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. 2025 Sep 1;13(9):e70884.
doi: 10.1002/fsn3.70884. eCollection 2025 Sep.

Omega-3 Fatty Acids Supplementation and Neuroprotection, Inflammation, Fatigue, and Physical Activity in Multiple Sclerosis: A Randomized Controlled Trial

Affiliations

Omega-3 Fatty Acids Supplementation and Neuroprotection, Inflammation, Fatigue, and Physical Activity in Multiple Sclerosis: A Randomized Controlled Trial

Sahar Golabi et al. Food Sci Nutr. .

Abstract

Omega-3 fatty acids have neuroprotective properties. The present study aimed to evaluate the influence of omega-3 fatty acids supplementation on the serum levels of brain-derived neurotrophic factor (BDNF), high-sensitivity C-reactive protein (hs-CRP), physical activity, and chronic fatigue in patients with multiple sclerosis (MS). In a double-blind, placebo-controlled trial, 68 MS patients were randomly assigned to the intervention group receiving omega-3 fatty acids soft gels (1000 mg) twice a day for 12 weeks and the placebo group similarly taking paraffin soft gels. Serum concentrations of BDNF and hs-CRP were assessed before and after the intervention. Chronic fatigue, physical activity, and dietary intake of omega-3 fatty acids were evaluated. Initial comparisons between the intervention and control groups showed no significant differences for BDNF and hs-CRP levels (p = 0.321 and p = 0.996, respectively). Following the intervention, both groups showed a significant increase in their BDNF levels (p < 0.001). However, there were no significant differences in post-intervention levels of BDNF and hs-CRP serum levels between groups (p = 0.427, p = 0.695, respectively). This finding was further supported by the Quade nonparametric analysis of covariance, adjusted for baseline values, which indicated that omega-3 fatty acid supplementation had no significant effect on BDNF or hs-CRP levels in patients with MS (p = 0.644 and p = 0.533, respectively). After the intervention, hs-CRP changes were 1.5 folds greater in female patients than in male patients (p = 0.005). Additionally, no significant differences were observed between the intervention and control groups in baseline or post-intervention physical activity levels or chronic fatigue (p > 0.05), suggesting that omega-3 fatty acid supplementation did not influence physical activity or fatigue. Omega-3 fatty acids supplementation has no significant effect on BDNF and hs-CRP serum levels, fatigue, or physical activity capacity among MS patients. However, gender-specific differential hs-CRP response suggests a possible sex-related anti-inflammatory effect, which deserves further investigation.

Keywords: brain‐derived neurotrophic factor; clinical trial; high‐sensitivity C‐reactive protein; multiple sclerosis; omega‐3 fatty acids; placebo.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
The schematic diagram of study design. The reasons for drop out from analysis are displayed.
FIGURE 2
FIGURE 2
The bar chart illustrates the frequency distribution of various MS types among study groups, revealing no significant differences (p = 0.424) after chi‐squared test analysis, with MS types defined as RRMS (relapsing–remitting), SPMS (secondary progressive), CIS (clinically isolated syndrome), and PPMS (primary progressive).
FIGURE 3
FIGURE 3
Within‐group and between‐group comparison of BDNF serum levels (ng/mL) of MS patients before and after the omega‐3 fatty acids supplementation and placebo administration. There was no significant difference before and after 12 weeks of follow‐up between the intervention and control groups.
FIGURE 4
FIGURE 4
The comparison of hs‐CRP serum levels (mg/L) in MS patients before and after 12 weeks of omega‐3 fatty acids supplementation and placebo showed no significant difference between the intervention and control groups.

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