Auricular acupressure for constipation in adults: a systematic review and meta-analysis

Introduction: Auricular acupressure (AA) has been widely utilized in the management of constipation, with several studies suggesting its efficacy in treating constipation patients. However, the safety and effectiveness of AA in constipation remain uncertain. Hence, the aim of this study was to assess the effectiveness and safety of AA for constipation. Methods and analysis: A total of eight electronic databases and three clinical trial registration platforms were searched from their inception to April 2023 for randomized controlled trials (RCTs) of AA for constipation. The included studies were appraised for quality using the Cochrane Collaboration’s Risk of Bias Assessment tool. The quality of evidence was assessed by two independent reviewers employing the Grading of Recommendations Assessment, Development, and Evaluation System (GRADE) evaluation tool. Meta-analysis of data and assessment of publication bias were performed using RevMan 5.4 and STATA 13.0 software, respectively. Results: This review included 34 randomized controlled trials conducted between 2007 and 2023, involving 2,465 participants. The findings of the study indicate that overall, AA is significantly associated with improved CSBMs (MD = 1.22, 95% CI [0.68, 1.77], p < 0.0001, I2 = 0%), BSF (MD = 0.72, 95%CI: [0.15,1.28], p = 0.01, I2 = 82%), CAS (MD = -3.28, 95%CI: [−5.95, −0.60], p = 0.02, I2 = 80%), responder rate (RR = 1.27, 95%CI: [1.16, 1.38], p < 0.00001, I2 = 79%), cure rate (RR = 1.84, 95% CI [1.56, 2.15], p < 0.00001, I2 = 0%), and PAC-QOL (MD = −2.73, 95% CI: [−3.41, −2.04], p < 0.00001, I2 = 98%) compared to the control group. However, no difference in PAC-SYM (MD = −0.15, 95%CI: [−0.38,0.07], p = 0.19, I2 = 67%) was found between the two groups. Additionally, there was no significant difference in adverse events (RR = 0.53, 95% CI: [0.24, 1.21], p = 0.13, I2 = 38%). Conclusion: Based on the available evidence, auricular acupressure appears to be a potentially safe and effective intervention for managing constipation in adults. Nonetheless, the overall quality of evidence for the identified outcomes was assessed as low to very low, highlighting the need for additional high-quality randomized controlled trials to further validate these findings. Systematic Review Registration: https://www.crd.york.ac.uk/prospero, identifier CRD42023425033.


Introduction
Constipation, characterized by difficult and infrequent bowel movements accompanied by symptoms like bloating and abdominal pain (Vriesman et al., 2020), has a higher prevalence in older adults due to age-related factors (Barberio et al., 2021).The estimated overall prevalence of constipation in older adults is 18.9% [95% CI (14.7%-23.9%)](Salari et al., 2023).Among the available treatment options, saline laxatives have shown robust evidence of effectiveness (Serra et al., 2020).However, concerns persist regarding the long-term safety of this approach (Serra et al., 2020), as laxative misuse and abuse can lead to weight loss, electrolyte imbalances, laxative dependence, and visceral organ dysfunction (Daniali et al., 2020).Non-pharmacological interventions, such as dietary guidance, regular physical activity, and potty training, are considered the initial management strategy for constipation (Vriesman et al., 2020).Nevertheless, successful implementation of these interventions relies heavily on patient compliance and persistence.Therefore, it is crucial to develop an effective, safe, and feasible therapy to alleviate constipation.
Auricular acupressure (AA) is a non-invasive therapy rooted in Traditional Chinese Medicine (TCM) that involves applying pressure to specific acupoints on the ear using Vaccaria seeds or magnetic pellets.AA offers several advantages over other therapies, including affordability, painlessness, and high patient acceptance.Under the guidance of a doctor, patients can easily complete the treatment procedure.Each organ in the body has a reflex point on the outer ear's surface, and acupoint stimulation aims to restore balance between yin and yang, harmonize the flow of vital energy (qi) and blood, and alleviate various ailments within the body (Zhu, 2014).The vagus nerve plays a crucial regulatory role in controlling smooth muscle contractions and glandular secretions in the intestines (Breit et al., 2018).AA may potentially have a similar effect on constipation as auricular vagal nerve stimulation (Shi et al., 2021;Zhang et al., 2021).
Several clinical studies have found it to be effective in treating constipation (Li et al., 2014;Shin and Park, 2018;Jung and Chang, 2020;Aminizadeh et al., 2023).To date, two systematic reviews (SRs) have been published demonstrating that AA can be used for the treatment of constipation in leukemia patients undergoing chemotherapy (Chen et al., 2018a;Jing et al., 2018a), however, both reviews included only five studies, and the overall quality of evidence was low.The safety and efficacy of AA on constipation are still unclear, hence a SR and metaanalysis regarding AA for constipation is necessary.Consequently, we aimed to evaluate the efficacy of AA for constipation through this meta-analysis of randomized controlled trials (RCTs) to provide evidence-based support for managing constipation.

