Just out June 2025! Journal of Human Nutrition and Dietetics, 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
Omega-3s (especially EPA and DHA) are known to support brain health and influence inflammation, neurotransmission, and cell function. A growing area of research has focused on whether they can also affect levels of BDNF (brain-derived neurotrophic factor)—a protein that plays a crucial role in neuroplasticity, synaptic function, and neuronal survival.
BDNF is often found in reduced levels in people with major depressive disorder and bipolar disorder. It’s considered a potential biomarker of treatment response in mood disorders.
Study Design: Small but Rigorous
- Participants: 60 adult men (aged 18–65) diagnosed with bipolar disorder
- Groups: Omega-3 group (2 g/day, 60% EPA + 40% DHA) vs. placebo group (edible paraffin)
- Duration: 8 weeks
- Measures: Blood BDNF levels and depression severity using the Hamilton Depression Rating Scale (HAM-D)
- Note: All participants continued their standard psychiatric medications throughout the study
The HAM-D is a clinician-rated scale widely used in clinical trials to assess the severity of depressive symptoms. Scores over 25 typically indicate major depression.
Results: Omega-3 May Support Brain Chemistry and Mood
BDNF levels increased significantly in the omega-3 group—from 0.499 to 0.756 ng/mL, a 33% rise. In contrast, the placebo group showed no meaningful change.
Why is this important?
BDNF is essential for maintaining healthy brain function. It supports the growth and differentiation of new neurons and synapses and is directly involved in regulating mood and cognitive function. Increasing BDNF levels is thought to enhance neuroplasticity, which may help stabilize mood in individuals with bipolar disorder. Some antidepressants may exert their therapeutic effects partly by elevating BDNF.
Depression scores dropped significantly in the omega-3 group, from 40.13 to 22.40 on the Hamilton scale—indicating a shift from major to moderate depression.
⚠️ The placebo group also improved slightly (from 42.38 to 29.35), likely reflecting the ongoing effect of standard treatment, but they remained in the major depression category.
Together, these findings suggest that omega-3 may help reduce depression symptoms in bipolar disorder—possibly by modulating neurotrophic signaling pathways.
How Might Omega-3 Increase BDNF?
Researchers outlined several biological pathways through which omega-3s might influence BDNF expression:
- Activation of PI3K/Akt and MAPK/ERK signaling cascades involved in cell survival and synaptic plasticity
- Phosphorylation of CREB (cyclic AMP response element-binding protein), a transcription factor that regulates BDNF gene expression
- Modulation of the endocannabinoid system, anti-inflammatory signaling, and membrane fluidity in neural tissue
While these mechanisms are supported by preclinical studies, more human research is needed to clarify exactly how omega-3s affect BDNF in the context of psychiatric illness.
Caution: Encouraging Evidence, But Not Proof
This trial was well-structured, but several limitations apply. It was short in duration (8 weeks), included only men, and had a modest sample size. Dietary factors weren’t controlled, and long-term outcomes remain unknown.
That said, the results are consistent with previous studies showing a potential antidepressant effect of omega-3s—especially in individuals with low baseline BDNF levels or high inflammatory markers.
Dr. Hunt on What This Means for You
“This study adds meaningful evidence that omega-3s may support brain health and improve depressive symptoms in people with bipolar disorder—likely by influencing BDNF. But it’s not definitive proof. Think of omega-3s as a potentially helpful adjunct, not a replacement for treatment.
If you’re considering supplements, talk to your doctor—especially since effects often build gradually over weeks or months.”