Eicosapentaenoic acid (EPA)-predominant fatty acid supplements and the treatment of depression

"Further RCTs [randomised-controlled trials] should be conducted on study populations with diagnosed or clinically significant depression of adequate duration using EPA [eicosapentaenoic acid] -predominant omega-3 HUFA [highly unsaturated fatty acids] formulations."

So went the conclusions of the review article published by Brian Hallahan and colleagues [1] who searched the peer-reviewed science literature for clinical trials "evaluating efficacy of omega-3 highly unsaturated fatty acids (HUFAs) in major depressive disorder." They found over 30 trials of omega-3 supplementation vs. placebo published between 1980 and 2014 that together included participant numbers in the thousands.

They reported that among those diagnosed with depression, the type of fatty acid supplement used might matter: "eicosapentaenoic acid (EPA)-predominant formulations (>50% EPA) demonstrated clinical benefits compared with placebo." When it came to that other commonly discussed omega-3 fatty acid - docosahexaenoic acid (DHA) - the results were not so great for those diagnosed with depression in terms of changes to symptom presentation(s). Importantly too, the authors noted that: "EPA failed to prevent depressive symptoms among populations not diagnosed for depression."

Interesting. More so when read alongside another recent review paper by Husted & Bouzinova [2] who similarly suggest that more targeted research is needed to "clarify an optimal dosage of EPA and DHA in [the] prevention of depression." They also described the idea that various processes particularly pertinent to the concept of inflammation (yes, depression and inflammation do seem to have some commonalities) might be a target for certain omega-3 fatty acids and onwards the presentation of depression. There may even be 'critical windows' where such supplementation might be more useful (see here) than others.

What's the critical difference between EPA and DHA that could account for the Hallahan findings? Well, there are a few good articles on how not all omega-3 fatty acids are the same, but I found one that is pretty informative (see here). Chemically-speaking, there are differences in structure which might account for where and when these compounds might fit when it comes to various chemical reactions in the body. Going back to the whole inflammation thing, I understand that EPA might also have some important effects on an enzyme called delta-5-desaturase (D5D) but I'd guess this is not the only difference that might be important.

I'll be keeping a watch out for developments in this area of study but for now, yet more evidence that food and nutrition might have some important influences on behaviour and psychiatry. Nutritional psychiatry is starting to come out from the clinical shadows perhaps...

Music: The Fall and Eat Y'Self Fitter ('Up the stairs mister').

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[1] Hallahan B. et al. Efficacy of omega-3 highly unsaturated fatty acids in the treatment of depression. The British Journal of Psychiatry. 2016; 209: 192-201.

[2] Husted KS. & Bouzinova EV. The importance of n-6/n-3 fatty acids ratio in the major depressive disorder. Medicina (Kaunas). 2016;52(3):139-47.

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Hallahan B, Ryan T, Hibbeln JR, Murray IT, Glynn S, Ramsden CE, SanGiovanni JP, & Davis JM (2016). Efficacy of omega-3 highly unsaturated fatty acids in the treatment of depression. The British journal of psychiatry : the journal of mental science PMID: 27103682