Outcome of the efficacy of Chinese herbal medicine for functional constipation: A systematic review and meta-analysis

Table 1 Summary of meta-analysis results

Outcomes	No. of studies in meta-analysis	No. of participants		Results			Heterogeneity
		T	C	OR/MD	95%CI	P value	Chi- square test	I2	P value
ER	97	4455	4238	3.62	(3.19, 4.11)	< 0.00001	85.79	0%	0.76
PEG	31	1429	1399	2.42	(1.91, 3.08)	< 0.00001	28.03	0%	0.57
Mosapride	21	881	834	3.49	(2.67, 4.56)	< 0.00001	14.87	0%	0.78
Lactulose	24	1102	1018	3.71	(2.86, 4.82)	< 0.00001	11.17	0%	0.98
Phenolphthalein	7	294	287	4.59	(2.71, 7.76)	< 0.00001	1.13	0%	0.98
Probiotics	8	410	362	4.95	(3.21, 7.65)	< 0.00001	0.63	0%	1
Placebo	6	339	338	7.09	(4.83, 10.43)	< 0.00001	4.84	0%	0.44
GS	78	3438	3288	4.03	(3.49, 4.65)	< 0.00001	70.74	0%	0.68
PEG	26	1078	1038	2.69	(2.06, 3.51)	< 0.00001	21.54	0%	0.66
Mosapride	17	714	673	3.98	(2.93, 5.41)	< 0.00001	10.92	0%	0.81
Lactulose	23	1046	978	3.89	(2.97, 5.09)	< 0.00001	8.08	0%	1
Phenolphthalein	1	57	57	5.85	(1.22, 28.05)	0.03	-	-	-
Probiotics	6	234	234	6.21	(3.60, 10.70)	< 0.00001	1.83	0%	0.87
Placebo	5	309	308	8.4	(5.64, 12.52)	< 0.00001	3.87	0%	0.42
BM	15	663	652	0.83	(0.67, 0.98)	< 0.00001	71.74	80%	< 0.00001
PEG	6	264	258	0.65	(0.28, 1.02)	0.0006	37.91	87%	< 0.00001
Mosapride	5	215	210	0.94	(0.64, 1.24)	< 0.00001	15.43	74%	0.004
Lactulose	1	55	55	0.98	(0.81, 1.15)	< 0.00001	-	-	-
Phenolphthalein	-	-	-	-	-	-	-	-	-
Probiotics	1	30	30	0.61	(0.39, 0.83)	-	-	-	-
Placebo	2	99	99	0.99	(0.87, 1.11)	< 0.00001	0	0%	1
BSS	7	303	284	1.63	(1.15, 2.32)	0.006	1.77	0%	0.94
PEG	4	187	183	1.48	(0.96, 2.28)	0.15	1.16	0%	0.76
Mosapride	2	60	61	1.88	(0.79, 4.44)	0.15	0.01	0%	0.92
Lactulose	-	-	-	-	-	-	-	-	-
Phenolphthalein	-	-	-	-	-	-	-	-	-
Probiotics	1	56	40	2.07	(0.90, 4.74)	0.09	-	-	-
Placebo	-	-	-	-	-	-	-	-	-
Recurrence	5	137	78	0.47	(0.22, 0.99)	0.05	4.42	9%	0.35
PEG	1	27	25	0.66	(0.20, 2.13)	0.49	-	-	-
Mosapride	-	-	-	-	-	-	-	-	-
Lactulose	1	42	40	0.31	(0.10, 0.91)	0.03	-	-	-
Phenolphthalein	-	-	-	-	-	-	-	-	-
Probiotics	-	-	-	-	-	-	-	-	-
Placebo	3	68	13	0.5	(0.08, 3.19)	0.46	3.47	42%	0.18

Ps: Data were meta-analyzed by using a random-effects model and are presented as OR or MD as appropriate. Statistical heterogeneity was assessed by using the chi-square test and quantified by using the I² statistic. ER: Efficacy rate; PEG: Polyethylene glycol; GS: Global symptom; BM: Bowel movement; BSS: Bristol Stool Scale; RR: Recurrence rate; AEs: Adverse effects.

