G. Kojima1, Y. Taniguchi2, T. Urano3
1. Department of Research, Dr. AGA Clinic, Tokyo, Japan; 2. Center for Health and Environmental Risk Research, National Institute for Environmental Studies, Tsukuba, Japan; 3. Department of Geriatric Medicine, International University of Health and Welfare, Chiba, Japan
Corresponding Author: Tomohiko Urano, MD, PhD, Department of Geriatric Medicine, International University of Health and Welfare, Kozunomori 4-3, Narita City, Chiba Prefecture, 286-8686, Japan, Phone: +81 (0)476-20-7701, Fax: +81 (0)476-20-7702, Email: firstname.lastname@example.org
J Frailty Aging 2021;in press
Published online September 2, 2021, http://dx.doi.org/10.14283/jfa.2021.32
Background: There is limited evidence regarding associations between fruit and vegetable consumption and incident frailty risk among older people.
Objectives: The objective of this study was to conduct a systematic review and meta-analysis regarding the association between fruit and vegetable consumption and incident frailty risk among older adults.
Methods: A systematic search of the literature was conducted according to the PRISMA guidelines using PubMed in January 2021 for studies that prospectively examined risk of incident frailty in relation to fruit and vegetable consumption in older adults aged 60 and older. Methodological quality and heterogeneity were assessed. Odds ratios (OR) were pooled using random-effects or fixed-effects meta-analysis, depending on the presence of heterogeneity.
Results: Among three studies included in this review, data of four cohorts were provided by two studies and used in meta-analysis. The highest fruit and vegetable consumption was significantly associated with lower risk of incident frailty compared with the lowest consumption (pooled OR=0.38, 95%CI=0.24-0.59, p=<0.001).
Conclusions: This study provided the pooled evidence that high fruit and vegetable consumption may be beneficial for preventing the development of frailty in older adults. Increasing fruit and vegetable consumption can be a relevant strategy to prevent frailty.
Key words: Frailty, fruit, vegetables, diet, Nutrition, meta-analysis.
Fruit and vegetables contain various nutrients, including micronutrients with anti-inflammatory and antioxidant properties and are important parts of healthy diet (1). Their benefits for human health have been extensively studied and well documented in the literature (1). Sufficient intake of fruit and vegetables is associated with reduced risk of cardiovascular diseases, certain cancers, and premature death (1, 2). Therefore, fruit and vegetables are widely recommended by most authorities and nutritional guidelines (1, 2). A joint report by The World Health Organization and The Food and Agriculture Organization of the United Nations recommends at least 400g of fruit and vegetables a day to prevent chronic diseases (3). Unfortunately, these health benefits of fruit and vegetable consumption are relatively understudied in the older adults (4).
Frailty is a state of vulnerability to stressors and age-related decreased functioning of various physiological systems (5). It is considered as one of the problematic expression of aging. Previous studies showed approximately 10% of older adults aged 65 or more are affected by frailty and the prevalence increases with age (6). Those who are frail are susceptible to multiple negative health outcomes, including falls (7), disabilities (8), dementia (9), and death (10). Frailty have also been shown to increase the use of healthcare resources, such as hospitalization (11), institutionalization (12), and emergency department visits (13). Given these detrimental negative impacts of frailty on older people as well as on societies, frailty has been recognized as one of the most important public health priorities (14, 15).
Inadequate intake of fruit and vegetable is common among older people due to various reasons (4), such as age-related physiological and social changes (16), and may be related to increased inflammation and oxidative stress. Evidence suggests that oxidative stress and inflammation play important roles in pathogenesis of sarcopenia, which is the decline in muscle mass and function with age and a core feature of frailty (17). Therefore, increasing fruit and vegetable consumption may be effective for preventing frailty. However, few studies focused specifically on fruit and vegetables in relation to frailty (18), although multiple studies have investigated associations between certain dietary patterns and frailty risk, i.e., Mediterranean diet (19). Although a previous systematic review on associations between fruit and vegetable intake and frailty found little evidence (18), there have been more evidence published in the literature since then. Therefore, the objectives of the current study were to perform an updated systematic literature search and to attempt to conduct a meta-analysis to pool the evidence regarding the association between fruit and vegetable consumption and incident frailty risk among community-dwelling older adults.
Search strategy and study selection
The protocol of this systematic review was developed according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statements (20) and registered at PROSPERO (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021225161). The PubMed was searched by one investigator (KG) in January 2021 using prespecified search terms, which included Fruit (MeSH) OR Vegetables (MeSH) OR Fruit and Vegetable Juices (MeSH) OR Antioxidants (MeSH) OR Diet (MeSH) OR Diet Therapy (MeSH) OR Nutrition Therapy (MeSH) OR fruit* OR vegetable* OR anti-oxidant* OR antioxidant* OR diet* OR nutrition* AND Frailty (MeSH) OR Frail Elderly (MeSH) OR OR frailty. Study may have been eligible if they were prospectively cohort studies examining baseline fruit and/or vegetable consumption and subsequent risk of developing frailty in community-dwelling older people with a mean age of 60 or over. Reference lists of included and relevant articles were also examined. The search period was from 2000 or later, since the most widely used frailty criteria, the Cardiovascular Health Study (CHS) criteria were published in 2001 (21). No language restriction was applied.
