Omega 3 EPA and DHA for Depression: what the current research says
Recent evidence suggests that Omega 3 fats EPA and DHA may help improve symptoms of depression. This is certainly a hot topic and many people on social media are suggesting that these nutrients are safer and more effective than antidepressants for most people, but is that really true? Let’s take a look at what the current research says when it comes to supplementing with these nutrients and if they could have a positive effect on depression.
Omega 3’s
Omega 3 fats EPA and DHA exert many positive health benefits for both cardiovascular and brain health. The efficacy of supplementation with omega-3’s EPA and DHA for depression is influenced by the proportion and dosage of EPA or DHA, as well as the characteristics of the sample size. Recent randomized controlled trials (RCTs) indicate that EPA, mostly at dosages of 1 or 2 g/d, is better when compared to placebo (no treatment) and taking DHA, as both a monotherapy (used alone) or adjuvant (used in combination with a psychiatric medication) in the treatment of mild to moderate depression. If EPA and DHA initiate their effects on depression, we are still unsure as to how these nutrients may do this. One hypothesis is through their anti-inflammatory effects.
Current Research
A 2019 meta-analysis reviewed 26 trials assessing the use of DHA, EPA, or combined EPA and DHA, and how that affected depression scores in adult populations who were clinically depressed. It reports that 12 of the studies suggest a positive effect on depressive symptoms. Here is a breakdown of the results: DHA-pure (DHA only) and DHA-major (more DHA than EPA) treatments failed to show significant efficacy in improving depression while EPA of at least 1 g/d, the EPA-pure (EPA only) and EPA-major (more EPA than DHA) groups demonstrated “significant” beneficial effects on the improvement of depression. The authors further write that the effect size for this significant result was “small to modest.” Effect sizes are important because they allow us to determine the strength between two variables. In this case, what is the strength of an effect that we will see between taking an Omega 3 supplement (EPA 1g/d, EPA pure, EPA major) and symptoms of depression. According to this review of studies, there may be a small to modest benefit taking an Omega 3 with at least EPA dosage of 1g/day or a Omega 3 supplement with more EPA than DHA if you have clinical symptoms of depression. We will talk about what this really means soon. Let’s keep looking at other studies to see if there’s similarity in findings.
Another more recent meta-analysis examined 34 studies involving a total of 1924 participants investigating the impact of Omega 3 supplementation compared to placebo (no treatment), and one study involving 40 participants investigating the impact of Omega-3 supplementation compared to antidepressant treatment on depressive symptoms. This paper included many of the same studies as the aforementioned meta analysis with the inclusion of new ones as well. Similarly, the authors report that Omega 3 supplementation resulted in a “small to modest” benefit for depressive symptoms, compared to placebo. The authors further state that this effect is unlikely to be clinically meaningful or significant. Here is a quote from the results section that highlights how the authors interpret this: This “represents a difference between groups in scores on the HDRS of approximately 2.5 points, where the minimal clinically important change score on this scale is 3.0 points.”
This is important because what is statistically significant in research studies is not the same as what is clinically significant. Statistical significance means that the results reveal a mathematical difference that was not caused by chance, but instead by the intervention. Clinical significance refers to the practical importance of a treatment effect. In other words, compared to nothing, supplementing with Omega 3 had a small effect on depressive symptoms where a person with depression, may or may not notice the difference because it may or may not make a significant difference in their day to day functioning. Only one study, involving 40 participants, compared Omega 3 supplementation to antidepressant medication. This study found no differences between treatment with Omega 3’s and treatment with antidepressants in depressive symptomology.
There is one interesting study that I found that has some additional findings and perhaps more important implications. Researchers from the National Institute of Health Research Maudsley Biomedical Research Center assessed 22 patients with major depression who were either given 3 grams of EPA or 1.4 grams of DHA daily for 12 weeks. Researchers also looked at the effects of high doses of EPA and DHA in lab-grown neurons (brain cells from the hippocampus) and then in the patients to help clarify how these nutrients help reduce inflammation and depression. The study showed that treating human hippocampal cells with EPA or DHA before being exposed to chemical messengers that signal inflammation (cytokines), helped to prevent increased cell death. The authors write that further investigation confirmed these effects were mediated by the formation of key lipid mediators produced by EPA and DHA. These metabolites of EPA and DHA were measured in the patient’s blood before and after the omega-3 treatment, along with depressive symptom scores. In both groups of patients, both EPA or DHA treatment was associated with an increase in their respective metabolites and a significant improvement in depressive symptoms. The authors report that an average reduction in symptom scores was 64% in the EPA group and 71% in the DHA group. In addition, higher levels of the same metabolites identified in the in vitro experiments (experiment with cells) were correlated with lower levels of depressive symptoms, meaning that, the higher levels of these metabolites, the lower their depressive symptoms were. This is pretty cool! The authors state that these results imply that if we are able to increase the availability of these metabolites after taking Omega 3 EPA and DHA supplements, we may be better able to effectively lower symptoms of depression in a clinically depressed population.
Takeaway
According to most of the current research, there seems to be only a small, non-clinically beneficial effect of Omega 3’s on depressive symptoms. This doesn’t mean that Omega 3’s have zero use or value when it comes to thinking about their role in our mental health or depression. Studies are really hard to conduct with precision when it comes to assessing a specific nutrient and how that affects something like depression in most adults. Many of the studies reviewed differed in terms of the depression scales used, the severity of depression the sample size had, as well as the dosages and lengths of time taking the Omega 3 supplements. More research is needed to assess the benefits of potentially using Omega 3’s as a supplement to help when it comes to decreasing depressive symptoms in a clinical population.
References
Appleton, K. M., Voyias, P. D., Sallis, H. M., Dawson, S., Ness, A. R., Churchill, R., & Perry, R. (2021). Omega-3 fatty acids for depression in adults. The Cochrane database of systematic reviews, 11(11), CD004692. https://doi.org/10.1002/14651858.CD004692.pub5
Borsini, A., Nicolaou, A., Camacho-Muñoz, D. et al. Omega-3 polyunsaturated fatty acids protect against inflammation through production of LOX and CYP450 lipid mediators: relevance for major depression and for human hippocampal neurogenesis. Mol Psychiatry 26, 6773–6788 (2021). https://doi.org/10.1038/s41380-021-01160-8
Liao, Y., Xie, B., Zhang, H., He, Q., Guo, L., Subramanieapillai, M., Fan, B., Lu, C., & McIntyre, R. S. (2019). Efficacy of omega-3 PUFAs in depression: A meta-analysis. Translational psychiatry, 9(1), 190. https://doi.org/10.1038/s41398-019-0515-5
Peet M, Horrobin DF. A dose-ranging exploratory study of the effects of ethyl-eicosapentaenoate in patients with persistent schizophrenic symptoms. J. Psychiatr. Res. 2002;36:7. doi: 10.1016/S0022-3956(01)00048-6.
