Association of Polyunsaturated Fatty Acid Intake on Inflammatory Gene Expression and Multiple Sclerosis: A Systematic Review and Meta-Analysis

Nutrients. 2022 Nov 2;14(21):4627. doi: 10.3390/nu14214627.


The health benefits of omega-3 fatty acid (FA) supplementation on inflammatory gene expression (IGE) and multiple sclerosis (MS) are becoming more evident. However, an overview of the results from randomized controlled trials is lacking. This study aimed to conduct a meta-analysis to evaluate the effect of omega-3 fatty acid intake on MS (based on the criteria of the Expanded Disability Status Scale (EDSS)) and inflammatory gene expression (IGE). A search was conducted of PubMed, EMBASE, and Web of Science for cohort studies published from the inception of the database up to May 2022 that assessed the associations of omega-3 polyunsaturated fatty acids (n-3 PUFAs), docosahexaenoic acid (DHA), α-linolenic acid (ALA), and eicosapentaenoic acid (EPA) with EDSS and inflammatory gene expression (peroxisome proliferator-activated receptor gamma (PPAR-γ), tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6), and interleukin-8 (IL-8)) outcomes. For the highest vs. lowest comparison, the relative risk (RR) estimates with a 95% confidence interval (CI) were pooled using the random-effect model. In total, 13 cohort studies with 1353 participants were included in the meta-analysis during periods of 3 to 144 weeks. A significant inverse relationship was found between DHA and EDSS scores (RR: 1.05; 95% CI: 0.62, 1.48; p < 0.00001). Our results also showed that omega-3 FAs significantly upregulated the gene expression of PPAR-γ (RR: 0.95; 95% CI: 0.52, 1.38; p < 0.03) and downregulated the expression of TNF-α (RR: −0.15; 95% CI: −0.99, 0.70; p < 0.00001) and IL-1 (RR: −0.60; 95% CI: −1.02, −0.18; p < 0.003). There was no clear evidence of publication bias with Egger’s tests for inflammatory gene expression (p = 0.266). Moreover, n-3 PUFAs and EPA were not significantly associated with EDSS scores (p > 0.05). In this meta-analysis of cohort studies, blood omega-3 FA concentrations were inversely related to inflammatory gene expression (IGE) and EDSS score, which indicates that they may hold great potential markers for the diagnosis, prognosis, and management of MS. However, further clinical trials are required to confirm the potential effects of the omega-3 FAs on MS disease management.

Keywords: EDSS; PPAR family; gene expression; inflammation; meta-analysis; multiple sclerosis; omega-3.

Publication types

  • Meta-Analysis
  • Systematic Review
  • Review

MeSH terms

  • Docosahexaenoic Acids / therapeutic use
  • Eicosapentaenoic Acid / therapeutic use
  • Fatty Acids, Omega-3* / pharmacology
  • Fatty Acids, Omega-3* / therapeutic use
  • Gene Expression
  • Humans
  • Immunoglobulin E
  • Interleukin-1
  • Multiple Sclerosis* / drug therapy
  • Multiple Sclerosis* / genetics
  • Peroxisome Proliferator-Activated Receptors
  • Tumor Necrosis Factor-alpha


  • Tumor Necrosis Factor-alpha
  • Peroxisome Proliferator-Activated Receptors
  • Fatty Acids, Omega-3
  • Eicosapentaenoic Acid
  • Docosahexaenoic Acids
  • Interleukin-1
  • Immunoglobulin E

Grants and funding

This research received no external funding.