J Food Bioact

Journal of Food Bioactives, ISSN 2637-8752 print, 2637-8779 online

Journal website www.isnff-jfb.com

Review

Volume 14, June 2021, pages 10-19

Are omega-3 fatty acids efficacious in the treatment of depression? A review

**Table 1.** Overview of findings and problems regarding omega-3 fatty acids and depression
Observational studies
Intake of fish or omega-3 fatty acids was inversely associated with the risk of depression (Hibbeln, 1998)
Fish consumption was associated with a decrease in the risk of depression (Grosso et al., 2016)
Intake of omega-3 fatty acids was negatively associated with depression (Silvers and Scott, 2002; Tanskanen et al., 2001)
Omega-3 fatty acid levels in erythrocytes in people with depression were low compared to controls (Edwards et al., 1998b; Peet et al., 1998)
No associations between the intake of omega-3 fatty acids and depression were found in cross-sectional studies (Appleton et al., 2007; Hakkarainen et al., 2004; Miyake et al., 2006)
No significant relationships between blood omega-3 fatty acid concentrations and depressive symptoms were found in cross-sectional studies (Appleton et al., 2008; Browne et al., 2006; Mamalakis et al., 2004)
Summary: Observational evidence suggesting a link between omega-3 fatty acids and depression may be subject to confounding and cannot establish causal relationships
Randomized controlled intervention studies
Omega-3 fatty acids showed beneficial effects in major depressive disorder (Nemets et al., 2002; Su et al., 2003) and other depressive conditions (Frangou et al., 2006; Stoll et al., 1999)
In other studies, omega-3 fatty acids showed no benefits in major depressive disorder (Grenyer et al., 2007; Silvers et al., 2005) or other depressive disorders (Keck et al., 2006; Rogers et al., 2008)
Beneficial effects of omega-3 fatty acids depended on the severity of depressive symptoms at baseline (benefits with severe depressive symptoms, no benefits with mild depressive symptoms) (Appleton et al., 2010)
The findings of meta-analyses of randomized controlled trials of omega-3 fatty acids for depressive disorders were inconclusive; the benefits of omega-3 fatty acids for depressive symptoms were small to moderate and of little or no clinical relevance (Appleton et al., 2010, 2016; Bloch and Hannestad, 2012; Lin and Su, 2007)
Summary: The effects of omega-3 fatty acid supplementation in depression were usually small or insignificant, with significant heterogeneity between studies
Problems
Available omega-3 fatty acid supplementation trials varied markedly in regard to participants, diagnostic criteria, severity of depression, intervention type, dosage, duration, baseline omega-3 status and outcome measures
EPA rather than DHA appears to mediate the beneficial effects of omega-3 fatty acids in major depressive disorders (Grosso et al., 2014; Hallahan et al., 2016; Martins, 2009; Martins et al., 2012)
Omega-3 fatty acid doses needed to elicit beneficial effects may depend on baseline levels (Carney et al., 2016; Messamore and McNamara, 2016)
The clinical significance of differences between antidepressants and placebo based on rating scales is in doubt (Moncrieff and Kirsch, 2015)
The long-term effects of omega-3 fatty acid supplementation are unclear
Opportunity cost of potentially ineffective therapies needs to be considered; other possibly more useful therapeutic approaches should be investigated (Lange, 2018)
Omega-3 fatty acid supplements may contain potentially toxic oxidation products; potential long-term adverse effects of vitamin E added as antioxidant should be considered (Lange et al., 2019)
Summary: Conclusive evidence of the efficacy of omega-3 fatty acids in depressive disorders is currently lacking

Table 1. Overview of findings and problems regarding omega-3 fatty acids and depression

Observational studies

Intake of fish or omega-3 fatty acids was inversely associated with the risk of depression (Hibbeln, 1998)

Fish consumption was associated with a decrease in the risk of depression (Grosso et al., 2016)

Intake of omega-3 fatty acids was negatively associated with depression (Silvers and Scott, 2002; Tanskanen et al., 2001)

Omega-3 fatty acid levels in erythrocytes in people with depression were low compared to controls (Edwards et al., 1998b; Peet et al., 1998)

No associations between the intake of omega-3 fatty acids and depression were found in cross-sectional studies (Appleton et al., 2007; Hakkarainen et al., 2004; Miyake et al., 2006)

No significant relationships between blood omega-3 fatty acid concentrations and depressive symptoms were found in cross-sectional studies (Appleton et al., 2008; Browne et al., 2006; Mamalakis et al., 2004)

Summary: Observational evidence suggesting a link between omega-3 fatty acids and depression may be subject to confounding and cannot establish causal relationships

Randomized controlled intervention studies

Omega-3 fatty acids showed beneficial effects in major depressive disorder (Nemets et al., 2002; Su et al., 2003) and other depressive conditions (Frangou et al., 2006; Stoll et al., 1999)

In other studies, omega-3 fatty acids showed no benefits in major depressive disorder (Grenyer et al., 2007; Silvers et al., 2005) or other depressive disorders (Keck et al., 2006; Rogers et al., 2008)

Beneficial effects of omega-3 fatty acids depended on the severity of depressive symptoms at baseline (benefits with severe depressive symptoms, no benefits with mild depressive symptoms) (Appleton et al., 2010)

The findings of meta-analyses of randomized controlled trials of omega-3 fatty acids for depressive disorders were inconclusive; the benefits of omega-3 fatty acids for depressive symptoms were small to moderate and of little or no clinical relevance (Appleton et al., 2010, 2016; Bloch and Hannestad, 2012; Lin and Su, 2007)

Summary: The effects of omega-3 fatty acid supplementation in depression were usually small or insignificant, with significant heterogeneity between studies

Problems

Available omega-3 fatty acid supplementation trials varied markedly in regard to participants, diagnostic criteria, severity of depression, intervention type, dosage, duration, baseline omega-3 status and outcome measures

EPA rather than DHA appears to mediate the beneficial effects of omega-3 fatty acids in major depressive disorders (Grosso et al., 2014; Hallahan et al., 2016; Martins, 2009; Martins et al., 2012)

Omega-3 fatty acid doses needed to elicit beneficial effects may depend on baseline levels (Carney et al., 2016; Messamore and McNamara, 2016)

The clinical significance of differences between antidepressants and placebo based on rating scales is in doubt (Moncrieff and Kirsch, 2015)

The long-term effects of omega-3 fatty acid supplementation are unclear

Opportunity cost of potentially ineffective therapies needs to be considered; other possibly more useful therapeutic approaches should be investigated (Lange, 2018)

Omega-3 fatty acid supplements may contain potentially toxic oxidation products; potential long-term adverse effects of vitamin E added as antioxidant should be considered (Lange et al., 2019)

Summary: Conclusive evidence of the efficacy of omega-3 fatty acids in depressive disorders is currently lacking