Omega-3 Fatty Acids and Depression

For any mental health condition, it is always worth stepping back and taking a functional view of what could be underlying a patient’s symptoms. One common component that is often a contributing factor is a patient’s omega-3 fatty-acid status.

Omega-3 fatty acids are essential nutrients that play a crucial role in maintaining health. They are found in foods such as fatty fish and other seafood, flaxseeds, hemp seeds, chia and walnuts. The long-chain omega-3 fatty acids include eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) found primarily in seafood.

Over the past three decades, a growing body of research evidence has implicated dietary deficiencies in the long-chain omega-3 fatty acids as an underlying component contributing to depression and mental illness. Initial research on dietary patterns and increased fish consumption identified potential correlations with a reduced incidence of depression (Li 2016).

Symptoms of Omega-3 Deficiency

While omega-3 fats are an essential part of the diet, most Americans are not consuming enough to meet basic dietary requirements. In fact, a recent study found that 68% of adults and a disconcerting 95% of children do not meet omega-3 recommendations (Murphy 2021).

Of additional serious concern, over 95% of pregnant women and women of reproductive age are not consuming enough omega-3s (Zhang 2018). Considering the increased need for omega-3 fatty acids for a developing fetus and baby, this low consumption raises obvious concerns for neonatal health.

The full consequences of potential deficiencies extend into mental health and beyond. Symptoms of a deficiency may include insomnia, changes in hair or skin (Thomsen 2020), inflammation, and mood changes, like depression and anxiety. In fact, a study exploring preventable causes of death in the United States concluded that approximately 84,000 premature deaths per year are due to inadequate omega-3 fatty acid intake (Danaei 2009).

Treating Depression with Omega-3s

Research has shown that people with depression have lower levels of omega-3 fatty acids in their blood (Lin 2010). Studies on dietary patterns have also found correlations between lower fish consumption and an increased incidence of depression (Jayedi 2020). This has led scientists to investigate whether increasing omega-3 intake could help treat depression  symptoms directly. While some studies have found that supplementing with omega-3s can reduce the symptoms of depression, nuances exist.

Omega-3 Supplementation for Depression

A recent review of fish oil supplementation and depression found that combined doses of EPA between 0.7 and 2 grams and DHA between 0.4 and 0.8 grams were beneficial for improving depressive symptoms (Thurfah 2022). An earlier study also highlighted the need for using higher levels of EPA, either as a stand-alone omega-3 supplement or as a supplement with a higher EPA-to-DHA ratio. In the research, long-chain omega-3 supplements with lower levels of EPA, or supplements with only DHA, were not typically effective for the treatment of depression (Song 2016).

Omega-3s and Inflammation: The Mechanisms of Action

While the exact mechanisms by which omega-3s may improve depression are not fully understood, it has been shown that they interact with inflammation and neurotransmitter function. Depression and other mental health conditions have strong links with chronic inflammation. Studies have found higher levels of inflammatory cytokines or signaling molecules in the blood of depressed patients. Specific inflammatory markers that correlate with treatment-resistant cases, including C-reactive protein (CRP) and interleukin-8 (IL-8), have also been identified (Gasparini 2022).

Omega-3 fatty acids have anti-inflammatory effects, helping quell inflammation in the body and brain (Layé 2018). As such, omega-3 fatty acids can help to directly reduce brain inflammation that contributes to mental health conditions, including depression.

Omega-3s and Neurotransmitters

Beyond inflammation, omega-3 fatty acids are also known to influence neurotransmitter function, including serotonin, dopamine and norepinephrine. These neurotransmitters work through cell-membrane receptors and transporters. To facilitate cell-membrane neurotransmitter activity, there are dense collections of fatty compounds in the cell membrane called “lipid rafts.” These lipid rafts are collections of cholesterol and specialized fats called sphingolipids. As a component of the outer cell membrane, lipid rafts are crucial to the function of neurotransmitter receptors and transporters (Liu 2016). Omega-3 fats have been shown to regulate the size and production of lipid rafts (Yaqoob 2010), thereby regulating numerous processes crucial for effective neurotransmitter signaling.

In short, without appropriate levels of omega-3 fatty acids, neurotransmission is severely dysregulated.

By influencing and regulating both inflammation and neurotransmitter activity, omega-3 fats are critical for normal, healthy brain function. These influences are likely why omega-3 fatty acids have been found to be effective for the treatment of depression.

