Review articleOmega-3 polyunsaturated fatty acids and reduction of depressive symptoms in older adults: A systematic review and meta-analysis
Introduction
Depression is a common psychiatric disorder significantly affecting more than 350 million people of all ages worldwide (Marcus et al., 2012). Depressive symptoms include feelings of sadness or hopelessness, loss of interest in most normal activities, change in appetite, sleep disturbances, tiredness and lack of energy, feelings of worthlessness or guilt, trouble concentrating, and suicidal ideation (Marcus et al., 2012). According to the Global Burden of Disease Study 2010 (Ferrari et al., 2014), mental and substance use disorders cause two thirds of all disability-adjusted life years allocated to suicide. Depression accounts for a large proportion (46.1%; range = 28.0–60.8%) of all suicides (Ferrari et al., 2014). In the rapidly growing aging population globally, more than 20% of adults aged 60 or older experience mental or neurological disorders. The most common neuropsychiatric disorders in older adults are dementia and depression (World Health Organization, 2013). A recent meta-analysis revealed that the pooled prevalence was 7.2% for major depression and 17.1% for depressive disorders in the oldest age groups (aged 75 years or older; Luppa et al., 2012). In contrast to young adults, older adults’ depression is related to cognitive impairments, cardio- and cerebrovascular diseases, and dementia (Barnes et al., 2006, Butters et al., 2008). Given that depression in older adults is associated with high morbidity, disability, and significantly high costs for medical services, home care, and pharmacotherapy, it is one of the most serious diseases affecting quality of life (Chen et al., 2015, Katon et al., 2003, Luppa et al., 2008, McCall and Kintziger, 2013).
Depressive symptoms are a sign indicating that clinicians should intervene as early as possible, particularly in older adult groups, to avoid the high occurrence rates of depression. Antidepressants can be an effective form of intervention for depressive symptoms, but older adults may be vulnerable to adverse effects and less tolerant of this approach (Dines et al., 2014, Felice et al., 2015). Psychotherapy is safer than drugs; however, it costs more (Lazar, 2014, Rodgers et al., 2012). Safe and cost-effective therapies are still being explored for depression among older adults.
Nutritional status plays an important role in mental health, and nutritional deficiencies may contribute to the pathogenesis of depression. Omega-3 (n-3) has been deemed a potential treatment for depression because poor omega-3 fatty acid status increases the risk of depression (Alpert et al., 2002, Shim et al., 2011). N-3 polyunsaturated fatty acids (PUFAs) belong to the family of long-chain PUFAs, are mainly composed of docosahexaenoic acid (DHA) and minute quantities of eicosapentaenoic acid (EPA) in the human body and brain, are limited in terms of synthesis in humans, and can be acquired by eating oily fish and seafood rich in EPA and DHA. Previous studies suggested that infrequent consumption of fish is associated with an elevated risk of depression compared to frequent consumption (Appleton et al., 2006, Davidson and Andrews, 2013, Li et al., 2011, Silvers and Scott, 2002, Tanskanen et al., 2001). Individuals with depression also have significantly lower levels of n-3 PUFAs, including both EPA and DHA, than those without depression (Lin et al., 2010, Peet et al., 1998). Possible mechanisms of n-3 PUFAs for alleviating depression including the production of proinflammatory cytokines and maintenance of neuronal membrane stability and fluidity (Deacon et al., 2017). A detailed review of these mechanisms can be found in Su (2009).
The effect of n-3 PUFAs has been studied on a wide variety of depressive conditions. Systematic reviews and meta-analyses have been conducted to synthesize the effect of n-3 PUFAs in reducing depressive symptoms, but these reviews were conducted across all age groups and found mixed results (Appleton et al., 2006, Appleton et al., 2010, Bloch and Hannestad, 2012, Grosso et al., 2014, Lin and Su, 2007, Martins, 2009, Sublette et al., 2011). Three reviews found no significant difference between n-3 PUFAs and a comparison group in treating depression among patients without a formal psychiatric diagnosis (Appleton et al., 2006, Bloch and Hannestad, 2012, Sublette et al., 2011). Four reviews found evidence that n-3 PUFAs was superior to a placebo on depressive symptoms among patients with a wide range of depression severity, including patients with depressive symptoms (Grosso et al., 2014) and bipolar disorder or major depression (Appleton et al., 2010, Ciappolino et al., 2017, Lin and Su, 2007, Ross et al., 2007, Martins, 2009). Previous reviews have also documented differences among EPA, DHA, and EPA–DHA combinations, finding that EPA seems to be more effective than DHA in treating major depression (Ciappolino et al., 2017, Grosso et al., 2014, Martins, 2009). In addition, previous studies found mixed results on the association between dosage of n-3 PUFAs and intervention effects in reducing depression (Bloch and Hannestad, 2012, Lin and Su, 2007). These studies included participants of all age ranges and did not identify the treatment effects of n-3 PUFAs on older adults.
