Effects on Transthyretin in Plasma and Cerebrospinal Fluid by DHA-Rich n – 3 Fatty Acid Supplementation in Patients with Alzheimer's Disease: The OmegAD Study
Affiliations: [a] Department of NVS, Section of Clinical Nutrition, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden | [b] Department of NVS, Section of Clinical Geriatrics, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden | [c] Department of Public Health and Caring Sciences, Division of Geriatrics, Uppsala University Hospital, Uppsala, Sweden | [d] Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden | [e] Department of Public Health and Caring Sciences, Division of Clinical Nutrition and Metabolism, Uppsala University Hospital, Uppsala, Sweden
Correspondence:
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Correspondence to: Gerd Faxén-Irving, Karolinska University Hospital Huddinge, SE-141 86 Stockholm, Sweden. Tel.: +46 8 58586071; Fax: +46 8 58580540; E-mail: gerd.faxen.irving@ki.se.
Abstract: Transthyretin (TTR) binds amyloid-β (Aβ) and may reduce brain Aβ, a pathological feature in Alzheimer's disease (AD). N − 3 fatty acids (FA), docosahexaenoic (DHA), and eicosapentaenoic acid (EPA) may increase TTR transcription in rat hippocampus. We studied effects of n − 3 FA supplementation on TTR-levels in patients with AD. Outpatients were randomized to receive 1.7 g DHA and 0.6 g EPA (n − 3/n − 3 group) or placebo (placebo/n − 3 group) during 6 months. After 6 months, all patients received n − 3 FA for another 6 months. TTR and FA were measured in plasma in all subjects, whereas TTR in cerebrospinal fluid (CSF) was measured in a subgroup. The study was completed by 89 patients in the n − 3/n − 3 group (75 y, 57% w) and 85 in the placebo/n − 3 group (75 y, 46% w). Baseline plasma-TTR was within normal range in both groups. After 6 months, plasma-TTR decreased in the placebo/n − 3 group (p < 0.001 within and p < 0.015 between the groups). No changes were observed in CSF TTR. From 6 to 12 months when both groups were supplemented, plasma-TTR increased significantly in both groups. Repeated measures ANOVA indicated an increase in TTR over time (p = 0.04) in those receiving n − 3 FA for 12 months. By linear regression analyses, n − 3 FA treatment was independently associated with increased plasma-TTR at 6 months (β = −0.172, p = 0.028). Thus, n − 3 FA treatment appeared to increase plasma-TTR in patients with AD. Since TTR may influence Aβ deposition in the brain, the results warrant further exploration.
