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Omega-3 fatty acids have been shown in some randomized trials to be more effective than placebo in the treatment of depression, but a Cochrane review concluded that they are no better than placebo. So, should you suggest omega-3 fatty acids for patients with depression? In a new meta-analysis, Katherine Deane and co-authors from the UK suggest that there is a strong public belief that polyunsaturated fats protect against and ameliorate depression and anxiety. Let’s have a look at the evidence. Now, this gets a little confusing because there are opposing conclusions from multiple different meta-analyses. I am going to name quite a few by their lead authors in case you want to look them up; however, the results are mixed. I think it is worth it to know some of these details because they lie behind your recommendations.
In this new extensive review from Dr. Deane and colleagues, they conclude that taking the supplements of omega-3s probably has little or no effect on the risk of depression or anxiety symptoms. In other words, no preventive benefit. Moreover, the evidence was of moderate quality, and they conclude that physicians should not recommend them. Maybe that goes against your impression of efficacy for omega-3s; it certainly did mine, although I will admit I have been disappointed that, clinically, they do not seem to have a whole lot of impact. It is an excellent idea, as it is natural, cheap, and right there on the grocery store.
I was surprised when, back in 2011, a meta-analysis by Sublette et al. found an effect size of 0.5. That is moderate, but it should be clinically noticeable, although only when using fish oil with at least 1 gram of EPA and at least 60% EPA relative to DHA. So, I started recommending that patients use only such versions, which narrows the options. You have to go to your local grocery store, write a field guide to the shelf, and guide patients right straight to the products that meet these criteria. Also, you will need a calculator while you stand in the aisle.
Deane and colleagues, in this new meta-analysis, reviewed the literature, and they were not impressed. They cite a 2015 Cochrane review by Appleton that concludes that the primary analyses suggest a small to modest nonclinically beneficial effect. They thought the quality of evidence was low or very low. If we do our own PubMed search for meta-analyses since the 2011 Sublette study and look for ourselves, we can find positive trials in pregnant women and the depressed elderly. However, a large meta-analysis in 2012 found nonsignificant benefit, and nearly all the efficacy observed might be attributed to publication bias. That was Browning et al., and that lines up with the Appleton Cochrane review.
In a 2019 meta-analysis, Liao and colleagues—a team that included Roger McIntyre, a prominent metabolic and inflammation researcher—used the same subdivision that Sublette et al. did, at least 60% EPA relative to DHA. Their result was the same as Sublette et al.—an effect size of 0.5 again. Their selection of articles yields a funnel plot; remember that it is the graphic assessment of publication bias, which looked a lot better than Sublette. So, it increases the confidence in these findings. They also did a subanalysis looking at EPA dose per day and concluded the optimum window is between 720 mg and 1000 mg per day. So, 720 mg is more achievable in the grocery store. Three out of 12 products in my local store could reach 720 mg in 2 or 3 pills per day.
In conclusion, if you are going to recommend omega-3 fatty acids for depression, you should specify the dose, 720 mg to 1000 mg, and their composition, at least 60% EPA relative to DHA. Anything else is not likely to be better than a placebo, although, admittedly, fish oils make great placebos, which might be useful sometimes when you need something plausible, cheap, and available and not only nearly harmless but perhaps something that confers additional benefits. For more detail on all this, start with the 2019 Liao meta-analysis, full text linked here at the Psychopharmacology Institute.
Abstract
Omega-3 and Polyunsaturated Fat for Prevention of Depression and Anxiety Symptoms: Systematic Review and Meta-Analysis of Randomised Trials
Katherine H O Deane, Oluseyi F Jimoh, Priti Biswas, Alex O’Brien, Sarah Hanson, Asmaa S Abdelhamid, Chris Fox, Lee Hooper
Background: There is strong public belief that polyunsaturated fats protect against and ameliorate depression and anxiety.
Aims: To assess effects of increasing omega-3, omega-6 or total polyunsaturated fat on prevention and treatment of depression and anxiety symptoms.
Method: We searched widely (Central, Medline and EMBASE to April 2017, trial registers to September 2016, ongoing trials updated to August 2019), including trials of adults with or without depression or anxiety, randomised to increased omega-3, omega-6 or total polyunsaturated fat for ≥24 weeks, excluding multifactorial interventions. Inclusion, data extraction and risk of bias were assessed independently in duplicate, and authors contacted for further data. We used random-effects meta-analysis, sensitivity analyses, subgrouping and Grading of Recommendations, Assessment, Development and Evaluations (GRADE) assessment.
Results: We included 31 trials assessing effects of long-chain omega-3 (n = 41 470), one of alpha-linolenic acid (n = 4837), one of total polyunsaturated fat (n = 4997) and none of omega-6. Meta-analysis suggested that increasing long-chain omega-3 probably has little or no effect on risk of depression symptoms (risk ratio 1.01, 95% CI 0.92-1.10, I2 = 0%, median dose 0.95 g/d, duration 12 months) or anxiety symptoms (standardised mean difference 0.15, 95% CI 0.05-0.26, I2 = 0%, median dose 1.1 g/d, duration 6 months; both moderate-quality evidence). Evidence of effects on depression severity and remission in existing depression were unclear (very-low-quality evidence). Results did not differ by risk of bias, omega-3 dose, duration or nutrients replaced. Increasing alpha-linolenic acid by 2 g/d may increase risk of depression symptoms very slightly over 40 months (number needed to harm, 1000).
Conclusions: Long-chain omega-3 supplementation probably has little or no effect in preventing depression or anxiety symptoms.
Declaration of interest: L.H. and A.A. were funded to attend the World Health Organization Nutrition Guidance Expert Advisory Group (NUGAG) Subgroup on Diet and Health meetings and present review results. The authors report no other conflicts of interest.
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Reference
Deane, K. H., Jimoh, O. F., Biswas, P., O’Brien, A., Hanson, S., Abdelhamid, A. S., Fox, C., & Hooper, L. (2019). Omega-3 and polyunsaturated fat for prevention of depression and anxiety symptoms: Systematic review and meta-analysis of randomised trials. The British Journal of Psychiatry, 1-8.
Related References
Liao, Y., Xie, B., Zhang, H., He, Q., Guo, L., Subramaniapillai, M., Fan, B., Lu, C., & Mclntyer, R. S. (2019). Efficacy of omega-3 PUFAs in depression: A meta-analysis. Translational Psychiatry, 9(1).
