Research report
Low dietary or supplemental zinc is associated with depression symptoms among women, but not men, in a population-based epidemiological survey

https://doi.org/10.1016/j.jad.2011.09.039Get rights and content

Abstract

Background

Prior studies indicate that the biochemical alterations of depressive episodes result in decreased serum zinc concentrations. Given these findings, it is plausible that consistently low dietary zinc intakes contribute to depressive symptoms, yet epidemiological data are lacking. The authors tested the hypothesis that low zinc intake is associated with depressive symptoms using cross-sectional data from the population-based Boston Area Community Health survey (2002–2005).

Methods

Dietary and supplement use data were collected by validated food frequency questionnaire. Current depressive symptoms were assessed by the abridged validated Center for Epidemiologic Studies Depression scale and analyzed using multivariate logistic regression, adjusting for sociodemographic, health and lifestyle characteristics.

Results

Results showed an interaction (P = 0.03) with gender, whereby zinc was associated with depressive symptoms in women (N = 2163), but not men (N = 1545). Women with low dietary or supplemental zinc intake were more likely to have depressive symptoms (e.g., dietary zinc quartile 1 vs. 4, OR = 1.76, 95% CI: 1.26, 2.45; P-trend = 0.004; supplemental zinc P-trend = 0.03). Associations were stronger among women using antidepressant medications (e.g., total zinc OR = 4.75, 95% CI: 1.98, 11.4; P-trend = 0.0005).

Limitations

The cross-sectional, observational nature of the study leaves uncertain whether the observed associations represent actual causal relationships between zinc intake and depressive symptoms.

Conclusions

These findings suggest: (1) gender-specific pathophysiological mechanisms of depression, (2) inadequate dietary zinc intake contributes to depressive symptoms in women, and (3) supplemental zinc is a beneficial adjunct to antidepressant therapy in women. Additional research on both men and women is needed to verify these novel findings. If confirmed by other studies, the potential importance of adequate zinc intake is underscored by the recognized limitations of pharmacotherapy for depression.

Introduction

Depression is a critical problem and a leading cause of disability worldwide (WHO, 2001). In the U.S. alone, over 40 million people – roughly 1 in 5 adults – have depressive symptoms, the majority of whom are not receiving treatment (Shim et al., 2011). Even among those on antidepressants, a substantial proportion fail to achieve remission of depressive symptoms (Mauskopf et al., 2009, Rush et al., 2006). A growing body of evidence indicates a role for zinc in depression and the mechanisms of antidepressant medications. Initially, clinical studies revealed that major depressive disorder was accompanied by decreased serum zinc concentrations, which corresponded to the severity of depressive symptoms, suggesting that depression alters zinc homeostasis (Little et al., 1989, Maes et al., 1994, Maes et al., 1997, McLoughlin and Hodge, 1990). Since then, various studies have confirmed that serum zinc was significantly lower during acute depressive episodes, and furthermore that levels were normalized after successful antidepressant pharmacotherapy (Nowak et al., 2003, Siwek et al., 2010).

There are numerous mechanisms by which zinc may play a role in depression. Zinc is an essential trace element found in abundance in the human brain where it acts as a neuromodulator, and zinc is required to regulate numerous aspects of cellular metabolism, including immune, antioxidant, transcription and replication functions (Bitanihirwe and Cunningham, 2009). Plausible pathways that zinc may affect depression and be capable of antidepressant function include NMDA receptor antagonism, inhibition of glycogen synthase-3β activity (Ilouz et al., 2002), and increasing levels of brain-derived neurotrophic factor (BNDF) (Bitanihirwe and Cunningham, 2009, Nowak et al., 2004). The mechanism most strongly supported by experimental evidence for decreased serum zinc during depressive episodes is the activation of inflammatory processes (Marcellini et al., 2008, Siwek et al., 2010, Szewczyk et al., 2010). Significant associations between treatment-resistant depression, lower serum zinc concentrations, and markers of the immune/inflammatory response (increased CD4+/CD9+ T-cell ratio, lower TSP, and lower serum Alb and Tf) suggest that lower serum zinc in depressive disorders is a marker of a (sub)chronic immune/inflammatory response (Maes et al., 1997).