Methods
This study was conducted in accordance with the PRISMA 2020 statement: an updated guideline for reporting systematic reviews.(Page et al., 2021).and the PRISMA for acupuncture checklist (Wang et al., 2019).The study was registered on the PROSPERO website (https://www.crd.york.ac.uk/prospero/) with the registration number: CRD42023425033.

Inclusion criteria
(1) Types of studies: Only RCTs with parallel group designs published in English or Chinese were included in this study.Non-RCTs, such as controlled before-and-after studies, historically controlled studies, cohort studies, and crosssectional studies, among others, were excluded.
(2) Types of participants: Adult patients (ages 18 years or older) who meet the diagnostic criteria of functional constipation Rome II (Drossman, 1999), Rome III (Drossman, 2006), Rome Ⅳ (Drossman, 2016) or other recognized diagnostic criteria were included, regardless of gender, age and race.Pregnant and lactating women were excluded in this study.
(3) Types of interventions: Auricular acupressure, defined as the application of pressure to ear acupoints using metallic beads (or actual seeds, ceramic beads, or magnetic beads), was considered.
The study included the use of auricular acupressure alone in the experimental group or in combination with the treatment in the control group.Other acupuncture therapies, such as manual acupuncture, electrical acupoint stimulation, acupoint embedding needle, and acupoint application, were excluded.

Data sources and search strategy
A comprehensive literature search was conducted from the inception of the databases until April 2023.The search was limited to articles published in Chinese and English.Eight electronic databases were searched, including four Chinese databases: China National Knowledge Infrastructure (CNKI), Wanfang, Cqvip (VIP), and Chinese Biomedical (CBM); and four English databases: PubMed, Embase, CENTRAL (Cochrane Central Register of Controlled Trials), and Web of Science.Additionally, three clinical trial registration platforms were searched: World Health Organization (WHO) International Clinical Trials Registry Platform (http://www.who.int/ictrp/en/),Chinese Clinical Trial Registry (http://www.chictr.org/en/),and ClinicalTrials.gov(https://www.clinicaltrials.gov/).The detailed retrieval process is provided in the Supplementary Material S1.

Study selection
Using NoteExpress 3.2.0, the literature retrieved from the different databases was imported, and duplicate records were identified and removed.Two independent researchers conducted an initial screening of titles, abstracts, and other relevant information.Following the initial screening, the full texts of potentially eligible studies were obtained, and the two researchers independently assessed the full texts against the predefined inclusion and exclusion criteria.In cases of disagreement between the two researchers, a third reviewer was consulted to resolve discrepancies and make a final decision.A PRISMA flowchart illustrating the study selection process is included as Figure 1.

Data extraction and management
Data was independently extracted by two reviewers using a standardized form, which including the following elements: basic information (title, year of publication, first author, language, country

Risk of bias assessment
Two independent reviewers evaluated the quality of the included studies using the Cochrane Collaboration's Risk of Bias Assessment tool (Cumpston et al., 2019).This assessment covered several domains, including random sequence generation (selection bias), allocation concealment (selection bias), blinding of participants and personnel (performance bias), blinding of outcome assessment (detection bias), incomplete outcome data (attrition bias), selective reporting (reporting bias), and other potential sources of bias.For instance, in the assessment of random sequence generation, the use of pseudo-random methods such as consultation dates, dates of birth, or ID numbers was considered a "high risk" of bias, while the use of true random methods such as simple random number tables or computerized random number generation was regarded as "low risk" of bias.If no specific method of randomization was stated, the risk was classified as "unclear."

