DARU Journal of Pharmaceutical Sciences (2019) 27:811–826

https://doi.org/10.1007/s40199-019-00297-w

REVIEW ARTICLE

Traditional, complementary and alternative medicine in children

constipation: a systematic review
Maryam Sadat Paknejad 1 & Monireh Sadat Motaharifard 1 & Shahdis Barimani 2 & Payam Kabiri 3 & Mehrdad Karimi 1

Received: 5 February 2019 / Accepted: 9 August 2019 / Published online: 16 November 2019
# Springer Nature Switzerland AG 2019

Abstract
Objectives This review aims to evaluate the efficacy and safety of complementary and alternative medicine methods for consti-
pation in the pediatric population.
Evidence acquisition Medical literature search was performed in several databases for a variety of Traditional, Complementary
and Alternative Medicine in childhood constipation. Databases included Web of Science, Scopus, Embase, Cochrane Library,
PubMed, ScienceDirect, Google scholar and a number of Persian databases including IranDoc, Magiran and SID. No time
limitation was determined. Clinical trials or case series that had evaluated the effectiveness of CAM therapies in functional
constipation of 1–18 year old children were included. Papers not in English or Persian language were excluded. Related articles
were screened independently by two reviewers according to their titles and abstracts. A data extraction form was filled in for each
eligible paper. Quality assessment of eligible documents was also performed.
Results 30 studies were included, comprising 27 clinical trials and 3 case series. Ten documents were on herbal medicine, nine on
traditional medicine, ten on manual therapies and one on homeopathy. Except for two herbal and one reflexology interventions,
all studies reported positive effects on childhood constipation, with the majority being statistically significant. As the number of
studies in each method was limited, we could not perform a meta-analysis.
Conclusion The scarcity of research on the efficacy and safety of different types of complementary and alternative medicine
methods in children with constipation necessitates conducting more studies in each field.

Keywords Complementary therapies . Alternative medicine . Traditional medicine . CAM . Constipation . Pediatrics

Objectives systems [1]. The prevalence of childhood constipation varies

in different countries, ranging from 0.7% to 29.6% [2].
Although initially a benign condition, functional constipation Approximately 30.8% of 2 to 12 year old Indian children are
in the pediatric population is an important issue in healthcare affected by this condition [3]. In Colombia, the prevalence is

Electronic supplementary material The online version of this article

(https://doi.org/10.1007/s40199-019-00297-w) contains supplementary
material, which is available to authorized users.

* Mehrdad Karimi Payam Kabiri

[email protected] [email protected]
Maryam Sadat Paknejad 1
[email protected] School of Traditional Medicine, Tehran University of Medical
Sciences, Building of the Ahmadiyeh, No 27, Corner Alley Tabriz,
Sarparast Shomali Str, Taleghani Ave, Tehran 1416663361, Iran
Monireh Sadat Motaharifard
2
[email protected] Department of Persian Medicine, Shiraz University of Medical
Sciences, Shiraz, Iran
3
Shahdis Barimani Department of Biostatics and Epidemiology, School of Public
[email protected] Health, Tehran University of Medical Sciences, Tehran, Iran
812 DARU J Pharm Sci (2019) 27:811–826

14.5% in children aged 8 to 12 years and 10% in 13 to 18 year Evidence acquisition

