Several randomized controlled trials have been performed utilizing omega-3 fatty acids as a monotherapy for depression, or as augmentation therapy (added to an antidepressant for major depressive disorder.)  Two recent meta-analyses aggregated these data, and found that there is evidence for an anti-depressant effect of omega-3 fatty acids when used in conjunction with anti-depressant medications for depression; however, there was evidence of publication bias in favor of positive studies.  That is, a normal distribution of the effect sizes showed an absence of small, negative studies that have been published.  The available evidence from randomized controlled trials is modest, but does support a role for omega-3 fatty acids as an augmentation therapy for depression.  However, randomized controlled trials do not at this time support a role for omega-3 fatty acids in monotherapy for major depressive disorder, nor for boosting “subclinical depression” (which is to say depressed mood that does not meet the criteria for major depressive disorder.)

Problem with Randomized Controlled Trials

All of these studies involve very short time courses (e.g. supplementation over the course of approximately twelve weeks.)  The epidemiological data suggests that it is the overall consumption of omega-3 fatty acids over years to a lifetime that has a protective effect.  None of our randomized controlled trials are done over a long enough time period to determine the full effect of omega-3 fatty acids on mood.

Conclusion: Omega-3 Fatty Acids Have a Protective Effect

It is important to aggregate the evidence across a range of different types of studies, including epidemiological, cellular and molecular in addition to randomized controlled trials.  When that is done, the potential effect of Omega-3 fatty acids on depression and other mood disorders looks to be far greater than the available evidence from randomized, controlled trials.  As the Committee on Research on Psychiatric Treatments of the American Psychiatric Association recently concluded, “The preponderance of epidemiologic and tissue compositional studies supports a protective effect of omega-3 EFA intake, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).”

Correlation Between Fish Consumption and Major Depression

In this classic article to the Lancet, JR Hibbeln demonstrated that there was an inverse correlation between annual fish consumption in a country, and that country’s incidence of depression (Hibbeln, 1998.)  As you can see from the graph, those countries that consumed the most fish per capita, such as Japan, had the lowest rates of depression.  Vice versa, those countries where people consumed the lowest amount of fish, such as the United States, had the highest rates of depression per capita.  Of course, correlation is not causation – the fact that two things are linked does not mean one causes the other.  For that reason, epidemiological studies such as this one must be confirmed by other methodologies: mechanistic studies in cell cultures, animal models of illness, and randomized clinical trials.  Research on why fish consumption might help prevent depression has focused on omega-3 fatty acids.  Cellular studies have confirmed that Omega-3 fatty acids, found mostly in certain kinds of fish, but also in walnuts, soybeans, flaxseed, and some other plants, are integral components of the cell membrane of brain cells.  Without adequate omega-3’s, membrane dysfunction may lead to cellular dysfunction, and from cellular dysfunction to conditions such as depression.

Next week: what randomized clinical trials show about omega-3 consumption and depression!