Biological Effects of Add-On Eicosapentaenoic Acid Supplementation in Diabetes Mellitus and Co-Morbid Depression: A Randomized Controlled Trial

Mocking, Roel J. T.; Assies, Johanna; Bot, Mariska; Jansen, Eugène; Schene, Aart H.; Pouwer, Frans

doi:10.1371/journal.pone.0049431

Cited by 33 publications

(25 citation statements)

References 72 publications

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“…Significant reductions in TC, LDL-C, and non–HDL-C have also recently been reported in a small study of patients with diabetes mellitus-2 and dyslipidemia following treatment with 1.8 g/day of purified EPA [17]. However, in another small study of patients with diabetes mellitus and comorbid major depressive disorder, 1.0 g/day of >90% pure EPA ethyl ester resulted in small but significant increases in TC and HDL-C but not in LDL-C [18]. The dose was notably low at 1 g/day and there were differences in tocopherol concentrations between the EPA intervention and placebo formulations.…”

Section: Discussionmentioning

confidence: 85%

Effects of icosapent ethyl on lipid and inflammatory parameters in patients with diabetes mellitus-2, residual elevated triglycerides (200–500 mg/dL), and on statin therapy at LDL-C goal: the ANCHOR study

Brinton

Ballantyne

Bays

et al. 2013

Cardiovasc Diabetol

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BackgroundIcosapent ethyl (IPE) is a high-purity prescription form of eicosapentaenoic acid (EPA) ethyl ester indicated as an adjunct to diet to reduce triglyceride (TG) levels in adult patients with severe (≥500 mg/dL) hypertriglyceridemia. ANCHOR was a 12-week, phase 3 study that evaluated the efficacy and safety of IPE in patients (N = 702) with residual high fasting TG levels (≥200 and <500 mg/dL) despite having optimized low-density lipoprotein cholesterol (LDL-C) levels (≥40 and <100 mg/dL) on statin therapy. Among patients randomized to IPE (4 g/day or 2 g/day) or placebo, 514 (73%) had diabetes mellitus.MethodsA post hoc subgroup analysis of the ANCHOR study was conducted to assess the effects of IPE on median placebo-adjusted percent change from baseline in efficacy end point parameters in 3 subgroups: total (all subjects with diabetes—overall median baseline glycosylated hemoglobin A1c [A1c] = 6.8%), better-controlled diabetes (below median baseline A1c), and less-controlled diabetes (above median baseline A1c).ResultsBaseline efficacy parameters were similar among all groups except high-sensitivity C-reactive protein (hsCRP), which was higher in the total and less-controlled diabetes groups. Compared with placebo, IPE 4 g/day significantly reduced TG, non-high-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol (VLDL-C), lipoprotein-associated phospholipase A2, apolipoprotein B (Apo B), total cholesterol, high-density lipoprotein cholesterol, VLDL-TG, oxidized LDL, and remnant-like particle cholesterol in all 3 diabetes groups, LDL-C in the total diabetes group, and hsCRP in the total and less-controlled diabetes groups. Decreases in hsCRP and Apo B were much greater in patients with less-controlled diabetes. There were no significant increases in fasting plasma glucose, A1c, insulin, or homeostasis model assessment-estimated insulin resistance in any group.ConclusionIPE 4 g/day significantly improved lipid and lipid-related parameters without worsening glycemic control in patients with diabetes and mixed dyslipidemia, with possibly greater effects among those with less-controlled diabetes.Trial registrationClinicaltrials.gov Identifier NCT01047501

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Section: Discussionmentioning

confidence: 85%

Effects of icosapent ethyl on lipid and inflammatory parameters in patients with diabetes mellitus-2, residual elevated triglycerides (200–500 mg/dL), and on statin therapy at LDL-C goal: the ANCHOR study

Brinton

Ballantyne

Bays

et al. 2013

Cardiovasc Diabetol

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“…Regarding the studies conducted on patients with CVDs, the analysis included very heterogeneous populations, namely patients with coronary heart disease [87], with diabetes mellitus [94], and post myocardial infarction [100], that may have been responsible for the inconclusive results. Moreover, it has been recently reported that supplementation of EPA in diabetes mellitus patients with comorbid MDD poorly affect biological risk factors for adverse outcome observed in this category of patients [113]. The RCTs conducted on patients with mild cognitive impairment or AD revealed poor efficacy of omega-3 PUFA in ameliorating the depressive symptoms.…”

