A Meta-analysis of Traditional Chinese Medicine constitution distribution in people with functional constipation

Abstract

OBJECTIVE:

To investigate the distribution of Traditional Chinese Medicine (TCM) constitution among individuals with functional constipation, which would provide insights for developing constitution-targeted prevention and treatment strategies.

METHODS:

A systematic search was conducted across eight databases (China National Knowledge Infrastructure Database, Wanfang Database, China Science and Technology Journal for Chinese Technical Periodicals, SinoMed, PubMed, Web of Science, Embase, and the Cochrane Library) to identify relevant observational studies assessing Traditional Chinese Medicine (TCM) constitution types among people with functional constipation. The protocol for this review has been registered on International Prospective Register of Systematic Reviews (registration number: CRD42022345996).

RESULTS:

A total of sixteen cross-sectional studies involving 2976 participants were included in this review. Among functional constipation patients, the proportions of Yin-deficiency, Yang-deficiency, and Qi-deficiency constitution were 27.0% [95% confidence interval (CI) 19.9% to 36.7%], 25.2% (95% CI 17.5% to 35.0%) and 23.7% (95% CI 15.8% to 34.0%), respectively. Besides, females accounted for a higher percentage of the population with functional constipation in the included studies, and most patients were aged 45 years or older. These findings may reflect the demographic characteristics of the general functional constipation population, where older adults and women are more commonly affected. The impact of gender and age on TCM constitution distribution merits further exploration.

CONCLUSION:

Our finding revealed that Yin-deficiency, Yang-deficiency, and Qi-deficiency are the predominant TCM constitution types in people with functional constipation. This study suggests that clinicians should focus on patients with these TCM constitution types in the prevention and management of functional constipation. Larger sample sizes and more rigorous methodological designs are needed in future studies. Furthermore, future researches should also focus on developing individualized prevention and treatment strategies based on different TCM constitution types.

1. INTRODUCTION

With changes in modern lifestyle, constipation has gradually become a common gastrointestinal condition.^1,2 The incidence of functional constipation (FC) is rising, with a global prevalence ranging from 8.6% to 11.6% among adults.^3,4 FC is a functional bowel disease that excludes organic causes, and its main clinical manifestations include reduced stool frequency (usually three times a week or less), dry stool, persistent difficulty, frequent or incomplete defecation.^5-7 This condition is often chronic, prone to relapse and associated with unsatisfactory treatment outcomes despite repeated interventions.⁶ FC not only adversely affects quality of life and psychological health, but may also give rise to systemic complications like cardiovascular and neurological disorders.⁸ In addition, the substantial economic burden on society caused by FC cannot be overlooked.^6,8-9

In recent years, the significant role of Traditional Chinese Medicine (TCM) in disease prevention has been confirmed, and it has been widely utilized across many countries worldwide.^10,11 According to TCM constitution theory, each individual has a unique body constitution.⁷ TCM constitution is influenced by various factors, including environmental conditions and personal health status.^1-2,7 Moreover, the efficacy of TCM constitution-based interventions in disease prevention has been empirically validated, and the implementation of these interventions at a national level in China has been integrated into public health management.^10,12 In line with the professional standards issued by the Chinese Association of Traditional Chinese Medicine (CACM) in April 2009, people can be divided into nine TCM constitution types, including balanced constitution (BC), Qi-deficiency constitution (QDC), Yang-deficiency constitution (YADC), Yin-deficiency constitution (YIDC), phlegm-dampness constitution (PDC), damp-heat constitution (DHC), blood-stasis constitution (BSC), Qi-stagnation constitution (QSC) and inherited-special constitution (ISC).³ This standard has been recognized by the national health authorities in China as the official guideline for determining TCM constitution types. TCM theory proposes that constitution can be the internal basis for disease occurrence and can predispose people to pathogenic factors.^1,14 Modern studies have found that TCM constitution can affect the susceptibility to certain diseases and disease prognosis.^1,14,15 In recent years, clinical researches on FC reveal that there may be a potential correlation between certain pathogenic TCM constitution and the incidence of FC.^2,4,8,16-19 The implementation of tailored interventions based on individual constitution types can effectively enhance the prevention and management of functional constipation, as previous studies have shown.^2,4,8,16-19

While the importance of TCM constitution in disease prevention is widely recognized, no systematic studies have yet evaluated the distribution of constitution types in patients with FC.⁶ This knowledge gap impedes the development of targeted prevention strategies in clinical practice. This study aims to systematically assess the distribution of TCM constitution types in FC patients, providing a foundation for constitution-based prevention approaches.

2. METHODS

The protocol of this study has been registered in the International prospective register of systematic reviews with the registration number CRD42022345996. Deviations from the original protocol are presented in the supplementary Table 1.

This study is reported according to the Meta-analysis Of Observational Studies in Epidemiology checklist for Meta-analysis of observational studies,²⁰ which is presented in the supplementary Table 2. Cross-sectional studies are the most appropriate design for describing the distribution of TCM constitution types in specific populations.²¹ Therefore, only cross-sectional studies were included in this study.

