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Plasma Omega-3 Fatty Acids and the Risk of Cardiovascular Events in Patients After an Acute Coronary Syndrome in MERLIN-TIMI 36.
Zelniker, TA, Morrow, DA, Scirica, BM, Furtado, JD, Guo, J, Mozaffarian, D, Sabatine, MS, O'Donoghue, ML
Journal of the American Heart Association. 2021;(8):e017401
Abstract
Background Plasma omega-3 polyunsaturated fatty acids (ω3-PUFAs) have been shown to be inversely correlated with the risk of cardiovascular death in primary prevention. The risk relationship in the setting of an acute coronary syndrome is less well established. Methods and Results Baseline plasma ω3-PUFA composition (α-linolenic acid, eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid) was assessed through gas chromatography with flame ionization detection in a case-cohort study involving 203 patients with cardiovascular death, 325 with myocardial infarction, 271 with ventricular tachycardia, and 161 with atrial fibrillation, and a random sample of 1612 event-free subjects as controls from MERLIN-TIMI 36 (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST-Elevation-Acute Coronary Syndrome-Thrombolysis in Myocardial Infarction 36), a trial of patients hospitalized with non-ST-segment-elevation -acute coronary syndrome. After inverse-probability-weighted multivariable adjustment including all traditional risk factors, a higher relative proportion of long-chain ω3-PUFAs (eicosapentaenoic acid, docosapentaenoic acid, docosahexaenoic acid) were associated with 18% lower odds of cardiovascular death (adjusted [adj] odds ratio [OR] per 1 SD, 0.82; 95% CI, 0.68-0.98) that was primarily driven by 27% lower odds of sudden cardiac death (adj OR per 1 SD, 0.73; 95% CI, 0.55-0.97). Long-chain ω3-PUFA levels in the top quartile were associated with 51% lower odds of cardiovascular death (adj OR 0.49; 95% CI, 0.27-0.86) and 63% lower odds of sudden cardiac death (adj OR, 0.37; 95% CI, 0.16-0.56). An attenuated relationship was seen for α-linolenic acid and subsequent odds of cardiovascular (adj OR, 0.92; 95% CI, 0.74-1.14) and sudden cardiac death (adj OR, 0.91; 95% CI, 0.67-1.25). No significant relationship was observed between any ω3-PUFAs and the odds of cardiovascular death unrelated to sudden cardiac death, myocardial infarction, atrial fibrillation, or early post-acute coronary syndrome ventricular tachycardia. Conclusions In patients after non-ST-segment-elevation-acute coronary syndrome, plasma long-chain ω3-PUFAs are inversely associated with lower odds of sudden cardiac death, independent of traditional risk factors and lipids. Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT00099788.
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Effects of omega-3 fatty acids on metabolic syndrome in patients with schizophrenia: a 12-week randomized placebo-controlled trial.
Xu, F, Fan, W, Wang, W, Tang, W, Yang, F, Zhang, Y, Cai, J, Song, L, Zhang, C
Psychopharmacology. 2019;(4):1273-1279
Abstract
RATIONALE Individuals with schizophrenia are at increased risk of developing metabolic syndrome (MetS) due to their lifestyle and antipsychotic treatment. Our previous study showed that patients with both schizophrenia and MetS present an increased expression and production of tumor necrosis factor-alpha (TNF-alpha). Omega-3 fatty acids have a documented role in suppressing TNF-alpha; therefore, we hypothesized that they may be of value in relieving inflammation and improving metabolic disturbance in patients with both schizophrenia and MetS. OBJECTIVES This study employed a randomized placebo-controlled trial to investigate the effects of omega-3 fatty acids on MetS in patients with schizophrenia. METHODS We recruited 80 patients with both schizophrenia and MetS who received long-term olanzapine monotherapy. The patients were randomly assigned to the OMG-3 group (n = 40) or the placebo group (n = 40). RESULTS Patients with both schizophrenia and MetS had significantly higher levels of TNF-alpha than the control subjects (Z = - 4.37, P < 0.01). There was a significant correlation between omega-3 fatty acid treatment and reduced triglyceride (TG) levels (Fgroup × time = 13.42; df = 1, 66; P < 0.01) when the patients completed this study. Along with metabolic improvement, omega-3 fatty acids decreased TNF-alpha levels after 12 weeks of treatment (Fgroup × time = 6.71; df = 1, 66; P = 0.012). We also found that the extent of TNF-alpha decrease was significantly correlated with that of TG decrease (r = 0.38, P = 0.001). CONCLUSIONS Our findings provide suggestive evidence that omega-3 fatty acids have beneficial effects on TG metabolism in patients with both schizophrenia and MetS that parallel decreased inflammation levels.
