Docosahexaenoic Acid Supplementation Improved Lipocentric but Not Glucocentric Markers of Insulin Sensitivity in Hypertriglyceridemic Men

ArticleinMetabolic syndrome and related disorders 10(1):32-8 · February 2012with9 Reads
DOI: 10.1089/met.2011.0081 · Source: PubMed
Increase in obesity and metabolic syndrome are associated with increases in insulin resistance (IR) and type 2 diabetes mellitus. Results from animal intervention studies and human epidemiological studies suggest that n-3 polyunsaturated fatty acids can prevent and reverse IR, but results from human intervention studies have varied. Results from some human and animal studies suggest that docosahexaenoic acid (22:6n-3; DHA) may be more effective than eicosapentaenoic acid (20:5n-3; EPA) in the prevention of IR. By using a placebo-controlled, parallel study design, we examined the effects of DHA supplementation (3 grams/day, 90 days) in the absence of EPA on glucocentric and lipocentric markers of IR in hypertriglyceridemic men (n=14-17/group). DHA supplementation increased fasting plasma glucose concentration by 4.7% (P<0.05), but did not alter other indices of IR based on fasting (insulin and homeostasis model assessment of insulin resistance [HOMA-IR]) or postprandial insulin and glucose concentrations (areas under curves for insulin and glucose, Matsuda index). Glucose increased by 2.7% in the placebo group and was not significant; increases in glucose in the two groups did not differ from each other. DHA decreased circulating concentrations of several lipocentric markers of IR, including plasma concentrations of nonesterified fatty acids (13.0%), small, dense low-density lipoprotein (LDL) particles (21.7%), and ratio of tryglycerides to high-density lipoprotein cholesterol (TG/HDL-C) (34.0%) (P<0.05). None of the variables changed in the placebo group. Our results suggest that lipocentric markers of IR are more responsive to DHA supplementation than the glucocentric markers. Future studies with DHA in prediabetic subjects and direct measures of insulin sensitivity are needed.
    • "Omega-3 fatty acids did not significantly increase plasma or high-molecular weight adiponectin levels in overweight-tomoderately obese healthy people [47]. DHA supplementation did not change fasting or postprandial insulin and glucose concentrations and insulin sensitivity, determined by insulin and homeostasis model assessment of insulin resistance (HOMA-IR) in hypertriglyceridemic men [48]. In a meta-analysis of 18 randomized clinical trials, omega-3 fatty acids had no effects on insulin resistance compared to placebo [49]. "
    [Show abstract] [Hide abstract] ABSTRACT: Background: Experimental studies demonstrate that higher intake of omega-3 fatty acids (n-3 FA) improves insulin sensitivity, however, we reported that n-3 FA 2g therapy, most commonly used dosage did not significantly improve insulin sensitivity despite reducing triglycerides by 21% in patients. Therefore, we investigated the effects of different dosages of n-3 FA in patients with hypertriglyceridemia. Methods: This was a randomized, single-blind, placebo-controlled, parallel study. Age, sex, and body mass index were matched among groups. All patients were recommended to maintain a low fat diet. Forty-four patients (about 18 had metabolic syndrome/type 2 diabetes mellitus) in each group were given placebo, n-3 FA 1 (O1), 2 (O2), or 4 g (O4), respectively daily for 2 months. Results: n-3 FA therapy dose-dependently and significantly decreased triglycerides and triglycerides/HDL cholesterol and improved flow-mediated dilation, compared with placebo (by ANOVA). However, each n-3 FA therapy did not significantly decrease high-sensitivity C-reactive protein and fibrinogen, compared with placebo. O1 significantly increased insulin levels and decreased insulin sensitivity (determined by QUICKI) and O2 significantly decreased plasma adiponectin levels relative to baseline measurements. Of note, when compared with placebo, each n-3 FA therapy did not significantly change insulin, glucose, adiponectin, glycated hemoglobin levels and insulin sensitivity (by ANOVA). We observed similar results in a subgroup of patients with the metabolic syndrome. Conclusions: n-3 FA therapy dose-dependently and significantly decreased triglycerides and improved flow-mediated dilation. Nonetheless, n-3 FA therapy did not significantly improve acute-phase reactants and insulin sensitivity in patients with hypertriglyceridemia, regardless of dosages.