2.1. Search strategy

We searched China National Knowledge Infrastructure Database, Wanfang Database, China Science and Technology Journal Database, SinoMed, PubMed, Web of Science, Embase and Cochrane Library from their inception to September 27, 2024. The search terms included “constipation,” “constitution,” “constitution of Traditional Chinese Medicine,” and “constitutional type.” The full search strategies and records for each database are presented in the supplementary Table 3.

2.2. Inclusion criteria

(a) We included studies in which the participants were adults aged 18 years or older who were diagnosed with FC. (b) Acceptable diagnosis criteria included the Consensus on the diagnosis and treatment of functional constipation in the integrative medicine (2017),²² the Rome III Criteria for Functional Constipation (Rome III)²³ and the Rome IV Criteria for Functional Constipation (Rome IV).²⁴ (c) Only cross-sectional studies that assessed the TCM constitution of the participants employing the Constitution in Chinese Medicine Questionnaire (CCMQ) were included.²⁵ (d) The CCMQ was developed based on the "Classification and Determination of Constitution in TCM" standard developed by the Chinese Association of Traditional Chinese Medicine (2009).¹³ Please refer to supplementary Table 4 for the specific content of the CCMQ. (e) Only the earliest published version of duplicate publications was included.

2.3. Exclusion criteria

(a) Conference abstracts. (b) Studies selecting participants with severe complications such as intestinal bleeding and comorbidities, such as coronary heart disease. (c) Studies that were not published in English or Mandarin.

2.4. Study selection and data collection

Two independent reviewers performed title and abstract screening to assess the eligibility of those studies, and then downloaded the full text for further assessment. At each step, the results of the two reviewers were compared. The data extracted from the studies included language of publication, date of publication, study setting, duration of the observation, source of participants, demographics (gender, age), sample size, FC diagnostic criteria, and the distribution of constitution types as assessed by the CCMQ. Data extraction was conducted independently by two reviewers who were trained in the conduction of systematic reviews. Discrepancies that were unrelated to human error were discussed between the two reviewers, and a third reviewer, expert in the conduction of systematic reviews, was invited to make the final decision if consensus was not reached. We used Note Express 3.4 (Beijing Aegean Lezhi Technology Co., Ltd., Beijing, China) for study selection and Microsoft Excel 2016 (Microsoft Corporation, Redmond, WA, USA) for data extraction.

We included both single constitution and combined constitution, which is defined as more than one type of constitution associated with the same person.²¹ For combined constitution, all the constitutions that were diagnosed were collected and encompassed in the Meta-analysis. For example, if a study identified ten participants with a simple YADC, five participants with a simple QDC, and four participants with the YADC and the QDC, we included fourteen participants with the YADC and nine with the QDC in the Meta-analysis.²¹

2.5. Assessment of study quality and reporting

The quality of the cross-sectional studies was assessed using the criteria recommended by the Agency for Healthcare Research and Quality (AHRQ) to determine the level of study quality.²⁶ The AHRQ scale contains eleven items,²⁷ all rated with 1 point for “yes” and 0 point for “no” or “unclear”.²⁷ A total score of 0 to 3 points represented a low methodological quality, 4 to 7 points represented a medium quality and 8 to 11 points represented a high quality.²⁸ The above steps were completed independently by two reviewers who were trained in conducting systematic reviews. Inconsistencies were discussed between the two reviewers and a third reviewer intervened if required. All the included studies were also assessed with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist.²⁹ We employed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to evaluate the quality of distribution proportions among patients with diverse TCM constitutional types.^30,31 According to the GRADE methodology, observational studies are initially classified as providing low-quality evidence. This initial rating is subject to downgrading based on assessments of risk of bias, inconsistency, indirectness, imprecision, and publication bias.^30,31 Upgrading considerations include a large effect size, a dose-response gradient, and plausible residual confounding.^30,31

2.6. Data analysis

The rate of distribution of each TCM constitution with 95% confidence interval (CI) were reported. An univariate regression analysis was used to assess the impact of between research characteristics such as geographical regions and the prevalence of different constitutions. The fixed-effect model was used when heterogeneity was low (I ² ≤ 50% and P > 0.10 for the Q statistic). The random-effects model was used when the I ² score for heterogeneity was superior to 50% or the Q statistic with P-value ≤ 0.10. When the I ² score was superior to 0% or the Q statistic with P-value ≤ 0.10, subgroup analyses based on the region where the study was conducted and the participant gender were also conducted to explore the source of heterogeneity. We used the GRADE approach to evaluate the quality of evidence regarding the distribution proportion of each TCM constitution type.

In addition, we took TCM constitution types that accounted for more than 20% of the constitution types in patients with FC as representatives. Sensitivity analysis was then performed by excluding these studies in a stepwise manner to assess the robustness of the Meta-analysis results.³² We assessed publication bias with a funnel plot if more than 10 studies with the same TCM constitution types were included, using the highest proportion of the constitution type as a standard.²¹ We conducted the Egger's linear regression analysis to test the presence of publication bias of nine types of TCM constitutions.³³

We presented the results of the Meta-analysis in the form of a forest plot for TCM constitution types that reached at least 20% of the studied sample. The remaining constitution types were presented in tables. The Meta-analysis was completed with the R 4.1.3 software (R Foundation for Statistical Computing, Vienna, Austria). Review Manager 5.4 software (The Cochrane Collaboration, Copenhagen, Denmark) was used to draw forest plots for the subgroup analysis of TCM constitution types based on gender.

