Freund-Levi Yvonne, Vedin Inger, Hjorth Erik, Basun Hans, Faxén Irving Gerd, Schultzberg Marianne, Eriksdotter Maria, Palmblad Jan, Vessby Bengt, Wahlund Lars-Olof, Cederholm Tommy, Basu Samar
Section of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet and Department of Geriatrics Karolinska University Hospital Stockholm, Sweden.
Division of Haematology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital at Huddinge, Stockholm, Sweden.
J Alzheimers Dis. 2014;42(3):823-31. doi: 10.3233/JAD-132042.
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.
The objective of this study was to evaluate systemic oxidative stress and inflammatory biomarkers following oral supplementation of dietary ω-3 FA.
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.
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.
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.
氧化应激和炎症是被认为参与阿尔茨海默病(AD)发病机制的两个关键机制。鱼类和鱼油中的ω-3脂肪酸(ω-3 FAs)具有多种生物学特性,可能对AD有益。然而,它们也可能自动氧化并在体内诱导脂质过氧化。
本研究的目的是评估口服补充膳食ω-3 FA后全身氧化应激和炎症生物标志物的情况。
40例中度AD患者被随机分为两组,分别接受1.7 g二十二碳六烯酸(DHA,22:6)和0.6 g二十碳五烯酸(EPA,20:5)或安慰剂,为期6个月。在补充前后收集尿液样本。测量主要F2-异前列腺素8-异前列腺素F2α(一种氧化应激的体内一致生物标志物)和15-酮二氢前列腺素F2α(前列腺素F2α的主要代谢产物和炎症反应生物标志物)的水平。
6个月后,安慰剂组尿液中的F2-异前列腺素增加,但补充和未补充患者在F2-异前列腺素和15-酮二氢前列腺素F2α尿液水平上的治疗效果没有明显差异。在基线时,15-酮二氢前列腺素F2α的水平与ω-3 FAs呈负相关,与亚油酸呈正相关。8-异前列腺素F2α与ω-6脂肪酸花生四烯酸呈负相关。
研究结果表明,给AD患者补充ω-3 FAs 6个月对自由基介导的F2-异前列腺素形成或环氧合酶介导的前列腺素F2α形成没有明显影响。与脂肪酸的相关关系表明脂肪酸在免疫调节中具有潜在作用。