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Aspirin and omega-3 fatty acid status interact in the prevention of cardiovascular diseases in Framingham Heart Study.
Block, RC, Shearer, GC, Holub, A, Tu, XM, Mousa, S, Brenna, JT, Harris, WS, Tintle, N
Prostaglandins, leukotrienes, and essential fatty acids. 2021;:102283
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Abstract
BACKGROUND The roles of omega-3 (n3) fatty acids [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] and low-dose aspirin in the primary prevention of ischemic cardiovascular disease (CVD) are controversial. Since omega-3 (n3) fatty acids and aspirin affect cyclooxygenase activity in platelets, there could be a clinically-relevant effect of aspirin combined with a particular n3 fatty acid level present in each individual. METHODS RBC EPA+DHA, arachidonic acid (AA) and docosapentaenoic acid (DPA) were measured in 2500 participants without known CVD in the Framingham Heart Study. We then tested for interactions with reported aspirin use (1004 reported use and 1494 did not) on CVD outcomes. The median follow-up was 7.2 years. RESULTS Having RBC EPA+DHA in the second quintile (4.2-4.9% of total fatty acids) was associated with significantly reduced risk for future CVD events (relative to the first quintile, <4.2%) in those who did not take aspirin (HR 0.54 (0.30, 0.98)), but in those reporting aspirin use, risk was significantly increased (HR 2.16 (1.19, 3.92)) in this quintile. This interaction remained significant when adjusting for confounders. Significant interactions were also present for coronary heart disease and stroke outcomes using the same quintiles. Similar findings were present for EPA and DHA alone but not for DPA and AA. CONCLUSIONS There is a complex interaction between aspirin use and RBC EPA+DHA levels on CVD outcomes. This suggests that aspirin use may be beneficial in one omega-3 environment but harmful in another, implying that a personalized approach to both aspirin use and omega-3 supplementation may be needed.
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Serum Fatty Acids Are Correlated with Inflammatory Cytokines in Ulcerative Colitis.
Wiese, DM, Horst, SN, Brown, CT, Allaman, MM, Hodges, ME, Slaughter, JC, Druce, JP, Beaulieu, DB, Schwartz, DA, Wilson, KT, et al
PloS one. 2016;(5):e0156387
Abstract
BACKGROUND AND AIMS Ulcerative colitis (UC) is associated with increased dietary intake of fat and n-6 polyunsaturated fatty acids (PUFA). Modification of fat metabolism may alter inflammation and disease severity. Our aim was to assess differences in dietary and serum fatty acid levels between control and UC subjects and associations with disease activity and inflammatory cytokines. METHODS Dietary histories, serum, and colonic tissue samples were prospectively collected from 137 UC subjects and 38 controls. Both histologic injury and the Mayo Disease Activity Index were assessed. Serum and tissue cytokines were measured by Luminex assay. Serum fatty acids were obtained by gas chromatography. RESULTS UC subjects had increased total fat and oleic acid (OA) intake, but decreased arachidonic acid (AA) intake vs controls. In serum, there was less percent saturated fatty acid (SFA) and AA, with higher monounsaturated fatty acids (MUFA), linoleic acid, OA, eicosapentaenoic acid (EPA), and docosapentaenoic acid (DPA) in UC. Tissue cytokine levels were directly correlated with SFA and inversely correlated with PUFA, EPA, and DPA in UC subjects, but not controls. 5-aminosalicylic acid therapy blunted these associations. CONCLUSIONS In summary, we found differences in serum fatty acids in UC subjects that correlated with pro-inflammatory tissue cytokines. We propose that fatty acids may affect cytokine production and thus be immunomodulatory in UC.
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Gene expression of desaturase (FADS1 and FADS2) and Elongase (ELOVL5) enzymes in peripheral blood: association with polyunsaturated fatty acid levels and atopic eczema in 4-year-old children.
Chisaguano, AM, Montes, R, Pérez-Berezo, T, Castellote, AI, Guerendiain, M, Bustamante, M, Morales, E, García-Esteban, R, Sunyer, J, Franch, A, et al
PloS one. 2013;(10):e78245
Abstract
BACKGROUND It is unknown if changes in the gene expression of the desaturase and elongase enzymes are associated with abnormal n-6 long chain polyunsaturated fatty acid (LC-PUFA) levels in children with atopic eczema (AE). We analyzed whether mRNA-expression of genes encoding key enzymes of LC-PUFA synthesis (FADS1, FADS2 and ELOVL5) is associated with circulating LC-PUFA levels and risk of AE in 4-year-old children. METHODS AE (n=20) and non-AE (n=104) children participating in the Sabadell cohort within the INfancia y Medio Ambiente (INMA) Project were included in the present study. RT-PCR with TaqMan Low-Density Array cards was used to measure the mRNA-expression of FADS1, FADS2 and ELOVL5. LC-PUFA levels were measured by fast gas chromatography in plasma phospholipids. The relationship of gene expression with LC-PUFA levels and enzyme activities was evaluated by Pearson's rank correlation coefficient, and logistic regression models were used to study its association with risk of developing AE. RESULTS Children with AE had lower levels of several n-6 PUFA members, dihomo-γ-linolenic (DGLA) and arachidonic (AA) acids. mRNA-expression levels of FADS1 and 2 strongly correlated with DGLA levels and with D6D activity. FADS2 and ELOVL5 mRNA-expression levels were significantly lower in AE than in non-AE children (-40.30% and -20.36%; respectively), but no differences were found for FADS1. CONCLUSIONS AND SIGNIFICANCE Changes in the mRNA-expression levels of FADS1 and 2 directly affect blood DGLA levels and D6D activity. This study suggests that lower mRNA-expressions of FADS2 and ELOVL5 are associated with higher risk of atopic eczema in young children.