3. RESULTS

3.1. Characteristics of the included studies

We identified 2516 studies from all the databases, from which 682 articles were excluded after duplicate checking. We included 49 studies after the preliminary screening and selected 16 studies after the full-text screening. The comprehensive explanations regarding the exclusion of the studies are presented in supplementary Table 5. The screening process of this systematic review is presented in Figure 1.

Figure 1. Flow chart of reports screening.

CNKI: China National Knowledge Infrastructure; VIP: China Science and Technology Journal Database; SinoMed: Chinese Biomedical Literature Database; TCM: Traditional Chinese Medicine.

A total of 16 cross-sectional studies were included, among which 44% (7/16) of them were journal articles,^4-5,34-38,45 50% (8/16) were academic dissertations^{2,7,16,35,39-42,44} and one was conference full-text article. The publication language was Mandarin for all involved studies. The earliest year of research publication was 2012, and the number of studies showed an increasing trend over time. A total of 2976 participants was included in the study, with an average sample size of 186 participants. The source of the participants included patients from hospitals, community, and college. Thirteen studies adopted the diagnostic criteria of Rome Ⅲ,^{2,4-5,7,16,35-37,40-44} three studies adopted the diagnostic criteria of Rome IV^39,40 and one study adopted the diagnostic criteria of “Expert consensus on diagnosis and treatment of constipation in TCM (2017)”³⁷ for the diagnosis of FC. No studies used the STROBE checklist format to report their findings. Six studies reported funding source,^4-5,35-38 and ten studies did not report the funding source.

The basic characteristics of the included studies are presented in Table 1. In all 16 studies, the patients completed the CCMQ under the guidance of physicians to determine their TCM constitution types.

Table 1.

Basic characteristics and quality score of the included studies

Study ID	Study area	Study setting	Duration	Sample size	Age (years)	Gender ratio (M/F)	Number of constitutions assessed	AHRQ score
Fu SH 202139	Liaoning province	Hospital	2018.10-2019.12	106	20-72	39/67	7 typesa	4
Zhang JY et al 202135	Shanghai	Hospital & University	2016.6-2018.1	180/181	40.00±14.44	T: 40/140 C: 71/110	9 types	4
Ding XJ et al 20205	Yantai	University	2016.10-2017.10	40	NR	NR	9 types	4
Wang CJ et al 202434	Qiannan Buyi and Miao Autonomous Prefecture	Hospital	2021.8-2023.1	210	20-81	82/128	9 types	4
Cheng XY et al 20184	Hubei province	Hospital	2014.1-2017.1	242	47.7±12.4	89/153	8 typesb	4
Luo WZ 20172	Jiangsu province	Hospital	2016.5-2017.3	184	20-85	78/106	9 types	3
Li M et al 201736	Nanjing	Hospital	2013.4-2016.1	211	15-80	81/130	9 types	3
Zhang Q et al 201738	Jiangsu province	Hospital	2016.1-2017.3	218	50.15±16.31	92/126	9 types	3
Zhao CY 201743	Guangdong province	Hospital	2016.3-2017.3	129	16-83	47/82	9 types	3
Guo R 201540	Harbin	Community	2014.3-2014.6	300	≥60	NR	9 types	4
Chen X 201541	Fuzhou	Hospital	2013.10-2015.2	142/142	52.83±7.72	T: 40/102 C: 40/102	9 types	4
Chen FM 201544	Unclear	Hospital	2014.3-2015.2	220	45-75	NR	5 typesc	2
Song YN 20157	Guangzhou	Hospital	2013.9-2015.1	52/24	18-80	NR	9 types	3
Shi GD 201442	Shandong province	Hospital	2012.12-2013.12	300	60-89	101/199	8 typesb	4
Yang M 201437	Fujian province	University	2012.5-2013.4	200	Unclear	66/134	9 types	3
Jia YT 201216	Chengdu & Hebei province & Nanjing	Hospital	2010.6-2012.1	242	18-80	96/146	9 types	7

Notes: AHRQ: Agency for Healthcare Research and Quality; BC: balanced constitution; YADC: Yang-deficiency constitution; PDC: phlegm-dampness constitution; BSC: blood-stasis constitution; ISC: inherited-special constitution; NR: not reported; FC: functional constipation; T: FC patient group; C: general healthy population group; M: male; F: female. ^a: ISC and BSC were not reported; ^b: ISC, PDC, YADC, and BC were not reported; ^c: ISC was not reported.

3.2. Methodology quality of the included studies

The methodological quality of the sixteen cross-sectional studies was evaluated with the AHRQ cross-sectional study evaluation criteria. Each study clarified the source of data and reported the time range of the study and the ranking criteria. Two studies were multicenter.^16,39 Three studies implemented several quality control measures.^5,16,41 One study explained the reasons for exclusion of participants from the analysis⁴² One study described measures to control confounding factors.⁴⁰ One study showed the processing method of missing data.¹⁶ Three studies reported the participants response rates and the completeness of data collection.^4,16,35 Therefore, the methodological quality of the included studies was generally low and in a high risk of bias. Evaluation details of AHRQ specific items and scores are presented in supplementary Figures 1, 2 and Table 6.

