Research paperDietary n-3 PUFA, fish consumption and depression: A systematic review and meta-analysis of observational studies
Introduction
Over the last four decades, polyunsaturated fatty acids (PUFA) have been studied in relation to prevention of cardiovascular diseases (CVD) (Sanchez-Villegas and Martinez-Gonzalez, 2013). The highest representative compounds consumed by humans belong to the n-3 and n-6 family of PUFA, including alpha-linolenic acid (ALA) and linoleic acid (LA), respectively (Grosso et al., 2014a). Once consumed in the diet, LA undergoes to transformation in arachidonic acid (AA), which is precursor of pro-inflammatory cytokines, whereas ALA is converted into eicosapentaenoic acid (EPA), with a subsequent elongation to docosahexaenoic acid (DHA). EPA and DHA may also be consumed directly through ingestion of fish and seafood. The beneficial effect of n-3 PUFA is supposed to depend on their capacity to positively modulate the immune and inflammatory response (Gil, 2002, Tapiero et al., 2002), as they demonstrated a certain efficacy in preventing illnesses with an inflammatory component (Parletta et al., 2013). An emerging body of data indicates n-3 PUFA as potential candidates in the prevention and treatment of psychiatric diseases involving inflammatory processes, such as depressive disorders (Bourre, 2007). Ecological studies showed that dietary intakes of fish correlate with lower prevalence of major depression (Hibbeln, 1998), bipolar disorder (Noaghiul and Hibbeln, 2003), and post-partum depression (Hibbeln, 2002). These findings suggested that cross-national variations in n-3 PUFA intake contained in fish are inversely correlated with the prevalence of depression.
The potential benefits of n-3 PUFA intake in preventing or treating psychiatric illnesses, such as depressive disorders, are biologically plausible. Major depression shares certain pathophysiological mechanisms with CVD, such as increased production of pro-inflammatory cytokines, endothelial dysfunction, and elevations in plasma homocysteine levels (Hepgul et al., 2010). Several studies have shown a positive correlation between the severity of the symptoms of depression and the increase in the inflammatory status (Maes et al., 2009). Major depression has been recently considered secondary to a systemic inflammatory disorder in which pro-inflammatory cytokines alter serotonin metabolism, reduce synaptic plasticity, and increase the risk of developing diseases associated with an inflammatory state (Caraci et al., 2010, Huffman et al., 2013, Maes et al., 2009). According to this scenario, the anti-inflammatory capacity of n-3 PUFA has been hypothesized to play a central role in counteracting inflammatory processes occurring in depression (Parletta et al., 2013). Another possible mechanism may depend on n-3 PUFA neuro-endocrine metabolism, release, uptake, and receptor action (Hibbeln et al., 1998). N-3 PUFA have been shown to interact with serotonin metabolism by facilitating its release by inhibiting the formation of E2-series prostaglandins and increasing membrane fluidity (Patrick and Ames, 2015). Their positive effects on depression may also depend on their physiological abundant content in the human nervous system and their involvement in neurogenesis and neuroplasticity (Bourre, 2004).
There is evidence that depressed patients have decreased content of n-3 PUFA in plasma and erythrocyte membrane, supporting the mechanistic links between n-3 PUFA deficiency and increased risk of depression (De Vriese et al., 2003, Edwards et al., 1998, Peet et al., 1998). A number of cross-sectional and prospective investigations have been performed to test the potential association between fish consumption, n-3 PUFA dietary intake and depression, but findings are contrasting (Giles et al., 2013). The use of n-3 PUFA supplements as add-on therapy for major depression (in addition to first and second generation antidepressant drugs) appears promising but observational studies analyzing free-living populations did not yield to strong conclusions on the potential protective role of n-3 PUFA in preventing depressive disorders (Grosso et al., 2014b). Indeed, it is still unclear whether a biological response to dietary n-3 PUFA can be obtained in a dose-dependent manner with clinically relevant effects in the general population. Thus, the main aim of this study was to systematically review observational studies exploring the association between fish, n-3 PUFA dietary consumption and depression. A meta-analysis of risk estimates to calculate effect-size and eventually define the dose-response effect was performed.
Section snippets
Search strategy and selection of the studies
A comprehensive search on MEDLINE, EMBASE, PsycInfo, and the Cochrane Database of Systematic Reviews of all observational studies evaluating the effects of n-3 PUFA on depression in cohort of individuals published up to August 2014 was performed. Articles of potential interest were identified using the following search terms: “omega-3”, “polyunsaturated fatty acids”, “PUFA”, “EPA”, “DHA”, “alpha linolenic acid”, “linoleic acid”, combined with the following terms: “depression”, “depressive
Study characteristics
The process of identification and inclusion of studies is summarized in Fig. 1. Among the 232 articles retrieved, observational studies were identified and screened by reading the abstract and, when necessary, the full text. Twenty-six out of the 57 articles considered potentially relevant were excluded and not assessed further for the following reasons: 2 reported insufficient statistics or did not present crucial data, 7 were conducted on n-3 PUFA in tissues, 7 had different study design, 10
Discussion
Results of this systematic review and meta-analysis supported the hypothesis that fish consumption and n-3 PUFA intake are associated with decreased risk of depression. To date, this is the first meta-analysis pooling together all relevant observational studies assessing the relation between fish, n-3 PUFA intake and depression, providing insights on dose-response relationship. A significant decreased risk was found for 50 g/d intake of fish, 1.8 g/d intake of n-3 PUFA, and 0.6 g/d intake of
Contributors
GG designed the research; GG and SC conducted research; GG and AM analyzed data; SM edited tables and images; GG wrote the paper; GG, FG, and AM provided important revision for final content. All authors reviewed and approved the study content.
