positive association between age and EPA in PC, CE and TAG, DPA in NEFA and CE, and DHA in PC and CE (P≤0·034). DPA was higher in TAG in males than females (P<0·001). There was a positive association between BMI and DPA and DHA in TAG (P<0·006 and 0·02, respectively). APOE genotype×sex interactions were observed: the APOE4 allele associated with higher EPA in males (P=0·002), and there was also evidence for higher DPA and DHA (P≤0·032). In conclusion, EPA, DPA and DHA in plasma lipids are associated with oily fish intake, sex, age, BMI and APOE genotype. Such insights may be used to better understand the link between plasma fatty acid profiles and dietary exposure and may influence intake recommendations across population subgroups.


Subject(s)
Age Factors , Apolipoproteins E/genetics , Body Mass Index , Diet , Fatty Acids, Omega-3/blood , Fish Oils , Sex Factors , Adult , Aged , Alleles , Animals , Cholesterol Esters/blood , Cross-Over Studies , Double-Blind Method , Fatty Acids, Unsaturated/blood , Female , Fishes , Genotype , Humans , Male , Middle Aged , Phosphatidylcholines/blood , United Kingdom , Young Adult
2.
J Nutr ; 146(3): 516-23, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26817716

ABSTRACT

BACKGROUND: Although many randomized controlled trials (RCTs) have examined the effects of the n-3 (ω-3) fatty acids eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3) on blood pressure (BP) and vascular function, the majority have used doses of EPA+DHA of >3 g/d, which are unlikely to be achieved by dietary manipulation. OBJECTIVE: The objective was to examine, by using a retrospective analysis from a multicenter RCT, the impact of recommended EPA+DHA intakes achievable through diet on systolic and diastolic BPs and microvascular function in adults in the United Kingdom. METHODS: In a double-blind, placebo-controlled RCT, healthy men and women (n = 312) consumed a control oil or fish oil (FO) providing 0.7 or 1.8 g EPA+DHA/d, in random order, each for 8 wk. Fasting BP and microvascular function (using laser Doppler iontophoresis) were assessed and plasma collected for the quantification of markers of vascular function. Participants were retrospectively genotyped for the endothelial nitric oxide synthase (eNOS) rs1799983 variant. RESULTS: No effects of n-3 fatty acid treatment or any treatment × eNOS genotype interactions were evident in the group as a whole for any of the clinical or biochemical outcomes. Assessment of response according to hypertension status at baseline indicated a significant (P = 0.046) FO-induced reduction (mean: 5 mm Hg) in systolic BP, specifically in those with isolated systolic hypertension (n = 31). No dose response was observed. CONCLUSIONS: These findings indicate that in adults with isolated systolic hypertension, daily doses of EPA+DHA as low as 0.7 g show clinically meaningful BP reductions, which, at a population level, could be associated with lower cardiovascular disease risk. Confirmation of findings in an RCT in which participants are prospectively recruited on the basis of BP status is required to draw definite conclusions.


Subject(s)
Blood Pressure/drug effects , Docosahexaenoic Acids/administration & dosage , Eicosapentaenoic Acid/administration & dosage , Fish Oils/administration & dosage , Hypertension/blood , Adult , Body Mass Index , Cross-Over Studies , Diet , Docosahexaenoic Acids/blood , Double-Blind Method , E-Selectin/blood , Eicosapentaenoic Acid/blood , Female , Fish Oils/blood , Humans , Intercellular Adhesion Molecule-1/blood , Male , Middle Aged , Nitric Oxide Synthase Type III/genetics , P-Selectin/blood , Retrospective Studies , United Kingdom , Vascular Cell Adhesion Molecule-1/blood
3.
Atherosclerosis ; 221(2): 467-70, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22365656

ABSTRACT

Here the impact of APOE genotype on CHD risk in UK adults is reported, along with an analysis of APOE genotype × BMI/age/sex interactions. APOE genotype had a significant impact on fasting total:LDL-cholesterol (TC:LDL-C) ratio, triglycerides, % HDL3, and the Framingham 10-year CVD risk score (P<0.05), with an overall trend towards lower and higher risk in E2- and E4-carriers, respectively, relative to the wild-type E3/E3 genotype. A greater impact of genotype on TC:HDL-C was observed in females, which explained 16% of the variability in this outcome versus 6% in males. APOE genotype was also associated with plasma C-reactive protein and adhesion molecule concentrations (P<0.05), with significant genotype × BMI interactions observed. Our observations indicate that the association between the APOE genotype and CHD risk is unlikely to be homogenous and highlights the risk of inaccurate estimations of genotype-phenotype associations in population subgroups without appropriate stratification for sex and adiposity.