3.3. Meta-analysis of TCM constitution distribution

Meta-analysis was performed based on the number of patients with FC reported in each study for each TCM constitution type.

3.3.1. Meta-analysis of the Yin-deficiency constitution

Sixteen studies reported the proportion of the YIDC in the total population (822/2976 cases). Meta-analysis using the random-effect model showed that the proportion of the YIDC in patients with FC was 27.0% [95 % CI (19.9%, 36.7%), I ² = 97%, P < 0.01, Figure 2].

Figure 2. Forest plots of the Meta-analyses of TCM constitution types that represented at least 20% of the sample.

A: YIDC; B: YADC; C: QDC. TCM: Traditional Chinese Medicine; YIDC: Yin-deficiency constitution; YADC: Yang deficiency constitution; QDC: Qi-deficiency constitution; CI: confidence interval.

3.3.2. Meta-analysis of the Yang-deficiency constitution

Fifteen studies reported the proportion of the YADC in the total population (7677/2756 cases). Meta-analysis using a random-effects model showed that the proportion of the YADC in the population with FC was 25.2% [95% CI (17.5%, 35.0%), I ² = 95%, P < 0.01, Figure 2].

3.3.3. Meta-analysis of the Qi-deficiency constitution

Sixteen studies reported the proportion of the QDC in the total population (737/2976 cases). Meta-analysis using the random-effect model showed that the proportion of the QDC in patients with FC was 23.7% [95% CI (15.8%, 34.0%), I ² = 96%, P < 0.01, Figure 2].

3.3.4. Meta-analysis results for the other constitution types

The results of the Meta-analyses for the six constitution types that represented less than 20% of the total sample are presented in Table 2.

Table 2.

Results of the Meta-analyses for the six least prevalent constitutions

Constitution type	Number of included studies	Sample size (events/total)	The proportion of the total sample (%)	95% CI (%)	I 2 (%)	P value
DHC	16	583/2976	18.2	(12.7, 26.2)	96	<0.01
QSC	16	463/2976	13.9	(9.7, 20.0)	96	<0.01
PDC	15	367/2756	10.2	(5.7, 18.1)	98	<0.01
BSC	15	330/3082	7.5	(0.4, 14.0)	97	<0.01
BC	15	279/2756	9.4	(5.7, 13.8)	93	<0.01
ISC	12	148/2108	5.3	(1.1, 12.4)	97	<0.01

Notes: DHC: damp-heat constitution; QSC: Qi-stagnation constitution; PDC: phlegm-dampness constitution; BSC: blood-stasis constitution; BC: balanced constitution; ISC: inherited-special constitution; CI: confidence interval; I ²: I-squared statistic.

3.3.5 The quality of evidence of the TCM constitution in patients with FC

We employed the GRADE approach to evaluate the quality of distribution proportions among patients with diverse TCM constitution types. The evidence was downgraded due to serious risk of bias (as many studies were of low quality), considerable inconsistency (high heterogeneity, I ² > 75%), and occasional imprecision. Criteria for large magnitude of effect, dose-response gradient, or effect robust to plausible confounding were not met, we did not upgrade the quality of evidence. The results of the quality evaluation can be found in supplementary Table 7.

3.4. Comparison of the distribution of TCM constitution in different regions

The studies were grouped according to the six administrative divisions of China, i.e. North China, Northeast China, East China, Central South China, Southwest China, and Southwest China.⁴⁷ Northeast China included Liaoning, Jilin, and Heilongjiang provinces.⁴⁷ East China included Shanghai, Jiangsu, Zhejiang, Anhui, Fujian, Jiangxi, and Shandong provinces and cities.⁴⁵ Central South China included Henan, Hubei, Hunan, Guangdong, Guangxi, and Hainan provinces.⁴⁷ Southwest China included Sichuan, Guizhou, and Yunnan provinces, Tibet autonomous region, and Chongqing municipality.⁴⁷ Among these involved studies, one study did not report on the geographical location where it was conducted. Another study was a multi-center trial, but due to inconsistent reporting, it was not possible to accurately extract data on the regional distribution of TCM constitution types and the study was not included in the analysis. Therefore, the geographic subgroup analysis included only 14 studies.

3.4.1. Yin-deficiency constitution

A total of 8 studies conducted in East China, 2 in Northeast China, 3 in Central South China, and 1 in Southwest China assessed the prevalence of YIDC. The proportion of the YIDC in patients with FC in Northeast China, East China, Central South China and Southwest China was respectively 39.7% [95% CI (20.5%, 77.0%)], 28.9% [95% CI (17.7%, 47.2%)], 22.5% [95% CI (8.5%, 59.8%)] and 20.0% [95% CI (14.8%, 26.1%)] (Figure 3).

Figure 3. Subgroup analyses of the distribution of TCM constitution types in people with functional constipation according to the location of the study.

