Fish, and particularly fish oil, contains molecules called omega-3 polyunsaturated fatty acids. Walnuts, soybeans, and flaxseeds are other dietary sources of omega-3, but fish definitely has the spotlight.
What’s all the buzz about then?
It all began a (not so) long time ago, in the 1970’s, when researchers discovered that Greenland Inuits suffered less from diabetes, atherosclerosis, and cardiovascular disease than their Danish counterparts. This was associated with their higher levels of blood omega-3 and fish consumption.
Decades down the line, evidence on the properties of omega-3 keeps adding up and principally attributes them to their anti-inflammatory actions.
And while physical health benefits were observed in the Inuit population, it now appears that the brain, and consequently mental health, can also gain from an increased intake of omega-3. Indeed, omega-3 are important components of brain cells, and can influence the way brain cells connect and communicate with each other, in addition to limiting inflammation.
These effects have been particularly relevant in conditions of the central nervous system such as Alzheimer’s disease or depression, which are linked to increased inflammation of the brain.
This inflammation namely affects a process called neurogenesis, whereby new brain cells (neurons) develop and are integrated to the existing brain circuitry.
Dysfunctions in processes related to neurogenesis can lead to problems with memory or storage of emotional information, which are commonly observed in neuropsychiatric and neurodegenerative conditions.
Depression rates are indeed lower in countries where fish consumption is higher, such as Japan, compared with European countries. This may be partly related to their increased intake of omega-3.
Additional evidence has shown that, through their anti-inflammatory effects, omega-3 are able to improve clinical symptoms of depression as well as cognition in Alzheimer’s disease patients. With regards to neurogenesis, omega-3 have also been proven to increase it at similar levels to antidepressants, in experiments, from our laboratory, using cells mimicking the inflammatory conditions observed in depression.
So, should you eat more fish?
Probably.
Compared with red meat, fish does not increase the overall risk of mortality or cardiovascular disease, and is a source of omega-3.
Unless you live in a high-income Asian country, chances are you do not meet the optimal daily intake of two portions of fish per week. Indeed, lower that recommended intake of omega-3 was highlighted as one of the leading dietary risk factors for mortality by the Global Burden of Disease Study 2017.
However — as I explain to my curious friends — my interest lies not so much in the fish but in how exactly its omega-3 contents are helpful to the brain.
So, what did I do?
Similar to an engineer taking apart a complicated machine to understand its functioning, I delved into the ocean of research on omega-3 with the hope of identifying how they affect and fit in the intricate machinery of the brain.
The outcome of this quest diving into the mechanisms of omega-3 in the brain are summarised in our recently published review.
But before telling you all about the results of our search, here are two key pieces of information that got us started.
Firstly, the main two omega-3 molecules are eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and they are broken down by the metabolism into smaller different molecules really quickly.
These molecules are called “metabolites”, which in this case simply means that the molecule originates from a specific series of breakdowns whereby the metabolism transforms the bigger initial molecule to obtain smaller molecules down the line.
For reference, EPA already goes through several metabolic transformations 45 seconds after its entry into the brain.
Secondly, a group of those metabolites derived from EPA and DHA, called “specialised pro-resolving mediators”, was getting a lot of attention because of its very potent actions against inflammation in the body.
Rather than shutting down the immune system and tipping the scales in the opposite direction, pro-resolving mediators re-establish a balance. They limit the inflammatory reaction of the body to its useful initial stage and prevent it from becoming chronic. Through this process, specialised pro-resolving mediators have been able, for example, to promote clearance of bacteria in human white blood cells and wound healing in animals.
But what about the brain then? Do these molecules have any potential for brain diseases?
So far, the research is mainly limited to animal studies, but yes, they do.
I narrowed the focus of my research on disorders where inflammation plays a role, particularly those where it is detrimental to neurogenesis and cognitive functions, including depression, neurodegenerative disorders like Alzheimer’s and Parkinson’s disease, and neurological conditions such as stroke or traumatic brain injury.
In essence, the body of literature reveals that the different pro-resolving mediators are not made equal: while all of them reduced inflammation, their effectiveness differ depending on the disease.
I also observed that this might be influenced by the different molecular interactions they trigger in brain cells.
For example, a subgroup of pro-resolving mediators named resolvin Es is more effective in alleviating depression-like symptoms in rodents, but others, such as maresins and protectins, are more beneficial in conditions like stroke or traumatic brain injury.
This is interesting, because resolvin E, maresin, and protectin are derived from different omega-3 via different processes. In this case, resolvin E is a molecule derived from EPA, contrary to the others, which are derived from DHA. The therapeutic effects of resolvin E in depression mirror the clinical situation, as analyses of clinical trials with patients suffering from depression show that EPA is better than DHA in terms of improving symptoms.
Now, what does this all mean?
These results indicate an avenue for personalised treatment with those omega-3 metabolites, meaning that specific molecules might be better at targeting biological and clinical symptoms of particular disorders.
More research is obviously needed to confirm this, and to eventually obtain the optimal therapeutic solution. We need more information on exactly how these molecules work in the human brain both in healthy people and patients, in order to figure out exactly how they might be helpful. Nonetheless, specialised pro-resolving mediators represent a possible treatment option without severe side-effects for patients suffering from these conditions.
Now I know what to study for the rest of my PhD!
Header image source: BRUNET