olds [4]. In china, 18.8% of the pediatric population suffer
from constipation in contrast to 8.2% in the general population Data sources
[5]. Moreover, 3% of all general pediatric visits and up to 25%
of visits by pediatric gastroenterologists in the USA are attrib- Medical literature search was performed in databases includ-
uted to constipation [6]. ing: Web of Science, Scopus, Embase, Cochrane Library,
The economic burden of constipation in the pediatric PubMed, ScienceDirect, Google scholar and some Persian
population is also variously reported [7]. The mean total databases including IranDoc, Magiran and SID to
unadjusted annual expenditure for children with consti- May 2019. All databases were searched without time limita-
pation is 3 times higher than those not affected by this tion. Only English or Persian papers were included.
condition [8]. Furthermore, some disorders such as
headache, depression, anxiety, influenza, otitis media, Study selection
and asthma are more prevalent in constipated children,
resulting in extra costs for healthcare systems [9]. In The search strategy was: constipation[Mesh Terms and free
2011, the number of 1–17-year-old children with consti- text terms] AND (pediatrics [Mesh Terms and free text terms]
pation visited in USA emergency wards was 50.7% OR pediatric [Mesh Terms and free text terms] OR
more than similar population in 2006. This increase child[Mesh Terms and free text terms]) AND (Acupuncture
can be attributed to a sedentary lifestyle, obesity, and OR acupressure OR “Guided imagery” OR “Alexander tech-
increased use of medications in the recent years [10]. nique” OR Hypnosis OR Massage OR Meditation OR
Accordingly, more burden can be expected in the future Reflexology OR Rolfing OR “structural integration” OR
years. Constipation obviously affects a child’s quality of “Tai chi” OR “Therapeutic touch” OR “Ayurvedic
life. This is demonstrated by lower scores in quality of Medicine” OR Ayurveda OR “Siddha Medicine” OR Yoga
life tests compared to healthy children. Their scores are OR Curanderismo OR “Native American Medicine” OR
even significantly less than those affected by GERD and TCM OR “Traditional Chinese Medicine” OR “Persian
IBD [11]. Drawing attention to the chronicity of the Medicine” OR “Traditional Iranian Medicine” OR “Iranian
condition, it has been demonstrated that only 60% of Traditional Medicine” OR “Tibetan Medicine” OR “Unani
children are symptom free 6–12 months following initi- Medicine” OR “Anthroposophic Medicine” OR Chiropractic
ation of treatment [12]. In longer follow-ups, symptoms OR Homeopathy OR Naturopathy OR Osteopathy OR herbal
remained in one out of four children, in some instances OR phytomedicine OR phytotherapy).
even persisting into adulthood [13]. Related papers were screened according to their titles and
Considering the mentioned condition altogether, it is abstracts. Papers with uncertain decisions were studied thor-
anticipated that some parents seek alternative or comple- oughly. Every paper was independently studied by two of the
mentary treatments hoping for probable better outcomes. three reviewers (MSP, MSM and SB). In case of disagree-
Lifetime usage of complementary and alternative thera- ment, reviewers made a decision after discussing the issue.
pies for children and adolescent varies from 10.9% to Otherwise the third reviewer would assist. Bibliography of
87.6% in different countries, with the current rate being papers were searched to find cross references.
0.8% to 48.5% [14]. In Germany, 26% of used remedies
are CAM remedies [15]. In gastroenterology clinics of the Eligibility criteria
Netherlands, CAM usage rate is 25.3% for functional and
17.2% for organic gastrointestinal problems. Among chil- Eligibility criteria included 1) clinical trials or case series eval-
dren with constipation, approximately 36.4% use CAM uating the effectiveness of CAM therapies in functional con-
therapies for various conditions, while 24.1% use them stipation in children; 2) study population in the age range of 1–
to treat their constipation. While 93% of the parents be- 18; 3) the study being on one of the aforementioned CAM
lieved in the necessity of clinical research on CAM, 51% methods; 4) language of evidence being English or Persian.
declared that they would consent to their child participat-
ing in such studies [16]. Data extraction
Beyond parent viewpoints, evaluating the effectiveness and
safety of CAM modalities in children is a realistic and even A data extraction form was designed to obtain necessary in-
urgent need that should be prioritized in more prevalent dis- formation of the documents such as age of participants, details
eases and those that cause more burden. of interventions, diagnostic criteria for constipation, tools used
This review aims to evaluate the efficacy and safety of a to follow up patients, criteria used to define response, meth-
variety of complementary and alternative medicine subtypes odological factors and primary and secondary outcomes of the
in childhood constipation. study. Each document was reviewed by two of three reviewers
DARU J Pharm Sci (2019) 27:811–826 813

(MSP, MSM and SB) independently. In case of different opin- In a study by Cai, 478 patients were allocated to interven-
ions that could not be resolved by discussion, the third review- tion and placebo groups in a ratio of 3:1 to ensure statistical
er would help. If information was not sufficient, further infor- significance and consider the research grant.
mation was obtained from the corresponding author via email.

Quality assessment Classification of interventions

JADAD score [17] was used to assess the quality of clinical We categorized included studies under four categories: herbal
trials. The quality of case series studies was evaluated by medicines, traditional medicines, manipulations and other.
CARE extensions for homeopathic and therapeutic massage
and bodywork [18, 19]. Two of the three reviewers performed
Herbal medicines
the quality assessments of every paper according to the afore-
mentioned procedure.
Ten studies had assessed herbal interventions in children
constipation.
Some herbal medicines are a compound of different plants.
Results Fruitlax is a blend of raisin, currant, prune, fig and date.
AFPFF is the mixture of acacia fiber, psyllium fiber, and fruc-
A total of 6993 studies were retrieved. 3995 studies were tose. Fijan Figs is a syrup containing fig and senna extract.
excluded because they were not English/Persian or were du- Glucomannan is a fiber gel polysaccharide derived from
plicate; consequently, 2998 studies were screened according Japanese Konjac tubers. Its efficacy on childhood constipation
to their titles and abstracts.132 records were studied thorough- was assessed in three studies.
ly to assess their eligibility. Their reference lists were screened PHGG is obtained from guar gum, a water-soluble fiber
to find more related studies other than those that were found in from seeds of Cyamopsis tetragonoloba. It has a smaller mo-
electronic searches, but no additional study was found. lecular weight and less viscosity than guar gum [23].
Finally, 30 records were included. The process is summarized Black strap molasses and red sugar are byproducts in the
in a flow diagram in Fig. 1. Detailed information of these 30 sugar-making process. Sugar syrup (molasses) is what causes
studies are summarized in Table 1. the color of red sugar. They are both derived from Saccharum
officinarum (sugarcane) [35, 36].