Table 2 Characteristics of the included studies

Study	Language	Inclusion criteria	No. of participants	Age median (range)	Intervention of treatment group	Intervention of control group	Duration in wk	Assessment of outcomes	Follow-up in mo	Dropout (T/C)	Cochrane
Bian et al[13], 2014	English	Rome III	120	55.6 (18-75)	CHM	Placebo	8	ER, BM, GS, ARs, RR	2	1/1	A
Bin et al[14], 2011	Chinese	Rome III	61	67.4 (60-85)	CHM	Mosapride	2	ER, BM, BSS, GS	NA	NA	B
Bu et al[15], 2019	Chinese	Rome III	57	57.9 (40-85)	CHM	Lactulose	4	ER, GS, ARs	NA	NA	B
Cai et al[16], 2020	Chinese	Rome IV	60	48.2 (45-78)	CHM	Lactulose	4	ER, GS	NA	NA	B
Cao et al[17], 2012	Chinese	Rome II	60	36.7 (18-65)	CHM	Peg	4	ER, GS	NA	NA	B
Chen et al[18], 2011	Chinese	Rome III	76	74.3 (60-92)	CHM	Peg	4	ER, GS	NA	NA	C
Chen et al[19], 2012	Chinese	Rome III	70	31.9 (28-75)	CHM	Peg	4	ER, GS	NA	NA	B
Chen et al[20], 2014	Chinese	Rome III	120	69.3 (60-75)	CHM	Lactulose	4	ER, GS, ARs	NA	NA	B
Chen et al[21], 2014	Chinese	Rome III	88	25.1 (17-55)	CHM	Mosapride	3	ER, GS	2	NA	B
Chen et al[22], 2016	Chinese	Rome III	112	62.5 (51-70)	CHM	Lactulose	4	ER, BM, GS	NA	1/1	B
Chen et al[23], 2018	Chinese	Rome III	120	49.2 (25-77)	CHM	Lactulose	4	ER, GS	1	NA	B
Chen et al[24], 2020	Chinese	Rome III	88	66.9 (60-75)	CHM	Lactulose	4	ER, GS, RR	1	2/4	B
Chen et al[25], 2020	Chinese	Rome IV	160	48.3 (37-52)	CHM	Lactulose	4	ER, GS	NA	NA	B
Cheng et al[26], 2010	English	Rome III	120	33.5 (18-65)	CHM	Placebo	8	ER, BM, GS, ARs, RR	2	9/8	A
Cheng et al[27], 2012	Chinese	Rome III	100	52.6 (23-67)	CHM	Mosapride	4	ER,GS	3	NA	C
Chi et al[28], 2010	Chinese	Rome III	70	NA	CHM	Peg	4	ER, BM, GS	NA	0/1	B
Deng et al[29], 2018	Chinese	Rome III	96	70.2 (50-85)	CHM	Lactulose	4	ER, GS	1	3/3	B
Dou et al[30], 2014	Chinese	Rome III	90	58.7 (45-72)	CHM	Lactulose	3	ER, GS	NA	NA	B
Fu et al[31], 2012	Chinese	Rome III	60	42.8 (18-65)	CHM	Probiotics	4	ER, BM, GS	NA	NA	B
Gao et al[32], 2013	Chinese	Rome III	60	55.7 (18-70)	CHM	Peg	8	ER, GS	NA	NA	B
Gao et al[33], 2015	Chinese	Rome III	80	58.3 (20-70)	CHM	Peg	2	ER, BM, GS	NA	NA	B
Gu et al[34], 2013	Chinese	Rome III	60	45.1 (21-60)	CHM	Lactulose	4	ER, GS, BSS, ARs	NA	0/1	B