A: Yin-deficiency constitution; B: Yang-deficiency constitution; C: Qi-deficiency constitution. E: East China; N: Northeast China; W: Southwest China; S: Central South China. TCM: Traditional Chinese Medicine; YIDC: Yin-deficiency constitution; YADC: Yang-deficiency constitution; QDC: Qi-deficiency constitution; CI: confidence interval.

3.4.2. Yang-deficiency constitution

A total of 8 studies from East China, 2 from Northeast China, 3 from Central South China, and 1 from Southwest China assessed the prevalence of YADC. The proportion of the YADC in patients with FC in East China, Central South China, Northeast China, and Southwest China was 36.3% [95% CI (23.9%, 50.8%)], 19.6% [95% CI (9.7%, 35.7%)], 13.2% [95% CI (5.6%, 27.9%)], and 10.5% [95% CI (6.7%, 15.4%)] (Figure 3).

3.4.3. Qi-deficiency constitution

A total of 8 studies from East China, 2 from Northeast China, 3 from South Central China, and 1 from Southwest China assessed the prevalence of QDC. The proportion of the QDC in patients with FC was 36.9% [95% CI (18.4%, 60.3%)], 23.0% [95% CI (12.1%, 39.4%)], 21.2% [95% CI (4.6%, 59.9%)] and 20.5% [95% CI (15.2%, 26.6%)] in Northeast, East, Central South and Southwest China (Figure 3).

3.4.4. Other constitution types

The results of the subgroup analyses of the distribution of the remaining six TCM constitutions in patients with FC according to the location of the study are presented in Table 3.

Table 3.

Subgroup analyses of the distribution proportion of six least prevalent constitutions according to the location of the study

Constitution type	Location	Proportion of the total population (%)	95% CI (%)		Number of included studies
DHC	E	20.0	(11.3, 35.2)	14
	S	19.9	(6.6, 60.4)
	N	9.2	(6.7, 12.7)
	W	14.3	(9.9, 19.8)
QSC	E	17.2	(9.7, 30.4)	14
	S	12.7	(4.8, 33.5)
	N	9.9	(7.4, 13.3)
	W	14.8	(10.3, 20.3)
PDC	E	12.4	(5.3, 29.1)	14
	S	12.4	(2.3, 66.3)
	N	7.2	(5.1, 10.2)
	W	10.0	(6.3, 14.9)
BSC	E	11.2	(4.8, 26.1)	13
	S	8.1	(1.5, 42.1)
	N	8.3	(5.5, 12.1)
	W	2.4	(0.8, 5.5)
BC	E	11.3	(5.7, 18.5)	14
	S	13.0	(9.9, 16.5)
	N	1.5	(0.2, 3.8)
	W	3.8	(1.1, 6.8)
ISC	E	6.7	(0.8, 17.6)	11
	S	12.7	(0, 55.2)
	N	0.0	(0, 1.2)
	W	3.8	(1.7, 7.4)

Notes: E: east China; N: northeast China; S: central south China; W: southwest China; DHC: damp-heat constitution; QSC: Qi-stagnation constitution; PDC: phlegm-dampness constitution; BSC: blood-stasis constitution; BC: balanced constitution; ISC: inherited-special constitution; CI: confidence interval.

3.4.5. Comparison of the distribution of TCM constitution types between East China, Northeast China, Central South China, and Southwest China

The four most prevalent TCM constitution types in East China were YADC 36.3% [95% CI (23.9%, 50.8%)], YIDC 28.9% [95% CI (17.7%, 47.2%)], QDC 23.0% [95% CI (12.1% to 39.4%)], and DHC 20% [95% CI (11.3%, 35.2%)]. The highest percentage of TCM constitution types in Central South China was the YIDC 22.5% [95% CI (8.5%, 59.8%)], QDC 21.2% [95% CI (4.6%, 59.9%)], YADC 19.6% [95% CI (9.7%, 35.7%)], and DHC 19.9% [95% CI (6.6%, 60.4%)]. In Northeast China, the highest percentage of the three types of TCM constitution types were YIDC 39.7% [95% CI (20.5%, 77.0%)], QDC 36.9% [95% CI (18.4%, 60.3%)], YADC 13.2% [95% CI (5.6%, 27.9%)], and QSC 9.9% [95% CI (7.4%, 13.3%)].The four most prevalent TCM constitution types in Southwest China were YIDC 20% [95% CI (14.8%, 26.1%)], QSC 14.8% [95% CI (10.3%, 20.3%)], QDC 13.2% [95% CI (5.6%, 27.9%)], and YADC 10.5% [95% CI (6.7%, 15.4%)] (supplementary Figure 3).

3.5. Comparison of the distribution of TCM constitution in different genders

A total of 4 studies^4,16,36,42 reported TCM constitution types by gender groups. Since only one of the included studies had a single participant with an ISC constitution, a subgroup analysis for the ISC constitution type was not conducted. We represented the TCM constitution types with statistically significant differences as forest plots.