Role of the funding source
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Conflict of interest
All authors declare no conflicts of interest.
Acknowledgments
None.
References (73)
- et al.
Depressed mood and dietary fish intake: direct relationship or indirect relationship as a result of diet and lifestyle?
J. Affect. Disord.
(2007) - et al.
Association of fish and long-chain n-3 polyunsaturated fatty acid intakes with the occurrence of depressive episodes in middle-aged French men and women
Prostaglandins Leukot. Essent. Fat. Acids
(2008) - et al.
Omega-3 fatty acid intakes are inversely related to elevated depressive symptoms among United States women
J. Nutr.
(2013) Dietary omega-3 fatty acids for women
Biomed. Pharm.
(2007)- et al.
Depression and Alzheimer's disease: neurobiological links and common pharmacological targets
Eur. J. Pharmacol.
(2010) - et al.
Higher dietary intake of long-chain omega-3 polyunsaturated fatty acids is inversely associated with depressive symptoms in women
Nutrition
(2009) - et al.
Lowered serum n-3 polyunsaturated fatty acid (PUFA) levels predict the occurrence of postpartum depression: further evidence that lowered n-PUFAs are related to major depression
Life Sci.
(2003) - et al.
Omega-3 polyunsaturated fatty acid levels in the diet and in red blood cell membranes of depressed patients
J. Affect. Disord.
(1998) Polyunsaturated fatty acids and inflammatory diseases
Biomed. Pharm.
(2002)Fish consumption and major depression
Lancet
(1998)
Seafood consumption, the DHA content of mothers' milk and prevalence rates of postpartum depression: a cross-national, ecological analysis
J. Affect. Disord.
Essential fatty acids predict metabolites of serotonin and dopamine in cerebrospinal fluid among healthy control subjects, and early- and late-onset alcoholics
Biol. Psychiatry
Healthy intakes of n-3 and n-6 fatty acids: estimations considering worldwide diversity
Am. J. Clin. Nutr.
Dietary polyunsaturated fatty acids and depression: when cholesterol does not satisfy
Am. J. Clin. Nutr.
Depression and cardiovascular mortality: a role for n-3 fatty acids?
Am. J. Clin. Nutr.
Dietary lipids and geriatric depression scale score among elders: the EPIC-Greece cohort
J. Psychiatr. Res.
Fish consumption and severely depressed mood, findings from the first national nutrition follow-up study
Psychiatry Res.
Dietary intake of n-3 and n-6 fatty acids and the risk of clinical depression in women: a 10-y prospective follow-up study
Am. J. Clin. Nutr.
Dietary intake of folate, other B vitamins, and omega-3 polyunsaturated fatty acids in relation to depressive symptoms in Japanese adults
Nutrition
Nutritional modulation of cognitive function and mental health
J. Nutr. Biochem.
Depletion of omega-3 fatty acid levels in red blood cell membranes of depressive patients
Biol. Psychiatry
Dietary eicosapentaenoic acid and docosahexaenoic acid equally incorporate as decosahexaenoic acid but differ in inflammatory effects
Nutrition
The importance of the ratio of omega-6/omega-3 essential fatty acids
Biomed. Pharm.
Evolutionary aspects of diet, the omega-6/omega-3 ratio and genetic variation: nutritional implications for chronic diseases
Biomed. Pharm.
Fish and long-chain n-3 polyunsaturated fatty acid intakes during pregnancy and risk of postpartum depression: a prospective study based on a large national birth cohort
Am. J. Clin. Nutr.
Dietary omega-6 fatty acid lowering increases bioavailability of omega-3 polyunsaturated fatty acids in human plasma lipid pools
Prostaglandins Leukot. Essent. Fat. Acids
Polyunsaturated fatty acids (PUFA) and eicosanoids in human health and pathologies
Biomed. Pharm.
Fish consumption and depression: the Northern Finland 1966 birth cohort study
J. Affect. Disord.
Omega-6 fatty acids and greater likelihood of suicide risk and major depression in early pregnancy
J. Affect. Disord.
No association between fish intake and depression in over 15,000 older adults from seven low and middle income countries--the 10/66 study
PLoS One
Depressed mood and n-3 polyunsaturated fatty acid intake from fish: non-linear or confounded association?
Soc. Psychiatry Psychiatr. Epidemiol.
Correlates of regular fish consumption in French elderly community dwellers: data from the three-city study
Eur. J. Clin. Nutr.
Associations of the ratios of n-3 to n-6 dietary fatty acids with longitudinal changes in depressive symptoms among US women
Am. J. Epidemiol.
Long-term fish intake is associated with less severe depressive symptoms among elderly men and women: the MEDIS (MEDiterranean ISlands Elderly) epidemiological study
J. Aging Health
Roles of unsaturated fatty acids (especially omega-3 fatty acids) in the brain at various ages and during ageing
J. Nutr. Health Aging
Essential fatty acids and human brain
Acta Neurol. Taiwan
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