Confidence in cumulative evidence
The Grading of Recommendations Assessment, Development, and Evaluation System (GRADE) evaluation tool (Guyatt et al., 2011) was independently used by two reviewers to assess the quality of evidence in terms of five dimensions: risk of bias, inconsistency, indirectness, imprecision, and publication bias.The quality of evidence will be classified as high, moderate, low, or very low.In the event of any disagreement, a third reviewer will be consulted to facilitate consensus.

Assessment of heterogeneity
Statistical heterogeneity between studies was considered acceptable when p ≥ 0.1 or I 2 ≤ 50%.p < 0.1 or I 2 >50% means that the statistical heterogeneity is deemed significant, indicating the need for an analysis to identify the source of the heterogeneity.Sensitivity analysis or subgroup analysis was used for the assessment.

Data synthesis
In this study, RevMan software (version 5.4, the Nordic Cochrane Centre, Copenhagen, Denmark) was used for data synthesis and analysis.Mean difference (MD) was employed as the effect size for continuous variables, while relative risk (RR) was used for dichotomous variables.The 95% confidence interval (CI) was calculated.A significance level of p < 0.05 was considered statistically significant.Statistical heterogeneity was assessed using chi-squared tests and the Higgins I 2 test.If p ≥ 0.1 and I 2 ≤ 50%, indicating a high degree of homogeneity, a fixed-effects model was applied for the pooled analysis.Conversely, if p < 0.1 or I 2 > 50%, indicating a significant degree of heterogeneity, a random-effects model was used.Significant clinical heterogeneity was addressed through methods such as subgroup analysis, sensitivity analysis, or a narrative summary if necessary.If the outcome data could not be pooled for meta-analysis, a narrative summary was provided instead.If there was significant heterogeneity between studies and the data were available, subgroup analyses were performed based on the varying characteristics of the included studies.If more than 10 studies were included in the analysis, the funnel plot method was used to assess publication biases.Additionally, an Egger's test was conducted to further evaluate publication bias.The analysis for publication bias was performed using STATA software (version 16.0, Stata Corp LP, United States).A significance level of p < 0.05 was considered indicative of significant publication bias.

Study selection
A total of 2,632 potentially relevant articles were identified through a systematic search across eight databases and three clinical trial registration platforms.

Risk of bias
All the included studies mentioned the term "randomized" or "random" in their methodology.One of the RCTs (Shin and Park, 2018)included in the study implemented concealed allocation and received a "low risk" rating for allocation concealment.The majority of the included RCTs received an "unclear" rating for blinding of participants and personnel, with the exception of two studies (Li et al., 2014;Aminizadeh et al., 2023) that utilized a sham AA procedure.One (Li et al., 2014) of the RCTs included in the study implemented blinding of outcome assessment and received a "low risk".Two studies (Ji et al., 2015;Wang et al., 2022) were classified as "high risk" due to without providing a description of the reasons for dropout.In terms of other biases, four studies were classified as high risk.Among them, two studies (Liu et al., 2011;Li et al., 2018) did not report baseline consistency, and two studies (Yang and Fu, 2013;Qu and Ye, 2016) did not report treatment duration.The detailed results are depicted in Figure 2.

Meta-analysis
The summary of the meta-analysis results is provided in Table 2, with a detailed explanation below.

FIGURE 3
Meta-analysis and forest plot for PAC-SYM.
2023; Xu, 2023) mentioned adverse events, of these, one study (Aminizadeh et al., 2023) could not be included for meta-analysis due to poor description.The results of meta-analysis showed AA alone or in combination with other treatments was equally safe compared to other treatments (RR = 0.53, 95% CI: [0.24, 1.21], p = 0.13, I 2 = 38%) (Figure 11).The adverse reactions were mostly minor, such as skin lesions or itching at the site of pressure, which typically resolved within a few days.

FIGURE 4
Meta-analysis and forest plot for CSBMs.