Characteristics of included studies Traditional medicines

Filho et al. [49] reported the effect of homeopathic interven- According to WHO, Traditional medicine is “the sum total of
tions on a variety of different patients. A group of constipated the knowledge, skills, and practices based on the theories,
children was among the cases, and so we extracted a case beliefs, and experiences indigenous to different cultures,
series of the effectiveness of homeopathy in childhood consti- whether explicable or not, used in the maintenance of health
pation. In the study conducted by Iwai et al., 15 constipated as well as in the prevention, diagnosis, improvement or treat-
patients were enrolled, five of which had a history of anorectal ment of physical and mental illness” [50].
malformations and were thus excluded. The remaining ten Dai-Kenchu-To is a traditional Japanese preparation that is
patients were included in our study. a combination of zanthoxylum fruit, ginseng root and dried
ginger rhizomes.
Xiao’er Biantong (XEBT) is a drug from Traditional
Description of included populations Chinese Medicine. It is the first Chinese patent medicine for
functional constipation in children and is composed of seven
Six studies included patients with disabilities. Although these herbs.
conditions can influence constipation, we decided not to ex- Mozaffarpur et al. Nimrouzi et al. and Esmaeilidooki et al.
clude them, due to the scarcity of studies about such interven- had designed their studies based on Persian Medicine, as well
tions in otherwise healthy children. Two studies were per- as Shahamat et al. that has studied the efficacy of dry cupping
formed on CP patients, two on mentally disabled, and one in on childhood constipation. Cupping is performed by placing a
patients with tertiary healthcare needs. In one study (Day cup on the skin and applying negative pressure by suction [34,
et al.) the characteristics of patients are mentioned as disability 51] .
in brief. These disabilities can be explained as Down syn- The study by Mali was designed according to Ayurveda,
drome, hemiplegia, Rette syndrome, and etc. one of the traditional medicinal systems of India.
814 DARU J Pharm Sci (2019) 27:811–826

Number of hits for electronic search (n=6993)

Cochrane:87
Embase: 89
Scopus: 273
Web of science: 143
Pubmed: 125
Sciencedirect: 2383
Google scholar: 3673
SID: 191
Magiran: 27
Irandoc: 2

Duplicates and non Englis/Persian removed (n=3995)

2998 records screened

2866 records excluded

132 full-text records assessed for eligibility

102 records excluded

Not RCT or case series: 44
Adult: 28
Not functional constipation: 25
Not CAM: 5

0 additional records achieved through hand searching of references list of full texts reviewed

30 records included
herbal medicine: 10
Persian medicine: 6
Trad onal Chinese Medicine: 1
Ayurvedic Medicine: 1
Japanese Trd onal Medicine: 1
Massage: 3
Reflexology: 2
Accupuncture: 1
Osteopathy: 1
Homeopathy: 1
Ch ce: 1
Visceral and neural manipu on: 1
Connective tissue manipulation and
Kinesiotaping: 1
Fig. 1 Flow diagram of assessment of identified studies
Table 1 Characteristics of included studies

First author (year) Study design Total sample (female patients) Age in Diagnostic criteria Criteria used to define response
other characteristics year

Herbal Day [20] Quasi experimental, single 7 (5) 3–9 Identified by a parent and a Improvement of frequency/ amount/ color/
Medicine (1995) subject, AB design Disability healthcare worker consistency of stool; defecation effort; need for
medication to relieve constipation
Loening-Baucke [21] Double blind 31 (15) 4.5–11.7 Delay or difficulty in DF/W > =3 and SE/3 w < =1 with no abdominal
(2004) crossover RCT defecation, for 2 w, causes pain
significant
distress
Castillejo [22] Double blind RCT 56 (34) 3–10 Rome II CTT
DARU J Pharm Sci (2019) 27:811–826

(2006)
Ustundag [23] RCT 61 (−) 4–16 Rome III Soft to formed stool; no pain/ stool withholding
(2010) /blood in stool/ palpable rectal or abdominal
mass
Chmielewska [24] Double blind RCT 80 (46) 3–16 Rome III >=3
(2011) Stools/w with no soiling
Quitadamo [25] RCT 100 (62) 4–10 Rome III ≥3 bowel movements/w, ≥2 stool consistency
(2012) grade on BSFS, no fecal incontinence, abdominal pain,
pain on defecation or fecal bleeding.
Horvath [26] Follow up of Chmielewska, 63 of 72 3–16 A standardized questionnaire DF > =3, no SE in last week, abdominal pain, or
(2013) et al need for laxatives
Staiano [27] Double blind RCT 19 5.7 ± 4.2 An arbitrary scoring system Stool habits, total and
(1999) (5) y segmental gastrointestinal transit times, and
severe brain damage anorectal motility
PerKin [28] Crossover RCT 21 Under 15 > = 3 months of History of Improvement in number and characteristics of
(1977) constipation stools
Closa-Monasterolo [29] Double blind RCT 17 2–5 Rome III Improvement in symptoms
(2017) (9) of constipation and stool characteristics
Traditional Iwai [30] CT 10* 6–13 Clinical scoring system Clinical scoring system
Medicine (2007) Severe constipation by JSGA by JSGA, anorectal manometry
Mozaffarpur [31] RCT 81 (29) 4–13 Rome III <=2 criteria from Rome ІІІ
(2012)
Nimrouzi [32] RCT 109 (61) 2–12 Rome III DF > =3, soft stool, convenient defecation, no SE
(2015) and bloody stool/w, exiting the Rome III
Esmaeilidooki [33] Open label RCT 109 (46) 2–15 Rome III To exit from Rome III
(2016)
Shahamat [34] RCT 120 (52) 4–18 Rome III DF > =3, soft stool, convenient defecation, no
(2016) soiling or bloody stool, not fulfilling Rome III
for constipation
Tajik [35] RCT 60 (20) 2–10 Physician decision Improvement in a designed questionnaire
(2018)
Dehghan [36] Double blind RCT 92 4–12 Rome III Improvement in DF, absence of lumpy or hard
(2019) stools, abdominal pain and retention,
soiling and blood-stained stool, sensation of
anorectal obstruction/
blockage
Mali [37] Single blind CT 10 (−) 2–8 Hard stool An assessment criteria**
(2016)
Cai [38] Double blind RCT 478*** (251) 1–14 Rome IV Improvement of median effectual time of
(2018) defecation, main
symptom score and disappearance rate of
symptoms and the differences between groups
Manipulations Broide [39] CT 32 (10) 2–14 A bowel habit questionnaire Increase of DF
(2001)
815
 816