3.5.1. The TCM constitution types with statistically significant differences

The distribution of the YADC subgroup in patients with FC differed in gender. The proportion of YADC in male participants was 0.35 times the proportion in female participants [OR = 0.35, 95% CI (0.22, 0.55), I ² = 46%, P < 0.001]. The proportion of YIDC in male participants was 0.31 times the proportion in female participants [OR = 0.31, 95% CI (0.14, 0.68), I ² = 79%, P = 0.004].The proportion of QSC in male participants was 0.53 times the proportion in female participants [OR = 0.53, 95% CI (0.33, 0.84), I ² = 9%, P = 0.008]. The proportion of QDC in male patients was 0.51 times the proportion in female patients [OR = 0.51, 95% CI (0.30, 0.86), I ² = 56%, P = 0.01]. The proportion of BSC in male patients was 0.37 times the proportion of BSC in female patients [OR = 0.37, 95% CI (0.19, 0.72), I ² = 0%, P = 0.004] (supplementary Figure 4).

3.5.2. Other constitution types

There was no statistically significant difference between the proportion of constitution types in male participants and in female participants. The proportion of DHC in male patients was 1.01 times the proportion of DHC in female patients [OR = 1.01, 95% CI (0.50, 2.03), I ² = 66%, P = 0.980]. The proportion of PDC in male patients was 1.38 times the proportion of PDC in female patients [OR = 1.38, 95% CI (0.76, 2.52), I ² = 37%, P = 0.290]. The proportion of BC in male patients was 1.71 times the proportion of BC in female patients [OR = 1.71, 95% CI (0.83, 3.51), I ² = 60%, P = 0.150].

3.5.3. Comparison of the nine TCM constitutions proportion between male and female

A total of 4 studies reported constitution types by gender. The results of the Meta-analysis showed that the main constitutions of male patients with FC were YADC 8% [95% CI (5%, 12%)], DHC 6% [95% CI (4%, 9%)], QDC 6% [10%)], and BC 6% [95% CI (2%, 12%)], followed by Yin-deficiency constitution (YIDC) (5%), Qi-stagnation constitution (QSC) (3%), phlegm-dampness constitution (PDC) (3%),. The main unbalanced constitution of female patients with FC were YADC 21% [95% CI (13%, 33%)], YIDC 13% [95% CI (8%, 100%)], and QDC 11% [95% CI (8%, 14%)], followed by QSC (6%), DHC (5%), BC (4%), BSC (3%), and PDC (1%). Overall, YADC, YIDC, QDC, and QSC were more common in females, whereas DHC, PDC, and BC were slightly more common in males.

3.6. Distribution of TCM constitution in different ages

A total of 8 studies reported the correlation between TCM constitution and age. However, due to a mismatch of age groups between the studies, the data of these studies could not be combined into a Meta-analysis. The age of the patients was mainly over 45 years old. The main TCM constitution types in patients over 60 with FC were the YADC, the YIDC, the BSC, and the PDC.

3.7. Meta-analysis of TCM constitution types of functional constipation patients compared with the general population

Three cross-sectional studies compared people with FC with the general population in terms of TCM constitution types. Due to potential limitations such as a limited sample size, the study did not establish any significant correlation between TCM constitution types and FC (Table 4).

Table 4.

Meta-analysis of TCM constitution types of people with FC compared with the general population

Constitution type	OR	95% CI	I 2 (%)	P value
YIDC	1.54	0.64,3.71	83	0.33
YADC	1.23	0.96,1.57	0	0.10
QDC	0.86	0.57,1.29	34	0.47
DHC	1.61	0.67,3.87	78	0.29
QSC	1.27	0.49,3.31	82	0.62
PDC	1.09	0.83,1.42	0	0.54
BSC	1.00	0.76,1.31	0	0.99
BC	0.28	0.06,1.23	88	0.09
ISC	1.24	0.88,1.76	52	0.22

Notes: YIDC: Yin-deficiency constitution; YADC: Yang-deficiency constitution; QDC: Qi-deficiency constitution; DHC: damp-heat constitution; QSC: Qi-stagnation constitution; PDC: phlegm-dampness constitution; BSC: blood-stasis constitution; BC: balanced constitution; ISC: inherited-special constitution; OR: odds ratio; CI: confidence interval.

3.8. Sensitivity analysis

The high heterogeneity observed in this study can be attributed to several factors, including the distinctive nature of TCM constitution (see Section 4.3) and inadequate control groups. Therefore, sensitivity analysis was performed by excluding studies one by one to further assess the robustness and credibility of the results. Sensitivity analysis also helps identify potential sources of heterogeneity. Since only a random-effects model was used to synthesize the data, a sensitivity analysis was conducted to validate the stability of the results and ensure the reasonableness and interpretability of the conclusions. For the main unbalanced constitutions of patients with FC (YIDC, YADC, QDC and DHC), the results of the sensitivity analysis did not show any significant difference with the original analysis, indicating that the results of this study were robust.³² More details are presented in supplementary Figure 5.

3.9. Publication bias

We used the proportion of YIDC in patients with FC as an indicator to assess publication bias with a funnel plot.²¹ The inverted funnel plot showed a scattered asymmetry (Figure 4), which indicated that publication bias may be present. The publication bias of the nine TCM constitutions in people with FC was analyzed with the Egger's method.³³ The results showed that, except for YADC, QDC, BC, and ISC, there is evidence of publication bias. More details are presented in the supplementary Table 8.