Guo et al[35], 2010	English	Rome II	70	64.7 (21-79)	CHM	Placebo	4	ER, GS, RR, RR	NA	NA	B
Guo et al[36], 2018	Chinese	Rome IV	60	61.8 (18-80)	CHM	Peg	4	ER, GS	NA	1/1	B
He et al[37], 2015	Chinese	Rome III	80	71.4 (60-79)	CHM	Peg	2	ER, BM, GS	2	NA	B
He et al[38], 2019	Chinese	Rome IV	120	72.5 (65-80)	CHM	Peg	2	ER, GS, ARs	2	NA	B
Hu et al[39], 2018	Chinese	Rome III	238	3.84 (1-14)	CHM	Placebo	1	ER, GS	NA	NA	B
Huang et al[40], 2012	English	Rome III	60	71.8 (60-85)	CHM	Lactulose	4	ER, GS, ARs	NA	NA	B
Hui et al[41], 2018	Chinese	Rome III	62	68.1 (55-90)	CHM	Lactulose		ER, GS, ARs	NA	NA	NA
Jiang et al[42], 2020	Chinese	Rome IV	72	51.6 (22-73)	CHM	Lactulose	4	ER, GS	NA	NA	B
Jiao et al[43], 2018	Chinese	Rome III	120	58.7 (50-70)	CHM	Placebo	1	ER, GS	NA	0/4	C
Kong et al[44], 2020	Chinese	Rome IV	100	69.4 (60-83)	CHM	Mosapride	2	ER, GS	1	1/3	B
Lai et al[45], 2012	Chinese	Rome III	90	NA	CHM	Mosapride	4	ER, GS	NA	NA	B
Li et al[46], 2012	Chinese	Rome III	60	49.7 (18-65)	CHM	Peg	4	ER, GS	NA	NA	C
Li et al[47], 2015	Chinese	Rome III	166	51.9 (18-65)	CHM	Peg	4	ER, ARs	2	NA	B
Li et al[48], 2016	Chinese	Rome III	160	47.2 (23-68)	CHM	Peg	4	ER, BM	NA	0/6	B
Li et al[49], 2019	Chinese	Rome IV	120	55.1 (49-63)	CHM	Mosapride	2	ER, GS, ARs	NA	NA	B
Lin et al[50], 2009	Chinese	Rome II	120	68.5 (65-80)	CHM	Peg	4	ER, ARs	NA	NA	C
Lin et al[51], 2012	Chinese	Rome III	80	47.1 (20-60)	CHM	Mosapride	6	ER, GS, ARs	NA	NA	B
Liu et al[52], 2013	Chinese	Rome III	66	49.6 (18-75)	CHM	Lactulose	4	ER, GS	NA	0/3	B
Liu et al[53], 2017	Chinese	Rome III	60	51.9 (18-65)	CHM	Mosapride	4	ER, GS, ARs	NA	NA	B
Liu et al[54], 2017	Chinese	Rome III	120	53.7 (45-64)	CHM	Lactulose	2.1	ER, GS	NA	NA	B
Liu et al[55], 2018	Chinese	Rome III	244	2.6 (1-14)	CHM	Probiotics	4	ER	NA	NA	B
Lv et al[56], 2012	Chinese	Rome III	280	67.1 (19-82)	CHM	Peg	3	ER	6	NA	B
Lv et al[57], 2018	Chinese	Rome III	80	54.9 (20-71)	CHM	Probiotics	1	ER, GS	NA	NA	C
Mu et al[58], 2019	Chinese	Rome IV	90	68.7 (62-81)	CHM	Peg	2	ER, GS, BSS	NA	NA	B
Qian et al[59], 2014	Chinese	Rome III	80	46.3 (18-65)	CHM	Mosapride	8	ER, GS, ARs	NA	2/4	B
Que et al[60], 2018	Chinese	Rome III	80	45.8 (16-70)	CHM	Lactulose	8	ER, GS	NA	NA	C
Ren et al[61], 2014	Chinese	Rome III	60	47.6 (18-65)	CHM	Peg	8	ER, GS, RR	1	NA	B
