Blackmores Institute

<h3>Depression</h3>Depression involves a persistent feeling of sadness and loss of interest, commonly alongside feelings of emptiness, fatigue and irritability, with these symptoms ranging from mild to severe.5 It significantly impacts quality of life and is associated with poor health outcomes, including increased comorbidity and early mortality.6Many factors increase the risk of developing depression, including genetics, traumatic events and the presence of another disease.4 There is also growing concern about the increasing prevalence of depression following infection with COVID-19.7Whilst the aetiology of depression is complex and is not entirely understood4, recent research indicates that it is much more than simply a “chemical imbalance in the brain”. In fact, a 2022 systematic review found no convincing evidence that depression is a result of lower serotonin concentrations or activity8, indicating a need to explore factors beyond serotonin in understanding the condition.Through their multi-faceted therapeutic benefits throughout the body, omega-3 long-chain PUFAs, EPA and DHA, are gaining increasing interest in their role in reducing depression symptoms. <h3>The role of omega-3 PUFAs in depression</h3>Although omega-3 PUFAs are well known for their range of health benefits including foetal development and healthy ageing, less than a quarter of Australian adults are meeting the recommendations for optimal health through dietary intake.9Omega-3 PUFAs are a major structural component of neuronal cell membranes, making up 20% of the brain’s dry weight.10 Given this, it is not surprising they can influence the structure, activity and function of the brain, supporting the growth of new neurons, increasing dopamine activity and boosting blood flow to the brain.11Omega-3 PUFAs can also increase synthesis of brain-derived neurotrophic factor (BDNF), a protein typically found in lower amounts in those with depression12 and plays a crucial role in neuronal health and neurotransmitter regulation.13Another important action of omega-3 PUFAs is through their ability to act as an antioxidant, exerting anti-inflammatory effects to reduce inflammation.14 Interestingly, selective serotonin reuptake inhibitors (SSRIs) have shown to have profound anti-inflammatory properties, with this possibly being a key action in their effect on depression.15 <h3>Emerging research</h3>Due to various studies showing conflicting results, researchers performed an umbrella review of 22 meta-analyses including 83 randomised clinical trials (RCTs) to conclusively evaluate the clinical impacts of omega-3 PUFA supplementation on depression symptoms.10The analysis revealed that omega-3 PUFA supplementation (EPA, DHA, and a combination of both) has a significant improvement effect on depression indices in most studies. A more pronounced effect was observed on depression symptoms when both EPA and DHA was supplemented at an average dose of &gt;3g/day for &gt;15 weeks.10Interestingly, benefits of omega-3 PUFA supplementation were greater for those with MDD, indicating the degree of depression plays a role in the significance of the impact.10 <h3>Conclusion</h3>Whilst additional research is required to further understand optimal recommendations, existing evidence shows promising results for considering omega-3 PUFA supplementation as a safe addition to an individual’s therapeutic approach to address or alleviate depression symptoms. <h3> References </h3><ol><li>Australian Institute of Health and Welfare. Prevalence and Impact of Mental Illness [Internet]. Australian Institute of Health and Welfare. Australian Government; 2023. Available from: https://www.aihw.gov.au/mental-health/topic-areas/mental-illness</li><li>Zakaria FH, Samhani I, Mustafa MZ, Shafin N. Pathophysiology of Depression: Stingless Bee Honey Promising as an Antidepressant. Molecules. 2022 Aug 10;27(16):5091.</li><li>Depressive disorder (depression) [Internet]. www.who.int. [cited 2023 Nov 12]. Available from: https://www.who.int/news-room/fact-sheets/detail/depression</li><li>Chand S, Arif H. Depression [Internet]. PubMed. Treasure Island (FL): StatPearls Publishing; 2023. Available from: https://www.ncbi.nlm.nih.gov/books/NBK430847/</li><li>Jesulola E, Micalos P, Baguley IJ. Understanding the pathophysiology of depression: From monoamines to the neurogenesis hypothesis model-are we there yet?. Behavioural brain research. 2018 Apr 2;341:79-90.</li><li>Forman-Hoffman VL, Nelson BW, Ranta K, Nazander A, Hilgert O, de Quevedo J. Significant reduction in depressive symptoms among patients with moderately-severe to severe depressive symptoms after participation in a therapist-supported, evidence-based mobile health program delivered via a smartphone app. Internet Interventions. 2021 Sep 1;25:100408.</li><li>Mazza MG, Palladini M, Villa G, Agnoletto E, Harrington Y, Vai B, Benedetti F. Prevalence of depression in SARS-CoV-2 infected patients: An umbrella review of meta-analyses. General Hospital Psychiatry. 2022 Dec 7.</li><li>Moncrieff J, Cooper RE, Stockmann T, Amendola S, Hengartner MP, Horowitz MA. The serotonin theory of depression: a systematic umbrella review of the evidence. Molecular psychiatry. 2022 Jul 20:1-4.</li><li>Meyer BJ. Australians are not meeting the recommended intakes for omega-3 long chain polyunsaturated fatty acids: Results of an analysis from the 2011–2012 national nutrition and physical activity survey. Nutrients. 2016 Feb 24;8(3):111.</li><li>Mehdi S, Manohar K, Shariff A, Kinattingal N, Wani SU, Alshehri S, Imam MT, Shakeel F, Krishna KL. Omega-3 Fatty Acids Supplementation in the Treatment of Depression: An Observational Study. Journal of Personalized Medicine. 2023 Jan 27;13(2):224.</li><li>Lü Y, Qiao D, Mi G. Clinical impacts of omega-3 fatty acids supplementation on depression symptoms: An umbrella review of meta-analyses. British Journal of Nutrition. 2023 Oct 27;1–26.</li><li>Yang T, Nie Z, Shu H, Kuang Y, Chen X, Cheng J, Yu S, Liu H. The role of BDNF on neural plasticity in depression. Frontiers in cellular neuroscience. 2020 Apr 15;14:82.</li><li>Bathina S, Das UN. Brain-derived neurotrophic factor and its clinical implications. Archives of Medical Science. 2015 Dec 10;11(6):1164-78.</li><li>DiNicolantonio JJ, O’Keefe JH. The importance of marine omega-3s for brain development and the prevention and treatment of behavior, mood, and other brain disorders. Nutrients. 2020 Aug;12(8):2333.</li><li>Patel S, Keating BA, Dale RC. Anti-inflammatory properties of commonly used psychiatric drugs. Frontiers in Neuroscience. 2023 Jan 10;16:1039379.</li></ol>

Key Takeaways <ul><li>Results of a recent large umbrella review of meta-analyses revealed that omega-3 polyunsaturated fatty acids (PUFA) supplementation significantly improved depression symptoms in most studies.</li><li>Benefits of omega-3 PUFA supplementation was more pronounced in major depressive disorder (MDD).</li><li>More significant effects were seen when both eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) was supplemented at an average dose of &gt;3g/day for &gt;15 weeks. </li></ul> Mental health conditions continue to be on the rise, with over 1 in 5 Australian adults estimated to have experienced a mental disorder in the past 12 months.1 Globally, depression is the most prevalent mental health condition across all age categories and is the leading cause of disability, incurring a significant emotional and economic burden.2 Around 280 million people are living with this debilitating condition, which is approximately 50% more prevalent in women.3 Alarmingly, almost 60% of people with depression do not seek medical support due to the fear and stigma around the condition.4

Recommended for you

Iron Absorption | Why form matters

From Traditional Medicine to Modern Therapeutics | Natural approaches to blood glucose control

Prioritising focus and cognition with L-theanine

Optimising magnesium prescribing