Nutrition 32 (2016) 296–302

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Nutrition
journal homepage: www.nutritionjrnl.com

Review

Fruit and vegetable consumption and the risk of depression:

A meta-analysis
Xiaoqin Liu M.D. a, Ying Yan Ph.D. b, Fang Li M.D. a, Dongfeng Zhang M.D. a, *
a
Department of Epidemiology and Health Statistics, The Medical College of Qingdao University, Qingdao, Shandong, People’s Republic of China
b
Department of Teaching Research, The Medical College of Qingdao University, Qingdao, Shandong, People’s Republic of China

a r t i c l e i n f o a b s t r a c t

Article history: Objective: Epidemiologic investigations evaluating the association of fruit and vegetable con-
Received 13 August 2015 sumption with depression risk have yielded controversial results. Therefore, a meta-analysis was
Accepted 13 September 2015 carried out to qualitatively summarize the evidence regarding association of fruit and vegetable
intake with risk of depression in the general population.
Keywords: Methods: PubMed, Embase, and Web of Knowledge were searched for relevant articles published
Fruit
up to June 2015. To evaluate the association of fruit and vegetable intake with depression risk,
Vegetable
combined relative risks were calculated with the fixed or random effects model. Meta-regression
Depression
Meta-analysis was conducted to explore potential sources of heterogeneity. Publication bias was estimated by the
Egger’s test and the funnel plot.
Results: Ten studies involving 227 852 participants for fruit intake and eight studies involving 218
699 participants for vegetable intake were finally included in this study. The combined relative risk
(95% confidence interval) of depression for the highest versus lowest category of fruit and vege-
table intake was 0.86 (0.81, 0.91; P < 0.01) and 0.89 (0.83, 0.94; P < 0.01), respectively. In subgroup
analyses stratified by study design, the inverse association of fruit (0.83 [0.77, 0.91; P ¼ 0.006]) and
vegetable (0.88 [0.79, 0.96; P ¼ 0.007]) intake with risk of depression was also observed in the
cohort study.
Conclusions: This meta-analysis indicated that fruit and vegetable consumption might be inversely
associated with the risk of depression, respectively.
Crown Copyright Ó 2016 Published by Elsevier Inc. All rights reserved.

Introduction depression, it is especially and extremely important to identify

Depression is a common mental health disorder
On a worldwide scale, about 400 million people suffer from
depression [1]. According to the report of World Health Orga-
nization, depression accounts for 4.3% of the global burden of
disease alone and is one of the largest single causes of disability
worldwide [2]. Although the etiology of depression has not been
fully explained, the dysfunction of noradrenergic and dopami-
nergic neurotransmission, disturbance of cellular plasticity,
including reduction of neurogenesis, chronic inflammation, and
higher oxidative stress may be related to pathogenesis of
depression [3–5]. Considering the serious consequences of
* Corresponding author. Tel.: þ8653282991712; fax: þ8653283801449.
E-mail address: zhangdf1961@126.com (D. Zhang).
the modifiable risk factors and develop prevention and control
strategy.
Some lifestyle behaviors have been reported to increase the
risk of depression, such as sedentary behavior [6], long-term
stress [7], and short or long hours of sleep [8]. In recent years,
the association between diet and depression has also drawn
much attention. Among the dietary factors, consumption of fruits
and vegetables, which are rich in antioxidants and antiin-
flammatory components, was hypothesized to play an important
role in depression development [9]. Several epidemiology
studies have been carried out to investigate the role of fruit and
vegetable intake in the development of depression, but the re-
sults are inconsistent. For fruit intake, although an inverse as-
sociation with the risk of depression was found in some studies
[9–12], the association was not observed in other studies [13–17].
For vegetable intake, though an inverse association was reported