Shao et al[62], 2019	Chinese	Rome IV	100	67.9 (65-80)	CHM	Mosapride	2	ER, GS	NA	NA	B
Su et al[63], 2019	Chinese	Rome IV	96	71.5 (64-78)	CHM	Mosapride	2	ER, BM	1	NA	B
Sui et al[64], 2012	Chinese	Rome III	120	54.9 (18-79)	CHM	Probiotics	2	ER, GS	NA	NA	B
Sun et al[65], 2011	Chinese	Rome III	80	68.3 (60-80)	CHM	Mosapride	1	ER, BM, GS	NA	NA	B
Tao et al[66], 2018	Chinese	Rome III	60	NA	CHM	Peg	4	ER	NA	NA	B
Wang et al[67], 2020	Chinese	Rome IV	94	69.3 (66-85)	CHM	Peg	4	ER, BM, GS	2	5/5	B
Wang et al[68], 2004	Chinese	Rome II	90	64.5 (56-75)	CHM	Phenolphthalein	4	ER	NA	NA	B
Wang et al[69], 2011	Chinese	Rome III	156	60.7 (NA)	CHM	Peg	2	ER, GS, BSS	NA	NA	B
Wang et al[70], 2013	Chinese	Rome III	112	73.6 (65-82)	CHM	Lactulose	3	ER, ARs	NA	0/12	B
Wang et al[71], 2014	Chinese	Rome III	60	1.9 (1-7)	CHM	Probiotics	8	ER	3	NA	B
Wang et al[72], 2015	Chinese	Rome II	116	66.7 (55-75)	CHM	Phenolphthalein	4	ER, GS	NA	1/1	B
Wu et al[73], 2008	Chinese	Rome III	54	76.4 (60-84)	CHM	Peg	4	ER, GS	NA	1/0	B
Wu et al[74], 2009	Chinese	Rome III	60	55.9 (50-75)	CHM	Probiotics	4	ER, GS, ARs	6	NA	B
Wu et al[75], 2013	Chinese	Rome III	60	56.3 (45-75)	CHM	Peg	4	ER, BM, ARs	NA	4/3	B
Wu et al[76], 2013	Chinese	Rome III	60	49.4 (NA)	CHM	Phenolphthalein	2	ER	NA	NA	B
Xin et al[77], 2008	Chinese	Rome II	130	66.8 (60-88)	CHM	Phenolphthalein	4	ER	NA	0/5	B
Xin et al[78], 2014	Chinese	Rome III	70	69.7 (60-85)	CHM	Phenolphthalein	4	ER	NA	NA	B
Xu et al[79], 2013	Chinese	Rome III	82	70.3 (NA)	CHM	Lactulose	4	ER, GS	NA	NA	C
Xu et al[80], 2016	Chinese	Rome III	70	47.2 (18-75)	CHM	Peg	8	ER, GS	NA	5/5	B
Xu et al[81], 2018	Chinese	Rome III	80	41.8 (18-54)	CHM	Peg	4	ER, GS	1	8/10	B
Xu et al[82], 2019	Chinese	Rome IV	60	42.3 (25-64)	CHM	Mosapride	4	ER, GS	3	NA	B
Yan et al[83], 2020	Chinese	Rome IV	80	46.7 (16-70)	CHM	Peg	4	ER, GS	2	NA	B
Yan et al[84], 2013	Chinese	Rome II	258	82.2 (80-93)	CHM	Peg	4	ER	NA	NA	B
Yan et al[85], 2016	Chinese	Rome III	60	43.1 (32-62)	CHM	Mosapride	4	ER, GS, BSS	1	NA	B
Yang et al[86], 2008	Chinese	Rome III	80	67.4 (60-82)	CHM	Peg	4	ER, GS	NA	NA	B
Yang et al[87], 2012	Chinese	Rome III	66	71.5 (NA)	CHM	Phenolphthalein	2	ER	NA	2/2	C
