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Omega-3 may be an “effective add-on therapeutic” for depression

Olivia Brown

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A new review investigating the effect of long-chain omega-3 supplementation on depressive symptoms concludes the majority of studies observe a significant effect, particularly in those with major depressive disorder.


Numerous ransomdised controlled clinical trials have shown significant reductions in depressive symptoms from adjunctive treatment with the omega-3 long-chain polyunsaturated fatty acids (LC-PUFA) found in fish and seafood - and particularly EPA - since initial reports more than 20 years ago. (Peet & Horrobin 2002 - A dose-ranging study of EPA treatment in depression)

This new review focused on published meta-analyses of clinical trials to date - of which a clear majority (16/22) showed benefits from dietary supplementation with omega-3 - and that the improvements appear to be greatest for:
  • patients with clinical level depression, and
  • doses of at least 1-2g/day of EPA
The conclusions reinforce those from the detailed treatment guidelines published 4 years ago, from a consensus of leading international researchers and expert clinicians from the International Society of Nutrition in Psychiatry Research:

For details of this new research, see:

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06/11/23 - Nutraingredients


A new umbrella review of meta-analyses investigating the effect of long-chain omega-3 supplementation on depressive symptoms concludes the majority of studies observe a significant effect, particularly in those with major depressive disorder (MDD).
The review also observed a direct relationship between the polyunsaturated fatty acids (PUFAs) dosage and the effect size on depression, with eicosapentaenoic acid (EPA) demonstrating a greater effect over docosahexaenoic acid (DHA).
Regarding the ‘British Journal of Nutrition’ published findings, the Chinese researchers conclude: “Omega-3 PUFAs supplementation could be considered as an effective therapeutic adjuvant approach in relieving depression symptoms.”

Omegas and the mind
Depression is a highly common condition of the modern world, affecting an array of areas​ such as sleep quality, energy levels, and appetite. The World Health Organization has previously predicted​ that it may affect 280 million people globally, with levels ever-increasing​ following the Covid-19 pandemic.
Research​ has shown that factors such as nutrition, genetics, environment, and hormones play major roles in the pathogenesis of depression, with alterations noted in the levels of serotonin, dopamine, and gamma -aminobutyric acid (GABA).
Following long-term concerns​ around the effectiveness and adversities associated with the use of anti-depressants, there has been significant interest in investigating further causes of depression and more natural treatment methods. It is known that long-chain fatty acids (n-3 PUFAs), specifically EPA and DHA, have significant benefits​ such as anti-inflammatory and subsequent neuro-inflammatory inhibitory activities.
Whilst previous meta-analyses​ have investigated the association between omega-3 FAs and depression, there has been a lack of a really conclusive outcome. Thus, the researchers conducted an umbrella review of such meta-analyses to further establish a definite conclusion.

Review findings
The researchers searched the databases of PubMed, Scopus, Embase, Web of Science, and Cochrane Central Library to collate meta-analyses investigating the effects of n-3 PUFAs on depressive symptoms. Twenty-two meta-analyses were included following the search.
The findings revealed a significant improvement effect on depressive symptoms in the majority of included studies, with 16 effect sizes displaying this association.
Supplement dosages displaying significant effects ranged from 0.09-3.4g of DHA and 0.009-6.2 g of EPA.
The association was observed to be more pronounced in those with major depressive disorder (MDD), when compared to those with mild depressive symptoms. Furthermore, there was a direct relationship between the dosages of omega-3 PUFAs and the effect size on depression, with EPA demonstrating a greater effect over DHA.

Based on the findings, the report concluded that omega-3 supplements may present an efficacious add-on therapeutic approach in relieving depression symptoms.
Explaining the mechanism of action, the researchers said:

“Omega-3 PUFAs have been proven to influence the activity and structure of brain through affecting adult neurogenesis and synaptogenesis by increasing the signalling factors involved in neurogenesis, such as brain-derived neurotrophic factor (BDNF), cAMP response element-binding protein (CREB), or calcium/calmodulin-dependent protein kinase II (CaMKII).
“In one pathway, omega-3 PUFAs might increase the expression of dopamine receptor; whereby increase dopamine activity as a neurotransmiter in restoring the mood (81).

"As well, omega-3 PUFAs were effective in balancing the low level of BDNF (brain-derived neurotrophic factor) among depressed patients. BDNF could boost the action of antidepressant agents,”
they added.
Yet, the report emphasised the need for further research to account for significant between-study heterogeneity and a lack of insight into factors such as dose, duration of supplementation and gender.