Omega-3 fatty acids may reduce symptoms of depression: King's College London researchers

We've known for some time now that Omega 3 polyunsaturated fatty acids (PUFAs) are good for us: they reduce inflammation, reduce the risk of heart attacks, and have an anti-depressant effect. Now, scientists at the King's College London (KCL) have solved a piece of the puzzle around how these "good fats" work in the context of depression and mental health.

To put it simply, the researchers found that when we consume some omega-3 fats, our body breaks them down into molecules called the lipid mediators. The researchers at KCL found that higher levels of certain lipid mediators in the blood protect the brain from inflammation - earlier research has shown a connection between depression and inflammation.

To double-check their findings, the KCL researchers measured the depressive symptoms score of 22 patients in the study, and found a marked improvement at the end of 12 weeks of Omega 3 therapy.

Why is this important?

When it comes to brain science, often pinpointing the mechanism for how things work can be at least as difficult as figuring out what works. Figuring out the "how" is important to develop therapeutic approaches to mental health disorders including depression.

So, what does this mean? The research could help medicine scientists come closer to a fatty acid-based therapy for depressive disorders. Depression affects 264 million people all over the world and 45.7 million in India (as of 2017).

For the general public, this information is more good-to-know than anything else. The reason: it is impossible for us to eat the levels of Omega 3 used by the scientists for the study. Having said that, there have been numerous studies on the benefits of diets, like the Mediterranean diet, that favour foods rich in these fats. It pays to eat well, and stay active.

The KCL scientists published their findings in the journal Molecular Psychiatry by Nature - the article became available online on June 16, 2021.

Which Omega-3 fatty acids?

At the centre of the KCL research were two key types of omega-3 (which are also found in our food) - eicosapentaenoic acid (EPA; found in fish like salmon and cod liver and fish oil supplements) and docosahexaenoic acid (DHA; found in ghee and fish such as Indian mackerel, Japanese threadfin bream and ilish).

To reiterate, the KCL researchers used EPA and DHA levels in excess of what can be consumed even through omega 3-rich foods like oily fish. (Consult a physician before taking any supplements.)

For the study, the researchers used lab-grown neurones - or nerve cells - to study the effects of high doses of EPA and DHA. Next, they studied the effects in 22 patients with major depression. Over a course 12 weeks, the patients received one of the two:

• 3 grams of EPA daily
• Or 1.4 grams of DHA per day

Here's what the researchers found: Higher levels of the lipid metabolites of EPA and DHA in the patients' blood after the Omega 3 treatment resulted in a decline in their depressive symptoms score. The average decline in patients who got DHA was 71%, compared with the EPA group with a decline of 64% on average.

Again, what does this mean?

This two-part process - to study the effects in a petri dish with human cells taken from a part of the brain called the hippocampus (the scientists called it "depression in a dish"), and then human subjects - helped the scientists understand the mechanism for how these fatty acids reduce inflammation and improve signs of depression.

Here's what they found:

• These fats are metabolised or broken down into lipid mediators that protect the brain from inflammation. (Normally, inflammation is a natural response of our immune system. It helps to start the healing process when we are injured, and to fight pathogens like bacteria and viruses that threaten our health. However, chronic inflammation has been linked with poor health outcomes, including depression.)
• During the study, the scientists treated brain cells in a petri dish with EPA or DHA and then exposed them to cytokines - cytokines are naturally occurring chemical messengers that our immune cells use to talk to each other. Some cytokines trigger in the body.
• Now, higher exposure to cytokines may result in increased cell death and reduced generation of new cells (neurogenesis). The KCL researchers found that when the brain cells were treated with EPA and DHA prior to cytokine exposure, they helped to prevent both the increase in cell death and decrease in neurogenesis.
• Further the action of these lipid mediators (specifically, epoxyeicosatetraenoic acid or EpETE, and epoxydocosapentaenoic acid or EpDPA) could be prolonged using certain enzyme inhibitors.

University of Manchester's Professor Anna Nicolaou, who led the team that measured the lipid mediators using mass spectrometry, explained in a news release: "The lipid mediators that our research identified are broken down in the body relatively quickly, which means they may only be available for a relatively short time. By testing the effect of inhibitors of the enzymes involved in the metabolism of omega-3 PUFA we showed that we can greatly improve how long they can have an effect in the body and ultimately, increase their efficacy. This is very important for the development of new treatments and means that patients could be given higher doses of EPA and DHA together with these enzyme inhibitors to increase the amount of these important compounds in their blood over time."