Section: Discussionmentioning

confidence: 99%

Role of Omega-3 Fatty Acids in the Treatment of Depressive Disorders: A Comprehensive Meta-Analysis of Randomized Clinical Trials

et al. 2014

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BackgroundDespite omega-3 polyunsaturated fatty acids (PUFA) supplementation in depressed patients have been suggested to improve depressive symptomatology, previous findings are not univocal.ObjectivesTo conduct an updated meta-analysis of randomized controlled trials (RCTs) of omega-3 PUFA treatment of depressive disorders, taking into account the clinical differences among patients included in the studies.MethodsA search on MEDLINE, EMBASE, PsycInfo, and the Cochrane Database of RCTs using omega-3 PUFA on patients with depressive symptoms published up to August 2013 was performed. Standardized mean difference in clinical measure of depression severity was primary outcome. Type of omega-3 used (particularly eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) and omega-3 as mono- or adjuvant therapy was also examined. Meta-regression analyses assessed the effects of study size, baseline depression severity, trial duration, dose of omega-3, and age of patients.ResultsMeta-analysis of 11 and 8 trials conducted respectively on patients with a DSM-defined diagnosis of major depressive disorder (MDD) and patients with depressive symptomatology but no diagnosis of MDD demonstrated significant clinical benefit of omega-3 PUFA treatment compared to placebo (standardized difference in random-effects model 0.56 SD [95% CI: 0.20, 0.92] and 0.22 SD [95% CI: 0.01, 0.43], respectively; pooled analysis was 0.38 SD [95% CI: 0.18, 0.59]). Use of mainly EPA within the preparation, rather than DHA, influenced final clinical efficacy. Significant clinical efficacy had the use of omega-3 PUFA as adjuvant rather than mono-therapy. No relation between efficacy and study size, baseline depression severity, trial duration, age of patients, and study quality was found. Omega-3 PUFA resulted effective in RCTs on patients with bipolar disorder, whereas no evidence was found for those exploring their efficacy on depressive symptoms in young populations, perinatal depression, primary disease other than depression and healthy subjects.ConclusionsThe use of omega-3 PUFA is effective in patients with diagnosis of MDD and on depressive patients without diagnosis of MDD.

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“…Interestingly, fatty acids influence both HPA-axis stimulation and feedback through their effects on corticotropin-releasing hormone (CRH)-secretion and glucocorticoid receptor-sensitivity. In brief, lower concentrations of omega-3 fatty acids and relatively higher concentrations of omega-6 fatty acids are thought to lead to HPA-axis hyperactivation, i.e., cortisol increases (Hibbeln and Salem 1995;Murck et al 2004;Mocking et al 2012aMocking et al , 2013bBazinet and Laye 2014;Mocking et al 2015). Vice versa, cortisol influences production, mobilization, and degradation of fatty acids by modulating key enzymes and increasing oxidative stress.…”

Section: Bidirectional Relation With Hypothalamic-pituitary-adrenal (mentioning

confidence: 99%

Focus on fatty acids in the neurometabolic pathophysiology of psychiatric disorders

Mocking

Assies

Ruhé

et al. 2018

J of Inher Metab Disea

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Continuous research into the pathophysiology of psychiatric disorders, such as major depressive disorder (MDD), posttraumatic stress disorder (PTSD), and schizophrenia, suggests an important role for metabolism. This narrative review will provide an upto-date summary of how metabolism is thought to be involved in the pathophysiology of these psychiatric disorders. We will focus on (I) the important role of fatty acids in these metabolic alterations, (II) whether fatty acid alterations represent epiphenomena or risk factors, and (III) similarities and dissociations in fatty acid alterations between different psychiatric disorders. (Historical) epidemiological evidence links fatty acid intake to psychiatric disorder prevalence, corroborated by altered fatty acid concentrations measured in psychiatric patients. These fatty acid alterations are connected with other concomitant pathophysiological mechanisms, including biological stress (hypothalamic-pituitary-adrenal (HPA)-axis and oxidative stress), inflammation, and brain network structure and function. Metabolomics and lipidomics studies are underway to more deeply investigate this complex network of associated neurometabolic alterations. Supplementation of fatty acids as disease-modifying nutraceuticals has clinical potential, particularly add-on eicosapentaenoic acid (EPA) in depressed patients with markers of increased inflammation. However, by interpreting the observed fatty acid alterations as partly (mal)adaptive phenomena, we attempt to nuance translational expectations and provide new clinical applications for these novel neurometabolic insights, e.g., to predict treatment response or depression recurrence. In conclusion, placing fatty acids in context can contribute to further understanding and optimized treatment of psychiatric disorders, in order to diminish their overwhelming burden of disease.

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Biological Effects of Add-On Eicosapentaenoic Acid Supplementation in Diabetes Mellitus and Co-Morbid Depression: A Randomized Controlled Trial

Cited by 33 publications

References 72 publications

Effects of icosapent ethyl on lipid and inflammatory parameters in patients with diabetes mellitus-2, residual elevated triglycerides (200–500 mg/dL), and on statin therapy at LDL-C goal: the ANCHOR study

Effects of icosapent ethyl on lipid and inflammatory parameters in patients with diabetes mellitus-2, residual elevated triglycerides (200–500 mg/dL), and on statin therapy at LDL-C goal: the ANCHOR study

Role of Omega-3 Fatty Acids in the Treatment of Depressive Disorders: A Comprehensive Meta-Analysis of Randomized Clinical Trials

Focus on fatty acids in the neurometabolic pathophysiology of psychiatric disorders

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