http://dx.doi.org/10.1016/j.nut.2015.09.009
0899-9007/Crown Copyright Ó 2016 Published by Elsevier Inc. All rights reserved.
 X. Liu et al. / Nutrition 32 (2016) 296–302
in three studies [12,13,18], no association was found in the others
[9,10,14–16].
Therefore, a meta-analysis was systematically performed to
evaluate the association of fruit and vegetable consumption with
the risk of depression.
Materials and methods
Literature search strategy
A literature search was performed on the databases of PubMed, Embase, and
Web of Knowledge for relevant articles published up to June 2015, using the
following search terms: “depression,” “depressive disorder,” “depressive symp-
toms,” “fruit,” “vegetable,” and “diet” without restrictions. Moreover, the refer-
ences of related reviews and original articles were also reviewed. The detailed
steps of the literature search are shown in Figure 1.
Inclusion criteria
The inclusion criteria were as follows: 1) observational study published as an
original article; 2) the exposure variable of interest was fruit or vegetable con-
sumption; 3) the outcome of interest was depression; 4) relative risks (RRs) or
odds ratio estimates (all results are presented with RRs in this study) with their
95% confidence intervals (95% CIs) were available. Depression was determined by
self-report based on doctor’s diagnosis, regular use of antidepressant drugs, or
depression rating scales. Studies on the postpartum depression and depression in
pregnancy were not included in this meta-analysis. If data were duplicated in
more than one study, the latest one or the one with the largest number of
samples was included. Two investigators searched articles and reviewed all
retrieved studies independently. If the two investigators could not reach a
consensus about the eligibility of an article, it was solved through discussion with
a third investigator.
Data extraction
Data extracted from each study were as follows: publication year, the first
author’s name, country where the study was performed, follow-up years, study
design, sample size, mean age or age range at baseline years, fruit and vegetable
consumption assessment, determination method of depression, RRs with cor-
responding 95% CIs for the highest versus lowest categories of fruit and vegetable
intake, and adjustment of covariates in the analysis. The RRs adjusted with the
most confounders in the original studies were extracted.
Fig. 1. Flowchart of the selection of studies included in the meta-analysis.
297
Statistical analyses
Pooled measure was calculated as the inverse-variance weighted mean of the
logarithm of RR (95% CI) of depression for the highest versus lowest category of
fruit and vegetable intake, respectively. The I2 [19] was used to assess hetero-
geneity among studies. If I2  50% [20], the random effect model (REM) was
adopted as the pooling method; otherwise (I2 < 50%), the fixed effect model
(FEM) was employed. Meta-regression was performed to access the potentially
important covariates (including publication year, continent, study design, status
for physical activity adjustment, and ascertainment method of depression) that
might exert substantial impacts on between-study heterogeneity [21]. To assess
whether the results could have been affected distinctly by a single study, an in-
fluence analysis was carried out with one study removed at a time [22]. The
leave-one-out sensitive analysis was conducted to evaluate the key studies that
have remarkable impact on the between-study heterogeneity. Publication bias
was evaluated with the visual inspection of funnel plot and Egger regression
asymmetry test [23]. Subgroup analysis was performed by study design (cross-
sectional or cohort study). All statistical analyses were conducted using Stata
V.12.0 (Stata Corp., College Station, TX, USA). A two-tailed P < 0.05 was consid-
ered statistically significant.
Results
Literature search and study characteristics
The flowchart for study inclusion is shown in Figure 1, and
4950 articles from PubMed, 2544 articles from Embase, and 5484
articles from Web of Knowledge were identified by the search
strategy. After excluding duplicates and reviewing the tiles or
abstracts, 104 possible related articles concerning fruit and
vegetable intake and depression risk were identified. Among
these articles, 4 were removed because of duplicate participants
[24–27], 62 were excluded because RR or 95% CI was not pro-
vided, and 28 were ruled out because the study subjects were the
patients of postpartum depression or depression in pregnancy.
Overall, 10 articles involving 4 cohort studies and 7
cross-sectional studies were included in this meta-analysis.
Table 1 displays the baseline characteristics of the studies.
Quantitative synthesis
Fruit intake and the risk of depression
For fruit intake, four cohort studies from four articles [9,10,12,
16] and six cross-sectional studies from five articles [11,13–15,17]
involving 227 852 participants were included. Among these
studies, three were conducted in Asia [11,13,16], four in Europe
[10,15,17], one in Oceania [9], one in North America [14], and one
in South America [12]. With regard to the depression diagnostic
criteria, eight studies used the scales or questionnaires [9,11–13,
15–17], and two studies were ascertained by interview or
self-reported physician diagnosis or use of regular antidepres-
sant medication [10,14]. The major adjusted confounding factors
included age, sex, education, body mass index, marital status,
smoking status, and physical activity.
Among the 10 studies, 4 reported that high fruit intake could
decrease the risk of depression [9–12], whereas the other 6
indicated no significant association [13–17]. The pooled RR (95%
CI) of depression for the highest versus lowest category of fruit
intake was 0.86 (0.81, 0.91; Pfor significance < 0.01, FEM, I2 ¼ 48.2%,
Pfor heterogeneity ¼ 0.043; Fig. 2). The pooled RRs for cross-sectional
and cohort studies were 0.84 (0.75, 0.95; Pfor significance ¼ 0.006,
REM, I2 ¼ 55.7%, Pfor heterogeneity ¼ 0.046) and 0.83 (0.77, 0.91;
Pfor significance ¼ 0.001, FEM, I2 ¼ 41.2%, Pfor heterogeneity ¼ 0.164),
respectively, for subgroup analysis stratified by study design
(Fig. 3).
 298
Table 1
Characteristics of included studies on fruit and vegetable intake and depression risk