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Intake levels of dietary long-chain PUFAs modify the association between genetic variation in FADS and LDL-C.
Hellstrand, S, Sonestedt, E, Ericson, U, Gullberg, B, Wirfält, E, Hedblad, B, Orho-Melander, M
Journal of lipid research. 2012;(6):1183-9
Abstract
Polymorphisms of the FA desaturase (FADS) gene cluster have been associated with LDL, HDL, and triglyceride concentrations. Because FADS converts α-linolenic acid (ALA) and linoleic acid into PUFAs, we investigated the interaction between different PUFA intakes and the FADS polymorphism rs174547 (T>C) on fasting blood lipid and lipoprotein concentrations. We included 4,635 individuals (60% females, 45-68 years) from the Swedish population-based Malmö Diet and Cancer cohort. Dietary intakes were assessed by a modified diet history method including 7-day registration of cooked meals. The C-allele of rs174547 was associated with lower LDL concentration (P = 0.03). We observed significant interaction between rs174547 and long-chain ω-3 PUFA intakes on LDL (P = 0.01); the C-allele was only associated with lower LDL among individuals in the lowest tertile of long-chain ω-3 PUFA intakes (P < 0.001). In addition, significant interaction was observed between rs174547 and the ratio of ALA and linoleic FA intakes on HDL (P = 0.03). However, no significant associations between the C-allele and HDL were detected within the intake tertiles of the ratio. Our findings suggest that dietary intake levels of different PUFAs modify the associated effect of genetic variation in FADS on LDL and HDL.
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Decreases in free cholesterol and fatty acid unsaturation in renal cell carcinoma demonstrated by breath-hold magnetic resonance spectroscopy.
Katz-Brull, R, Rofsky, NM, Morrin, MM, Pedrosa, I, George, DJ, Michaelson, MD, Marquis, RP, Maril, M, Noguera, C, Lenkinski, RE
American journal of physiology. Renal physiology. 2005;(4):F637-41
Abstract
Increased utilization of cross-sectional imaging has resulted in increased detection of incidental renal tumors. The noninvasive characterization of renal tissue has important implications for the diagnosis of renal malignancies and treatment monitoring. Recently, multiple breath-hold averaged proton magnetic resonance spectroscopy ((1)H-MRS) performed at high field has enabled the use of this noninvasive metabolic profiling technique for the investigation of the abdomen. Multiple breath-hold averaged (1)H-MRS at high field (3T) was obtained in the kidneys of 10 healthy volunteers and in renal cell carcinoma tumors of 14 patients. The spectra of normal kidneys showed four main groups of resonances: 1) at 5.4-5.6 ppm, attributed to C6 of cholesterol and the unsaturated parts of the olefinic region of fatty acids; 2) at 4.7 ppm, attributed to the residual water signal; 3) at 3.2 ppm, attributed to trimethylamine moiety of choline metabolites; and 4) at 1.3 and 0.9 ppm, attributed to the methylenes and terminal methyls of lipids. The ratio of the signal at 5.4 ppm to that of 1.3 ppm was 19-fold lower in renal cell carcinomas than in healthy kidneys, tied P = 0.0003 Mann-Whitney U-test, suggesting a decrease in both free cholesterol and the degree of unsaturation of fatty acids in the malignant tissue. This metabolic shift is in agreement with previous ex vivo studies of human renal cell carcinoma. The ability to detect renal metabolic shifts noninvasively may improve the specificity of preoperative renal tissue characterization and may provide a new modality for treatment monitoring.
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Rationale and design of the GISSI heart failure trial: a large trial to assess the effects of n-3 polyunsaturated fatty acids and rosuvastatin in symptomatic congestive heart failure.
