Supplementation of Omega-3 Increases Serum Levels of Brain-Derived Neurotrophic Factor and Decreases Depression Status in Patients With Bipolar Disorder: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

J Hum Nutr Diet. 2025 Jun;38(3):e70076. doi: 10.1111/jhn.70076.

Abstract

Background: There is a direct relationship between omega-3 and major depression. This study was conducted to investigate the effect of supplementation of omega-3 fatty acids on serum levels of brain-derived neurotrophic factor (BDNF) and depression status in patients with bipolar disorder (BD).

Methods: This double-blind clinical trial was conducted on 60 men with BD. The patients were grouped into two groups and received 2 g/day of omega-3 supplements or a placebo daily for 2 months. The serum concentrations of BDNF and depression scores were investigated before and after the intervention. Afterward, the data were analyzed using the non-parametric Wilcoxon and Mann-Whitney tests.

Results: The supplementation of omega-3 fatty acids significantly increased the serum concentration of BDNF compared to pre-intervention (0.449 ± 0.110 ng/mL vs. 0.756 ± 0.160 ng/mL) and also decreased the scores on the Hamilton test (40.13 ± 9.51 vs. 22.40 ± 7.49) (p < 0.05). The results also showed that supplementation with omega-3 fatty acids significantly increased the serum concentration of BDNF (0.756 ± 0.160 ng/mL vs. 0.504 ± 0.154 ng/mL) and decreased the scores on the Hamilton test compared to the placebo group (22.40 ± 7.49 vs. 29.35 ± 6.08) (p < 0.05).

Conclusions: In conclusion, daily supplementation with 2 g of omega-3 fatty acids for 2 months decreased depression scores and increased serum concentrations of BDNF in BD patients compared to the placebo group.

Keywords: bipolar disorder; brain‐derived neurotrophic factor; depression; omega‐3.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Bipolar Disorder* / blood
  • Bipolar Disorder* / drug therapy
  • Bipolar Disorder* / psychology
  • Brain-Derived Neurotrophic Factor* / blood
  • Depression* / blood
  • Depression* / drug therapy
  • Dietary Supplements*
  • Double-Blind Method
  • Fatty Acids, Omega-3* / administration & dosage
  • Fatty Acids, Omega-3* / therapeutic use
  • Humans
  • Male
  • Middle Aged
  • Treatment Outcome

Substances

  • Brain-Derived Neurotrophic Factor
  • Fatty Acids, Omega-3
  • BDNF protein, human