Table 1 (continued)

First author (year) Study design Total sample (female patients) Age in Diagnostic criteria Criteria used to define response
other characteristics year

Gordon [40] Single blind RCT 176 (81) 1–12 Rome II Mean increase of 4.5 complete bowel movements
(2007) per week in 4 weeks
Alcantara [41] Case series 3 (2) 21,7,21 m – Improved bowel movements
(2008)
Tarsuslu [42] CT (Pilot study) 13 (5) 2–16 CAS CAS, VAS,
(2009) CP DF
Silva [43] Triple blind RCT 72 (42) 4–18 Rome III –
(2013) tertiary healthcare needs
Bromley [44] CT 25 (−) 3 m- 19 y NICE (2010a & 2014) –
(2014) Mental disability
Orhan [45] RCT 45 (19) 4–18 Rome III VAS, PEDsQL, BSFS and 7-day bowel diaries
(2016) CP (4.5–1-
1.5)
Elbasan [46] RCT 40 (16) 3–15 Modified Constipation Modified Constipation Assessment Scale (MCAS)
(2018) CP Assessment Scale (MCAS)
Canbulat Sahiner [47] RCT 40 3–6 Rome III Defecation number and consistency
(2017)
Zollars [48] Case series 5 (2) 3–18 Rome II criteria modified for Improvement in radiographically assessed colonic
(2018) CP children with cerebral motility, DF or quality of stool
palsy
Others Filho [49] Case series 5 (3) 1–7 Patient complaint (3), An improvement scale
(2005) Mental disability homeopath diagnosis (2)

Experimental intervention Control intervention Follow up (s) Primary outcome measures Main results

Herbal Fruitlax No control group Baseline A (2 w), Frequency/ amount/ color/ consistency of Each child experienced individual
Medicine 18 m-6y:4 ts/d, if stool still hard on 3rd day, increased intervention stool; defecation effort; need for changes in bowel pattern
daily until stool became soft (max: 7 ts/d) period B (> = 3 medication to relieve constipation.
scales for 6–12 y and > 12 y were also developed w)
4 w glucomannan and 4 w placebo, both 100 mg/kg (maximum of5 g/d) 4th, 8th w DF, soiling Glucomannan is beneficial
frequency, and disappearance of abdominal in childhood constipation ±
pain in the last 3 encopresis
weeks of a 4-week treatment
Cocoa husk supplement sachet (containing 4 g of cocoa Placebo + 4th w CTT Significant differences between
husk) standardized toilet training groups when total basal intestinal
3–6 y: 1 procedures transit
7–10 y: 2 time was in the 50th percentile
before lunch and dinner +
standardized toilet training procedures
PHGG in fruit juice during or between meals lactulose (1 ml/kg/d, in divided 4th w ND No statistical difference between
4–6 y: 3 g/d; 6–12 y: 4 g/d; 12–16 y: 5 g/d doses) groups
(P > 0.05)
Glucomannan 2.52 g/d Placebo (maltodextrine) 2.52 g/d 4th w Treatment success (> = 3 Treatment success
stools/w with no soiling) was similar in both groups
(relative
risk 0.95, 95% CI 0.6 to 1.4)
AFPFF PEG 3350 with electrolytes (PEG+ 1st, 2nd, 4th, 8th w Improvement of constipation 77.8% of AFPFF group and 83%
16.8 g daily (up to 22.4 g, while not improved after at E) of
least 3 d of treatment) (0.5 g/kg daily) PEG+E group improved
(P = .788)
DARU J Pharm Sci (2019) 27:811–826

– – Treatment success
Table 1 (continued)

Experimental intervention Control intervention Follow up (s) Primary outcome measures Main results