Subject(s)
Adiposity/genetics , Apolipoproteins E/genetics , Cardiovascular Diseases/genetics , Adult , Age Factors , Biomarkers/blood , Body Mass Index , C-Reactive Protein/analysis , Cardiovascular Diseases/blood , Cardiovascular Diseases/physiopathology , Cell Adhesion Molecules/blood , Cholesterol/blood , Cholesterol, LDL/blood , Female , Genetic Predisposition to Disease , Humans , Inflammation Mediators/blood , Linear Models , Male , Middle Aged , Phenotype , Prospective Studies , Risk Assessment , Risk Factors , Sex Factors , Triglycerides/blood , United Kingdom
4.
Mol Nutr Food Res ; 54(12): 1842-50, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20658496

ABSTRACT

SCOPE: Paraoxonase-1 (PON-1), associated with HDL, is regarded as anti-atherogenic, attributed to its ability to hydrolyze oxidized lipids. Here, the impact of PON and apolipoprotein E genotypes, age, alcohol and HDL-cholesterol (HDL-C) on PON activity is examined. METHODS AND RESULTS: In total, 104 healthy UK adults participated in the study, with basal (PONA) and stimulated (PONB) PON-1 activities and arylesterase activity determined in these individuals. In univariate and correlation analysis age, HDL-C, alcohol intake and both PON genotypes were significantly associated with PONA and PONB activities (p<0.05). However, in the standard linear regression model, which explained 69% of the variability in both PONA (p<0.001) and PONB activities (p<0.001) only PON Q192R genotype emerged as a significant independent determinant, with four to fivefold higher levels in the RR versus wild-type QQ genotype groups. For PON arylesterase, HDL-C (p=0.030), apolipoprotein E (p=0.023) and PON Q192R (p=0.002) and PON L55M (p=0.002) genotypes collectively explained 14% of the total variability in the regression model. CONCLUSION: Our results indicate that PON genotypes are stronger determinants of PON activity relative to the other potential modulators assessed. The relative impact of dietary components on PON activities remains to be established.


Subject(s)
Apolipoproteins E/genetics , Apolipoproteins E/metabolism , Aryldialkylphosphatase/genetics , Aryldialkylphosphatase/metabolism , Adult , Age Factors , Aged , Alcohols/administration & dosage , Carboxylic Ester Hydrolases/metabolism , Cholesterol, HDL/blood , Female , Genotype , Humans , Linear Models , Male , Middle Aged , Young Adult
5.
Am J Clin Nutr ; 88(3): 618-29, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18779276

ABSTRACT

BACKGROUND: The lipid-modulatory effects of high intakes of the fish-oil fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are well established and likely to contribute to cardioprotective benefits. OBJECTIVES: We aimed to determine the effect of moderate EPA and DHA intakes (<2 g EPA+DHA/d) on the plasma fatty acid profile, lipid and apolipoprotein concentrations, lipoprotein subclass distribution, and markers of oxidative status. We also aimed to examine the effect of age, sex, and apolipoprotein E (APOE) genotype on the observed responses. DESIGN: Three hundred twelve adults aged 20-70 y, who were prospectively recruited according to age, sex, and APOE genotype, completed a double-blind placebo-controlled crossover study. Participants consumed control oil, 0.7 g EPA+DHA/d (0.7FO), and 1.8 g EPA+DHA/d (1.8FO) capsules in random order, each for an 8-wk intervention period, separated by 12-wk washout periods. RESULTS: In the group as a whole, 8% and 11% lower plasma triacylglycerol concentrations were evident after 0.7FO and 1.8FO, respectively (P < 0.001): significant sex x treatment (P = 0.038) and sex x genotype x treatment (P = 0.032) interactions were observed, and the greatest triacylglycerol-lowering responses (reductions of 15% and 23% after 0.7FO and 1.8FO, respectively) were evident in APOE4 men. Furthermore, lower VLDL-cholesterol (P = 0.026) and higher LDL-cholesterol (P = 0.010), HDL-cholesterol (P < 0.001), and HDL2 (P < 0.001) concentrations were evident after fish-oil intervention. CONCLUSIONS: Supplements providing EPA+DHA at doses as low as 0.7 g/d have a significant effect on the plasma lipid profile. The results of the current trial, which used a prospective recruitment approach to examine the responses in population subgroups, are indicative of a greater triacylglycerol-lowering action of long-chain n-3 polyunsaturated fatty acids in males than in females.


Subject(s)
Biomarkers/analysis , Diet , Fatty Acids/analysis , Fish Oils/administration & dosage , Genotype , Oils/chemistry , Sex Characteristics , Adult , Aged , Apolipoproteins/blood , Fatty Acids, Nonesterified/analysis , Female , Humans , Lipoproteins/blood , Male , Middle Aged , United Kingdom
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