Takeaway

Omega-3 fatty acids are an essential part of the diet that need to be consumed on a regular basis for both physical and mental health. Unfortunately, the majority of individuals in the United States do not meet standard dietary recommendations for omega-3 fats. This is likely contributing significantly to both mental illness and overall mortality rates due to omega-3 fatty acid deficiencies.

To help lower elevated inflammation and for supporting healthy neurotransmitter function, consuming appropriate levels of omega-3 fatty acids with a higher EPA-to-DHA ratio is typically recommended. Generally, in cases of depression, evaluating omega-3 intake, or testing levels directly, should be a part of any functional and integrative assessment. In my own experience, omega-3 fats are often an indispensable component of an effective, comprehensive treatment plan to help facilitate remission and recovery.

References

Danaei G, Ding EL, Mozaffarian D, et al. The preventable causes of death in the United States: comparative risk assessment of dietary, lifestyle, and metabolic risk factors [published correction appears in PLoS Med. 2011 Jan;8(1). doi: 10.1371/annotation/0ef47acd-9dcc-4296-a897-872d182cde57]. PLoS Med. 2009;6(4):e1000058. doi:10.1371/journal.pmed.1000058

Gasparini A, Callegari C, Lucca G, Bellini A, Caselli I, Ielmini M. Inflammatory Biomarker and Response to Antidepressant in Major Depressive Disorder: a Systematic Review and Meta-Analysis. Psychopharmacol Bull. 2022;52(1):36-52.

Jayedi A, Shab-Bidar S. Fish Consumption and the Risk of Chronic Disease: An Umbrella Review of Meta-Analyses of Prospective Cohort Studies. Adv Nutr. 2020;11(5):1123-1133. doi:10.1093/advances/nmaa029

Layé S, Nadjar A, Joffre C, Bazinet RP. Anti-Inflammatory Effects of Omega-3 Fatty Acids in the Brain: Physiological Mechanisms and Relevance to Pharmacology. Pharmacol Rev. 2018;70(1):12-38. doi:10.1124/pr.117.014092

Li F, Liu X, Zhang D. Fish consumption and risk of depression: a meta-analysis. J Epidemiol Community Health. 2016;70(3):299-304. doi:10.1136/jech-2015-206278

Lin PY, Huang SY, Su KP. A meta-analytic review of polyunsaturated fatty acid compositions in patients with depression. Biol Psychiatry. 2010;68(2):140-147. doi:10.1016/j.biopsych.2010.03.018

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Murphy RA, Devarshi PP, Ekimura S, Marshall K, Hazels Mitmesser S. Long-chain omega-3 fatty acid serum concentrations across life stages in the USA: an analysis of NHANES 2011-2012. BMJ Open. 2021;11(5):e043301. Published 2021 May 10. doi:10.1136/bmjopen-2020-043301

Song C, Shieh CH, Wu YS, Kalueff A, Gaikwad S, Su KP. The role of omega-3 polyunsaturated fatty acids eicosapentaenoic and docosahexaenoic acids in the treatment of major depression and Alzheimer’s disease: Acting separately or synergistically?. Prog Lipid Res. 2016;62:41-54. doi:10.1016/j.plipres.2015.12.003

Thomsen, B, Chow E, Sapijaszko M. The Potential Uses of Omega-3 Fatty Acids in Dermatology: A Review. Journal of Cutaneous Medicine and Surgery. 2020;24(5). doi.org/10.1177/1203475420929925

Thurfah JN, Christine, Bagaskhara PP, Alfian SD, Puspitasari IM. Dietary Supplementations and Depression. J Multidiscip Healthc. 2022;15:1121-1141. Published 2022 May 17. doi:10.2147/JMDH.S360029

Yaqoob P, Shaikh SR. The nutritional and clinical significance of lipid rafts. Curr Opin Clin Nutr Metab Care. 2010;13(2):156-166. doi:10.1097/MCO.0b013e328335725b

Zhang Z, Fulgoni VL, Kris-Etherton PM, Mitmesser SH. Dietary Intakes of EPA and DHA Omega-3 Fatty Acids among US Childbearing-Age and Pregnant Women: An Analysis of NHANES 2001-2014. Nutrients. 2018;10(4):416. Published 2018 Mar 28. doi:10.3390/nu10040416