Omega-3: paving a new way to treat depression

Omega-3: paving a new way to treat depression


More than 17 million adults had an episode of depression in 2017, according to the National Institute of Mental Health. Right now, the strain on mental health is only getting worse, furthermore according to a study published in September 2020 in JAMA Network Open; people reported symptoms of depression at three times the rate they did before the pandemic.

 Fish Oil–Mental Health Connection

Fish oil, the fat that comes from fish and seafood, contains two types of omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), according to the National Center for Complementary and Integrative Health. Furthermore, a third omega-3 fatty acid, alpha-linolenic acid, occurs in plant sources, like walnuts, flax, and chia. While the body needs all three omega-3s, EPA and DHA appear to have some of their own benefits.

Numerous studies suggest that a deficiency in omega-3s is linked to an increased risk of several psychiatric disorders, including depression, bipolar disorder, and dementia. That’s prompted researchers to investigate if fish oil — and the EPA and DHA in it — can help prevent or treat the various mental health conditions it’s been linked with, according to a review published in March 2020 in the Global Health Journal.

Evidence suggests that omega-3s can travel through the cell membranes of brain cells and interact with molecules which play a role in mood regulation, according to Harvard Health Publishing. More specifically, one theory is that the anti-inflammatory properties of the omega-3s found in fish oil help stabilize mood.

There are some indications that depression involves inflammation in different parts of the nervous system, according to research published in 2019 in Frontiers in Immunology. “And omega-3s reduce a variety of inflammatory products, including tumor necrosis factor and interleukin-2, -6 , and -1 beta,” Dr. Muskin says. Moreover, it may be that this anti-inflammatory process helps regulate mood.

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.


What the earlier Researches say about omega-3s and depression ?

Your brain needs the type of fatty acids that are in omega-3s for proper functioning. Some believed that those who experience depression may not have enough EPA and DHA . Researchers are using this premise as they study the possible benefits of using omega-3 and fish oil to treat depression.

In 2009, researchers reviewed data from three studies that used EPA in the treatment of three different types of depression: recurrent major depression in adults, major depression in children, and bipolar depression. The large majority of subjects taking EPA in all types showed significant improvement and benefited from the EPA as compared to those with a placebo.

An overview of research from 2004 on omega-3s and depression showed that DHA may also play an important role along with EPA in the treatment of various types of depression. Those with minor depression, postpartum depression, and suicidal ideation had lower levels of EPA and DHA. Hence, these studies showed that a combination of EPA and DHA found in fish oil seemed to improve the depression symptoms of most tested participants.

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.

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 for the study. Still, having said that, there have been numerous studies on the benefits of diets, like the Mediterranean diet, that favour foods rich in these fats. Thus, it pays to eat well, and stay active.

Omega-3 forms and doses

We add Omega-3s to your diet in a variety of ways. Some of these are:

adding more fish to your diet, especially salmon, trout, tuna, and shellfish

fish oil supplements

flaxseed oil

algae oil

canola oil

The U.S. Food and Drug Administration (FDA) recommends that you eat 2-3 servings of fish each week, including a variety of types. A serving for an adult is 4 ounces. A serving for a child is 2 ounces.

The current study

The researchers first applied omega-3 polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in high doses to lab-grown neurons and then in patients to understand the mechanism by which they reduce inflammation and depression.

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.)

The researchers used lab-grown neurones – or nerve cells – to study the effects of high doses of EPA and DHA. The investigators used a validated in vitro human cell model referred to as “depression in a dish,” which uses cells from the hippocampus, a part of the brain fundamental in many cognitive, memory, and learning areas. The hippocampus is thought to be important in depression and also hippocampal cells play an important part in the production of new neurons.

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.

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 linked with depression. (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 they treated the brain cells with EPA and DHA prior to cytokine exposure, they (EPA and DHA) 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: “The lipid mediators that our research identified break 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.”


  1. Omega-3 and Depression. Medically reviewed by Timothy J. Legg, Ph.D., CRNP — Written by Diana Wells — Updated on September 18, 2018
  2. https://www.moneycontrol.com/news/trends/health-trends/omega-3-fatty-acids-may-help-reduce-symptoms-of-depression-kings-college-london-study-shows-7040791.html
  3. What Are the Benefits of Fish Oil for Depression? By Jessica Migala. Medically Reviewed by Allison Young, MD. February 17, 2021
  4. Omega-3 Fatty Acids Could Reduce Depression Symptoms Through Anti-Inflammatory Effects. June 18, 2021. Skylar Kenney, Assistant Editor

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