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Abnormal lipoprotein oxylipins in metabolic syndrome and partial correction by omega-3 fatty acids.
Shearer, GC, Borkowski, K, Puumala, SL, Harris, WS, Pedersen, TL, Newman, JW
Prostaglandins, leukotrienes, and essential fatty acids. 2018;:1-10
Abstract
Metabolic syndrome (MetSyn) is characterized by chronic inflammation which mediates the associated high risk for cardiovascular and other diseases. Oxylipins are a superclass of lipid mediators with potent bioactivities in inflammation, vascular biology, and more. While their role as locally produced agents is appreciated, most oxylipins in plasma are found in lipoproteins suggesting defective regulation of inflammation could be mediated by the elevated VLDL and low HDL levels characteristic of MetSyn. Our objective was to compare the oxylipin composition of VLDL, LDL, and HDL in 14 optimally healthy individuals and 31 MetSyn patients, and then to determine the effects of treating MetSyn subjects with 4g/day of prescription omega-3 fatty acids (P-OM3) on lipoprotein oxylipin profiles. We compared oxylipin compositions of healthy (14) and MetSyn (31) subjects followed by randomization and assignment to 4g/d P-OM3 for 16 weeks using LC/MS/MS. Compared to healthy subjects, MetSyn is characterized by abnormalities of (1) pro-inflammatory, arachidonate-derived oxylipins from the lipoxygenase pathway in HDL; and (2) oxylipins mostly not derived from arachidonate in VLDL. P-OM3 treatment corrected many components of these abnormalities, reducing the burden of inflammatory mediators within peripherally circulating lipoproteins that could interfere with, or enhance, local effectors of inflammatory stress. We conclude that MetSyn is associated with a disruption of lipoprotein oxylipin patterns consistent with greater inflammatory stress, and the partial correction of these dysoxylipinemias by treatment with omega-3 fatty acids could explain some of their beneficial effects.
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The Effects of Flaxseed Oil Omega-3 Fatty Acids Supplementation on Metabolic Status of Patients with Polycystic Ovary Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial.
Mirmasoumi, G, Fazilati, M, Foroozanfard, F, Vahedpoor, Z, Mahmoodi, S, Taghizadeh, M, Esfeh, NK, Mohseni, M, Karbassizadeh, H, Asemi, Z
Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association. 2018;(4):222-228
Abstract
OBJECTIVE This study was conducted to evaluate the effects of flaxseed oil omega-3 fatty acids supplementation on metabolic status of patients with polycystic ovary syndrome (PCOS). METHODS This randomized double-blind, placebo-controlled trial was conducted on 60 women with PCOS according to the Rotterdam criteria aged 18-40 years old. Participants were randomly assigned into two groups to receive either 1,000 mg flaxseed oil omega-3 fatty acids (n=30) or placebo (n=30) twice a day for 12 weeks. Metabolic, endocrine, inflammatory factors were quantified at baseline and after the 12-week intervention. RESULTS After the 12-week intervention, compared to the placebo, flaxseed oil omega-3 supplementation significantly decreased insulin values (-2.6±7.7 vs.+1.3±3.9 µIU/mL, P=0.01), homeostasis model of assessment-estimated insulin resistance (-0.7±1.7 vs.+0.3±0.9, P=0.01), mF-G scores (-1.2±1.7 vs. -0.1±0.4, P=0.001), and increased quantitative insulin sensitivity check index (+0.01±0.02 vs. -0.01±0.02, P=0.01). In addition, supplementation with flaxseed oil omega-3 resulted in significant decreases in serum triglycerides (-5.1±20.9 vs.+9.7±26.1 mg/dL, P=0.01), VLDL-cholesterol (-1.0±4.2 vs.+1.9±5.2 mg/dL, P=0.01) and high-sensitivity C-reactive protein (hs-CRP) (-1.6±3.1 vs.+0.2±1.5 mg/L, P=0.004) compared to the placebo. We did not see any significant effect of flaxseed oil omega-3 supplementation on hormonal and other lipid profiles, and plasma nitric oxide levels. CONCLUSIONS Overall, flaxseed oil omega-3 supplementation for 12 weeks in women with PCOS had beneficial effects on insulin metabolism, mF-G scores, serum triglycerides, VLDL-cholesterol and hs-CRP levels, but did not affect hormonal and other lipid profiles, and plasma nitric oxide levels.
