{"id":57941,"date":"2024-06-25T11:56:14","date_gmt":"2024-06-25T11:56:14","guid":{"rendered":"https:\/\/biomedpharmajournal.org\/?p=57941"},"modified":"2024-07-03T16:42:20","modified_gmt":"2024-07-03T16:42:20","slug":"a-systematic-review-and-meta-analysis-of-kiwifruits-impact-on-functional-constipation","status":"publish","type":"post","link":"https:\/\/biomedpharmajournal.org\/staging\/vol17no2\/a-systematic-review-and-meta-analysis-of-kiwifruits-impact-on-functional-constipation\/","title":{"rendered":"A Systematic Review and Meta-Analysis of Kiwifruit\u2019s Impact on Functional Constipation"},"content":{"rendered":"\n

Introduction<\/strong><\/p>\n\n\n\n

Functional constipation occurs when the waste\ndisposal system does not function correctly without comorbidities and medication\nside effects. This type of constipation can be caused by slow food transit and\nobstruction in the gastrointestinal tract 1<\/sup>. According to a systematic review of\npatients with constipation from 1990 to 2020, the prevalence of functional\nconstipation was 15.3% 2<\/sup>. Meanwhile, a study conducted in Japan with\n5,155 participants reported that the incidence of functional constipation was\n52.2% compared to other types of chronic constipation 3<\/sup>. Dietary adjustment and lifestyle\nmodification can serve as effective preventive measures and alternatives to\npharmacological medications, which may entail potential side effects like\nmagnesium toxicity, cramping, and nutrient malabsorption4,5<\/sup>. By\nimplementing these changes, individuals can help prevent the onset of this\ndisorder and alleviate constipation without relying solely on medication5,6<\/sup>. Dietary\nfiber, categorized as a type of bulk laxative medication, is widely regarded as\nthe safest treatment option when compared to other classes of laxatives4<\/sup>. As a\nresult, it is highly recommended for effectively managing functional\nconstipation. Fiber can enhance stool water retention, create gel-like\nsubstances to lubricate the stool, increase stool volume, and stimulate\nperistalsis, aiding in regular bowel movements 2<\/sup>. In addition to fiber, certain functional\nfoods like psyllium and wheat bran can contribute to maintaining a healthy gut.\nIt is noteworthy that multiple studies have consistently recommended whole\ngreen kiwifruit as an effective remedy for relieving constipation over an\nextended period of time7\u201310<\/sup>. <\/p>\n\n\n\n

Kiwifruit belongs to the genus Actinidia and\ncontains about 1.4 – 3 g of fiber per 100 g, with one-third soluble fiber and\ntwo-thirds insoluble fiber 7<\/sup>. The most common kiwifruit species are Actinidia\ndeliciosa <\/em>and Actinidia\nchinensis<\/em>, known as green and gold kiwifruit, respectively. In\naddition to fiber, kiwifruit also contains vitamins, minerals, phytonutrients,\nand proteins, including actinidin, a natural proteolytic enzyme that helps in\nprotein breakdown and digestion 7,11<\/sup>. Numerous randomized controlled trials\n(RCTs) showed that kiwifruit can enhance bowel movement frequency, with\nconflicting results 12\u201314<\/sup>. Therefore, this systematic review and\nmeta-analysis was undertaken to provide an up-to-date study on the\neffectiveness of kiwifruit in <\/p>\n\n\n\n

treating functional constipation symptoms. The scope of this research included kiwifruit\nspecies, namely Actinidia chinensis <\/em>var.\ndeliciosa, which consists of both green and gold kiwifruit.<\/p>\n\n\n\n

Methods<\/strong><\/p>\n\n\n\n

Research Design<\/strong><\/p>\n\n\n\n

We prepared this\nmeta-analysis using the Cochrane Handbook for Systematic Reviews of\nInterventions as a guideline.15<\/sup>. The results were\nreported according to the Preferred Reporting Items of Systematic Reviews and\nMeta-Analysis (PRISMA) statement.<\/p>\n\n\n\n

Eligibility Criteria <\/strong><\/p>\n\n\n\n

Using the population, intervention, comparator, and outcome (PICO)\napproach, participants were chosen based on inclusion criteria. The inclusion criteria\nwere healthy patients with functional constipation aged \u2265 18 years and no\nhistory of comorbidities. Meanwhile, the intervention criteria were kiwifruit\nin whole fruit or supplement form, non-combination, with the placebo or without\ntherapy as the comparator. The primary outcome was bowel movement, with\ndefecation frequency as the measured parameter. The secondary outcome included\nstraining events, stool texture, and side effects of kiwifruit. This analysis\nfocused on studies with both parallel and crossover RCT designs. Meanwhile,\nstudies that did not comply with predetermined PICO criteria, including those\ninvolving patients taking laxatives or dietary fiber supplements, were\nexcluded.<\/p>\n\n\n\n

