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Higher dose of omega-3 fatty acid reduced Major Depressive Disorder (MDD) in overweight adults at 12 weeks

Robert Herpen, MA

Omega-3 supplements

Doses of EPA higher than the usually recommended 1-2 grams per day may be more effective for depression in some patients with obesity and chronic inflammation.


Systematic reviews of controlled clinical trials have already shown that in patients with clinical-level depression, dietary supplementation with the long-chain omega-3 EPA can be effective as an adjunctive treatment.  For detailed, evidence-based guidelines for clinicians on the use of omega-3 in the management of depression, by leading international researchers and clinicians in this area. See:

As depression is strongly linked with inflammation, the anti-inflammatory properties of EPA are just one of the many possible mechanisms by which this omega-3 may help to reduce depressive symptoms.  

This new study therefore explored the effects of different doses of EPA on biomarkers of inflammation in patients wth both depression and obesity - another condition linked with excessive inflammation.

Only the 4g/day dose of EPA - not the lower doses of 1g or 2g that were also tested - was more effective than placebo in reducing depressive symptoms in this population.  Effects of EPA in reducing inflammation met pre-specified endpoints for only one of the 3 biomarkers (and only for the 2g/day dose).

While this was only a small trial, its findings are important in showing that

(1) for patients with both depression and obesity, higher doses of EPA may be needed to reduce depressive symptoms than the 1-2g EPA usually recommended

(2) anti-depressant effects of EPA may reflect other mechanisms in addition to its well-documented anti-inflammatory effects.

For details of this research, see:

See also:

And for further information on the effects of omega-3 on depression (and related mood disorders), see:

See also the following lists, which are regularly updated:

Listen to this Free Podcast where Dale Pinnock interviews Dr Alex Richardson, from Oxford University, to discuss her specialist field - omega 3 fatty acids, particularly in brain function:

24/08/2022 - Healio Psychiatry

Eicosapentaenoic acid at a dose of 4 g per day reduced effects of major depressive disorder in overweight individuals with elevated inflammatory markers better than placebo at 12 weeks, according to a recently published study.

“Omega-3 polyunsaturated fatty acids (PUFA) have been studied in many conditions including cardiovascular disease, risk of psychosis, attention deficit disorder, bipolar disorder and major depressive disorder,” David Mischoulon, MD, PhD, of the depression clinical and research program in the department of psychiatry at Massachusetts General Hospital, and colleagues wrote in the Journal of Clinical Psychiatry.

“Although meta-analyses for cardiovascular disease and MDD suggest that PUFA treatment may be effective, findings overall are mixed.”

Mischoulon and fellow researchers sought to compare the impact of three doses of eicosapentaenoic acid (EPA) — an omega-3 fatty acid found in salmon and fish oil supplements — with placebo on inflammatory biomarkers and depressive symptoms.

The parallel group, double-blind, randomized controlled trial was conducted at Emory University and Massachusetts General Hospital, and included 61 unmedicated adults (75% female) diagnosed with MDD, with a BMI greater than25 kg per square meter and plasma high-sensitivity C-reactive protein (hs-CRP)greater than or equal to 3.0 mg/L.

Participants were randomly assigned to receive a dose of either 1, 2 or 4 grams per day of EPA, or placebo for 12 weeks. Prespecified endpoints were a 0.40 effect size decrease in plasma interleukin (IL)-6, peripheral blood mononuclear cell (PBMC) cytokines, and lipopolysaccharide-stimulated tumor necrosis factor (TNF) production. Response was defined as a decrease of 50% or more of Inventory of Depressive Symptomatology, Clinician-Rated version (IDS-C30) scores. Outcomes were additionally compared for the three EPA doses against placebo.

Results showed that, among 45 trial completers, only median PBMC TNF decreased at 2 g/d EPA. No EPA dose produced 0.35 effect size reduction in plasma IL-6 or mitogen-stimulated TNF.

Response rates for EPA 4 g per day were 64%, compared with 40% for placebo (OR,2.63; Cohen d = 0.53), 38% for EPA 1 g per day, and 36% for EPA 2 g per day. EPA 4 g per day showed a significant correlation between percent decrease in plasma hs-CRP and IDS-C30 symptom reduction at 12 weeks.

“Doses of EPA higher than the usually recommended 1-2 grams per day may be more effective for depression in some patients with obesity and chronic inflammation, and reduction in hs-CRP may play a role in this process,” Mischoulon and colleagues wrote.