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Association between fruit and vegetable consumption and depression symptoms in young people and adults aged 15-45: A systematic review of cohort studies

Higher consumption of fruit and vegetables has been associated with a lower risk of various chronic diseases including coronary heart disease, obesity, and certain cancers. Recently, fruit and vegetable intake has also been linked with mental health, including depression. This systematic review aimed to evaluate the association between fruit and vegetable intake and depressive symptoms in young people and adults aged 15-45. The systematic review focused on peer-reviewed cohort studies published from 1 January 2000 to 31 August 2020 using searches of six electronic databases. The exposure was fruit and vegetable consumption analysed both separately and/or together, and the outcome was depression or depressive symptoms. Data from eligible studies were extracted according to predefined criteria and the studies were appraised using the Newcastle-Ottawa Scale (NOS) for Cohort Studies to evaluate for study quality and risk of bias. To evaluate the association between fruit and vegetable consumption and depressive symptoms, a narrative synthesis was conducted. Of 9667 potentially relevant studies that were screened for title and abstracts, 144 full text studies were evaluated, and 12 studies from seven countries were deemed eligible and included in the qualitative synthesis. Using the NOS framework one study was categorised as ‘very good’ quality, ten studies were ‘good’ quality, and two studies were ‘moderate’ quality. With respect to combined fruit and vegetable consumption, two studies demonstrated an inverse association with depression. When the effects of fruit and vegetable on depression were analysed separately, five studies showed significant associations in fruit consumption, and two studies showed significant associations in vegetable consumption. Four studies showed no association between combined fruit and vegetable consumption and depression, one study showed no association between fruit consumption and depression, and two studies showed no association between vegetable consumption and depression. Despite some contradictory results in the studies included in this review, the evidence seems to be building that a possible association exists, and this may have implications for addressing the burden of mental illness in young people and adults aged 15-45 years. Well-designed prospective cohort studies are needed to provide more robust evidence on the diet-depression relationship.


Introduction
Depression is a debilitating, chronic and reoccurring condition that has become a major public health concern worldwide. In 2017 it was estimated that 300 million people, accounting for 4.4% of nutritional needs; and (8) were unique populations which are less likely to be representative of the general population (e.g., monks).

Search strategy
The systematic review focused on peer-reviewed cohort studies published from 1 January 2000 to 31 August 2020. Prespecified search terms and Medical Subject Headings (MeSH) terms were utilised to identify potentially relevant articles from six databases, namely Medline, EMBASE, PreMedline, and PsycINFO via Ovid, CINAHL via EBSCO, and Scopus. Two reviewers (PNAD & MJ) conducted a comprehensive search using the following keywords: (a) type of food ('fruit' OR 'vegetable' OR 'FV') (b) 'consumption' OR 'intake' (c) mental disorders ('depression' OR 'depressive disorder' OR 'depressive symptoms') (d) population ('young people' OR 'young adults' OR 'adults') (e) study design ('longitudinal stud*' or 'cohort stud*'). Full details of the search strategy can be found in Supplementary Table S2.

Study selection
All studies identified were imported into EndNote X9 citation management software (Thomson Reuters, Toronto, Canada). At the first stage studies were verified and screened based on title and abstract by two reviewers (PNAD & MJ). At the second stage, all potentially relevant studies were independently screened and scrutinised for eligibility by three reviewers (PNAD, MJ & SM). Any discrepancies in judgement were resolved by discussion between researchers. Reference lists of eligible studies were manually searched to identify any additional studies. The procedure of identification and screening process for selection of cohort studies is presented in Figure 1.

Data extraction
Data extraction was independently conducted by two reviewers (PNAD & MJ) and then validated by SM using a pre-determined data extraction table. Key study components were extracted including (1) characteristics of participants (age, gender, country of origin), (2) study details (cohort assessed, number of participants, follow up period), (3) outcome and exposure assessment methods (diet and depression), (4) main results (including  coefficients, OR, HR, 95% CI, and P values) and (5) confounding factors (including all models of adjustment).

Quality Assessment
Two researchers (PNAD & SM) independently appraised the study quality and risk of bias of each eligible studies using the Newcastle-Ottawa Scale (NOS) for Cohort Studies [25]. This framework used following criteria to categorise studies: selection (scale from 0 to 4), comparability (scale from 0 to 2), and outcome (scale from 0 to 3). The overall score of each included study was used to categorise studies as: 'very good' quality (8-9 NOS points), 'good' quality (6-7 NOS points), 'moderate' quality (4-5 NOS points), and 'low' quality (0-3 NOS points) [26]. Differences in scores regarding the quality assessment were resolved by discussion and consensus between the two researchers. Fig. 1 Flowchart of identification and screening process for selection of cohort studies exploring the association between fruit and vegetable intake and depressive symptoms in young people and adults aged 15-45 years.

