Can omega-3 fatty acids really treat depression? Fishing for answers

I am a graduate in Biomedical Sciences with Professional Experience from Brunel University London. During my studies, I have grown to become fascinated by mental health and more specifically this topic of alternative treatments to depression due to the considerable lack of adequate understanding of the fundamental causes and the mechanisms involved in the development of mental disorders. Therefore I would not only like to have the opportunity to conduct research in this area but I would also like to inform the general public about the science behind mental health and ultimately contribute to ending the stigma surrounding the idea that mental disorders are all in the head.


According to the World Health Organisation (WHO), depression has become the major cause of disability in the world.


The current treatment for depression involves using conventional antidepressants, which have been limited in terms of their effectiveness, safety and how well they’re tolerated. In other words, they display modest therapeutic benefit but are frequently associated with side effects.

So, attention has shifted to questioning whether changes in lifestyle and diet can be a novel therapeutic strategy for this disease.


What are omega-3 fatty acids?


Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) are a class of compounds that include essential fatty acids like eicosapentanoic acid (EPA) and docosahexanoic acid (DHA), which must be obtained through dietary intake since the body cannot produce them. These compounds are mainly found as components of fish oils derived from oily fish such as salmon, herring, sardines and mackerel.


What are their functions?


You may be asking, what impact do fish oil supplements actually have on the human body?

Well, it turns out that ω-3 PUFAs — like EPA and DHA — have an important role in brain function.

Interestingly, these compounds are not only involved in the signalling that takes place between neurons and in maintaining the structure of neuron membranes, but they are also involved in regulating the function of the immune system and have an anti-inflammatory action in the brain — meaning that these compounds are able to decrease inflammation.


This anti-inflammatory action is thought to be one of the mechanisms by which ω-3 PUFAs mediate their antidepressant effects.


Additional information on this area can be found in two excellent reviews from the Neurosignals and Nature journals.


Furthermore, a diet supplemented with ω-3 PUFAs can significantly reduce cortisol (a hormone produced in response to stress) after the induction of mental stress in one study, thus indicating their possible impact on our stress response system.


The role of stress, the immune system, and inflammation on the development of depression has been widely discussed in the scientific literature and is the central theme of discussion for some of the blog posts on ‘InSPIre the Mind’, such as those written by Andrew Perrin and Professor Carmine Pariante (which I highly recommend you to read).


Therefore, ω-3 PUFAs could not only improve the symptoms of depression but could also be therapeutically beneficial for patients with conditions such as diabetes, coronary heart disease and cancer, for which chronic inflammation is an important contributing factor. ω-3 PUFAs have also been implicated in the treatment of Alzheimer’s disease and ADHD (Attention Deficit Hyperactivity Disorder), suggesting their probable role in cognition and neurodevelopment.


What do the studies say?


As a result of their discovered antidepressant effects, ω-3 PUFAs have been gaining a lot of attention from the clinical and medical community, with a large number of scientific articles being published in the last two decades discussing their potential use as treatment for depression.


Depressed patients have lower levels of ω-3 PUFAs in the brain than in healthy controls, suggesting a link between dietary fish consumption and the risk of depression. In fact, countries that consume a larger amount of oily fish rich in ω-3 PUFAs as part of their diet such as Taiwan, Japan and Korea have lower incidences of depression.

So, does that mean that the more oily fish or fish oil supplements you consume, the higher the levels of ω-3 PUFAs in your brain, and thus resulting in a reduced risk of depression? Well, not quite — before running off to your local fishmonger or chemist, it’s important to note that further validation is needed.

Results from various studies have been encouraging and support the use of ω-3 PUFAs as adjunctive treatment. This means that they can be taken in addition to conventional antidepressants to enhance antidepressant effects, rather than being a treatment used alone. The tolerability and safety of these compounds have also been noted, with the occurrence of side effects being very rare.

There are also studies that focus on the development of personalised treatment strategies and have identified biomarkers — such as inflammation, which can be detected in the blood — to predict how individuals will respond to ω-3 PUFAs.

For example, one such study reported that patients with depression displaying higher levels of inflammation before treatment, were shown to have better responses to EPA than those displaying low inflammation. This could mean that ω-3 PUFAs are more effective in patients with inflammation-associated depression.

And you might have read a recent blog on this platform talking about another study (admittedly, not in depression) which found that children with ADHD and lower levels of endogenous ω-3 PUFAs are more likely to respond to EPA than children with normal or high endogenous levels — another example of ‘personalised treatment’.

 

As mentioned above, two forms of ω-3 PUFAs are EPA and DHA. Studies have shown that EPA may display stronger antidepressant effects than DHA, with EPA successfully preventing depression but DHA only delaying the start of the disorder.


This may be the type of findings that have informed the recently published guidelines by the ‘International Society for Nutritional Psychiatry Research’ (ISNPR) for the treatment of depression using ω-3 PUFAs.


But what about children and pregnant women with depression?


The ISNPR agrees to the use of ω-3 PUFAs for the treatment of depression in pregnant women and children, as well as the elderly, and for the prevention of depression in high-risk populations. The research suggests that ω-3 PUFAs seem to hold great potential as a safer alternative for these patients.


However, despite the evidence demonstrating the therapeutic benefit of ω-3 PUFAs used as a standalone treatment in children and pregnant women with depression, due to the use of small sample sizes in research studies as well as an overall low number of studies investigating these populations, the ISNPR urges clinicians to carefully consider the use of this treatment for these patients until there is further research evidence.



 

So, what does this all mean for the future of ω-3 PUFAs as treatment for depression?

As discussed above, there is a lot of evidence supporting the use of ω-3 PUFAs in combination with conventional antidepressants — potentially being more beneficial in their effectiveness in depressed patients with underlying inflammation.

Undeniably, this is all very promising for the field of mental health research, and a step in the right direction.

But, there is still a way to go before ω-3 PUFAs are implemented regularly by clinicians in their treatment strategies for patients.

More randomised clinical trials, comparing the use of ω-3 PUFAs against a placebo (i.e. a sugar pill) or even other treatments, with larger populations are needed to validate the efficacy of these compounds both as an add-on treatment in adults and as a standalone treatment in pregnant women and children.

There is also the prospect of a personalised approach to the treatment of depression based on biomarkers that deserves further study, including levels of endogenous ω-3 PUFAs themselves. With further research, this has the potential to help predict an individual patients’ response to different types of treatments, as well as identify the mechanisms behind the disorder.

The potential side effects cannot be ignored either — gastrointestinal (stomach and digestive system) and dermatological (skin, hair and nail) problems should be monitored, according to the ISNPR.

Nonetheless, I am looking forward to what future studies uncover and whether this evidence will have an impact in the clinic, and I hope you are too!

 

NOTE FROM THE EDITORS: We would like to extend a big thank you to Nare Amasi-Hartoonian for this wonderful blog. Nare is a Biomedical Sciences graduate from the University of Brunel who became interested in mental health during her undergraduate studies and it is a great pleasure that she has written a piece for our InSPIre the Mind readers!





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