24 m after Treatment success in 57%,

completion of functional
previous study constipation in
27%, need for laxatives 21%
no differences
between groups
Glucomannan Placebo 4th, 8th, 12th w Number of bowel movements per Glucomannan significantly
100 mg/kg BD week, stool consistency, presence of painful increased
defecation, abdominal distention, use of stool frequency (P < .01),
DARU J Pharm Sci (2019) 27:811–826

laxative or suppository decreased

painful defecation per week
(P < .01)
And improved stool consistency
Lactulose (10–15 ml daily) or Senna syrup (10–20 ml daily) in 1st w, no treatment in 2nd w, the Beginning of 2nd Number Significant difference, in favor of
alternative treatment in 3rd w and 3rd w of patients passing stools of any kind each lactulose, in the number of days on
day which
normal stools were passed
during the
treatment
weeks
Orafti® inulin-type fructans Placebo (maltodextrin) 6th w Stool consistency Stool consistency improved from
2 g BD, mixed into a non-pre or probiotics dairy product 2 g BD, mixed into a non-pre or 2.2 to
probiotics dairy product 2.6 on the modified Bristol
scale for
children in intervention group
(p = 0.040). no improvement in
control
group
Traditional 0.3 g/kg/d of DKT No control group Before and after Clinical score for bowel function, DKT improved clinical score for
Medicine ,from 3 m to 1 y duration intervention manometric study bowel
function (P < 0.02), threshold
sensation volume and rectal
compliance (P < 0.05) and
maximum
tolerable volume (P < 0.01)
CFE, 0.1 g/kg in three-separated doses (after each meal) Mineral oil: 1 ml/kg/d 1st, 2nd, 3rd w Improvement in 1) DF, 2) fecal incontinence DF was higher in CFE group
episodes, (P < 0.001),
3) retentive posturing episodes, severity of pain during
4)average of severity of defecation pain (by defecation and
VAS) consistency of stool were better
5)average of consistency of stool (by VAS) in CFE
per week group (P < 0.05)
Oral solution of Descurainia sophia L. seeds PEG 40% without electrolyte Weekly Proportion No significant difference between
2–4 y: 2 g/d (0.4 g/kg) of patients who had responded to treatment groups
4–12 y: 3 g/d for 8 w in DF, Hard stool, Painful
defecation
and soiling
1 cc/kg /d of CFE in 3 divided doses, for 4 0.7–0.8 g/kg/d of water 1st, 2nd, 3rd,4th w DF, consistency of stools, severity of pain All measures improved in both
w soluble PEG twice during defecation, retentive posturing and groups. no
daily fecal incontinence per week. significant difference, except
for DF
that was significantly
more in CFE group
817
 818

Table 1 (continued)

Experimental intervention Control intervention Follow up (s) Primary outcome measures Main results

than PEG group (P < 0.0001)

Dry cupping, fourteen 8 min sessions, 4–6 cups, PEG (40% solution without 2nd, 4th, 8th, 12th Improvement of constipation decreased constipation in PEG
1.5–5 cm in diameter (10–100 cc), every other day electrolyte), 0.4 g/kg once daily w group
(P < 0.01) at 2nd and in
cupping group (P=
0.03)
at 4th w
no significant difference
at 8th and 12th w
Red sugar powder Fijan (containing figs and 2nd, 4th w Functional characteristics of constipation Red sugar was more effective in
2 g / kg / day senna extract) such as DF reducing
2 cc / kg / day anorexia and abdominal pain
(p < 0.001);
No significant difference between
groups
in DF and pain during fecal
excretion
BSM (black strap molasses) PEG syrup 2nd, 4th w Improvement in DF, absence of lumpy or Significantly improvement of DF
1 mL/kg daily for 1 month. hard stools, abdominal pain and retention, in both
soiling and blood-stained stool, sensation of groups; Decreased volitional
anorectal obstruction/ stool
blockage retention, large diameter stool,
painful
or hard stool and large fecal
mass in the
rectum (P < 0.05); no
significant
difference between groups
except for
the rate of large diameter stool
Haritaki Churna (Terminalia chebula) + Madhu (honey), No control group 5th d Improvement of constipation Constipation improvement
0.7 - 2 g/d (acc. to Dilling formula) BD + Dietary (P < 0.001)
advices
Xiao’er Biantong (XEBT) granules Placebo granules 1st, 2nd, 4th w Frequency of spontaneous SBM for 14 days were 8.89 in
1–3 y: 2.5 g, TDS 1–3 y: 2.5 g, TDS bowel movements (SBM) for 14 days XEBT group and 5.63 in
4–6 y: 5 g, BD; 4–6 y: 5 g, BD; placebo group (p = 0.0001)
>7 y: 5 g, BD >7 y: 5 g, BD
Manipulations 5 weeks of placebo followed by 10 weeks of true Healthy controls received no After 5, 10, 15 DF and DF↑ (P < 0.001)
acupuncture up to treatment acupuncture panopioid activity panopioid activity↑ (P < 0.001)
3 needles for 20 min session
Group 1: Reflexology Group 2: Foot massage, both by Standard treatment 12th, 24th, 36th w Number of complete bowel movements in In the 12th w, the reflexology
parents/care givers + conventional treatment in both 4 weeks group experienced the greatest
period reduction in total constipation
score 9.91 (SD 8.153)
95% CI 7.87–11.94 compared to
13.91 (SD11.491) 95% CI
10.86–16.96 in control
and 13.67 (SD 10.120) 95% CI
10.94–16.41 in massage group
(p = 0.047)
Full spine chiropractic care (high velocity – 1–3 y follow up Bowel movement Normal bowel movements in all
low amplitude thrusts and the activator technique) 3 w patients
to 3 m
DARU J Pharm Sci (2019) 27:811–826
Table 1 (continued)

