title: Effects of supplementation with omega-3 fatty acids on oxidative stress and inflammation in patients with Alzheimer's disease: the OmegAD study.
abstract: BACKGROUND
  Oxidative stress and inflammation are two key mechanisms suggested to be involved in the pathogenesis of Alzheimer's disease (AD). Omega-3 fatty acids (ω-3 FAs) found in fish and fish oil have several biological properties that may be beneficial in AD. However, they may also auto-oxidize and induce in vivo lipid peroxidation.
  
  
  OBJECTIVE
  The objective of this study was to evaluate systemic oxidative stress and inflammatory biomarkers following oral supplementation of dietary ω-3 FA.
  
  
  METHODS
  Forty patients with moderate AD were randomized to receive 1.7 g DHA (22:6) and 0.6 g EPA (20:5) or placebo for 6 months. Urinary samples were collected before and after supplementation. The levels of the major F2-isoprostane, 8-iso-PGF2α, a consistent in vivo biomarker of oxidative stress, and 15-keto-dihydro-PGF2α, a major metabolite of PGF2α and biomarker of inflammatory response, were measured.
  
  
  RESULTS
  F2-isoprostane in urine increased in the placebo group after 6 months, but there was no clear difference in treatment effect between supplemented and non-supplemented patients on the urinary levels of F2-isoprostanes and 15-keto-dihydro-PGF2α. At baseline, the levels of 15-keto-dihydro-PGF2α showed negative correlative relationships to ω-3 FAs, and a positive correlation to linoleic acid. 8-iso-PGF2α correlated negatively to the ω-6 FA arachidonic acid.
  
  
  CONCLUSIONS
  The findings indicate that supplementation of ω-3 FAs to patients with AD for 6 months does not have a clear effect on free radical-mediated formation of F2-isoprostane or cyclooxygenase-mediated formation of prostaglandin F2α. The correlative relationships to FAs indicate a potential role of FAs in immunoregulation.
authors.affiliation: Section of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet and Department of Geriatrics Karolinska University Hospital Stockholm, Sweden.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Freund-Levi
authors.affiliation: Division of Haematology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital at Huddinge, Stockholm, Sweden.
authors.forename: Inger
authors.initials: I
authors.lastname: Vedin
authors.affiliation: Division of Neurodegeneration, Department of Neurobiology, Care Sciences & Society, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Hjorth
authors.affiliation: Division of Geriatrics, Uppsala University, Uppsala, Sweden and Chaire d'Excellence Program, Department of Biochemistry, Molecular Biology and Nutrition, Universite d'Auvergne, Clermont-Ferrand, France.
authors.forename: Hans
authors.initials: H
authors.lastname: Basun
authors.affiliation: Divisions of Clinical Nutrition, Karolinska Institutet, Karolinska University Hospital at Huddinge, Stockholm, Sweden.
authors.forename: Gerd
authors.initials: G
authors.lastname: Faxén Irving
authors.affiliation: Division of Neurodegeneration, Department of Neurobiology, Care Sciences & Society, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Marianne
authors.initials: M
authors.lastname: Schultzberg
authors.affiliation: Section of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet and Department of Geriatrics Karolinska University Hospital Stockholm, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Eriksdotter
authors.affiliation: Division of Haematology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital at Huddinge, Stockholm, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Palmblad
authors.affiliation: Clinical Nutrition and Metabolism, Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Bengt
authors.initials: B
authors.lastname: Vessby
authors.affiliation: Section of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet and Department of Geriatrics Karolinska University Hospital Stockholm, Sweden.
authors.forename: Lars-Olof
authors.initials: LO
authors.lastname: Wahlund
authors.affiliation: Clinical Nutrition and Metabolism, Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Tommy
authors.initials: T
authors.lastname: Cederholm
authors.affiliation: Division of Oxidative Stress and Inflammation, Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden and Chaire d'Excellence Program, Department of Biochemistry, Molecular Biology and Nutrition, Universite d'Auvergne, Clermont-Ferrand, France.
authors.forename: Samar
authors.initials: S
authors.lastname: Basu
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000544:Alzheimer Disease / Q000150:complications / Q000178:diet therapy* / Q000503:physiopathology* / Q000652:urine; D003072:Cognition Disorders / Q000178:diet therapy / Q000209:etiology; D016207:Cytokines / Q000378:metabolism*; D003863:Depression / Q000178:diet therapy / Q000209:etiology; D019587:Dietary Supplements; D015237:Dinoprost / Q000652:urine; D004281:Docosahexaenoic Acids / Q000008:administration & dosage*; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage*; D028441:F2-Isoprostanes / Q000652:urine; D005260:Female; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D011569:Psychiatric Status Rating Scales; D012189:Retrospective Studies
chemical_list: D016207:Cytokines; D028441:F2-Isoprostanes; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid; D015237:Dinoprost
keywords: $F_2$-isoprostane; Alzheimer's disease; eicosanoids; inflammation; lipids; omega-3 fatty acids; oxidative stress; prostaglandin $F_{2 \alpha}$