Research reportDietary zinc is associated with a lower incidence of depression: Findings from two Australian cohorts
Introduction
Depression is a mental disorder with high morbidity and mortality; more than 350 million people of all ages worldwide suffer from depression (WHO, 2012). Depression is a major risk factor for self-inflicted injury and, at its worst, can lead to suicide. It has been estimated that suicide is responsible for 1 million deaths every year (WHO, 2012). Depression is also associated with decreased productivity, poor psychosocial outcomes, and decreased quality of life and wellbeing. In Australia, mental disorders were identified as the leading cause of healthy years of life lost due to disability in 2003 (AIHW, 2008). Depression-associated disability costs the Australian economy $14.9 billion annually and depression is forecast to come second only to heart disease as the leading medical cause of death and disability within 20 years (The Department of Health, 2009).
Even though there are treatments for depression, pharmacotherapy is usually costly. Medications have the potential for adverse side effects (Gartlehner et al., 2007) and a significant proportion of people fail to achieve a reduction in their depressive symptoms (Mauskopf et al., 2009). Hence, there is a need to investigate alternative treatments and prevention strategies. In recent years, there has been an increasing interest in the role of nutrition in depression (Lai et al., 2014). Micronutrients of particular interest in depression are zinc and magnesium (Jacka et al., 2012a, Szewczyk et al., 2008). Zinc is an immunomodulatory trace mineral found in abundance in the human brain where it is required to regulate numerous aspects of cellular metabolism. It has been suggested that zinc supplementation enhances antidepressant therapy by lowering depressive scores in patients (Lai et al., 2012). Zinc may produce antidepressant-like effects through modulating the functions of serotonergic and N-methyl-D-aspartate (NMDA) receptors and increasing levels of brain derived neurotrophic factor (BDNF) (Szewczyk et al., 2009, Szewczyk et al., 2011, Takeda and Tamano, 2009). In animal models of depression, zinc induces an antidepressant-like effect that appears to be mediated through its interaction with NMDA receptors (Kroczka et al., 2001, Rosa et al., 2003, Sowa-Kućma et al., 2008) and enhances the effect of antidepressant medication (Kroczka et al., 2001). In humans, recent population-based studies have shown an association between low dietary zinc intake and depression (Jacka et al., 2012a, Maserejian et al., 2012, Roy et al., 2010) in women and men (Lehto et al., 2013).
Although animal and human studies have demonstrated a role for zinc in reducing depression, there have been no longitudinal studies looking at the link between dietary intake of zinc and depression in both men and women. To date there has been only one prospective study carried out to look at dietary zinc intake and risk of incident depression (Lehto et al., 2013); however, this was only carried out in men. Therefore, the aim of this study was to determine if dietary zinc is associated with depression using Centre for Epidemiological Studies Depression Scale (CESD) scores in both men and women from two large Australian cohorts. In addition, this study examined the association of dietary zinc to iron ratio with depression, because minerals with similar physical or chemical properties such as iron and zinc may compete with each other biologically (Hill and Matrone, 1970) and previous studies in humans have shown that iron interferes with the absorption of zinc (Solomons, 1986).
Section snippets
The Hunter Community Study (HCS)
Data for this study was obtained from the Hunter Community Study (HCS), a cohort of community-dwelling men and women aged 55–85 years of age in Newcastle, NSW, Australia. Approval to conduct the research was granted by the University of Newcastle Human Research Ethics Committees. This study has been described in detail elsewhere (McEvoy et al., 2010). In brief, participants were randomly selected from the NSW State Electoral Roll and contacted between December 2004 and May 2007. Data collection
Statistical analysis
Zinc and iron were adjusted for total energy intake, using the residual method (Willett, 1998). The natural logs of zinc and iron were each regressed on the natural log of energy using linear regression and the standardised residuals from the model with a constant added to it; these were used as the values of zinc and iron. The zinc to iron ratio was calculated after energy-adjustment. Alcohol was not adjusted for total energy intake.
Associations between baseline characteristics and quintiles
Results
Table 1 shows the baseline characteristics of the HCS and ALSWH participants by quintile of energy-adjusted dietary zinc (quintile 1=lowest intake; quintile 5=highest intake). Table 2, Table 3 show the predictors of incident depression (CESD ≥16 at follow-up) for HCS and ALSWH, respectively.
Discussion
Findings from both cohorts showed dietary zinc intake was associated with a lower incidence of depression in men and women 50 years and older, even after adjusting for potential confounders. However, it was not a dose-response relationship. For example, the men and women in quintile 2 who still had relatively low zinc intakes had roughly the same reduction in risk of depression as those in the higher intake quintiles (quintile 4 for HCS and 5 for ALSWH). We also observed no association between
Conclusion
In conclusion, the results from the two independent cohort studies show that lower total dietary zinc intake is associated with a higher incidence of depression in both men and women. This finding is futher reinforced by the sensitivity analysis which showed that the association persists despite excluding those with zinc deficiency. The relationship between zinc to iron ratio with regards to depression needs to be explored further and future research should examine this association between
Role of funding source
The funding source had no role in the concept formation, study design and writing of the study manuscript.
The corresponding author declares that I had full access to all the data in the study and have the final responsibility to make the decision to submit for publication.
Conflict of interest
All authors declare that they have no conflict of interest.
The corresponding author declares that I had full access to all the data in the study and have the final responsibility to make the decision to submit for publication.
Acknowledgements
The authors would like to thank the men and women participating in the HCS as well as all the staff, investigators and collaborators who have supported or been involved in the project to date. We thank Professors Paul Mitchell and Victoria flood of the Blue Mountain Eye study for permission to use their food frequency questionaire.
The ALSWH was conceived and developed by groups of interdisciplinary researchers at the University of Newcastle and the University of Queensland. The authors wish to
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2022, General Hospital PsychiatryCitation Excerpt :All of the eligible RCTs followed their participants for less than six months, therefore, whether the effect of zinc supplementation persists for a longer period of time remains unknown, and therein represents a viable avenue for further research. An important limitation present in most of the included studies was that they were conducted in a relatively low range of geographical locations (3 from 4 cohort studies established in Australia [39,48], and 6 from 8 RCTs conducted in Iran [20,30,31,51,52]), thus, the association between zinc status and risk of depression may not be congruent in different populations, and clearly warrants further investigation. Although we conducted several subgroup analyses, we were unable to adequately detect the sources of heterogeneity.