Search results
A total of 9557 potentially relevant studies were identified using the search strategy on six electronic databases, (Medline = 2035, EMBASE= 4083, PsychINFO= 488, PreMedline= 901, CINAHL= 1945, Scopus= 105) which was reduced to 7635 after removal of duplicates. After abstract and title screening in the first stage, 7491 studies were excluded leaving 144 full-text articles. Of 144 studies that were screened in full-text publications for eligibility, 12 studies were deemed eligible and included in the qualitative synthesis [27][28][29][30][31][32][33][34][35][36][37][38]. No additional articles were retrieved from reference list searching. The flowchart in Figure 1 displays the process of selection. Those full-text studies which were deemed ineligible with reasons are reported in Supplementary Table S3.   [28]. The earliest publication date was 2009 and the most recent 2020. Duration of the study follow-up period ranged from 2-14 years with the number of participants varying from 139 to over 45,000. The age ranges at baseline of some of the studies also included participants that were outside the 15-45 years age group, although they were recruited in this age range, as was the nature of the longitudinal cohort. One commentary study [28] was also included as an eligible study because it presented an extra evidence regarding depression and anxiety using the same cohort data from previous study conducted by the same authors [39]. In terms of analysis, one study analysed only vegetable intake [27], and one study exclusively analysed fruit intake [ [36] reported raw data from only female participants as results in the male participants were not significant. This study also separated analysis into measurements taken at two different time points: 5-years and 10-years.

Quality assessment
The Newcastle-Ottawa Scale for cohort studies was used to assess the study quality. The detailed results of the quality assessment are seen in Supplementary table 5, where the total score for the Newcastle-Ottawa Scale is given. One study was deemed as 'very good' quality,[34] the majority of studies (n= 10) categorised as 'good' quality [27][28][29][30][31][32]35,36,38], and two studies were categorised as 'moderate' quality [33,37]. Most of the studies failed to meet the requirements on ascertainment of exposure and assessment of outcome because written self-report was used to collect the exposure and outcome information, which was likely to introduce bias. Furthermore, the studies of moderate quality [33,37] only received one point each for selection and outcome criteria. No studies were excluded on the basis of their quality assessment.

Outcomes
A pooling of the results was not possible because the differences in the ways that outcomes were reported and thus results were tabulated and described qualitatively. Results are presented in Table 2.
Impact of fruit and vegetable intake on depressive symptoms Two good quality studies and one moderate quality study explored the impact of fruit and vegetable intake on depressive symptoms [31,33,36]. Two studies used the CES-D instrument [33,36], and one study used the MFQ to assess depressive symptoms [31]. At individual study level, in the 5-year analysis of the Whitehall II cohort [36], a greater consumption of both vegetables and fruit decreased the odds of recurrent depressive symptoms in women while no significant results were seen in men. In the 10-year analysis an improvement or maintenance of vegetable intake was associated with reduced odds of recurrent depressive symptoms in women, while women whose consumption decreased over the same time frame had higher odds of recurrent depressive symptoms. Similarly, an increased fruit intake decreased the odds of depression development in the 10-year analysis, however, no significant association was observed when women maintained or decreased fruit intake. In contrast, Winpenny et al. [31] reported no prospective association between fruit and vegetable intake at age 14 years and depression symptomatology at age 17 years after adjusting for risk factors, such as depressive symptoms at baseline, socio-economic status, physical activity, and total energy intake. Similarly, the finding from the SU.VI.MAX study [33] illustrated that adherence to the French nutrition guidelines resulted in a decrease in depressive symptom development due to an overall healthy diet. This was ascertained by comparing the guidelines score without inclusion of fruit and vegetables and the result was still protective.

Impact of fruit and vegetable intake on depression
One very good quality study and four good quality studies examined the association between fruit and vegetable intake and depression, of which four studies measured the depression doctors diagnosis or medication use [28,34,35,38], and one study used the CES-D instrument [32]. Two good quality studies reported the protective effect of fruit intake against risk of developing depression [35,38]. Moreover, a significant protective effect was observed from greater intakes of legumes and "fruits and nuts" [38]. Citrus fruits and juices were also shown to reduce the odds of depression in women from the Nurses' Health Study [35]. However, a greater intake of vegetables had no significant effect on the development of depression in individuals in the SUN cohort [38]. One very good quality study showed fruit and vegetable intake not to be associated with depression development or distress after adjusting for the key confounders [34]. Contrastingly, Mujcic and Oswald [28] found an inverse association between fruit and vegetable consumption and the probability of being diagnosed with depression/anxiety within the next 24 months. An interesting finding in the Add Health cohort [32] was that the association between fruit consumption during adolescence and reduced odds of depression in adulthood was not significant after adjustment for adolescent depression. Contrary to that, consuming vegetables once a day was significantly related to reduced odds of adult depression among females after adjustment for adolescent depression, but not at higher intakes (twice or more a day). However, this association was substantially attenuated after further controlling for relevant confounders.