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Dietary supplementation with omega-3 fatty acids and oleate enhances exercise training effects in patients with metabolic syndrome.
Ortega, JF, Morales-Palomo, F, Fernandez-Elias, V, Hamouti, N, Bernardo, FJ, Martin-Doimeadios, RC, Nelson, RK, Horowitz, JF, Mora-Rodriguez, R
Obesity (Silver Spring, Md.). 2016;(8):1704-11
Abstract
OBJECTIVE We studied the effects of exercise training alone or combined with dietary supplementation of omega-3 polyunsaturated fatty acids (Ω-3PUFA) and oleate on metabolic syndrome (MSyn) components and other markers of cardiometabolic health. METHODS Thirty-six patients with MSyn underwent 24 weeks of high-intensity interval training. In a double-blind randomized design, half of the group ingested 500 mL/day of semi-skim milk (8 g of fat; placebo milk) whereas the other half ingested 500 mL/day of skim milk enriched with 275 mg of Ω-3PUFA and 7.5 g of oleate (Ω-3 + OLE). RESULTS Ω-3 + OLE treatment elevated 30% plasma Ω-3PUFA but not significantly (P = 0.286). Improvements in VO2peak (12.8%), mean blood pressure (-7.1%), waist circumference (-1.8%), body fat mass (-2.9%), and trunk fat mass (-3.3%) were similar between groups. However, insulin sensitivity (measured by intravenous glucose tolerance test), serum concentration of C-reactive protein, and high-density lipoprotein improved only in the Ω-3 + OLE group by 31.5%, 32.1%, and 10.3%, respectively (all P < 0.05). Fasting serum triacylglycerol, glucose, and plasma fibrinogen concentrations did not improve in either group after 24 weeks of intervention. CONCLUSIONS Diet supplementation with Ω-3PUFA and oleate enhanced cardiometabolic benefits of intense aerobic exercise training in patients with MSyn.
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One month of omega-3 fatty acid supplementation improves lipid profiles, glucose levels and blood pressure in overweight schoolchildren with metabolic syndrome.
García-López, S, Villanueva Arriaga, RE, Nájera Medina, O, Rodríguez López, CP, Figueroa-Valverde, L, Cervera, EG, Muñozcano Skidmore, O, Rosas-Nexticapa, M
Journal of pediatric endocrinology & metabolism : JPEM. 2016;(10):1143-1150
Abstract
BACKGROUND This study sought to investigate the effects of omega (ω)-3 polyunsaturated fatty acid (PUFA) supplementation on the lipid profiles and glucose (GLU) levels of overweight (OW) schoolchildren with metabolic syndrome (MS). METHODS Thirty-nine OW schoolchildren with MS, including 19 girls and 20 boys, received 1-month of dietary supplementation with gel capsules containing ω-3 fatty acids. Fasting lipid profiles and GLU levels were measured before and after supplementation. RESULTS Both sexes of OW schoolchildren with MS who received daily supplementation with 2.4 g of ω-3 fatty acids for 1 month displayed improved lipid profiles, reduced fasting GLU levels and reduced blood pressure (BP). CONCLUSIONS These findings support the addition of omega-3 fatty acid supplementation to programs aiming to improve the metabolic status of OW children with MS, although additional research on the longer-term safety and efficacy of this treatment in this population is required.
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Insulin resistance determines a differential response to changes in dietary fat modification on metabolic syndrome risk factors: the LIPGENE study.
