Treatment with high-dose n-3 PUFAs has no effect on platelet function, coagulation, metabolic status or inflammation in patients with atherosclerosis and type 2 diabetes

Abstract

BackgroundDespite numerous studies on cardioprotective effects of omega-3 polyunsaturated fatty acids (n-3 PUFAs), there is limited evidence for n-3 PUFA-mediated effects, especially at its higher dose, on cardiovascular risk in patients with type 2 diabetes (DM2) and established atherosclerosis.PurposeTo investigate the effect of daily treatment with a higher dose (2 g) of n-3 PUFAs on platelet function, coagulation parameters, fibrin clot properties, markers of systemic inflammation and metabolic status, in patients with atherosclerotic vascular disease and DM2 who receive optimal medical therapy.MethodsWe conducted a prospective, double-blind, placebo-controlled, randomized, double-center study, in which thrombin generation (plasma thrombogenic potential from automated thrombogram), fibrin clot properties (plasma fibrin clot permeability; lysis time), platelet aggregation (light transmission aggregometry with adenosine diphosphate and arachidonic acid used as agonists), HbA1c, insulin level, lipid profiles, leptin and adiponectin levels, as well as markers of systemic inflammation (i.e., hsCRP, IL-6, TNF-α, ICAM-1, VCAM-1, and myeloperoxidase) were determined at baseline and at 3 months after treatment with 2 g/day of n-3 PUFAs (n = 36) or placebo (n = 38). Moreover, we assessed serum fatty acids of the phospholipid fraction by gas chromatography both at baseline and at the end of the study.ResultsMajority of patients were treated with optimal medical therapy and achieved recommended treatment targets. Despite higher serum levels of eicosapentaenoic acid (EPA) (by 204%; p < 0.001) and docosahexaenoic acid (DHA) (by 62%; p < 0.0001) in n-3 PUFA group at the end of treatment no changes in platelet aggregation, thrombin generation, fibrin clot properties or markers of systemic inflammation were observed. No intergroup differences in the insulin, HbA1c and lipid levels were found at the end of the study. There was no change in adiponectin and leptin in interventional group, however leptin increased in control group (p = 0.01), therefore after study period leptin levels were lower in the interventional group (p = 0.01). Additionally, resolvin D1 did not differ between interventional and control group.ConclusionsIn conclusion, our study demonstrated that in patients with long-standing, well-controlled DM2 and atherosclerotic disease the treatment with a high dose of n-3 PUFAs (namely, 1 g/day of EPA and 1 g/day of DHA for 3 months) does not improve coagulation, metabolic, and inflammatory status when measured with the specified tests.The study was registered in ClinicalTrials.gov; identifier: NCT02178501. Registration date: April 12, 2014Electronic supplementary materialThe online version of this article (doi:10.1186/s12933-017-0523-9) contains supplementary material, which is available to authorized users.

High-dose omega-3 fatty acids have no effect on platelet aggregation or coagulation measured with static and flow-based aggregation instruments and Sonoclot; an observational study in healthy volunteers

“…aggregation [12][13][14][15]17]. Our results are in line with these as well as with a recently published randomized controlled study in which Poreba et al [16] demonstrated that highdose omega-3 fatty acids did not affect either platelet function as measured with Born aggregometry or coagulation in patients with atherosclerosis and type-2 diabetes. Neither did it improve metabolic status or inflammation markers in the same cohort, which can interact with platelet adhesiveness.…”

“…It has been suggested that the tendency of omega-3 fatty acids to increase bleeding may be caused by inhibition of platelet function through several proposed mechanisms [10,11]. Yet, others have shown that high doses of omega-3 fatty acids do not affect platelet aggregation or function [12][13][14][15][16][17].…”

“…There is no platelet function or coagulation test that covers all aspects of platelet function and coagulation. Based on what previous studies have shown [10][11][12][13][14][15][16][17][18], this study used three methods to measure different aspects of platelet function and coagulation that were likely to be affected by omega-3 fatty acid intake. Firstly, the Sonoclot coagulation analyzer (Sienco, Boulder, CO) was utilized instead of the ROTEM instrument used in the pilot study.…”

Serum phospholipid cis-palmitoleic acid in patients with type 2 diabetes and chronic coronary syndrome: an assessment of the relationship with diabetes duration, systemic low-grade inflammation and circulating oxidized low-density lipoprotein

“…Methods The study design is described in detail elsewhere. 7 Briefly, 74 patients, including 26 women (35.1%), with a mean (SD) age of 65.6 (6.8) years, with T2D (median diabetes duration 10 years) and CCS were prospectively enrolled in the study. All subjects had angiographically documented ASCVD, defined as coronary artery disease (74 patients) or peripheral arterial disease between serum phospholipid POA and biomarkers of systemic inflammation.…”

“…Results and discussion Individuals with POA less than 14.9 µmol/l, compared with patients with POA of 14.9 µmol/l or greater had similar clinical and demographic characteristics, except for longer diabetes duration (median [IQR], 11 [8][9][10][11][12][13][14][15][16][17][18][19][20] vs 8 [5][6][7][8][9][10] years; P = 0.01) and lower prevalence of obesity (54.1% vs 78.4%; P = 0.03) (Supplementary material, Table S1). Patients with POA of 14.9 µmol/l or greater had higher levels of insulin, C -peptide, triglycerides, and estimated SCD1 activity (TAblE 1).…”