Literature Search<\/strong><\/p>\n\n\n\n

A research librarian guided the search protocol for this review.\nLiterature searches were conducted until May 2023 on several databases,\nincluding Cochrane Central Register of Controlled Trials (CENTRAL), Medline,\nScience Direct, and ProQuest.For the Medline, CENTRAL, and Proquest databases,\nthe exact MeSH terms used included: ((((((actinidia[MeSH Terms]) OR\n(Actinidia*[Title\/Abstract])) OR (kiwifruit[Title\/Abstract])) OR\n(kiwi[Title\/Abstract])) OR (“Actinidia chinensis”[Title\/Abstract]))\nOR (“Actinidia deliciosa”[Title\/Abstract]) AND (randomizedcontrolledtrial[Filter]))\nAND ((constipation[MeSH Terms]) OR (constipation[Title\/Abstract])). RCT was\nused as a filter for Medline, whereas books, book <\/p>\n\n\n\n

chapters, conference papers and proceedings, dissertations and theses,\narticles, evidence-based healthcare, and other sources were used as filters for\nProquest. Meanwhile, for the Science Direct database, we used exact keywords as\nfollows: (Actinidia OR kiwifruit OR kiwi OR “Actinidia chinensis” OR\n“Actinidia deliciosa”) AND (constipation). For an additional search, we conducted a hand\nsearch via the Google Scholar database to find related articles. <\/p>\n\n\n\n

Selection\nof Studies and Data Extraction<\/strong><\/p>\n\n\n\n

To\nassess the feasibility of research that satisfied the inclusion criteria, two\nresearchers independently reviewed the title, abstract, and contents of\nfull-text papers. The selected studies were tabulated based on PICO analysis.\nRelated interventions were mentioned in detail regarding species and varieties\nof kiwi fruit, dosage form, dosage, and frequency of interventions. The flow\nfrom the literature searches to the study selection was carried out following\nthe guidelines from the PRISMA, and any discrepancies were explored until an\nagreement was reached.<\/p>\n\n\n\n

Qualitative Analysis<\/strong><\/p>\n\n\n\n

Two\nresearchers independently analyzed the quality of each RCT study by conducting\ncritical appraisals based on Cochrane Review guidelines. The qualitative\nanalysis was carried out using the Risk of Bias 2 (RoB2) instrument, and the\nrisk of bias was evaluated across six major domains. For parallel RCT studies,\nthe five domains included were the randomization process, deviations from the\nintended intervention, missing outcome data, measurement of the outcome, and\nselection of the reported result. Furthermore, period and carryover effects, or\nDomain S, were assessed as additional domains for cross-over RCT studies.\nQuestions from each domain can be answered with multiple choices, such as \u201cYes,\u201d\n\u201cProbably Yes,\u201d \u201cNo,\u201d \u201cProbably No,\u201d or \u201cNo Information.\u201d The overall risk of\nbias criteria was expressed as \u201cLow\u201d for the low RoB, \u201cSome Concerns\u201d for some\ndomains that need attention but are not in the form of a high RoB, and \u201cHigh\u201d\nfor the high RoB. GRADE tool was used in systematic reviews to assess\nthe quality of an evidence body. This tool graded the RoB, indirectness, inconsistency, the risk of\npublication bias, and imprecision. The conclusion of the GRADE was reflected in\nthe certainty level, which started from very low to high certainty 16<\/sup>.<\/p>\n\n\n\n

Quantitative Analysis<\/strong><\/p>\n\n\n\n

The\nmeta-analysis was conducted using the fixed-effect model generated from the\nCochrane Collaboration’s Review Manager software version 5.4.1, and the\nincluded studies were displayed through a forest plot. The results were\npresented as a weighted mean difference (WMD) or standardized mean difference\n(SMD) for continuous outcomes. For continuous data on the same scale, weighted\nmean difference (WMD) was used to present the overall meta-analysis result, and\n95% confidence intervals (CI95%) were applied. Heterogeneity was also evaluated\nand presented as I2<\/sup>>50%. <\/p>\n\n\n\n