Yubero-Serrano, EM, Delgado-Lista, J, Tierney, AC, Perez-Martinez, P, Garcia-Rios, A, Alcala-Diaz, JF, Castaño, JP, Tinahones, FJ, Drevon, CA, Defoort, C, et al
The American journal of clinical nutrition. 2015;(6):1509-17
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Abstract
BACKGROUND Previous data support the benefits of reducing dietary saturated fatty acids (SFAs) on insulin resistance (IR) and other metabolic risk factors. However, whether the IR status of those suffering from metabolic syndrome (MetS) affects this response is not established. OBJECTIVE Our objective was to determine whether the degree of IR influences the effect of substituting high-saturated fatty acid (HSFA) diets by isoenergetic alterations in the quality and quantity of dietary fat on MetS risk factors. DESIGN In this single-blind, parallel, controlled, dietary intervention study, MetS subjects (n = 472) from 8 European countries classified by different IR levels according to homeostasis model assessment of insulin resistance (HOMA-IR) were randomly assigned to 4 diets: an HSFA diet; a high-monounsaturated fatty acid (HMUFA) diet; a low-fat, high-complex carbohydrate (LFHCC) diet supplemented with long-chain n-3 polyunsaturated fatty acids (1.2 g/d); or an LFHCC diet supplemented with placebo for 12 wk (control). Anthropometric, lipid, inflammatory, and IR markers were determined. RESULTS Insulin-resistant MetS subjects with the highest HOMA-IR improved IR, with reduced insulin and HOMA-IR concentrations after consumption of the HMUFA and LFHCC n-3 diets (P < 0.05). In contrast, subjects with lower HOMA-IR showed reduced body mass index and waist circumference after consumption of the LFHCC control and LFHCC n-3 diets and increased HDL cholesterol concentrations after consumption of the HMUFA and HSFA diets (P < 0.05). MetS subjects with a low to medium HOMA-IR exhibited reduced blood pressure, triglyceride, and LDL cholesterol levels after the LFHCC n-3 diet and increased apolipoprotein A-I concentrations after consumption of the HMUFA and HSFA diets (all P < 0.05). CONCLUSIONS Insulin-resistant MetS subjects with more metabolic complications responded differently to dietary fat modification, being more susceptible to a health effect from the substitution of SFAs in the HMUFA and LFHCC n-3 diets. Conversely, MetS subjects without IR may be more sensitive to the detrimental effects of HSFA intake. The metabolic phenotype of subjects clearly determines response to the quantity and quality of dietary fat on MetS risk factors, which suggests that targeted and personalized dietary therapies may be of value for its different metabolic features. This study was registered at clinicaltrials.gov as NCT00429195.
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Effects of niacin and omega-3 fatty acids on the apolipoproteins in overweight patients with elevated triglycerides and reduced HDL cholesterol.
Savinova, OV, Fillaus, K, Harris, WS, Shearer, GC
Atherosclerosis. 2015;(2):520-5
Abstract
OBJECTIVE Prescription omega-3 acid ethyl esters (P-OM3) and extended release niacin (ERN) both have beneficial effects on plasma lipids and lipoproteins. The purpose of this study was to describe the effects of mono- and combination (Combo) therapy of these agents in patients with the metabolic syndrome. METHODS Very low density (VLDL), intermediate/low density (IDL/LDL, hereafter LDL), and high density lipoproteins (HDL) were isolated from 56 overweight patients with elevated triglyceride/HDL-C ratios at baseline and after 16 weeks of treatment with placebo, ERN (2g/day), P-OM3 (4g/day), or Combo and then analyzed by quantitative electrophoresis for apolipoproteins (apo) A1, A2, B, C2, C3 and E. Total plasma concentrations and the ratios of each apo with apoB (in VLDL and LDL) and with apoA1 (in HDL) were calculated. An apoC3 glycosylation index (a ratio between di- and mono-sialylated isoforms) was also determined in plasma and in each lipoprotein fraction. RESULTS ERN reduced plasma apoB (-11%, p < 0.05). Combo increased LDL apoE/apoB ratio (64%, p < 0.01) and LDL apoA1/apoB (91%, p < 0.05). ERN increased the apoC3 glycosylation index only in HDL (37%, p < 0.05), whereas P-OM3 and Combo increased the index in whole plasma (48% and 49%, respectively, p < 0.05 for both) and in every lipoprotein class (VLDL: 26%, p < 0.01 and 26%, p < 0.05; LDL: 55%, p < 0.01 and 61%, p < 0.01; HDL: 43%, p < 0.001 and 44%, p < 0.001, respectively). All findings were significant after adjustment for age, sex, body mass index (BMI), smoking, medications, and baseline apo value. CONCLUSIONS ERN produced a beneficial reduction in plasma apoB. The enrichment of LDL with apoE and apoA1 was unique to the Combo group and might be beneficial owing to the atheroprotective properties of apoE and HDL2 (a likely source of apoA1 in LDL fraction). The effect of therapies on the apoC3 glycosylation index is a novel finding, the implications of which will require further study.
