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Scope: Tissue concentrations of omega-3 fatty acids may reduce cardiovascular disease risk, and genetic variants are associated with circulating fatty acids concentrations. Whether dietary fatty acids interact with genetic variants to modify circulating omega-3 fatty acids is unclear. We evaluated interactions between genetic variants and fatty acid intakes for circulating alpha-linoleic acid, eicosapentaenoic acid, docosahexaenoic acid, and docosapentaenoic acid., Methods and Results: We conducted meta-analyses (N = 11 668) evaluating interactions between dietary fatty acids and genetic variants (rs174538 and rs174548 in FADS1 (fatty acid desaturase 1), rs7435 in AGPAT3 (1-acyl-sn-glycerol-3-phosphate), rs4985167 in PDXDC1 (pyridoxal-dependent decarboxylase domain-containing 1), rs780094 in GCKR (glucokinase regulatory protein), and rs3734398 in ELOVL2 (fatty acid elongase 2)). Stratification by measurement compartment (plasma versus erthyrocyte) revealed compartment-specific interactions between FADS1 rs174538 and rs174548 and dietary alpha-linolenic acid and linoleic acid for docosahexaenoic acid and docosapentaenoic acid., Conclusion: Our findings reinforce earlier reports that genetically based differences in circulating fatty acids may be partially due to differences in the conversion of fatty acid precursors. Further, fatty acids measurement compartment may modify gene-diet relationships, and considering compartment may improve the detection of gene-fatty acids interactions for circulating fatty acid outcomes., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Very long-chain saturated fatty acids (VLSFAs) are saturated fatty acids with 20 or more carbons. In contrast to the more abundant saturated fatty acids, such as palmitic acid, there is growing evidence that circulating VLSFAs may have beneficial biological properties. Whether genetic factors influence circulating levels of VLSFAs is not known. We investigated the association of common genetic variation with plasma phospholipid/erythrocyte levels of three VLSFAs by performing genome-wide association studies in seven population-based cohorts comprising 10,129 subjects of European ancestry. We observed associations of circulating VLSFA concentrations with common variants in two genes, serine palmitoyl-transferase long-chain base subunit 3 (SPTLC3), a gene involved in the rate-limiting step of de novo sphingolipid synthesis, and ceramide synthase 4 (CERS4). The SPTLC3 variant at rs680379 was associated with higher arachidic acid (20:0 , P = 5.81 × 10(-13)). The CERS4 variant at rs2100944 was associated with higher levels of 20:0 (P = 2.65 × 10(-40)) and in analyses that adjusted for 20:0, with lower levels of behenic acid (P = 4.22 × 10(-26)) and lignoceric acid (P = 3.20 × 10(-21)). These novel associations suggest an inter-relationship of circulating VLSFAs and sphingolipid synthesis., (Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.)

Few epidemiological studies have examined the association between an overall fatty acid (FA) profile and CHD risk. The aim of the present study was to examine a novel index that summarises individual FA levels based on FA affinity and fluidity in relation to CHD risk in men. In a prospective nested case–control study, FA in plasma and erythrocytes were measured in 459 CHD cases and 879 matched controls. Lipophilic index (LI) was computed by summing the products between FA levels and melting point of each FA to reflect the overall FA lipophilicity. Among controls, higher plasma LI was significantly correlated with adverse profiles of blood lipids, inflammatory markers and adiponectin. After multivariate adjustment for age, smoking, BMI and other CHD risk factors, plasma LI was significantly associated with an increased risk of CHD: the relative risk was 1·61 (95% CI 1·03, 2·53; P for trend¼0·04) comparing extreme quintiles. This association was attenuated to 1·21 (95% CI 0·48, 3·09; P for trend¼0·77) after adjusting for plasma levels of total trans-FA, long-chain n-3 FA and polyunsaturated:saturated fat ratio. Erythrocyte LI was not significantly associated with CHD risk. The present data indicate that a novel LI is associated with an adverse profile of cardiovascular risk markers and increased risk of CHD in men; its usefulness as a complement of individual FA in assessing disease risk needs to be elucidated in future studies.

Purpose: We investigated effects of ground whole flaxseed supplementation on erythrocyte polyunsaturated fatty acids (PUFAs) and serum biomarkers of inflammation, endothelial dysfunction, oxidative stress, and thrombosis in Chinese with risk factors of metabolic syndrome (MetS)., Methods: This study was a secondary analysis of a 12-week, randomized, parallel-group trial in participants screened for MetS. The analysis included only those with 2 or more components of MetS before receiving either lifestyle counseling (LC, n = 90) or LC + 30 g/day flaxseed supplementation (LCF, n = 83)., Results: Compared to the LC group, those in the LCF group experienced significant increases in total erythrocyte n-3 PUFAs, α-linolenic acid, eicosapentenoic acid, and docosapentenoic acid (all P < 0.001), while total n-6 PUFAs (P < 0.05) and n-6/n-3 ratio decreased (P < 0.001). Arachidonic acid increased significantly in the LC group (P < 0.001), and serum high-sensitivity C-reactive protein, interleukin-18, soluble intracellular adhesion molecular-1, E-selectin, and plasminogen activator inhibitor-1 declined significantly in both groups (all P < 0.05), but no between-group differences were observed. There was no significant change in serum interleukin-6, tumor necrosis factor-α, soluble vascular adhesion molecular-1, monocyte chemoattractant protein-1, and oxidized low-density lipoprotein in either group., Conclusions: These data suggest that flaxseed supplementation increases erythrocyte n-3 PUFAs, decreases n-6 PUFAs and n-6/n-3 ratio in participants with risk factors of MetS, but has no additional benefits beyond the lifestyle consulting for the multiple biomarkers tested in the current study.

The lipophilic index (LI), a mean measure of fatty acid melting points, has been proposed to capture overall fatty acid profile and may play an important role in the etiology of coronary heart disease. We aimed to determine the association between LI in diet and in adipose tissue and metabolic risk factors for myocardial infarction (MI) and risk of MI. We used a population-based, matched case-control study of nonfatal first acute MI conducted in Costa Rica between 1994 and 2004, with 1,627 case-control pairs. The LI is defined as the mean of the melting points of specific fatty acids in diet or adipose tissue. LIs in diet and adipose tissue were significantly associated with higher plasma triglyceride concentrations, low-density lipoprotein cholesterol concentrations, and low-density:high-density lipoprotein cholesterol ratio. Comparing extreme quintiles for the LI in diet or adipose tissue, the odds ratios for MI were 1.57 (95% confidence interval: 1.22, 2.02; P for trend < 0.001) for dietary LI and 1.30 (95% confidence interval: 1.00, 1.69; P for trend = 0.02) for adipose tissue LI in the multivariable models. We hypothesize that a higher LI in diet and in adipose tissue represents decreased fatty acid fluidity and could play an important role in the etiology of coronary heart disease.