For meta-analysis, eligible studies prospectively examined risk of incident frailty in relation to consumption of fruit, vegetables, or both at baseline in samples of older adults with a mean age of 60 or over. Studies including selected samples, such as patients with dementia or hospitalized patients, or focusing on dietary patterns were not considered. Frailty should be defined by validated criteria designed to measure frailty. Studies defining frailty status as a continuous score or index, such as the Frailty Index, were not included. Reviews, conference abstracts, editorials, comments, or letters were not included.
Two investigators (GK, YT) screened the titles, abstracts, and full-texts of the identified studies for eligibility. Any disagreement was solved by discussion.
The data extracted from the included studies were first author, publication year, cohort name, location, sample size, proportion of women in the cohort, mean age, age range, dietary assessment tool, frailty criteria, follow-up period, and findings.
Methodological Quality Assessment
The methodological quality of the included studies was assessed using the Newcastle-Ottawa scale for cohort studies (22). This tool has nine criteria and a study meeting five or more criteria was considered to have adequate methodological quality.
If two or more prospective studies provided the same effect measures, such as odds ratio (OR) or hazard ratio (HR), they were pooled by meta-analysis using the inverse variance method. The heterogeneity across the studies were examined using chi-square, and the degree of heterogeneity was assessed using the I2 statistic. A random-effects model was used when significant heterogeneity was present, and a fixed-effects model was used when absent. If a study provided both unadjusted and adjusted effect measures, the ones with full adjustment were used for meta-analysis. Publication bias was assessed by visually inspecting the funnel plots. Sensitivity and subgroup analyses were not possible due to the small number of included studies.
The results of the systematic review and the study selection processes were presented in Figure 1. The systematic search of the literature found 290 studies, of which 278 studies were excluded by title screening. Among twelve studies left, 8 studies and 1 study were further excluded due to not providing sufficient data and using the same cohort, respectively. Finally, three studies were included for this review, among which two studies were used for meta-analysis. One study was excluded since it used frequency of fruit and vegetable consumption.
Table 1 presents the summary of included studies. Three studies used quantity of fruit and vegetable consumption. A recent US study used data of 78,336 older female nurses from the Nurses’ Health Study in the US and examined risk of incident frailty (23). They found that those who consumed 7 or more servings of fruit and vegetables per day had a significantly decreased risk than those who consumed less than 3 servings per day over 20 years (23). Another study from the England investigated the associations between fruit and vegetable consumption at baseline and risk of developing frailty 4 years later in 2,634 non-frail older men and women, however, failed to find any significant associations (24). The third study used three cohorts of older adults (1 from Spain and 2 from France), and two of them showed that those consuming 5 or more portions of fruit and vegetables a day had a significantly higher risk of developing frailty compared with those consuming less than 1 portions a day, and the other showed non-significant results (25). The food assessments were either self-administered questionnaires (23-25) or questionnaires with a help of trained research assistant (25).
aHR: Adjusted hazard ratio; aOR: Adjusted odds ratio; BMI: Body mass index; ELSA: English Longitudinal Study of Ageing; FFQ: Food Frequency Questionnaire; MMSE: Mini-Mental State Examination; Senior-ENRICA: Study on Nutrition and Cardiovascular Risk Factors in Spain
Methodological quality assessment
Three studies (23-25) were evaluated using the Newcastle-Ottawa scale for cohort studies and were considered to have adequate methodological quality, with the mean score of 6.8 (range=6-8).
Fruit and vegetable consumption and incident frailty risk
OR of incident frailty risk according to fruit and vegetable consumption (combined) were provided from four cohorts (3 cohorts in 1 study (25) and 1 cohort in another study (24); Figure 2A). The OR for the highest category of fruit and vegetable consumption compared with the lowest category were combined using the fixed-effects meta-analysis. The highest fruit and vegetable consumption was significantly associated with lower risk of incident frailty (pooled OR=0.38, 95%CI=0.24-0.59, p=<0.001) than the lowest consumption. The degree of heterogeneity across the included cohort data was low (I2=0%).