Author [Ref.] Study design Country Year Age range Sex Sample RR (95% CI) Method Depression method
or mean age
Allgower et al. [17] Cross-sectional 16 countries 2001 21.6 F 3438 0.81 (0.66, 1.01) for fruit Interview 13-item short BDI  5
study in Europe 21.6 M 2091 0.85 (0.62, 1.17) for fruit
Hintikka et al. [15] Cross-sectional Finland 2005 44.04 FþM 2011 0.92 (0.79, 1.07) for fruit FFQ 21-item BDI  15

X. Liu et al. / Nutrition 32 (2016) 296–302

study 44.04 FþM 2011 0.95 (0.78, 1.17) for vegetable
Woo et al. [13] Cross-sectional Hong Kong 2006 65 FþM 3394 0.71 (0.48, 1.05) for fruit 7-d food frequency GDS  8
study 65 FþM 3394 0.63 (0.44, 0.92) for vegetable questionnaire
Liu et al. [11] Cross-sectional Chengdu, Hangzhou, 2007 20.4 FþM 2541 0.69 (0.57, 0.84) for fruit FFQ 20-item CES-D
study Shenyang, Wuhan,
Harbin, Kunming, Qingdao
Sanchez-Villegas Cohort study Spain 2009 37.18 FþM 10094 0.61 (0.45, 0.82) for fruit Validated 136-item Self-reported physician diagnosis
et al. [10] 37.18 FþM 10094 0.93 (0.69, 1.24) for vegetable food frequency of depression or use of regular
antidepressant medication or DSM-IV
Shahar et al. [18] Cross-sectional Malaysia 2011 68.56–70.44 FþM 71 0.3 (0.1, 0.94) for vegetable 1-d food weighing GDS  5
study and 24-h diet recall
McMartin et al. [14] Cross-sectional Canada 2013 12 FþM 125428 0.97 (0.87, 1.08) for fruit Dietary history method CIDI-SF  5 or self-reported
study 12 FþM 125428 0.91 (0.83, 1.01) for vegetable physician diagnosis of depression
Mihrshahi et al. [9] Cohort study Australia 2014 55.45 F 6271 0.82 (0.7, 0.96) for fruit FFQ CES-D  10
55.45 F 5117 0.83 (0.62, 1.1) for vegetable
Chi et al. [16] Cohort study Taiwan 2015 53 FþM 2630 0.82 (0.64, 1.07) for fruit FFQ CES-D  10
53 FþM 2630 0.79 (0.49, 1.27) for vegetable
Gangwisch et al. [12] Cohort study Columbia 2015 50–79 F 69954 0.88 (0.79, 0.99) for fruit 145-item FFQ Burnam 8-item scale
50–79 F 69954 0.88 (0.79, 0.99) for vegetable

