Association of oily fish intake, sex, age, BMI and APOE genotype with plasma long-chain n-3 fatty acid composition

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

Consumption of fish oil providing amounts of eicosapentaenoic acid and docosahexaenoic acid that can be obtained from the diet reduces blood pressure in adults with systolic hypertension: a retrospective analysis

Background: Although a large number of randomized controlled trials (RCTs) have examined the impact of the n-3 (ω-3) fatty acids EPA (20:5n-3) and DHA (22:6n-3) on blood pressure and vascular function, the majority have used doses of EPA+DHA of > 3 g per d,which are unlikely to be achieved by diet manipulation. Objective: The objective was to examine, using a retrospective analysis from a multi-center RCT, the impact of recommended, dietary achievable EPA+DHA intakes on systolic and diastolic blood pressure and microvascular function in UK adults. Design: Healthy men and women (n = 312) completed a double-blind, placebo-controlled RCT consuming control oil, or fish oil providing 0.7 g or 1.8 g EPA+DHA per d in random order each for 8 wk. Fasting blood pressure 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 eNOS rs1799983 variant. Results: No impact 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) fish oil-induced reduction (mean 5 mmHg) in systolic blood pressure specifically in those with isolated systolic hypertension (n=31). No dose response was observed. Conclusions: These findings indicate that, in those with isolated systolic hypertension, daily doses of EPA+DHA as low as 0.7 g bring about clinically meaningful blood pressure reductions which, at a population level, would be associated with lower cardiovascular disease risk. Confirmation of findings in an RCT where participants are prospectively recruited on the basis of blood pressure status is required to draw definite conclusions

Chromosomal translocations t(4;14), t(11;14) and proliferation rate stratify patients with mature plasma cell myelomas into groups with different survival probabilities: a molecular epidemiologic study on tissue microarrays

Plasma cell myelomas (PMs) exhibit clinical and molecular heterogeneity. To date, morphology and immunohistochemistry on bone marrow trephines are of limited value to stratify patients into different prognostic categories. However, some chromosomal translocations are of prognostic and/or of predictive importance in PMs. In this study, the prognostic significance of morphology, CyclinD1 expression, proliferation index (Mib1) and presence of the translocations FGFR3/IgH [t(4;14)] and CCND1/IgH [t(11;14)] are compared in 119 patients with PM. Immunohistochemistry and fluorescence in situ hybridization analysis were carried out on a tissue microarray containing bone marrow trephines. Hundred and one PMs showed a mature morphology whereas 10 were immature. All but one PM carrying a translocation showed a mature morphology. Patients with a t(4;14) (12%) had a statistically significant shorter 1-year survival (P=0.004), whereas those with a t(11;14) (21%) had a trend towards a better clinical outcome. CyclinD1 protein expression was not significantly associated with survival. Besides the t(4;14), an immature morphology (P<0.001) and a proliferation index (Mib1) of more than 10% (P=0.002) were associated with a significantly worse outcome. A high occurrence of strong CyclinD1 protein expression in the tumor cells was predictive of either a t(11;14) or of a low level amplification of the CCND1 gene, suggesting that different molecular mechanisms may have lead to an over-expression of the CyclinD1 protein in PMs. These findings demonstrate that a high proliferation rate and translocations involving the IgH locus can stratify mature PMs into groups with distinct survival probabilities

Effect of sex and genotype on cardiovascular biomarker response to fish oils: the FINGEN Study

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