title: Biological effects of add-on eicosapentaenoic acid supplementation in diabetes mellitus and co-morbid depression: a randomized controlled trial.
abstract: 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 α-tocopherol [estimate (95% CI); 3.62 (1.14-6.11) µmol/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): -121.93 (-240.20--3.47) min×nmol/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].
  
  
  CONCLUSIONS
  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 α-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.
authors.affiliation: Program for Mood Disorders, Department of Psychiatry, Amsterdam Medical Center, Amsterdam, The Netherlands.
authors.forename: Roel J T
authors.initials: RJ
authors.lastname: Mocking
authors.forename: Johanna
authors.initials: J
authors.lastname: Assies
authors.forename: Mariska
authors.initials: M
authors.lastname: Bot
authors.forename: Eugene H J M
authors.initials: EH
authors.lastname: Jansen
authors.forename: Aart H
authors.initials: AH
authors.lastname: Schene
authors.forename: François
authors.initials: F
authors.lastname: Pouwer
mesh_terms: D000328:Adult; D000368:Aged; D003865:Major Depressive Disorder / Q000150:complications* / Q000188:drug therapy* / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000188:drug therapy* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000188:drug therapy* / Q000378:metabolism; D015118:Eicosapentaenoic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D007249:Inflammation / Q000378:metabolism; D008074:Lipoproteins / Q000378:metabolism; D008297:Male; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects; D010913:Pituitary-Adrenal System / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D005227:Fatty Acids; D008074:Lipoproteins; D015118:Eicosapentaenoic Acid