Key factor in fish oil’s antidepressant effects revealed


A key molecular mechanism that underpins the anti-inflammatory, antidepressant and neuroprotective effects of omega-3 fatty acids has been identified.

In evidence that could lead to the development of new treatments for depression, research provides “first evidence” that hippocampal neurons are capable of producing two major lipid metabolites from eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) – lipoxygenase and cytochrome P450, senior investigator Alessandra Borsini, PhD, told Medscape Medical News.

This is how EPA and DHA unfold their anti-inflammatory and neurogenic properties in vitro, as well as their antidepressant properties in patients with depression, said Borsini of King’s College London, UK.

“We have indeed found evidence of a correlation between increased levels of these metabolites and a decrease in the severity of depressive symptoms in patients with major depressive disorder,” said Borsini.

The study was published online in Molecular Psychiatry on June 16.

“Depression in a Bowl”

Despite the known role of inflammation in depression, there is a lack of data showing anti-inflammatory strategies that are effective, safe for everyday use, and with a clear mechanism of action, the researchers note.

Borsini and colleagues tested the theory that when EPA and DHA are metabolized, some of their metabolites, or lipid mediators, can protect the brain from the harmful effects of inflammation. They used a validated “Depression in a Dish” in vitro model of human hippocampal cells to test their theory.

They found that treating human hippocampal cells with EPA or DHA before exposure to cytokines prevented increased cell death and decreased neurogenesis. Both effects had previously been seen in cells exposed only to cytokines.

They confirmed that these effects were mediated by the formation of several key lipid mediators produced by EPA and DHA – namely, hydroxyeicosapentaenoic acid, hydroxydocosahexaenoic acid, epoxyeicosatetraenoic acid (EpETE), and epoxydocosapentaenoic acid (EpDPA).

It’s the first time these lipid mediators have been detected in human hippocampal neurons, the researchers say.

They also found that treating the neurons with an enzyme inhibitor increased the availability of two of these metabolites (EpETE and EpDPA), suggesting a possible avenue for optimizing future treatments.

The results were replicated in 22 major depression patients who received either EPA (3 g / day) or DHA (1.4 g / day) for 12 weeks. In both groups, EPA or DHA treatment was associated with an increase in their respective metabolites and a significant improvement in depressive symptoms.

The mean reduction in symptom scores was 64% and 71%, respectively, in the EPA and DHA groups, and there was some evidence that higher levels of the same metabolites correlated with less severe depressive symptoms.

“We have known for some time that omega-3 [polyunsaturated fatty acid (PUFA)] can produce antidepressant and anti-inflammatory effects, but without further understanding of how this happens in the human brain, treatments have been difficult to develop, “Borsini said in a press release.

“Our study helped shed light on the molecular mechanisms involved in this relationship that may influence the development of potential new treatments for depression with omega-3 PUFAs,” added Borsini.

“We need to be careful in interpreting data generated from the correlation between metabolite levels and depressive symptoms as the results require further validation in a larger patient population,” said Borsini.

“It’s important to emphasize that our research has not shown that simply increasing the omega-3s in our diet or taking supplements can reduce inflammation or depression,” said study author Carmine Pariante, MD, PhD, from King’s College London, said in the press release.

“The mechanisms behind the associations between depression and omega-3 PUFAs are complex and require further research and clinical trials to fully understand how they work and inform future therapeutic approaches,” said Pariante.

No clinical effects

Kevin McConway, Professor Emeritus of Applied Statistics at the Open University, Milton Keynes, Great Britain, acknowledged this research in a statement from the Science Media Center: “The purpose of the study was to shed light on the mechanisms in the body through the omega-3 fatty acids Can reduce inflammation or depression. “

“The research mainly involved cells in laboratory dishes, but it also involved treating a small group of patients with major depression by being given a supplement of one or the other of the two omega-3 acids studied for 12 weeks,” he noted.

“The researchers found that patient average scores on a set of standard questions used to diagnose and measure depression improved for each of the two fatty acids over that 12-week period.

While symptoms of depression improved over 12 weeks with omega-3 treatment, “depression symptoms change over time for many reasons” and depressive symptoms may have improved over 12 weeks even if the patient was given the omega -3 acids would not have been administered. said McConway.

“We just can’t tell because every patient is getting omega-3 fatty acids. So these results may suggest that omega-3s might help with depression, but it is far from being the case with any degree of certainty, ”he warned.

“In fact, the researchers didn’t do this part of their study to see if the omega-3 supplements would help with depression – they did it to see if the biochemical changes they’d seen in cell cultures in the laboratory, too could occur in the human body. “,” he remarked.

Mol psychiatry. Published online 16.06.2021. Full text

This research was funded in part by grants to researchers from the UK Medical Research Council, the European Commission Horizon 2020 and the National Institute for Health Research (NIHR) Maudsley Biomedical Research Center (BRC) in South London and the Maudsley NHS Foundation Trust and Kings College London. Borsini has received research funding from Johnson & Johnson for research into depression and inflammation. McConway is a trustee of the Science Media Center and a member of its advisory board.

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