Depression and anxiety are amongst the most common illnesses with significant disease burden worldwide (Holmes et al., 2018; Kessler et al., 2005). Many people who experience mental illness do not benefit from traditional interventions, such as psychotherapy or medication (Cuijpers et al., 2016; Locher et al., 2017; Weisz et al., 2017).
One modifiable factor which may contribute to better mental health is diet. Modern Western diets have led to the overconsumption of energy-dense foods, sacrificing essential nutrients which cannot be synthesised by the body – such as omega-3 polyunsaturated fatty acids. These are naturally occurring in oily fish, flax seeds and walnuts, play a key role in the development and functioning of the central nervous system (Li et al., 2021). Omega-3 can target processes of inflammation (Grosso et al., 2014, Matsuoka et al., 2017), which has previously been linked to depression in a past Active Ingredients review (Simmons et al., 2020). Observational and correlational studies have also suggested that rates of depression and anxiety may be lower in countries with high fish intake (e,g, Matsuoka et al, 2017). Consequently, this has led to an increased research interest in omega-3 supplementation for depression and anxiety.
A recent meta-analysis by Deane and colleagues (2021) synthesised and reviewed the latest evidence for using omega-3, omega-6 or total polyunsaturated fat as a treatment for depression and anxiety in adults. In this blog, we will be focusing on the findings relating to omega-3.
The authors of this review (Deane et al, 2021) searched Cochrane Central, Medline and EMBASE for trials lasting at least 6 months for adults with or without clinical diagnoses of depression or anxiety, supplemented with omega-3, omega-6, or total polyunsaturated fat as a standalone treatment. Studies were assessed for their risk of bias. Data extracted included depression and anxiety symptoms as measured by a verified scale or formal diagnosis and secondary mental health outcomes. The aggregated effect of various polyunsaturated fatty acids on depression and anxiety across studies was assessed using a random-effects meta-analysis. Pre-specified sensitivity analyses were conducted to examine if the results were consistent compared to when the poorer-quality studies were excluded. Finally, pre-specified subgroup analyses were conducted to examine if differences in study methodologies may have affected findings.
31 trials were assessed, totalling 41,470 participants. Findings from the meta-analysis indicated that omega-3 did not have an effect on symptoms of depression (risk ratio 1.01, 95%, CI 0.92 to 1.,10, I2 = 0%, median dose 0.95 g/d, duration 12 months) or anxiety (standardised mean difference 0.15, 95% CI 0.05 to 0.26, I2 = 0%, median dose 1.1g/d, duration 6 months).
Whilst most studies were assessed as low quality, 12 studies were assessed as low risk of bias.
Intervention type, replacement nutrients, or omega-3 dose did not influence the effect of omega-3 supplementation on depressive symptoms.
Moderators were not investigated, so it is unknown which genetic or environmental influences may affect the efficacy of omega-3 supplementation.
No notable side effects were found, however, increasing the dosage of alpha-linolenic acid by 2g/d may increase the risk of depression symptoms slightly over 40 months. No notable effect on secondary outcomes was found.
The authors concluded that the evidence quality was low for omega-3 preventing or reducing depression or anxiety and that it should not be recommended by clinicians for this purpose. Additional research is needed to confirm how omega-3 may affect other aspects of mental health.
Strengths and limitations
The broad inclusion of omega-3 and omega-6 fatty acids, and polyunsaturated fat, allowed for a comprehensive review. Given the heterogeneity of studies included, the authors used subgrouping to accurately analyse whether different factors affected the results of supplementation. Publication bias was also minimised by including unpublished data.
Studies had a lack of consistency in measuring baseline metabolic markers, making it difficult to track what deficits, if any, may exist in participants prior to supplementation. For instance, baseline omega-3 was measured through incomparable metabolic markers. Studies were also primarily conducted in middle to high-income countries, limiting the generalisability of the results. Finally, differences between studies, such as how symptoms of anxiety and depression were measured, may have affected the conclusions.
Implications for practice
- Omega-3 supplementation is unlikely to be useful as a treatment or preventative tool for depression and anxiety in adults and it should not be recommended by clinicians for this purpose based on current evidence.
- Policymakers are advised to update practice guidelines around the use of omega-3 supplements for mental illness to ensure that they are evidence-based.
