Effects of Supplementation with Omega-3 Fatty Acids on Oxidative Stress and Inflammation in Patients with Alzheimer's Disease: The OmegAD Study

Article type: Research Article

Authors: Freund-Levi, Yvonne^{a; 1} | Vedin, Inger^{d; 1} | Hjorth, Erik^c | Basun, Hans^e | Faxén Irving, Gerd^b | Schultzberg, Marianne^c | Eriksdotter, Maria^a | Palmblad, Jan^d | Vessby, Bengt^f | Wahlund, Lars-Olof^a | Cederholm, Tommy^{f; 2} | Basu, Samar^{g; 2; *}

Affiliations: [a] Section of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet and Department of Geriatrics Karolinska University Hospital Stockholm, Sweden | [b] Divisions of Clinical Nutrition, Karolinska Institutet, Karolinska University Hospital at Huddinge, Stockholm, Sweden | [c] Division of Neurodegeneration, Department of Neurobiology, Care Sciences & Society, Karolinska Institutet, Stockholm, Sweden | [d] Division of Haematology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital at Huddinge, Stockholm, Sweden | [e] 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 | [f] Clinical Nutrition and Metabolism, Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden | [g] 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

Correspondence: [*] Correspondence to: Samar Basu, Oxidative Stress and Inflammation, Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden. Tel.: +46 18 6117958; E-mail: samar.basu@pubcare.uu.se.

Note: [1] Yvonne Freund-Levi and Inger Vedin authors contributed equally to this work.

Note: [2] Tommy Cederholm and Samar Basu authors contributed equally to this work.

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:TThe 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. Conclusion: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.

Keywords: Alzheimer's disease, eicosanoids, F₂-isoprostane, inflammation, lipids, omega-3 fatty acids, oxidative stress, prostaglandin F_2α

DOI: 10.3233/JAD-132042

Journal: Journal of Alzheimer's Disease, vol. 42, no. 3, pp. 823-831, 2014