Yang et al[88], 2015	Chinese	Rome III	80	54.9 (NA)	CHM	Probiotics	4	ER, GS, BSS, ARs	NA	NA	B
Yao et al[89], 2016	Chinese	Rome III	160	66.1 (60-80)	CHM	Lactulose	4	ER, GS	NA	NA	B
Ye et al[90], 2020	Chinese	Rome IV	120	57.8 (18-78)	CHM	Peg	4	ER, GS	NA	NA	B
Ye et al[91], 2016	Chinese	Rome III	60	68.4 (60-85)	CHM	Lactulose	4	ER, GS	NA	NA	B
Yuan et al[92], 2016	Chinese	Rome III	64	47.4 (30-75)	CHM	Peg	4	ER, GS, ARs	1	NA	B
Zeng et al[93], 2017	Chinese	Rome III	88	47.2 (18-65)	CHM	Mosapride	4	ER, BM, GS	3	1/3	B
Zhan et al[94], 2016	Chinese	Rome III	60	56.3 (18-75)	CHM	Lactulose	4	ER, GS, ARs	NA	NA	B
Zhang et al[95], 2020	Chinese	Rome IV	80	44.5 (18-65)	CHM	Lactulose	4	ER, GS, ARs	3	5/5	B
Zhang et al[96], 2014	Chinese	Rome III	64	56.7 (18-75)	CHM	Mosapride	4	ER, ARs	NA	NA	B
Zhang et al[97], 2014	Chinese	Rome III	104	68.2 (60-80)	CHM	Mosapride	4	ER, GS, ARs	1	NA	B
Zhang et al[98], 2014	Chinese	Rome III	90	65.3 (NA)	CHM	Peg	4	ER, GS	NA	NA	C
Zhang et al[99], 2018	Chinese	Rome III	60	72.4 (60-85)	CHM	Phenolphthalein	4	ER	NA	NA	C
Zhang et al[100], 2018	Chinese	Rome III	106	33.5 (24-58)	CHM	Mosapride	8	ER, BM	1	0/2	B
Zhang et al[101], 2019	Chinese	Rome III	68	41.7 (19-69)	CHM	Probiotics	4	ER, GS	3	NA	B
Zhao et al[102], 2009	Chinese	Rome III	76	42.4 (NA)	CHM	Mosapride	2	ER, GS	1	11/11	B
Zhao et al[103], 2014	Chinese	Rome III	76	56.7 (15-80)	CHM	Peg	4	ER, GS	NA	NA	C
Zhao et al[104], 2015	Chinese	Rome III	68	51.4 (18-70)	CHM	Mosapride	4	ER, GS, ARs	NA	NA	B
Zhao et al[105], 2015	Chinese	Rome III	100	4.2 (1-14)	CHM	Lactulose	8	ER, GS	14	1/2	B
Zhao et al[106], 2018	Chinese	Rome III	90	53.7 (23-67)	CHM	Lactulose	8	ER, GS	NA	NA	B
Zhao et al[107], 2019	Chinese	Rome III	66	68.4 (65-84)	CHM	Peg	3	ER, BSS	3	0/1	C
Zhong et al[108], 2018	English	Rome III	194	44.6 (18-70)	CHM	Placebo	8	ER, BM, GS, ARs	2	3/7	A
Zhou et al[109], 2018	Chinese	Rome III	80	51.3 (30-70)	CHM	Mosapride	4	ER, GS, ARs	NA	7/9	B

CHM: Chinese herbal medicine; PEG: Polyethylene glycol; ER: Efficacy rate; BM: Bowel movement; GS: Global symptom; BSS: Bristol Stool Scale; RR: Recurrence rate; AEs: Adverse effects; A: Methodology with a low risk of bias; B: Methodology with an unclear risk of bias; C: Methodology with a high risk of bias.