Figure 4. Funnel plot analysis of the distribution of the Yin-deficiency constitution.

4. DISCUSSION

4.1. Analysis of TCM constitution types in patients with functional constipation

This study included 16 studies involving a sample of 2976 participants. The YIDC, the YADC, and the QDC had the highest proportion, accounting for respectively 27.0% [95 % CI (19.9%, 36.7%)], 25.2% [95% CI (17.5%, 35.0%)] and 23.7% [95% CI (15.8%, 34.0%)] of the total sample. The results of this study suggest that the YIDC, the YADC, and the QDC are the main constitution types for patients with FC. The results of this study are consistent with previous research. The distribution of TCM constitution in FC patients differs from that in the general population. A nationwide survey in China showed that the most common constitutions in the general population are the BC, the QDC and the YADC. This indicates that the high proportion of specific constitutions in FC patients may have particular significance. The predominance of the YIDC, the YADC, and the QDC may be related to the pathophysiology of FC.¹ Identifying the distribution of these constitutions in FC patients can help develop more individualized and effective prevention and treatment strategies.^1,2 Clinical studies have already explored constitution-based interventions, and results suggest that diet therapy and warm needle acupuncture targeting specific constitutions can achieve good outcomes.^40,48 Therefore, it is important to identify the TCM constitution of patients with FC. Healthy exercise and full rest are important to prevent the body from developing an unbalanced constitution.²¹ Adjusting constitutions of people with YIDC, YADC, and QDC to restore the BC is also crucial for prevention the occurrence of FC.^21,35,38

The studies included in this Meta-analysis were mainly conducted in East China, followed by Central South China, Southwest China, and the Southwest China. From the perspective of TCM physiology, the environment affects the constitution of local people. The differences in the TCM constitution distribution in different regions may be related to the local climate, food habits, and the degree of economic development.^7,26 The same phenomenon was observed in a national scale constitution survey study.⁴⁹ Our study shows that in East China, in addition to YIDC and YADC, the DHC is the most prevalent constitution in patients with FC. Residents of coastal cities live in a humid environment and take food that have a hot and humid nature according to TCM theory such as fish, shrimp, and crab, so their constitution is mostly the DHC.^7,43 FC patients in East China mostly come from coastal cities. Therefore, the DHC may be closely related to FC. Other possible causes remain to be studied. It is assumed that the result of this study may be related with age and dietary habit factors.

The present study sample found that the number of women (1513/2364) with FC was much higher than that of men (851/2364). Our study found that the most common constitution of male and female patients with FC was the YADC. National epidemiological surveys of the general population indicate that the proportion of the BC is significantly higher in men than in women.⁴⁹ Men also have higher proportion of the PDC and the DHC, while women show higher prevalence of the BSC, the YADC, and the QSC.⁴⁹ These findings are not entirely consistent with those of our study, further suggesting that the high proportion of specific constitutions in FC patients may have particular significance. This did not identify any studies that explored the possible correlation between TCM constitution and FC from a gender perspective, making the discrepancy between our study and the national survey harder to interpret. Moreover, studies with gender subgroup were mostly conducted in Southern and coastal provinces, where the weather is wet and cold in winter, possibly leading to Yang deficiency.⁵⁰ The proportion of constitution types among women was higher than that of males, except for the DHC, the PDC, and the BC. The second most prevalent constitution among women is the YIDC. Physiological mechanisms such as menstruations, raising a fetus during pregnancy and raising a young child with breast milk all put the female organism in a state of deficiency of Yin, blood, and fluids.³⁶ Therefore, people with a female gender are more susceptible to the YIDC than males. In contrast, the main constitution types for males are YADC, DHC, and BC. Compared to females, males have a stronger tendency to consume tobacco, wine and spicy and barbecued food, which tends to produce damp heat, making them more susceptible to develop the DHC.⁵¹ This reflects a close association between DHC and males with FC, which can be explored in further studies.

4.2. Implications for future clinical practice

The results of this study indicate that we should focus on the YIDC, YADC, QDC, DHC, and QSC in the prevention and management of FC. Clinicians should take the patient's constitution type into account when designing personalized treatment strategies. It is recommended that clinicians should also observe the relationship between the constitution and the symptoms. For example, clinicians should pay attention to whether male patients have DHC and damp-heat symptoms and female patients have YIDC and Yin deficiency symptoms. However, longitudinal interventional studies are needed to further evaluate these findings.

We suggest to conduct a case-control study or prospective cohort study on people with high-risk constitutions for FC.²¹ Further research needs to clarify the causal relationship between Yin deficiency constitution, FC and TCM syndromes. In the process of research implementation, confounding factors should be controlled, demographic information and disease information related to constitution should be collected with as much details as possible, and the influencing factors of the constitution should be discussed. Investigators of studies exploring the constitution type of people with FC should use the STROBE formal reporting statement to improve the methodological quality and provide high-quality primary evidence for systematic evaluation.²⁹

Besides, our study found that there are still many methodological problems in the cross-sectional study of TCM constitution types in patients with FC. For a cross-sectional study of TCM constitution and disease, it is suggested to formulate and perfect a scientific and feasible research plan before implementing the research design plan. Cross-sectional studies can also establish a control group selected from the general population to explore the relationship between constitution types and diseases.