BDI, Beck Depression Inventory; BMI, body mass index; CES-D, Center for Epidemiologic Studies Depression Rating Scale; CI, confidence interval; CIDI-SF, Composite International Diagnostic Interview-Short form; DSM,
Diagnostic and Statistical Manual of Mental Disorders; FFQ, Food Frequency Questionnaire; GDS, Geriatric Depression Scale; RR, relative risk.
 X. Liu et al. / Nutrition 32 (2016) 296–302
Fig. 2. Meta-analysis of the association between fruit intake and depression risk. The size of gray box is positively proportional to the weight assigned to each study, which is
inversely proportional to the standard error of the relative risks (RRs), and horizontal lines represent the 95% confidence intervals (95% CI).
Vegetable intake and the risk of depression
For vegetable intake, four cohort studies [9,10,12,16] and four
cross-sectional studies [13–15,18] involving 218 699 participants
were included. Among these studies, three were conducted in
Asia [13,16,18], two in Europe [10,15], one in Oceania [9], one in
North America [14], and one in South America [12]. With regard
to the depression diagnostic criteria, six studies used the scales
or questionnaires [9,12,13,15,16,18], and two were ascertained by
interview or self-reported physician diagnosis or use of regular
antidepressant medication [10,14]. The major confounding fac-
tors adjusted in studies included age, sex, education, body mass
index, and physical activity.
Among the eight studies, three reported that high vegetable
intake could decrease the risk of depression [12,13,18], whereas
the other five indicated no significant association [9,10,14–16].
The pooled RR (95% CI) of depression for the highest versus
lowest category of vegetable intake was 0.89 (0.83, 0.94;
Pfor significance < 0.01, FEM, I2 ¼ 14.1%, Pfor heterogeneity ¼ 0.319;
Fig. 4). The pooled RRs for cross-sectional and cohort studies
were 0.83 (0.68, 1.02; Pfor significance ¼ 0.078, REM, I2 ¼ 60.4%,
Pfor heterogeneity ¼ 0.056) and 0.88 (0.79, 0.96; Pfor significance ¼
0.007, FEM, I2 ¼ 0.0%, Pfor heterogeneity ¼ 0.923), respectively, for
subgroup analysis stratified by study design.
Sources of heterogeneity and sensitive analysis
As shown in Figure 2, moderate heterogeneity (I2 ¼ 48.2%,
Pfor heterogeneity ¼ 0.043) was found in the analysis of fruit intake
and depression. Therefore, univariate meta-regression was per-
formed with the covariates of publication year (P ¼ 0.513),
continent (P ¼ 0.089), study design (P ¼ 0.610), status for
physical activity adjustment (P ¼ 0.134), and depression ascer-
tainment (P ¼ 0.751) to investigate potential sources of the
heterogeneity. None of these covariates had an excessive
299
influence on the pooled effects (P > 0.05). For the leave-one-out
sensitivity analysis, one study [14] was found to contribute to the
between-study heterogeneity. After excluding this study, the
heterogeneity (I2 ¼ 27.5%, P ¼ 0.200) was reduced and the pooled
RR was 0.83 (0.78, 0.88).
Influence analysis and publication bias
Influence analysis showed that no individual study had an
excessive influence on the pooled association of fruit and vege-
table intake with the risk of depression. The visual inspection of
the funnel plot (Fig. 5) and Egger’s test showed no evidence of
publication bias for the analysis of vegetable intake with
depression (P ¼ 0.053). For fruit intake, publication bias was
found in both the Egger’s test (P ¼ 0.022) and the visual in-
spection of the funnel plot. However, after excluding one study
[14], the publication bias was not evident with the Egger’s test
(P ¼ 0.078).
Discussion
To our knowledge, this is the first meta-analysis to explore the
relationship between fruit and vegetable intake and depression
risk. A total of 227 852 participants for fruit intake and 218 699
participants for vegetable intake were included in this meta-
analysis. Findings from the meta-analysis indicated that both
fruit intake and vegetable intake were significantly associated
with the decreased risk of depression. Subgroup analysis was
also conducted by study design. The significantly inverse asso-
ciation was observed in both cross-sectional and cohort studies
for fruit intake and depression risk. For vegetable intake, the
significantly inverse association was also found in the cohort
studies.
300
Fig. 3. Forest plot of the relative risks (RRs) with corresponding 95% confidence intervals (95% CI) of studies on fruit intake and depression for cross-sectional and cohort
studies. The size of gray box is positively proportional to the weight assigned to each study, which is inversely proportional to the standard error of the RRs, and horizontal
lines represent the 95% CIs.
The exact biological mechanisms underlying fruit and vege-
table intake and depression risk are still not fully understood.