Experimental intervention Control intervention Follow up (s) Primary outcome measures Main results

Osteopathy: Osteopathy+ lactulose 3rd, 6th m CAS, VAS, DF CAS↓ (P < .05), constipation
fascial release, iliopsoas )initiated 10 mL/d for children <6 improvement (P < .05) in both
muscle release, sphincter release, and bowel y, 15 mL/d for children older. groups.
mobilizations After 1 w, doses were No difference between groups
during 30 halved in either
minutes, 3 /w for 6 m aspects (P > .05)
Abdominal muscle training+ breathing exercises+ Magnesium hydroxide at least 6th w DF and retentive fecal incontinence Higher DF in physiotherapy
abdominal massage 2 mg/kg PRN + fiber dietary group than in medication
40 min × 2 sessions /w foods, water and toilet training group (P = 0.01)
DARU J Pharm Sci (2019) 27:811–826

+ control group interventions

Abdominal massage by parents, 20 min/d No control group 6th w Constipation improvement Improved quality of life (100%),
(as preferred e.g., 5 min × 4 or 10 min × 2) symptom relief
(87.5%), reduced laxative use
(58%),
improved dietary intake (41%).
CTM: Lifestyle advice 4w DF Among the CTM, KT, and control
Three 15–20 min sessions/w + lifestyle advice. groups, there were statistically
lower thoracic, scapular, inter-scapular and cervical significant differences
regions regarding
KT: 3/w + lifestyle advice the changes in DF (2.46, 3.00,
0.30, ES 1.16, P < 0.001),
Foot reflexology, 20 min sessions, twice a week for Neurodevelopmental treatment 8th w MCAS score Decrease in MCAS scores in
8 weeks + neurodevelopmental therapy program, 45–60 min sessions, reflexology
twice a week, for 8 weeks. group (<0.001)
no significant difference between
groups
Foot massage with baby oil Toilet/diet/motivation training for 1st, 2nd, 3rd, 4th w Stool number and consistency No significant differences in stool
(10 min × 5 / w) parents (30 min, once per week) frequency and consistency
toilet/diet/ between groups (p > .05)
motivation training for parents
(30 min, once per week)
Visceral and neural manipulation focused on abdomen – 8th, 16th, 24th and Radiographically assessed colonic motility, Number of bowel movements
and related aspects of the nervous system, 45 min 36th w DF and quality of stool increased
sessions, every 2 w for a total of 24 w during the study for all
participants
Others Individually according to homeopath decision – Individually Improvement of constipation 2 cases: clear improvement,
1 case: partial improvement,
2 cases: no changes

AFPFF a mixture of acacia fiber, psyllium fiber, and fructose, BSFS Bristol Stool Scale, CAS Constipation Assessment Scale, 2006, CFE Cassia fistula emulsion, CT Clinical Trial, CTM Connective Tissue
Manipulation, CTT Colonic Transit Time, d day/ days, DF defecation frequency (times/week) DKT Dai-Kenchu-To, ES Effect Size, JSGA Japanese Study Group of Anorectal Anomalies, KT Kinesio
Taping, m month/ months, ND No Declaration, NICE National Institute for Health and Care Excellence, PEDsQL Pediatric Quality of Life Questionnaire, PEG Poly Ethylene Glycol, PHGG partially
hydrolyzed guar gum, RCT Randomized Controlled Trial, SE Soiling Episode, Ts teaspoon, VAS Visual Analogue Scale (VAS), w week/ weeks, y year/years
*Five children with constipation after surgery for anorectal malformations were excluded from the study
**Vibandha (difficult stool pass)
1 Normal: 00
2 Alpasha, Grathita Malapravrutti: 01
3 Avashthambhit Malapravrutti: 02
***359 patients in intervention and 119 patients in control group
819
820 DARU J Pharm Sci (2019) 27:811–826

