Effects of Peroral Omega-3 Fatty Acid Supplementation on Cerebrospinal Fluid Biomarkers in Patients with Alzheimer’s Disease: A Randomized Controlled Trial—The OmegAD Study

Article type: Research Article

Authors: Tofiq, Avin^a | Zetterberg, Henrik^{b; c; d; e} | Blennow, Kaj^{b; c} | Basun, Hans^{f; g; h} | Cederholm, Tommy^{i; j} | Eriksdotter, Maria^{j; k} | Faxén-Irving, Gerd^k | Hjorth, Erik^l | Jernerén, Fredrik^m | Schultzberg, Marianne^l | Wahlund, Lars-Olof^{j; k} | Palmblad, Janⁿ | Freund-Levi, Yvonne^{a; k; o; p; q; *}

Affiliations: [a] School of Medicine, Örebro University, Örebro, Sweden | [b] Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden | [c] Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden | [d] UK Dementia Research Institute at UCL, London, United Kingdom | [e] Department of Neurodegenerative Disease, UCL Institute of Neurology, London, United Kingdom | [f] BioArctic AB, Stockholm, Sweden | [g] Spinemedical AB, Stockholm, Sweden | [h] Uppsala University Hospital, Uppsala, Sweden | [i] Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University, Uppsala, Sweden | [j] Theme Ageing, Karolinska University Hospital, Stockholm, Sweden | [k] Department of Neurobiology, Care Sciences and Society, Division of Clinical Geriatrics, Center for Alzheimer Research, Karolinska Institutet, Stockholm, Sweden | [l] Department of Neurobiology, Care Sciences and Society, Division of Neurogeriatrics, Center for Alzheimer Research, Karolinska Institutet, Stockholm, Sweden | [m] Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden | [n] Department of Medicine, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden | [o] Center for Alzheimer Research, Division of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden | [p] Department of Psychiatry, University Hospital Örebro, Örebro, Sweden | [q] Department of Old Age Psychiatry, Psychology & Neuroscience, King’s College London, London, United Kingdom

Correspondence: [*] Correspondence to: Yvonne Freund-Levi, MD, PhD, Associate Professor, School of Medicine Örebro University and Dep of NVS Karolinska Institutet, Stockholm, Sweden. E-mail: [email protected].

Abstract: Background:Studies have suggested a connection between a decrease in the levels of polyunsaturated fatty acids (PUFAs) and Alzheimer’s disease (AD). We aimed to assess the effect of supplementation with omega-3 fatty acids (n-3 FAs) on biomarkers analyzed in the cerebrospinal fluid (CSF) of patients diagnosed with AD. Objective:To investigate the effects of daily supplementation with 2.3 g of PUFAs in AD patients on the biomarkers in CSF described below. We also explored the possible correlation between these biomarkers and the performance in the cognitive test Mini-Mental State Examination (MMSE). Methods:Thirty-three patients diagnosed with AD were randomized to either treatment with a daily intake of 2.3 g of n-3 FAs (n  =  18) or placebo (n  =  15). CSF samples were collected at baseline and after six months of treatment, and the following biomarkers were analyzed: Aβ 38, Aβ 40, Aβ 42, t-tau, p-tau, neurofilament light (NfL), chitinase-3-like protein 1 (YKL-40), acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), soluble IL-1 receptor type II (sIL-1RII), and IL-6. Results:There were no significant differences between the groups concerning the level of the different biomarkers in the CSF at baseline. Within the treatment group, there was a small but significant increase in both YKL-40 (p = 0.04) and NfL (p = 0.03), while the other CSF biomarkers remained stable. Conclusion:Supplementation with n-3 FAs had a statistically significant effect on NfL and YKL-40, resulting in an increase of both biomarkers, indicating a possible increase of inflammatory response and axonal damage. This increase in biomarkers did not correlate with MMSE score.

Keywords: Chitinase-3-like protein 1, dementia, inflammation, mini-mental state examination, neurodegeneration, neurofilament light, YKL-40

DOI: 10.3233/JAD-210007

Journal: Journal of Alzheimer's Disease, vol. 83, no. 3, pp. 1291-1301, 2021