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Effects of omega-3 on metabolic markers in postmenopausal women with metabolic syndrome.
Tardivo, AP, Nahas-Neto, J, Orsatti, CL, Dias, FB, Poloni, PF, Schmitt, EB, Nahas, EA
Climacteric : the journal of the International Menopause Society. 2015;(2):290-8
Abstract
OBJECTIVE The aim of this study was to evaluate the effect of diet alone or combined with omega-3 supplementation on metabolic and inflammatory markers in postmenopausal women with metabolic syndrome. METHODS This randomized, controlled trial included 87 Brazilian women (age ≥ 45 years and with amenorrhea ≥ 12 months). Exclusion criteria were: cardiovascular disease, insulin-dependent diabetes, cancer, autoimmune diseases and use of either statins or hormone therapy. Participants were randomized to diet alone (n = 43, control) or diet plus omega-3 supplementation, 900 mg/day orally (n = 44). All women were provided with an individualized dietary prescription. Clinical, anthropometrical (body mass index and waist circumference) and biochemical variables were measured. The inflammatory profile included C-reactive protein, tumor necrosis factor α and interleukins (IL-1β and IL-6). The intervention time was 6 months, with assessments at initiation and completion. Data were analyzed according to intention-to-treat, using the independent t-test and ANOVA. RESULTS There were significant reductions in body mass index and waist circumference in both groups (p < 0.05) without significant changes in body fat or muscle mass. Intervention with diet plus omega-3 was associated with significant reduction in systolic (< 12.2%) and diastolic (< 8.2%) blood pressure, serum triglyceride concentration (< 21.4%), and insulin resistance (< 13.1%) (p < 0.05), as well as a reduction in serum IL-6 concentration (< 28.5%) (p = 0.034). CONCLUSION In postmenopausal women with metabolic syndrome, dietary intervention plus supplementation of omega-3 resulted in a further decrease in triglycerides and blood pressure and also in an improvement in insulin resistance and inflammatory markers, important components of metabolic syndrome.
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Isoenergetic diets differing in their n-3 fatty acid and polyphenol content reflect different plasma and HDL-fraction lipidomic profiles in subjects at high cardiovascular risk.
Bondia-Pons, I, Pöhö, P, Bozzetto, L, Vetrani, C, Patti, L, Aura, AM, Annuzzi, G, Hyötyläinen, T, Rivellese, AA, Orešič, M
Molecular nutrition & food research. 2014;(9):1873-82
Abstract
SCOPE Dysregulation of lipid homeostasis is related to multiple major healthcare problems. The aim of this study was to investigate the effects of n-3 fatty acid (FA) and polyphenol rich diets on plasma and HDL fraction lipidomic profiles in subjects at high cardiovascular risk. METHODS AND RESULTS Ultra performance LC coupled to quadrupole TOF/MS mass spectrometry global lipidomic profiling was applied to plasma and HDL fraction from an 8 wk randomized intervention with four isoenergetic diets, differing in their natural n-3 FA and polyphenols content, in 78 subjects with a high BMI, abdominal obesity, and at least one other feature of the metabolic syndrome. Dependency network analysis showed a different pattern of associations between lipidomics, dietary, and clinical variables after the dietary interventions. The most remarkable associations between variables were observed after the diet high in n-3 FA and polyphenols, as the inverse association between gallic acid intake and LDL cholesterol levels, which was indirectly associated with a HDL cluster exclusively comprised lysophospholipids. CONCLUSION This is the first human randomized controlled trial showing direct and indirect associations with lipid molecular species and clinical variables of interest in the evaluation of the metabolic syndrome after diets naturally rich in polyphenols.