    Full-text · Article · Aug 2014
    • "It is universally agreed that ω3 FA decrease the production of VLDL, thereby reducing plasma triglycerides by as much as 30-50% [9]. The effects on lipoprotein particle distribution, including a decrease in VLDL size, increases in LDL and HDL size, and increases or decreases in LDL and HDL cholesterol are inconsistent and may be due to differences in the specific effects of the individual long chain ω3 EPA and DHA101112 as well as genetic factors [13], however, the variability in these responses has not been well characterized to date. Additionally, ω3 FA have been implicated in decreasing inflammation via direct effects on lipid signaling mediators, or oxylipins. "
    [Show abstract] [Hide abstract] ABSTRACT: Conflicting findings in both interventional and observational studies have resulted in a lack of consensus on the benefits of ω3 fatty acids in reducing disease risk. This may be due to individual variability in response. We used a multi-platform lipidomic approach to investigate both the consistent and inconsistent responses of individuals comprehensively to a defined ω3 intervention. The lipidomic profile including fatty acids, lipid classes, lipoprotein distribution, and oxylipins was examined multi- and uni-variately in 12 healthy subjects pre vs. post six weeks of ω3 fatty acids (1.9 g/d eicosapentaenoic acid [EPA] and 1.5 g/d docosahexaenoic acid [DHA]). Total lipidomic and oxylipin profiles were significantly different pre vs. post treatment across all subjects (p=0.00007 and p=0.00002 respectively). There was a strong correlation between oxylipin profiles and EPA and DHA incorporated into different lipid classes (r(2)=0.93). However, strikingly divergent responses among individuals were also observed. Both ω3 and ω6 fatty acid metabolites displayed a large degree of variation among the subjects. For example, in half of the subjects, two arachidonic acid cyclooxygenase products, prostaglandin E2 (PGE2) and thromboxane B2 (TXB2), and a lipoxygenase product, 12-hydroxyeicosatetraenoic acid (12-HETE) significantly decreased post intervention, whereas in the other half they either did not change or increased. The EPA lipoxygenase metabolite 12-hydroxyeicosapentaenoic acid (12-HEPE) varied among subjects from an 82% decrease to a 5,000% increase. Our results show that certain defined responses to ω3 fatty acid intervention were consistent across all subjects. However, there was also a high degree of inter-individual variability in certain aspects of lipid metabolism. This lipidomic based phenotyping approach demonstrated that individual responsiveness to ω3 fatty acids is highly variable and measurable, and could be used as a means to assess the effectiveness of ω3 interventions in modifying disease risk and determining metabolic phenotype.
    Full-text · Article · Oct 2013
    • "However, some randomized clinical trials have not demonstrated reduction in CHD mortality with omega-3 fatty acid consumption [17]. The Japan EPA Lipid Intervention Study (JELIS), an open-label, mixed primary and secondary trial, did not demonstrate the effect of EPA on cardiac death in 18,645 patients with hypercholesterolemia , although it found modest benefits for non-fatal coronary artery Increase expression of endothelial NO synthase [27,28] Enhance NO production [34,35] Increase NO bioactivity by ameliorating oxidative stress [27,28] Enhance endothelial NO synthase activity [36] Enhance endothelial NO synthase activity [29] Inflammation VCAM-1 ↓, ICAM-1 ↓ [38,40] VCAM-1 ↓, ICAM-1 ↓, E-selectin ↓ [46] CRP ↓ [19,20,42] CRP ↔ [20,48] Interleukin-6 ↓ [41] Interleukin-6, 8 ↓ [46] MCP-1 ↓ [39] TNF-α ↓, down regulation of TNF-α mRNA [18,66] Hemostasis Tissue factor activity ↔ [18] PAI-1 ↓, PAI-1 antigen ↓fibrinogen ↓ [18,19,50] Fibrinogen ↔ [20] Bleeding time ↑(only very high dose) [17] No consistent effects on platelet aggregation or coagulation factors [17,515253 Metabolic effects Expression of adiponectin mRNA ↑ [57] Decrease adiponectin gene expression [77] Reduce PPARγ mRNA [77] Plasma adiponectin ↑ [19,20] Total adiponectin ↑73747576 Plasma adiponectin, high molecular weight adiponectin ↔ [20,78] Improve insulin sensitivity [19,20,68] Insulin sensitivity ↔ [20,79,80] Modest higher incidence of type 2 diabetes mellitus [81,82] TG: triglycerides, HDL-C: high-density lipoprotein-cholesterol, LDL-C: low-density lipoprotein-cholesterol, NO: nitric oxide, VCAM: vascular cell adhesion molecule, ICAM: intercellular adhesion molecule, CRP: C-reactive protein, MCP: monocyte chemoattractant protein, TNF: tumor necrosis factor, PAI: plasminogen activator inhibitor, PPAR: peroxisome proliferator activated receptor. events [101]. "
    [Show abstract] [Hide abstract] ABSTRACT: Even with the aggressive reduction of low-density lipoprotein cholesterol by statin therapy, a high residual risk of cardiovascular events remains substantially and attracts attention to the need for additional preventive therapies. Therefore, effective reductions of residual risk of cardiovascular disease have emerged as therapeutic targets. Fibrates and omega-3 fatty acids have been introduced to reduce triglycerides and to increase high-density lipoprotein cholesterol and have shown anti-atherosclerotic, vascular and metabolic effects. However, some effects are controversial and very recent randomized clinical trials report different results from the earlier ones. In this review, we address the vascular and metabolic effects and the results of recent clinical trials of fibrates and omega-3 fatty acids. We also compared their effects under modern guideline therapy regarding potential drugs to reduce a residual cardiometabolic risk of cardiovascular disease.
    Full-text · Article · Feb 2013
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