Biological effects of add-on eicosapentaenoic Acid supplementation in diabetes mellitus and co-morbid depression: a randomized controlled trial

R.J.T. Mocking, J. Assies, M. Bot, E.H.J.M. Jansen, A.H. Schene, F. Pouwer

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Background: Eicosapentaenoic acid (EPA) may reduce increased risks for (cardiovascular) morbidity and mortality in patients with diabetes mellitus (DM) and comorbid major depressive depression (MDD). Yet, effects of EPA-supplementation on biological risk factors for adverse outcomes have not been studied in DM-patients with MDD. Methods: We performed a randomized, double-blind trial (n = 25) comparing add-on ethyl-EPA-supplementation to placebo on (I) oxidative stress, (II) inflammatory, (III) hypothalamic-pituitary-adrenal (HPA)-axis, (IV) one-carbon-cycle, (V) fatty acid metabolism and (VI) lipoprotein parameters during 12-weeks' follow-up. Results: Besides increases in supplemented alpha-tocopherol [estimate (95% CI); 3.62 (1.14-6.11) mu mol/l; p = 0.006] and plasma and erythrocyte EPA, the intervention did not influence other oxidative stress, inflammatory or one-carbon-cycle parameters compared to placebo. HPA-axis reactivity significantly decreased in the EPA-group (N = 12) [AUC(i): 2121.93 (-240.20-3.47) minxnmol/l; p = 0.045], not in the placebo-group (N = 12). Furthermore, EPA-supplementation increased erythrocyte and plasma docosapentaenoic acid, and decreased plasma arachidonic acid (AA) concentrations [-1.61 (-3.10-0.11) %; p = 0.036]. Finally, EPA had a multivariate influence on lipoprotein concentrations (p = 0.030), reflected by relative increases in high density lipoprotein [HDL; 0.30 (0.02-0.58) mmol/l; p = 0.039] and total cholesterol concentrations [1.01 (0.29-1.72) mmol/l; p = 0.008]. Conclusion: Overall, add-on EPA-supplementation had limited effects on biological risk factors for adverse outcome in this sample of DM-patients with comorbid MDD. Besides increases in concentrations of supplemented a-tocopherol and EPA, AA decreased, and inconclusive effects on HPA-axis (re) activity and lipoprotein concentrations were observed. Therefore, further studies on the alleged beneficial effects of EPA-supplementation on biological risk factors for adverse outcome in DM-patients with comorbid MDD seem warranted, preferably using clinical outcomes such as (cardiovascular) DM-complications
Original languageEnglish
Article numbere49431
Pages (from-to)e49431
Issue number11
Publication statusPublished - 2012

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