AMI: Integrated Multidisciplinary Approach cohort, CI: confidence interval, IV: inverse variance, SE: standard error
The meta-analysis was repeated for fruit and vegetable alone separately (Figures 2B and 2C). Although the highest vegetable consumption was significantly associated with decreased risk of incident frailty (pooled OR=0.54, 95%CI=0.32-0.91, p=0.02; Figure 2C), there was no significant association observed between fruit and incident frailty risk (pooled OR=0.75, 95%CI=0.35-1.60, p=0.46; Figure 2B). It was not possible to properly assess the publication bias due to the small number of the included cohorts.
This study systematically searched the literature for associations between fruit and vegetable consumption and incident frailty risk and was able to provide the pooled evidence that higher fruit and vegetable consumption is associated with lower risk of incident frailty among community-dwelling older adults.
We found a few studies focusing on frequency of consuming fruit and vegetable, or vegetable alone (26-28). Two studies using the British Whitehall II study cohort, consisting of middle-aged civil servants aged 35-55 at recruitment showed similar results. In the first study, consuming fruit and vegetables at least twice a day when 50 years old was associated with a decreased risk of frailty 20 years later compared with consuming less than once a day (adjusted HR=0.70, 95%CI=0.53-0.92) (26). It should be noted that this study did not examine frailty status at baseline, although prevalence of frailty at the age of 50 would have been very low (26). The second study of the Whitehall II cohort showed that those consuming fruit and vegetables less than daily at the age of 45-55 had significantly higher risk of developing frailty approximately 18 years later compared with those consuming more than daily (adjusted OR=1.29, 95%CI=1.05-1.58). A Swedish study conducted a secondary data analysis of 371 independent community-dwelling Swedish men and women aged 80 years or older who participated in a randomized trial designed to evaluate the effects of a preventive home visit and multi-professional senior group meetings (28). According to this study, frequency of vegetable intake at baseline was not significantly associated with frailty risk at any time points: baseline, 12 months, or 24 months (Unadjusted OR=1.22, 95%CI=0.86-1.73 at 1 year, unadjusted OR=1.03, 95%CI=0.71-1.49 at 2 years) (28). Potential limitations of the discussed studies may include a small sample size, unadjusted effect measures, selection bias, and a relatively short study period.
“Inflammaging” is referred to an age-related low-grade chronic inflammation status and has been considered to be associated with the development of frailty (29). Multiple studies showed that those who are frail have significantly higher levels of inflammatory markers than those who are not (29). Another possible cause of frailty is oxidative stress. The oxidative stress plays an important role in the aging process and is associated with accelerated aging. Previous studies showed that frailty was associated with higher oxidative stress and lower anti-oxidative parameters (30). Fruit and vegetables are rich in flavonoids, which form a group of natural products with various phenolic structures and are known for their health-beneficial effects, including anti-inflammatory and anti-oxidative characteristics (31). These properties may be attributed to the decreased risk of developing frailty.
In the meta-analysis, fruit consumption only was not associated with incident frailty. Since high degree of heterogeneity was observed, a random-effect meta-analysis was used. In a sensitivity analysis, excluding one study showing very high OR (24) significantly decreased the heterogeneity from 69% to 0%. A meta-analysis involving the remaining three cohorts showed that the highest fruit consumption group had a significantly lower risk of incident frailty (pooled OR=0.51, 95%CI=0.31-0.83, p<0.01). These findings suggest that the results of the meta-analysis of the fruit consumption and incident frailty may not be robust and that it is not necessarily true that fruit is not associated with a lower incident frailty risk.
The current review has potential limitations. First, the number of cohorts included in the meta-analysis were relatively small. However, the result of the meta-analysis showed the significant inverse association between fruit and vegetable consumption and incident frailty risk was persistent and that the degree of heterogeneity was low. Second, a systematic search of the literature was conducted using PubMed only, therefore, some important studies may have been missed. Nonetheless, the chance may be limited since the comprehensive search strategy with an extensive array of search terms, including MeSH terms, was applied and the reference list of the relevant papers was scrutinized.
This study has multiple strengths. First, the robust search protocol was developed following the PRISMA statements. Second, the comprehensive search strategy, including screening done by two researchers independently, assessment of heterogeneity and methodological quality. In addition, it was possible to perform the meta-analysis and show the significant inverse association between fruit and vegetable consumption and incident frailty risk.
This systematic review and meta-analysis provided the pooled evidence that high fruit and vegetable consumption may be beneficial for preventing the development of frailty in older adults. As increasing fruit and vegetable consumption is feasible and relatively cheap without significant side effects, this can be a relevant strategy to prevent frailty. Randomized controlled trials are warranted to confirm the positive effects against frailty (32, 33).
Funding: We had no specific funding to support this study.
Conflict of interests: All authors declare no conflict of interest.
Acknowledgment: We are grateful to the authors who provided additional data.
Ethical standards: This systematic review and meta-analysis study was conducted according to the PRISMA guidelines and the prespecified protocol was registered at PROSPERO.
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