Manipulations Effectiveness of interventions

Ten studies evaluated the effects of manual techniques on Most interventions had positive effects on childhood consti-
constipation in children. Some definitions are provided in pation, with the majority being statistically significant. An
the following. except was the Chmielewska research on the efficacy of
glucomannan and its follow up study by Horvath et al.
Reflexology: application of specific massage technique Likewise, Elbasan et al. could not demonstrate a positive ef-
on hands, feet and ears believed to impress function of fect of foot reflexology in children’s constipation. A previous
organs. [46]. study by Canbulat Sahiner had also failed to demonstrate an
Osteopathy: hands on techniques used to rectify and effect for foot massage in such patients.
regulate structural and functional systems by careful
examination of the tonus and texture of tissues and
correction of restrictions and abnormal movements Adverse effects
consequently [42].
Chiropractic: the conservative management of Reported adverse effect (AE) of interventions are listed in
neuromusculoskeletal system with special emphasis on Table 2. Thirteen studies did not represent any information
the spine [52, 53]. about AEs. In four studies no AE was observed, while no
Visceral and neural manipulation focuses on fascia, significant AEs were reported in yet three other research.
nerves, bones, joints, body organs and the vasculature. Other studies reported gastrointestinal AEs, such as vomiting,
Visceral manipulation is a hands-on method that involved diarrhea, abdominal pain and distention.
in normal mobility, tone, and tissue motion of the viscera
and their connective tissues attachments. Neural
Manipulation is a manual therapy that recognizes and Risk of bias of included studies
treats neural and dural restrictions in association with
cranium and spinal hard frame [48]. The quality assessment of included studies are listed in
Connective Tissue Manipulation: a manual therapy that Tables 3 and 4.
stimulates segmental and supra-segmental cutaneo-vis-
ceral reflexes, which can retrieve autonomic balance
and result in better functioning of organs [45]. Discussion
Kinesio Taping: In Kinesio Taping, elastic, latex-free,
adhesive and thin bands are used. They can be stretched Constipation is a common health problem in the pediatric
up to between 40% and 60% of its original length, similar population [54]. In this age group, constipation is a family
to the elasticity of the skin [45]. issue that has a negative impact on children’s physical, social,
emotional, and school functions. Moreover, this condition has
It seems that in the recent years, more trials are being car- a significant impact on the use and cost of medical services
ried out on the efficacy of various manipulations on constipa- [8].
tion in the pediatric population. Due to the various underlying causes of constipation in
No clinical trials or case series were found in fields of pediatrics, more treatment options are available compared to
Alexander technique, Guided imagery, Hypnosis, defaecatory dysfunction. This review focuses on the evidence
Meditation, Rolfing/structural integration, Tai chi, for treatment options of this type of constipation based on
Therapeutic touch, Yoga, Curanderismo, Native American CAM.
medicine, Siddha medicine, Tibetan medicine or Insofar as we searched, our study is the first systematic
Anthroposophic medicine. review on the efficacy of various CAM interventions on pe-
Treatment durations differed based on intervention type; diatric constipation. A comprehensive search across multiple
for example, Terminalia chebula was administered for 5 days databases with no time limit ensured maximum results for the
and osteopathy was studied in a six month period. current study. A systematic review of herbal medicine efficacy
Intervention durations were not prearranged in some studies in GI disorders (2017) [55] discovered one eligible study for
such as Filho et al. (homeopathy) [49], Alcantara et al. herbal medicine in childhood constipation [25], whereas our
(chiropractic) [41] and Iwai (Traditional Japanese Medicine) study included ten studies in this field (See Table 1). In addi-
[30], instead being determined depending on patient tion, we tried to include most CAM methods, even less rec-
conditions. ognized ones.
DARU J Pharm Sci (2019) 27:811–826 821

Table 2 Adverse effects of interventions

First author (year) Adverse effects

Herbal Day [20] ND

medicine (1995)
Loening-Baucke None
[21]
(2004)
Castillejo [22] No significant adverse effect
(2006)
Ustunda [23] Abdominal pain or distension, emesis, no significant difference between groups
(2010)
Chmielewska [24] Similar in both groups (gastroenteritis possibly not related, vomiting probably related to medication)
(2011)
Quitadamo [25] No significant adverse effect except for transient diarrhea, relieved by dose reduction
(2012)
Horvath [26] ND
(2013)
Staiano [27] None
(1999)
Perkin [28] The number and frequency of side-effects (diarrhea, colic, distension) in senna treatment week were very much
(1977( higher (P < 0.001) than in the lactulose week
Closa-Monasterolo No increase in distension or flatulence
[29]
(2017)
Traditional Iwai [30] ND
medicine (2007)
Mozaffarpur [31] Diarrhea decreased by dose reduction (12 patients), sputum like stool (one patient)
(2012)
Nimrouzi [32] Flatulence and Abdominal Pain
(2015) No significant difference between groups
Esmaeilidooki [33] CFE: Diarrhea (25%) and abdominal pain
(2016) (3.8%) ameliorated
by decreasing drug dose
PEG: (26.3%) diarrhea, (8.7%) abdominal pain relieved by dose adjustment, except for 1 patient.
Shahamat [34] ND
(2016)
Tajik [35] No side effects
(2018)
Dehghani [36] No significant side-effects, except for abdominal pain in seven patients in the PEG group and four in black strap
(2019) molasses group in the first week of treatment, which disappeared with continuation of the treatment
Mali [37] ND
(2016)
Cai [38] Loose stools, diarrhea and vomiting but no significant differences between groups
(2018)
Manipulations Broide [39] ND
(2001)
Gordon [40] None
(2007)
Alcantara [41] ND
(2008)
Tarsuslu [42] ND
(2009)
Silva [43] None
(2013)
Bromley [44] ND
(2014)
Orhan [45] No serious side effects
(2016)
Elbasan [46] ND
(2018)
Canbulat Sahiner ND
[47]
(2017)
822 DARU J Pharm Sci (2019) 27:811–826

Table 2 (continued)

First author (year) Adverse effects

Zollars [48] ND
(2018)
Others Filho [49] ND
(2005)