Results and Discussion<\/strong><\/p>\n\n\n\n

Selection of Studies<\/strong><\/p>\n\n\n\n

The literature search was conducted until May 2023 using the 2020 PRISMA flowchart guide, which was divided into three flow sections: identification, screening, and inclusion, as presented in Figure 1. Numerous studies were excluded for several reasons, including irrelevant reporting outcomes, participants who also had comorbid irritable bowel syndrome, used non-placebo comparators, had unfinished clinical trials, and originated in the same trial. Databases yielded information on 160 studies in total. After critically appraising the individual studies, five studies were selected for systematic review and meta-analyses by considering feasibility study, inclusion, and exclusion criteria. <\/p>\n\n\n\n\n\n
\"\"<\/td>\n\n

Figure 1: PRISMA Flowchart<\/strong><\/p>\n

<\/p>\n

Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n

Characteristic of Studies<\/strong><\/p>\n\n\n\n

The characteristics of each selected study are displayed in Table 1. From 2002 to 2018, the research included four cross-over RCT studies and one parallel RCT study. This study involved 175 subjects: 93 from a cross-over study and 82 from a parallel study design. There were more female subjects than males in the overall RCT studies. All participants in each study were healthy individuals with symptoms of constipation and aged between \u226518 years old. Constipation was characterized as having less than three bowel movements each week, straining at least 25% of the defecation process, and experiencing a minimum of 25% of the bowel movement incompletely. Kiwifruit interventions varied in powder, extract, and whole fruit forms. The duration of the intervention ranged from three days to four weeks. Of the five studies, four utilized green kiwifruit, and one employed green and gold species 12\u201314,17<\/sup>.<\/p>\n\n\n\n\n\n
\"\"<\/td>\n\n

Table 1: Characteristic of Studies<\/strong><\/p>\n

<\/p>\n

Click here to view Table<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n

Qualitative Analysis<\/strong><\/p>\n\n\n\n

We used the RoB2 application to analyze the studies\u2019 quality. Our results indicate that low-risk bias was present in one study, and high-risk bias was present in three studies, as in Table 2 and Figure 2. Among all studies, the highest RoB occurred in deviations from the intended intervention (D2). Finally, low certainty results were obtained after assessing the RoB by the GRADE system, as seen in Table 3.<\/p>\n\n\n\n

Table 2: Risk of Bias (RoB2) Results of Each Study<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n
\n

Study<\/strong><\/p>\n<\/td>\n

\n

D1<\/strong><\/p>\n<\/td>\n

\n

DS<\/strong><\/p>\n<\/td>\n

\n

D2<\/strong><\/p>\n<\/td>\n

\n

D3<\/strong><\/p>\n<\/td>\n

\n

D4<\/strong><\/p>\n<\/td>\n

\n

D5<\/strong><\/p>\n<\/td>\n

\n

Overall Bias<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

Study A<\/strong><\/p>\n

Udani et al. (2013)<\/strong><\/p>\n<\/td>\n

\n

+<\/strong><\/p>\n<\/td>\n

\n

N\/A<\/strong><\/p>\n<\/td>\n

\n

+<\/strong><\/p>\n<\/td>\n

\n

+<\/strong><\/p>\n<\/td>\n

\n

+<\/strong><\/p>\n<\/td>\n

\n

+<\/strong><\/p>\n<\/td>\n

\n

+<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

Study B<\/p>\n

Kindleysides et al. (2015)<\/p>\n<\/td>\n

\n

!<\/p>\n<\/td>\n

\n

+<\/p>\n<\/td>\n

\n

+<\/p>\n<\/td>\n

\n

+<\/p>\n<\/td>\n

\n

+<\/p>\n<\/td>\n

\n

+<\/p>\n<\/td>\n

\n

!<\/p>\n<\/td>\n<\/tr>\n

\n

Study C<\/p>\n

Wilkin-Smith et al. (2019)<\/p>\n<\/td>\n

\n

–<\/p>\n<\/td>\n

\n

+<\/p>\n<\/td>\n

\n

–<\/p>\n<\/td>\n

\n

+<\/p>\n<\/td>\n

\n

–<\/p>\n<\/td>\n

\n

+<\/p>\n<\/td>\n

\n

–<\/p>\n<\/td>\n<\/tr>\n

\n

Study D<\/p>\n

Ansell et al. (2015)<\/p>\n<\/td>\n

\n

+<\/p>\n<\/td>\n

\n

+<\/p>\n<\/td>\n

\n

–<\/p>\n<\/td>\n

\n

+<\/p>\n<\/td>\n

\n

+<\/p>\n<\/td>\n

\n

+<\/p>\n<\/td>\n

\n

–<\/p>\n<\/td>\n<\/tr>\n

\n

Study E<\/p>\n

Rush et al. (2002)<\/p>\n<\/td>\n

\n

!<\/p>\n<\/td>\n

\n

–<\/p>\n<\/td>\n

\n

–<\/p>\n<\/td>\n

\n

+<\/p>\n<\/td>\n

\n

–<\/p>\n<\/td>\n

\n

+<\/p>\n<\/td>\n

\n

–<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Description:     +    Low risk              <\/em>!  Some concerns         <\/em>–  High risk<\/p>\n

