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:

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-PGF_2α, a consistent in vivo biomarker of oxidative stress, and 15-keto-dihydro-PGF_2α, a major metabolite of PGF_2α 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-PGF_2α. At baseline, the levels of 15-keto-dihydro-PGF_2α showed negative correlative relationships to ω-3 FAs, and a positive correlation to linoleic acid. 8-iso-PGF_2α 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 F_2α. The correlative relationships to FAs indicate a potential role of FAs in immunoregulation.