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

J Alzheimers Dis. 2021;83(3):1291-1301. doi: 10.3233/JAD-210007.


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

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Aged
  • Alzheimer Disease / blood
  • Alzheimer Disease / cerebrospinal fluid*
  • Alzheimer Disease / diet therapy*
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Biomarkers* / blood
  • Biomarkers* / cerebrospinal fluid
  • Fatty Acids, Omega-3 / blood
  • Fatty Acids, Omega-3 / cerebrospinal fluid*
  • Fatty Acids, Omega-3 / therapeutic use*
  • Female
  • Humans
  • Male
  • Mental Status and Dementia Tests / statistics & numerical data
  • Neurofilament Proteins / cerebrospinal fluid
  • tau Proteins / cerebrospinal fluid


  • Amyloid beta-Peptides
  • Biomarkers
  • Fatty Acids, Omega-3
  • Neurofilament Proteins
  • neurofilament protein L
  • tau Proteins