DS     Period and carry-over effects<\/p>\n

D1     Randomization process<\/p>\n

D2     Deviations from intended intervention<\/p>\n

D3     Missing outcome \u00dfdata<\/p>\n

D4     Measurement of the outcome<\/p>\n

D5     Selection of the reported result<\/p>\n

N\/A     Parallel group<\/p>\n\n\n\n
\"\"<\/td>\n\n

Figure 2: <\/strong>Overall Results of Risk of Bias (RoB2).<\/strong><\/p>\n

<\/p>\n

Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n\n
\"\"<\/td>\n\n

Table 3: <\/strong>Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) Analysis Results<\/strong><\/p>\n

<\/p>\n

Click here to view Table<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n

Quantitative Analysis<\/strong><\/p>\n\n\n\n

Five studies were analyzed quantitatively regarding defecation frequency as the primary outcome of this study. According to Ansell et al<\/em>., kiwifruit intervention consisted of low-dose green, high-dose green, and gold kiwifruit. Therefore, the outcome values were entered separately in the forest plot. Udani et al<\/em>. displayed outcome scores separately for both the intervention and comparator groups from week 1 to week 4 in the forest plot following the original study 12<\/sup>. Meanwhile, Rush et al<\/em>. displayed two data sets: the preliminary data, including healthy adults, and the main data, including healthy elderly 18<\/sup>. According to the forest plots, the kiwifruit intervention significantly increased defecation frequency (p = 0.0008), with a WMD of 0.07 (95% CI 0.03\u20130.11), as seen in Table 4.<\/p>\n\n\n\n\n\n
\"\"<\/td>\n\n

Table 4: Forest Plot of Defecation Frequency Outcome<\/strong><\/p>\n

<\/p>\n

Click here to view Table<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n

The\ninability to convert studies into forest plots is due to the small amount of\nresearch that expresses secondary outcomes by means, standard deviation (SD),\nor mean standard error (SE) and the fact that not all studies evaluate\nsecondary outcomes. Although some minor side effects, such as flatulence,\nbloating, and nausea, were reported in several studies, no serious side effects\nwere found after consuming kiwifruit. The two RCTs conducted by Wilkinson-Smith\net al<\/em>. and Ansell et al<\/em>. demonstrated non-significant\nadverse effects between groups 13,14<\/sup>.<\/p>\n\n\n\n

The quantitative analysis of five studies showed that kiwifruit significantly increased the frequency of defecation. Our results are similar to the previous study, which included subjects with irritable bowel syndrome (IBS), where kiwifruit was effective in increasing defecation frequency. However, the prior meta-analysis’s studies had a very high level of heterogeneity (I2<\/sup>>50%) 19<\/sup>, while this analysis included more homogenous studies (I2<\/sup>=46%). This indicated that kiwifruit could be recommended in constipation patients without comorbidities to support the role of fibers and actinidin in promoting defecation 7,20<\/sup>. Heterogeneity is also an essential component of meta-analysis to draw overall conclusions 21<\/sup>. <\/p>\n\n\n\n

In this study, we also consider the term clinically\nsignificant, which can be used in which clinically relevant outcomes are used\nto assess the effectiveness of a treatment modality 22<\/sup>.\nDespite statistically significant findings, the therapeutic advantages of\nkiwifruit are negligible. WMD was found to increase defecation frequency by\n0.07, which is not considerably different from the placebo group. The clinical\nimpact of kiwifruit on functional constipation has to be confirmed by more\nclinical studies. <\/p>\n\n\n\n

