title: 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.
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.
authors.affiliation: Department of NVS, Section of Clinical Nutrition, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden. gerd.faxen.irving@ki.se
authors.forename: Gerd
authors.initials: G
authors.lastname: Faxén-Irving
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Freund-Levi
authors.forename: Maria
authors.initials: M
authors.lastname: Eriksdotter-Jönhagen
authors.forename: Hans
authors.initials: H
authors.lastname: Basun
authors.forename: Erik
authors.initials: E
authors.lastname: Hjorth
authors.forename: Jan
authors.initials: J
authors.lastname: Palmblad
authors.forename: Inger
authors.initials: I
authors.lastname: Vedin
authors.forename: Tommy
authors.initials: T
authors.lastname: Cederholm
authors.forename: Lars-Olof
authors.initials: LO
authors.lastname: Wahlund
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000178:diet therapy*; D019587:Dietary Supplements; D018450:Disease Progression; D004281:Docosahexaenoic Acids / Q000627:therapeutic use*; D004311:Double-Blind Method; D015525:Fatty Acids, Omega-3 / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D011228:Prealbumin / Q000032:analysis* / Q000134:cerebrospinal fluid; D013997:Time Factors
chemical_list: D015525:Fatty Acids, Omega-3; D011228:Prealbumin; D004281:Docosahexaenoic Acids