Tavazzi, L, Tognoni, G, Franzosi, MG, Latini, R, Maggioni, AP, Marchioli, R, Nicolosi, GL, Porcu, M, ,
European journal of heart failure. 2004;(5):635-41
Abstract
BACKGROUND The GISSI Heart Failure project is a large-scale, randomized, double-blind study designed to investigate the effects of n-3 polyunsaturated fatty acids and rosuvastatin on mortality and morbidity in patients with symptomatic heart failure. METHODS AND RESULTS Patients with New York Heart Association classes II to IV heart failure, already receiving optimized recommended therapy, will be recruited in a nation-wide network of more than 300 cardiology and internal medicine services to be randomly allocated to treatment with n-3 polyunsaturated fatty acids (1 g daily) or the corresponding placebo. Patients with no clear indication or contraindication to cholesterol-lowering therapy will be further randomized to receive low-dose rosuvastatin (10 mg daily) or placebo. According to data available in heart failure registries, it is expected that 70% of the patients will be suitable to enter both components of the trial, which assume the same co-primary endpoints: (a) 15% reduction of all-cause mortality and (b) 20% reduction of all-cause mortality or cardiovascular hospitalizations. The trial is event-driven and will continue either until at least 1252 deaths have been recorded or a reduction of all-cause mortality will satisfy the significance boundaries, which have been established to stop the study. The recruitment of the planned sample size of approximately 7000 patients randomized in the n-3 PUFA trial is expected to be completed within 18 months from the trial start. As of February 29, 2004, 4624 heart failure patients have been included in the trial. CONCLUSION The GISSI-HF project, with its protocol articulated into two independent randomization schemes, has the aim and the power to verify the hypothesis that n-3 polyunsaturated fatty acids and rosuvastatin can favorably modify the prognosis of patients with symptomatic heart failure.
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Urinary level of 1,N(6) -ethenodeoxyadenosine, a marker of oxidative stress, is associated with salt excretion and omega 6-polyunsaturated fatty acid intake in postmenopausal Japanese women.
Hanaoka, T, Nair, J, Takahashi, Y, Sasaki, S, Bartsch, H, Tsugane, S
International journal of cancer. 2002;(1):71-5
Abstract
Excretion of 1,N(6)-ethenodeoxyadenosine (epsilon dA), a marker for lipid peroxidation (LPO)-derived DNA damage was analyzed in urine of nonsmoking postmenopausal women participating in a dietary intervention trial in Northern Japan. Hereby the efficacy of dietary consultation in reducing salt and increasing vitamin C and carotenes during 1 year was estimated. Thirty postmenopausal women, 60-69 years of age, from the intervention group and 30 age-matched women from the control group were randomly selected. The subjects completed a self-administered diet history questionnaire and in the pre- and post-intervention period 48 hr urine and fasting blood samples were collected. epsilon dA in urine was analyzed by an immuno-precipitation-high performance liquid chromatography-fluorescence detection method. epsilon dA excretion (/48 hr) in the 59 postmenopausal Japanese women with complete urine collection ranged from 12-226 pmol at the pre-intervention. At the pre-intervention, epsilon dA excretion was positively associated with urinary salt excretion (R = 0.33, p = 0.01) and omega-6 polyunsaturated fatty acid intake (%energy value, R = 0.28, p = 0.03) in the 59 women. The average epsilon dA excretion in the intervention group was 61 pmol at pre-intervention and 44 pmol at post-intervention (p = 0.14). In the control group, it was 58 pmol at pre-intervention and 75 pmol at post-intervention (p = 0.24). During the intervention period, 18/29 (62%) of the subjects in the intervention group exhibited the decreased excretion and 10/26 (38%) in the control group (p = 0.08). Results from this pilot study suggest urinary epsilon dA as a potential biomarker of DNA damage possibly derived from salt-induced inflammation and LPO; further exploration of epsilon dA in human biomonitoring studies is warranted.
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Effects of dietary supplementation with n-3 fatty acids compared with n-6 fatty acids on bronchial asthma.
Okamoto, M, Mitsunobu, F, Ashida, K, Mifune, T, Hosaki, Y, Tsugeno, H, Harada, S, Tanizaki, Y
Internal medicine (Tokyo, Japan). 2000;(2):107-11
Abstract
OBJECTIVE The effects of perilla seed oil (n-3 fatty acids) on bronchial asthma were compared with the effects of corn oil (n-6 fatty acids) in relation to the pulmonary function and the generation of leukotriene B4 (LTB4) and C4 (LTC4) by leucocytes. METHODS AND SUBJECTS 14 asthmatic subjects were divided randomly into two groups: one group (7 subjects) consumed perilla seed oil-rich supplementation and the other group (7 subjects) consumed corn oil-rich supplementation for 4 weeks. Generation of LTs by leucocytes and respiratory function were compared between the two groups. RESULTS The generation of LTB4 and LTC4 by leucocytes tended to increase in subjects (N=7) with corn oil-rich supplementation, and decrease in subjects (N=7) with perilla seed oil-rich supplementation. Significant differences between the two groups were observed in the generation of LTB4 at 2 weeks (p<0.05) and LTC4 at 2 weeks (p<0.05) after dietary supplementation. Significant increases in the value of PEF (p<0.05), FVC (p<0.01), FEV(1.0) (p<0.05) and V(25) (p<0.05) were found in subjects who received perilla seed oil supplementation for 4 weeks. And significant differences in the value of FVC (p<0.05) and FEV(1.0) (p<0.05) were observed between the two groups after 4 weeks of dietary supplementation. CONCLUSION These results suggest that perilla seed oil-rich supplementation is useful for the treatment of asthma in terms of suppression of LTB4 and LTC4 generation by leucocytes, and improvement of pulmonary function.