Regarding quality, these results must be applied carefully; although promising heterogeneity levels exist, some studies had a high RoB. A study with the largest overall number of participants (n = 86) by Rush et al<\/em>. had 68.9% of the overall weight of the defecation frequency outcome, which significantly affected this meta-analysis since it comprised more than half of the overall weighted effect, categorized as high RoB. Meanwhile, the second largest study, with 29.8% of the overall weighted effect, was ranked as low RoB, followed by high bias with 0.8% and 0.3% overall weighted effects from the third and fourth largest studies. Half of the studies had insufficient D2 components of RoB due to a failure in implementing the intervention on several participants to have sufficient power. Studies with D2 insufficiency had several participants drop out, lowering their power and influencing the study\u2019s validity 23<\/sup>. Regarding the D1 component of RoB, the insufficiency was found in three studies, where no detailed explanation about the sequence allocation was shown, including the blinding process of allocation, specifically for the parallel RCT design study. The recipients of the intervention were known to both the participants and the researchers, which can interfere with the results. Two of the studies did not meet the criteria for the D4 component of RoB, and blinding of intervention was not performed. This study also used diary filling as a patient-reported outcome. The absence of patients’ blinding increased impact estimates by an average SD of 0.56 (0.71 to 0.41) when outcomes were patient-reported, as indicated in the systematic review 24<\/sup>, which can cause a potential bias. Regarding the DS component, one cross-over study did not implement a wash-out period that could lead to carry-over effects. <\/p>\n\n\n\n

We carried\nout a GRADE analysis to evaluate the feasibility of this study 25<\/sup>. Our result from the GRADE\nanalysis emphasized the importance of further studies on kiwifruit’s efficacy\nin overcoming constipation symptoms. Serious imprecision and the possibility of\nplausible residual confounding detected in two studies, where diet control\nstill needs to be implemented, could be undiagnosed confounders, thus affecting\nthe measured outcomes 26<\/sup>. <\/p>\n\n\n\n

The\nlimitations of this meta-analysis included the variation between studies’\ndosages and formulations. Regarding\nthe dosage, one study showed that consuming two kiwifruits every day can\nincrease the laxative effect. It is also possible that the Wilkin-Smith et al.\nstudy showed significant results in increasing defecation after participants\nconsumed two kiwifruits with an average weight of 150 g for one kiwi.\nMeanwhile, other studies used smaller doses of kiwifruit 27<\/sup>.\nAlthough subgroup analysis was not\nperformed due to the need for a larger number of studies and data, the\nmeta-analysis of defecation frequency showed considerably low heterogeneity\nbetween studies. Secondly, the inability to perform sensitivity analysis is due\nto the limited number of studies included. To overcome the RoB, performing\nsensitivity analysis is highly recommended. The third weakness of this study is\nthe varied definitions of constipation in the included studies that can\ncause differences among the subjects. ROME III was used in two studies, while\nthe rest did not apply the standardized definition of functional constipation.\nStudies showed that varied definitions might lead to various prevalence 28<\/sup>, which could interfere with the\nstudy results. The fourth\nlimitation is the limited access to EMBASE, which should have enhanced the\ncomprehensiveness of the search. However, since we used the CENTRAL database,\nwhich supports EMBASE29<\/sup>, we anticipated that all\narticles would be noticed. Meanwhile, this limitation was compensated by using\nother databases 30<\/sup>. <\/p>\n\n\n\n

Conclusion<\/strong><\/p>\n\n\n\n

Based on statistical research, daily\ningestion of kiwifruit is regarded safe and may have a considerable impact on\nincreasing the frequency of bowel movements. However, there is no clinical\nevidence to support this claim. Additional research is required to ascertain\nthe clinical and statistical impact of kiwifruit on functional constipation.<\/p>\n\n\n\n

Acknowledgement<\/strong><\/p>\n\n\n\n

Fonny Cokro: Conceptualization, Methodology,\nFormal Analysis, Investigation, Resources, Writing \u2013 Review and Editing<\/p>\n\n\n\n

Ervina Vashti: Methodology,\nInvestigation, Validation, Formal Analysis, Writing \u2013 Original Draft<\/p>\n\n\n\n

Agustina Dwi Retno Nurcahyanti:\nMethodology, Formal Analysis, Investigation, Writing \u2013 Review, and Editing<\/p>\n\n\n\n

Anton Sumarpo: Methodology, Formal\nAnalysis, Investigation, Writing \u2013 Review, and Editing<\/p>\n\n\n\n

Rungnapa Malasao: Methodology, Formal\nAnalysis, Investigation, Writing \u2013 Review, and Editing<\/p>\n\n\n\n

Conflict of Interest<\/strong><\/p>\n\n\n\n

The authors declare there are no\ncompeting interests.<\/p>\n\n\n\n

Funding Source<\/strong><\/p>\n\n\n\n

This research did not receive any\nspecific grant from funding agencies in the public, commercial, or\nnot-for-profit sectors.<\/p>\n\n\n\n

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