- However, given the heterogeneity of studies included, further research is needed to assess how baseline levels of omega-3, demographic characteristics, and other potential moderators may influence its effect.
- Future research should focus on robust and high-quality trials of longer duration, given that many existing trials were found to have a high risk of bias.
- Additionally, involving people with lived experience in future research could offer greater insight into how omega-3 may be used within the community for mental health purposes.
Our Active Ingredients review on omega-3 supplements for youth depression and anxiety
A group led by Dr. Natalie Reily from the Black Dog Institute and the University of New South Wales, conducted an Active Ingredients review on omega-3 supplements for improving youth mental health. At present (Dec 2021), this review has not yet been published, so what follows is a summary of what the researchers did and what they found.
Over the course of COVID-19, it is estimated that the global prevalence of youth depression and anxiety has increased by 25.2% and 20.5% respectively (Racine et al., 2021). Omega-3 supplementation has not shown much promise as a treatment in children (Trebatická et al., 2020), and there is mixed evidence for efficacy in adults (Appleton et al., 2015). In our review, we sought to extend the work done by Deane and colleagues (2021) by focusing on young people, as there is a gap in current research in this demographic.
Our Active Ingredients review aimed to assess the efficacy and potential mechanisms of action of omega-3 supplements for improving youth mental health. We consulted a group of young people and parents of young people with lived experiences of depression and anxiety, alongside healthcare professionals, to see what they wanted to know about omega-3 in mental health. This helped to guide the focus of our research.
How does it actually help with mental health is a good question… cause we know about the brain, but exactly how does it help with depression and anxiety?
– A young person with lived experience of depression and/or anxiety
We reviewed scientific literature and online information to understand the efficacy and potential mechanisms of omega-3 as a viable treatment. Based on our review, we found:
- There was significant variation in the dosage, population type, and intervention length of studies in the scoping review, and there were no common factors amongst studies; other than having a higher, or equal ratio, of eicosapentaenoic acid to docosahexaenoic acid, two key components of omega-3
- Only 3 of 13 studies showed significant improvement in depressive symptoms
- 3 out of 5 studies showed significant improvement in anxiety symptoms in comparison to placebo
- Some studies investigated biological outcomes of omega-3 supplementation, however, none were specifically designed to understand the potential mechanism of action. Omega-3 supplementation was associated with changes to certain biological outcomes including tumor necrosis factor-alpha, some interleukins, and arachidonic acid, suggesting a link between omega-3 and inflammation
- Online sources (12) overwhelmingly endorsed the use of omega-3 in youth anxiety and depression, despite limited evidence for their efficacy; indicating publishers should review quality, peer-reviewed evidence when disseminating information on omega-3 supplementation and its effect on mental health.
When we presented our findings to the stakeholder group, they were generally surprised at the lack of efficacy in RCTs and the small number of studies given the prevalence of youth depression and anxiety. Notably, stakeholders indicated that they would not be opposed to taking omega-3 supplements as they may indirectly affect mental health through physical or cognitive wellbeing. Stakeholders recognised the need for more research to determine whether omega-3 is an effective treatment.
The way I see it, if it’s not going to hurt me, there’s no point in stopping, because even if I’m on a low dose…it must help something physically at least, and if it happens to help me mentally in any way shape or form, then I guess I’m winning either way.
– A young person with lived experience of depression and anxiety
Our findings suggest omega-3 supplements as a standalone treatment, or as an adjunct to traditional therapies, may not be effective in young people for depression or anxiety, despite its perception as overwhelmingly effective in online spaces. Current research is investigating how omega-3 supplementation may impact cognitive outcomes and other aspects of physical health, which ultimately may have a flow-on effect on mental health.
This #ActiveIngredientsMH blog is one of many blogs summarising Wellcome Trust funded research that have been published by The Mental Elf. You can read all of the #ActiveIngredientsMH blogs here. You can read more about the Wellcome Active Ingredients work here.
The author of the blog is thankful for the contributions of the rest of the team in the final version of this work – Dr. Natalie Reily, Dr. Samantha Tang, and Daniel Z.Q. Gan.
Statement of interests
This work was funded by a Wellcome Trust Mental Health ‘Active Ingredients’ commission awarded to Dr. Natalie Reily at the Black Dog Institute and University of New South Wales.
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