FIGURE 5
Meta-analysis and forest plot for BSF.

FIGURE 6
Meta-analysis and forest plot for BSF (a study has been excluded).

FIGURE 7
Meta-analysis and forest plot for CAS.

FIGURE 8
Meta-analysis and forest plot for responder rate.
Frontiers in Physiology frontiersin.org14 Jiang et al. 10.3389/fphys.2023.12576603.5 Quality of evidence Table 3 presents the quality evaluation of each outcome of AA on constipation.The GRADE system was used to assess the evidence quality based on different intervention measures.The results revealed one outcome with moderate-quality evidence, nine with low-quality evidence, seven with very low-quality evidence, and no evidence with high quality.Most studies had limitations in their experimental design, such as inadequate description of random sequence generation, allocation concealment, and blinding.Consequently, they were downgraded.Additionally, the presence of publication bias in most studies contributed to their downgrading.Frontiers in Physiology frontiersin.org15

Reporting bias
Due to the limited number of studies reporting outcome results, funnel plots and Egger's tests were conducted only for response rate and cure rate.The funnel plot of included studies on responder rate displays an asymmetrical distribution, with four studies lying outside the pseudo 95% CI, indicating significant publication bias (Figure 12A).The funnel plot of included studies on cure rate indicates a roughly symmetrical distribution, suggesting a certain degree of publication bias and the presence of a small sample size effect (Figure 12B).Egger's tests revealed significance levels of p < 0.05 for both response rate (p = 0.00) and cure rate (p = 0.003) (Figure 13).

FIGURE 11
Meta-analysis and forest plot for adverse events.
Constipation, a prevalent gastrointestinal condition, is characterized by persistent difficulties in bowel movements, incomplete defecation, and decreased frequency of bowel movements.This condition significantly impacts patients' daily lives and can impair social functioning, leading to work or education limitations in a considerable proportion of individuals (Rao et al., 2007).Initial management strategies for constipation in both children and adults typically involve non-pharmacological approaches, as they have demonstrated beneficial effects in many cases (Daniali et al., 2020;Vriesman et al., 2020).AA, a non-invasive and non-pharmacological treatment modality, has gained widespread utilization for managing various chronic conditions, including constipation.Several studies have reported positive outcomes of AA in alleviating constipation symptoms (Li et al., 2014;Shin and Park, 2018;Jung and Chang, 2020;Aminizadeh et al., 2023).However, the safety and efficacy of AA for constipation in adults remain uncertain.
As is widely known, SRs and meta-analyses generate the highest level of clinical evidence (Izzo et al., 2016).Therefore, we conducted this study to assess the efficacy and safety of AA for constipation in adults.Overall, our study revealed statistically significant differences between the AA and control groups in terms of CSBMs, BSF, CAS, PAC-QOL, responder rate and cure rate, whereas it showed no statistical difference in PAC-SYM.However, when comparing AA with sham AA, AA could significantly reduce the PAC-SYM score (MD = -3.04,95% CI: [-0.49, −0.19], p < 0.0001).These findings suggest that AA has the potential to alleviate constipation symptoms, increase the frequency of spontaneous bowel movements, improve stool consistency, and enhance overall quality of life.These results are consistent with previous studies examining the effects of AA on constipation in leukemia patients undergoing chemotherapy (Chen et al., 2018a;Jing et al., 2018a).Adverse events reported in seven studies were primarily mild, such as itching at the application site, with no serious adverse reactions documented.
It is worth noting that various outcome measures have been employed to assess the efficacy of constipation treatments.Some measures focus on single-item scores related to constipation (e.g., CSBMs), while others provide a comprehensive evaluation of different aspects of constipation (e.g., CAS).However, certain measures may not precisely reflect specific treatment efficacy, such as response rate or cure rate.To ensure the selected measures adequately capture the effectiveness of constipation treatments, future studies are recommended to include CSBMs per week as one of the outcome measures.This measure provides a straightforward and intuitive reflection of treatment effectiveness and has been widely adopted in recent high-quality clinical studies (Camilleri et al., 2022;Rao et al., 2023;Wang et al., 2023).In our study, AA was found to increase the number of complete spontaneous bowel movements [MD = 1.22,95% CI (0.68, 1.77), p < 0.0001], with low heterogeneity (I 2 = 0%).AA, derived from traditional Chinese Medicine (acupuncture), focuses on manipulating specific acupoints on the ear to achieve therapeutic effects.This technique is based on the concept of Qi, the vital energy flow within the body.Through applying pressure to these acupoints, practitioners aim to regulate Qi and restore balance (Yang et al., 2013).During auricular acupressure, individuals may experience sensations such as soreness, tingling, or numbness, indicating the activation of acupoints and the desired therapeutic response.Among the included studies, only one study (Li et al., 2014) did not require pressure application to achieve the intended stimulation of Qi.In most other studies, participants were instructed to apply pressure 3-5 times daily.This practice is widely accepted in China (Bao et al., 2017).Furthermore, based on the included research findings, AA involves applying pressure to the acupoints on one side at a time and alternating between both sides.However, there is considerable variation in treatment duration among the studies, ranging from 1 week to 8 weeks.Further research is needed to evaluate the optimal duration and effectiveness of AA.The selection of ear acupoints primarily follows the TCM Zang-fu theory (Liu et al., 2021).The most frequently used acupoints include the Large Intestine and Rectum points to increase intestinal peristalsis, the Spleen point to strengthen transportation and transformation functions, and the San Jiao point to regulate the flow of qi and fluid in the body.When these points are used together, they are believed to promote smooth qi flow in the Large Intestine, ensuring normal transmission function.
However, it is important to acknowledge the limitations of this study.The variations in selected acupoints, comorbid conditions, treatment courses, and number of compressions may introduce significant clinical heterogeneity.Additionally, the restriction to English and Chinese clinical trials may introduce publication bias, as only four out of the 35 included studies were published in English.Most studies did not provide specific details regarding randomization, allocation concealment, and blinding methods, and some failed to comprehensively report trial details according to standard reporting guidelines such as CONSORT.As a result, the quality of evidence for the majority of outcomes was deemed low or very low.