Impact of fruit and vegetable intake on mental health/well-being
Four studies investigated the impact of fruit and/or vegetable intake independently on mental health [27,29,30]. Three good quality studies used the GHQ-12 [27,29,30] and one moderate study used the SF-12 Health Survey to assess mental health [37]. In the J-MICC study [27], an inverse association between vegetable intake and a GHQ score > 4 was not significant after controlling for confounders. In contrast to that, the study from Sweden highlighted that daily consumption of fruit and berries was a substantial determinant to predict stability in mental health among the 18-29 age group [30]. Similar results were observed in a longitudinal UK study [29] which showed the importance of both frequency and quantity of intake of fruit and vegetables on mental well-being. It was highlighted that daily consumption of fruit and/or vegetable (at least one portion) contributed to maintenance of mental well-being. Moreover, frequent vegetable consumption had a greater effect on mental wellbeing than frequent consumption of fruit. One moderate quality study that assessed emotional and mental health found fruit and vegetable consumption had no significant association with mental health and the results indicated that increased physical activity had a positive association with better mental health, irrespective of fruit and vegetable consumption [37]. The 12-item General Health Questionnaire (the GHQ-12) (psychological distress and social dysfunction factors)

Mujcic & Oswald,[28] Australia, 2019
Age range: > 15y Age mean: -Gender (female): -7,108 2y The Household, Income, and Labour Dynamics in Australia (HILDA) Survey Short questions on usual intake and frequency intake: "how many days in a usual week do you eat fruit?" and "how many days in a usual week do you eat vegetables?" "On a day when you eat fruit, how many serves of fruit do you usually eat?" and "On a day when you eat vegetables, how many serves of vegetables do you usually eat?" [39] "Have you ever been told by a doctor or nurse that you have any of long-term health conditions listed below? Please only include those conditions that have lasted or are likely to last for six months or more: Depression/Anxiety"

Ocean et al.,[29] UK, 2019
Age range at baseline: 15-104y Age mean: 47.1 Gender (female): -Over 45,000 6y The UK Household Longitudinal Study (UKHLS) Short questions on portion intake: "on a day when you eat fruit or vegetables, how many portions of fruit and vegetables in total do you usually eat?" The 12-item General Health Questionnaire (the GHQ-12) (psychological distress and social dysfunction factors) 7 **Study included data from NHS as well however characteristics were described independently and thus those from the NHSII are only presented in this table There is no decisive evidence whether fruit and vegetable consumption in the future can be predicted from the rate of depression or anxiety in the current period. Increasing one's consumption of fruit and vegetables by one portion (on a day where at least one portion is consumed) leads to a 0.133-unit increase in mental well-being (p < 0.01).

Confounders
The more often fruit and vegetables are consumed in a week, the more likely individuals have a higher mental well-being.
Specification (2)  Main finding: A greater fruit and vegetable consumption at the initial measurement was associated with a lower risk of depression at the next. This association was evident in Model 2 adjustments however disappeared once obesity was included in the adjustment (Model 3).
A greater fruit and vegetable consumption at the initial measurement was associated with lower distress scores at the next. This association was evident in Model 2 adjustments however disappeared once social support smoking and physical activity were added to the model (Model 3).  Inverse association showed that depression and distress at initial measurements predicted lower consumption of fruits and vegetables at the next measurement.
These associations were no longer evident once social support, smoking and physical activity were added to the model. Main findings: Large differences observed between men and women with regard to association between diet and depression. In women a higher adherence to the AHEI was related to lower risk of DepS assessed over 5 years. In women as AHEI score increased odds of recurrent depression decreased. No such association was observed in men. Main findings: Women who increased or maintained a high AHEI score over the 10y period resulted in 68% and 65% lower odds of subsequent depression, respectively, compared to women who maintained a low AHEI score. Women who decreased AHEI score over the 10y had a 2 fold increased odds of developing subsequent depression than those who maintained a high AHEI score. No association was observed in men Model 2: Adjusted for model 1 (age, ethnicity and total EI) +SES, retirement status, marital status, smoking, physical activity, CAD, hypertension, HDL cholesterol and central obesity at phase 3.  Main findings: Greater adherence to the Mediterranean dietary pattern resulted in more than a 30% reduction in depression development.

Compared to participants
with the lowest consumption fruit and nut those with the highest intake had a 39% decreased risk of developing depression.
There was no significant association between vegetable intake and depression.
Compared to participants with lowest consumption of legumes those with highest intake had a 27% decreased risk of developing depression.
Mediterranean diet adjusted for: Sex, age, smoking status, BMI, physical activity during leisure time, energy intake, employment status and excludes participants who reported the use of antidepressant medication during follow up by not a physician-made diagnosis of depression.
Fruits and nuts, vegetables, and legumes adjusted for: Sex, age, smoking status, BMI, physical activity during leisure time, energy intake, employment status.

78
Another study also illustrated that vegetable consumption once a day among women was 79 prospectively associated with a reduced risk of adult depression although the association

82
There were large variations in the methods used to assess intake of fruits and vegetables. For

88
Such disparities were also seen in a study conducted in Australian middle-aged women [43]. A 89 higher intake of fruits was seen to be protective of depressive symptoms in both cross sectional and 90 longitudinal analyses whereas vegetables were only protective using cross sectional analyses.
antioxidants and anti-inflammatory components such as carotenoids, flavonoids, and resveratrol.
consumed in quantities high enough to see protective effects, or that the types of vegetables 96 consumed in larger amounts do not contain the corresponding nutrients suggested to be protective.

97
Interestingly, of the two good quality studies, there was evidence of differences in the