To date, the presumed direction of the association is that biochemical alterations of depressive episodes result in decreased serum zinc concentrations. However, it is plausible that consistently low dietary zinc intakes could contribute to depressive symptoms by further lowering available zinc and thereby adversely affecting numerous relevant biochemical processes. A reasonable hypothesis is that zinc consumed through diet helps prevent or mediate depressive symptoms. The latter notion has been supported by preliminary clinical trials showing benefits of zinc supplementation on depressive symptoms. In small trial (n = 14) of patients with major depression beginning antidepressant treatment, zinc supplements significantly promoted a reduction in depression rating scores (Nowak et al., 2003). A study of mood states among young women found that zinc supplementation (7 mg/d) plus multivitamin led to a significantly improved depression–dejection scores compared to multivitamin alone (Sawada and Yokoi, 2010).

Epidemiological data in this research area are lacking. While laboratory studies elucidate mechanisms and small trials support the utility of zinc supplements for depressive symptoms, no large population-based studies have examined the role of zinc intake in relation to depressive symptoms in the general adult population. One study of older European adults aged 60–84 y found that those with low dietary zinc intakes had lower serum zinc concentrations and were more likely to have depressive symptoms (Marcellini et al., 2006). A study of 46 female students aged 20–25 y in Iran showed that dietary zinc intake, which was significantly correlated with serum zinc levels, was inversely correlated with depressive symptoms (Amani et al., 2010). Neither study accounted for antidepressant treatment, zinc supplement use, or other medical, lifestyle, or sociodemographic factors that may have had a role in explaining the observed associations.

Our objective was to examine the association between dietary and supplemental zinc intake and depressive symptoms in a large sample of women and men from the general population. We use data from a racially/ethnically diverse population-based random sample survey considering numerous lifestyle and medical characteristics as well as antidepressant and zinc supplement use.

Section snippets

Study design and population

We analyzed cross-sectional, observational epidemiological data from the Boston Area Community Health (BACH) Survey, a population-based, random stratified cluster sample survey (McKinlay and Link, 2007). From 2002 to 2005, BACH recruited 2301 men and 3201 women aged 30–79 y from three racial/ethnic groups (Hispanic, non-Hispanic black, and non-Hispanic white) to be representative of those in Boston, MA, USA. Data were obtained during a 2-hour, in-person home interview by a trained

Results

Preliminary analyses revealed a statistically significant interaction by gender (P-interaction = 0.028). Therefore, all subsequent analyses were stratified by gender. Table 1 describes characteristics of men and women, overall and by depressive symptoms status. Depressive symptoms were present in 15.9% of men and 23.5% of women, with a common mean score of 6.3 (SEM = 0.1) among those with ≥ 5 symptoms on the abridged CES-D. Overall, 16.9% of women and 11.3% of men currently used antidepressant

Discussion

In this population-based study, low dietary zinc intake was positively associated with depression symptoms among women, but not men. Furthermore, the association was considerably stronger among women using SSRI antidepressants, whereby those with low zinc intake were almost five times as likely to have ongoing depressive symptoms while on treatment, compared to women with high zinc intake. The significant findings in women were robust to consideration of numerous relevant sociodemographic and

Role of funding source

This project was supported by the National Institute of Diabetes and Digestive and Kidney Diseases, Grant nos. R21DK081844 and DK56842. The content of this work is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Diabetes and Digestive and Kidney Diseases or the National Institutes of Health.

The funding source had no further role in the study design, collection, analysis and interpretation of data; in the writing of the

Conflict of interest

The authors report no conflicts of interest.

Acknowledgments

None.

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