Late-life depression is associated with comorbidities such as cognitive impairment, insomnia, and physical illness (Fiske et al., 2009). Older individuals may have a different reaction to n-3 PUFAs compared to adults. However, the effect of n-3 PUFAs on depression in later life is unclear. A recently published systematic review of six RCTs (published before 2012) investigated the efficacy of omega-3-fatty acids in treating depression among older adults. This study suggested that omega-3 fatty acids was only efficacious in alleviating depressive symptoms among older adults with mild to moderate depression, but not among non-depressed older adults (Bae and Kim, 2018). It is unknown that how intervention characteristics (e.g., dosage of n-3 PUFAs, ratio of EPA and DHA, intervention duration) and participants’ comorbidity affect the treatment effects of n-3 PUFAs on depressive symptoms among older adults (Arnold et al., 2017). Therefore, it is necessary to conduct a meta-analysis to synthesize the existing evidence of efficacy and effectiveness of n-3 PUFAs on depressive symptoms in the older adult population and explore potential moderators that might alter the treatment effect. The aims of this systematic review and meta-analysis are to (a) assess the effects of n-3 PUFAs on depressive symptoms among older adults; and (b) explore how participants’ comorbidity, baseline depression, dosage of n-3 PUFAs, ratio of EPA and DHA, and intervention duration affect the effects of the interventions.
Section snippets
Search strategy
The following electronic databases were searched for eligible studies published from their inception to June 4, 2018: MEDLINE, EMBASE, Web of Science, Cochrane Library, PsycINFO, Global Health, CINAHL, China National Knowledge Infrastructure (CNKI), ClinicalTrials.gov, and Chinese Biomedical Medicine Database. Different combinations of the following terms were searched: aged, elderly, older adults, depressive disorder, depression, omega-3, fish oil, fatty acids, eicosapentaenoic acid,
Summary of included studies
Nine studies were included in this meta-analysis. The process of identification and inclusion of trials following PRISMA guidelines is summarized in Fig. 1. Initial searches yielded 778 records from electronic databases (Medline: n = 245; Embase: n = 162; Web of Science: n = 146; Cochrane Library: n = 82; CBM: n = 11; PsycINFO: n = 68; CINHAL: n = 38; Global Health: n = 3; CNKI: n = 23; Clinical trial.gov: n = 0). Additional 17 records were identified through reference tracking. After excluded
Discussion
The meta-analysis of 9 RCTs found mixed findings of the efficacy of n-3 PUFA in the treatment of depressive symptoms among older adults aged 60 and above. We only found supportive evidence of treatment with dosage over 1.5 g n-3 PUFA/d compared with placebo in reducing depressive symptoms among this population. We did not find supportive evidence for the effect of n-3 PUFA supplementation with mixed dosages or with dosages less than 1.5 g/d. The eligible studies varied in characteristics of
Conclusion
The present study found n-3 PUFA treatment with dosage greater than 1.5 g/d are efficacious in reducing depressive symptoms among older adults aged 60 and above. The current study found the dosage of n-3 PUFA alters intervention effects. Meta-regression did not find significant moderating effects of depression via comorbid condition, intervention duration, or the ratio of EPA–DHA < 1.5, potentially due to limited statistical power. More high-quality, large-scale RCTs are needed to confirm the
Declaration of conflicting interest
There are no ethical/legal conflicts involved in the article. The author(s) declared no potential conflicts of interest with respect to the research, authorship, and publication of this article.
Author statement contributors
Zheng-Gang Bai drafted the study protocol, conducted literature searching and screening, and wrote the manuscript.
Ai Bo conducted data analysis, wrote and revised the manuscript.
Si-Jie Wu extracted the data from the included studies and wrote the manuscript.
Qiong-Yan Gai extracted the data, screened the literature according to the inclusion criteria.
Iris Chi supervised the manuscript writing process and revised the manuscript.
Role of the funding source
This work was supported by the Fundamental Research Funds for the Central Universities”, no. 30918013115.
Acknowledgments
Rui Zhao (Key Laboratory of Evidence Based Medicine and Knowledge Translation of Gansu Province, Lanzhou City, China) and Ren-Hao Ji (Public Affair School of Nanjing University of Science & Technology, Nanjing, China) equally contributed to this study on literature screening.
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