In addition, we recommend that future cross-sectional studies examining the correlation between TCM constitution types and diseases should adhere to evidence-based medicine standards for implementation and reporting. Norms associated with evidence-based medicine. This will enhance methodological quality, allow for deeper exploration of the factors influencing TCM constitution types, and clarify the relationship between constitution types and disease. Such improvements will provide high-quality evidence to inform the clinical management of FC.

We conducted a systematic evaluation and Meta-analysis of the cross-sectional studies that assessed the prevalence of TCM constitution types in people with FC. The results and methods of this study can be used as a reference for clinicians and researchers.

Research on the distribution of TCM constitution in patients with FC can provide more insight into the individualized characteristics of FC. By identifying the distribution patterns of different TCM constitutions in FC patients, researchers can better understand the relationship between TCM constitutions and FC. This understanding is crucial for developing more precise individualized treatment strategies. Additionally, it provides a theoretical basis for further studies on the etiology of FC and for evaluating the effectiveness of TCM interventions, ultimately optimizing clinical practice.

4.3. Limitations

This study evaluated the methodological quality of the included studies. Many methodological issues were identified in the cross-sectional studies of TCM constitution types in patients with FC. In terms of the overall quality of the article, no study used the STROBE format to report their findings.²⁹ The AHRQ was low in most studies. Few studies clearly reported quality control measures in the research process, resulting in a high risk of bias in the results. A Meta-analysis of TCM Constitution showed significant heterogeneity (large I² value) between studies.

The studies included in this study presented significant heterogeneity, which suggests a potentially high risk of bias. Despite efforts to mitigate this through subgroup analysis and sensitivity analysis, complete elimination of heterogeneity was not possible. Several factors may have contributed to the high heterogeneity observed in this Meta-analysis. including the region in which the study was conducted, sample characteristics such as age, gender, region, climate, and dietary habits, sample size, and measurement methods.⁴⁶ Sample characteristics may have influenced the formation of TCM constitution types, further contributing to heterogeneity.²¹ The significant heterogeneity observed in this study raises concerns about the consistency and generalizability of the findings.

The TCM theory considers that constitution can be affected by factors such as geography and gender. This TCM constitution variability feature is also reflected in the results of the national norm survey.^21,49 This study grouped studies by geographical and gender groups to obtain more accurate results. We also investigated the relationship between the TCM constitution and region and gender. However, due to the lack of data related to participants ethnicity, occupation, duration of illness, and dietary habits and other factors in the included primary studies, this study could not use Meta-regression analysis to explore the correlation between participant characteristics and constitution types, thus preventing further exploration into the factors influencing the constitution in this study.

Additionally, publication bias was detected through the funnel plot and Egger's test, indicating a potential distortion in the overall conclusions. Studies with significant or positive findings may have been more likely to be published, leading to an overestimation or underestimation of the association between specific TCM constitution types and FC.⁴⁶ This limits the objectivity and reliability of the results.

The methodological reporting of the study design was also problematic throughout the studies. The basic information related to the studies was not reported comprehensively, such as the methodological details of the assessment of the constitution, the refusal rate, and the funding status of the studies. The statistical data analysis from several studies only described the number of people in each TCM constitution type. It lacked studies on the correlation between the constitution type and related factors such as gender, age, and dietary habits. Some investigators did not provide sufficient details in reporting the results of individual studies. In addition, the terminology of some studies was not standardized. For example, “the Blood-stasis constitution " was written as "the Stasis-blood constitution."

Since the research on TCM constitution was conducted in different regions and groups, there are significant differences in climate, environment, lifestyle, and other factors. These variations, along with a tendency for studies with significant or positive results to be more likely published, may have contributed to the publication bias observed between the studies.⁴⁶ This situation is related to the specificity of the TCM constitution, with significant differences due to the geographical environment and lifestyle. We recommend conducting an observational study of the TCM constitution in people with FC with a large sample size and conducted in different geographical areas of the country.

In conclusion, this Meta-analysis of cross-sectional studies, including 2976 participants, shows that the YIDC, YADC, and QDC are the main TCM constitution types of patients with FC. This study found that TCM constitution types differ between genders and geographic regions. These findings may provide guidance for constitution-based prevention and management of FC. Longitudinal interventional studies are required to assess the preventative and therapeutic effects of constitution-based interventions in people with FC. Future research should focus on exploring individualized prevention and treatment strategies for patients with different TCM constitution types and developing prevention and treatment models tailored to these constitution types. This will further enhance health management strategies for FC.

5. ACKNOWLEDGEMENTS

We are grateful to all who contributed to the successful completion of this systematic review.

6. SUPPORTING INFORMATION

Supporting data to this article can be found online at http://www.journaltcm.com.

Funding Statement

Supported by Mixed Research Was Conducted to Formulate Countermeasures for the Output Bottleneck of Clinical Research Results in International First-Class Chinese Patent Medicine (No. 90020172120032); Design, Data Management, and Statistical Analysis of a Post-Marketing Cross-Sectional Survey of Biantong Brand Tiantian Capsules (No. 90020171720006)