First, various minerals and vitamins, such as magnesium, zinc,
selenium, and vitamin B12, are present in fruits and vegetables.
Some of them were found to exert influence on the mechanisms
of depression. For instance, magnesium intake could reduce
plasma concentrations of C-reactive protein, which is a marker of
low-grade inflammation, and depression was found to be related
to chronic inflammation [14]. Vitamin B12 affects the biochem-
ical processes in the central nervous system. Vitamin B12 defi-
ciency could lead to hyperhomocysteinemia by activation of N-
methyl-D-aspartate receptors, oxidative stress, and lesions in
vascular endothelium, which could result in neurotoxicity and
then lead to the depression incident [28]. Zinc deficiency induces
neurologic and somatic symptoms as well as psychopathological
symptoms that are connected with depressive disorder [29,30].
In addition, antioxidants such as vitamin C, vitamin E, and folic
acid, which play an important role in the endothelial cell
signaling cascades, could dampen the detrimental effects of
oxidative stress on mental health [31,32]. As a good source of
antioxidants, fruit and vegetable intake might be beneficial to
protect against depression.
Between-study heterogeneity occurs frequently in meta-
analysis [20], and it is essential to explore the potential sources
of between-study heterogeneity. In this meta-analysis, moderate
heterogeneity was found in the analysis between fruit intake and
depression risk. An indeterminate number of characteristics that
X. Liu et al. / Nutrition 32 (2016) 296–302
varied among the studies could be the sources, such as publi-
cation year, continent, study design, status for physical activity
adjustment, depression ascertainment, and other covariates.
Thus, meta-regression for fruit intake analysis was performed to
explore the potentially important causes for between-study
heterogeneity. Meta-regression analysis did not find any of the
above-mentioned covariates as the important contributors to the
between-study heterogeneity. To further explore the potential
sources of between-study heterogeneity, the leave-one-out
sensitivity analysis was carried out. After excluding one study
that had a strong effect on the heterogeneity, the heterogeneity
decreased to 27.5% and no publication bias was found in the
analysis between fruit intake and depression risk. What’s more,
the results still remained significant after reducing the hetero-
geneity in the analysis of fruit intake and depression, strongly
identified the stability of results.
The study has several strengths. First, a large number of par-
ticipants were included in this study, allowing a much greater
possibility of achieving reasonable conclusions. Second, an
inverse association was found in cohort studies, indicating a po-
tential causal relationship between fruit and vegetable intake and
depression. Third, RRs with the most adjusted covariates were
extracted, which could reduce the confounding. Fourth, after
excluding one study, the heterogeneity was decreased, and the
summary result of sensitive analysis did not change substantially.
However, this meta-analysis was limited in some aspects as
well. First, confounders adjusted in each study were inconsistent.
 X. Liu et al. / Nutrition 32 (2016) 296–302
Fig. 4. Meta-analysis of the association between vegetable intake and depression risk. The size of gray box is positively proportional to the weight assigned to each study,
which is inversely proportional to the standard error of the relative risks (RRs), and horizontal lines represent the 95% confidence intervals (95% CI).
For example, body mass index and physical activity were
adjusted in some studies, whereas not adjusted in other studies.
Second, publication bias was observed in the analysis of fruit
intake and depression. However, after removing one study that
had a strong effect on the heterogeneity, the bias was not evident
anymore, and the overall summary RR did not substantially
change, suggesting that the result was stable. Third, the diag-
nostic criteria of depression were inconsistent. Different scales,
including Beck Depression Inventory, Geriatric Depression Scale,
and Center for Epidemiologic Studies Depression Rating Scale,
were used in some studies, and depression was ascertained by
physician diagnosis or beginning use of regular antidepressant
medication in the others. Fourth, diet assessment methods var-
ied among the studies and dose-response relationship could not
Fig. 5. Funnel plot for the analysis of vegetable intake and depression risk.
301
be accessed because of the limited information in the included
studies.
In summary, the present meta-analyses indicated that fruit
and vegetable intake was inversely associated with the risk of
depression.
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