Conclusion
Our findings suggest that AA may be a safe and effective treatment for constipation in adults to improving symptoms of constipation and increasing the frequency of spontaneous bowel movements.Nevertheless, it is important to note that the current evidence quality is considered insufficient, and further validation is required through a greater number of high-quality RCTs.
The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.

FIGURE 1
FIGURE 1PRISMA flow diagram of the study selection process.

FIGURE 2
FIGURE 2 Risk of bias of RCTs (A) Risk of bias summary; (B) Risk of bias graph.
mean difference; RR, risk ratio; CI, confidence interval; T, test group; C, control group; F, fixed effects model; R, random effects model; PAC-SYM, Patient Assessment of Constipation-Symptom; CSBMs, Complete spontaneous bowel movements; BSF, bristol stool form; CAS, constipation assessment scale; PAC-QOL, Patient Assessment of Constipation-Quality of Life questionnaires; AA, auricular acupressure; UC, usual care; CT, conventional treatment; RCT, randomized controlled trial.

FIGURE 9
FIGURE 9Meta-analysis and forest plot for cure rate.

FIGURE 10
FIGURE 10Meta-analysis and forest plot for PAC-QOL.

FIGURE 12
FIGURE 12Funnel plots of included studies on responder rate (A), cure rate (B).

TABLE 1
Basic characteristics of the included studies.

TABLE 2 (
Continued) Summary of meta-analysis results.

TABLE 3
Quality of evidence included RCTs by GRADE.
MD, weighted mean difference; RR, risk ratio; CI, confidence interval; PAC-SYM, Patient Assessment of Constipation-Symptom; CSBMs, Complete spontaneous bowel movements; BSF, bristol stool form; CAS, constipation assessment scale; PAC-QOL, Patient Assessment of Constipation-Quality of Life questionnaires; AA, auricular acupressure; P, p-value represents clinical significance; T, test group; C, control group; F, fixed effects model; R, random effects model; GRADE, grades of recommendation, Assessment, Development, and Evaluation; Very low, very low quality; Low, low quality; Moderate, Moderate quality.