ND Not Declared

Most CAM methods have their own rationales [56] those Dietary fibers like glucomannan may influence defecation by
can influenced relevant researches. For example, blinding in several possible mechanisms: 1) the increased colonic con-
some CAM interventions is a limitation. Designing a placebo tents may accelerate colonic transit and reduce colonic absorp-
for acupuncture, manual therapies and herbal remedies with tion of fluid; 2) fermentation of fiber releases gases, which
their special smell, taste and color is a complex process with may be trapped in colonic contents, contributing to their bulk;
certain difficulties. However, it can partly be compensated by 3) the fiber may slow down absorption in the small intestine.
blinding evaluators [57], an issue that has been considered in The results of the study by Closa-Monasterolo, reinforces
some included studies. the possible beneficial effects of the use of inulin-type fructans
Since diagnosis and treatment in CAM is usually complex as fully fermentable dietary fibers from chicory roots to coun-
and nonlinear [56], durations of interventions were deter- teract constipation in young children and return bowel habits
mined individually in some studies. Nowadays, this is not an to a normal state [29].
unusual approach as “Individualized Medicine” has emerged Polysaccharides of molasses can serve as dietary fibers and
in medical literatures. Indeed, some attempts are being made bulking agents in the bowels. The naturally high potassium
to provide molecular biology evidences for individualized di- content of molasses syrup make this product an efficient treat-
agnostic and interventional approaches of many CAM modal- ment option for pediatric functional constipation [36].
ities [58–61]. Other mechanisms can also be considered for herbal rem-
Diversity of treatment and follow up duration is another edies. Xiao’er Biantong which is a Chinese traditional remedy,
point. Perhaps shorter treatment duration is a variable that consists of seven herbal medicine; each can take a role in
can result in better patients’ compliance, although it does not ameliorating constipation via the following mechanisms: 1)
guarantee more persistent outcomes necessarily. acetyl choline and serotonin, which regulate GI motility, 2)
The distinct circumstances of CAM modalities have moti- magnolol, which can adjust brain function, 3) anthraquinones,
vated some methodologists to employ special methods [56] which improve colon motor function, 4) reactive Aloeemodin,
and checklists [62] to assess CAM studies, although most the drug metabolite by colonic flora that reinforces peristalsis
researchers still prefer common methods [63]. and reduce fluid absorption via cholinergic receptors, 5) direct
Some studies selected individuals with disabilities such as effect on specific on distal colon longitudinal muscles [38,
CP, or mentally disabled patients that can affect the outcomes. 66–68].
Nevertheless, we did not exclude such papers because little Purgative mechanism of action of D. sophia has not been
surveys were found in some types of interventions. Reasons elucidated yet. Water absorbing mucilage may soften the
may contain the less popularity of theme, small area in which stool. Allyl disulfide (sulfur glycoside such as descurainoside)
they practiced, being hard to be examined in a standard trial or in D. sophia seed may results in smooth muscles relaxation
lack of efficient connections to scientific communities. and assist to defecation [69]. Nor-lignans, secondary metabo-
Meanwhile, the number of pediatric surveys are generally less lites of the plant such as descuraic acid, can be effective in
than studies conducted on adults. It can be interpreted on the ameliorating constipation.
basis of children studies nature that make their studies more It seems that DKT display its laxative properties by con-
difficult regarding medical ethics considerations. tractile effect on small intestine [70].
Lack of control groups was a pitfall in some included stud- Anthraquinone derivatives are the most probable responsi-
ies that lowers the quality of such researches. Although many ble agents for cathartic and laxative effects of Cassia fistula
CAM interventions seem safe, monitoring and reporting ad- fruits pulp [31, 71]. Anthraquinone glycone and anthraqui-
verse effects is imperative. This fact, which is a conclusion none glycosides are two forms of anthraquinones which have
Wu TX et al. has declared about Chinese herbal medicine laxative properties. The degree of laxative potency is depen-
researches [64], was ignored in several included studies. dent on the content of anthraquinone [72].
One of the main probable mechanisms of action for herbal Although more studies are needed to understand the exact
drugs in constipation is the mechanism of fibers. Low-fiber mechanism of action of manual therapies, some mechanisms
intake has been associated with constipation in children [65]. can be assumed. The effects of reflexology on constipation in
DARU J Pharm Sci (2019) 27:811–826 823

Table 3 Quality assessment of included clinical trials

First author (year) Randomization Blinding An account of all Score

patients
Mentioned Appropriate Inappropriate Mentioned Appropriate Inappropriate fate of all patients
known, if not reason
is stated

Herbal Day [20] 0 0 1 1

medicine (1995)
Loening-Baucke 1 1 1 1 1 5
[21]
(2004)
Castillejo [22] 1 1 1 1 1 5
(2006)
Ustundag [23] 1 1 0 1 3
(2010)
Chmielewska [24] 1 1 1 1 1 5
(2011)
Quitadamo [25] 1 1 0 1 3
(2012)
Horvath [26] 1 1 1 1 1 5
(2013)
Staiano [27] 1 0 1 0 1 3
(1999)
PerKin [28] 1 1 0 1 3
(1977(
Closa-Monasterolo 1 1 1 1 1 5
[29]
(2017)
Traditional Iwai [30] 0 0 1 1
medicine (2007)
Mozaffarpur [31] 1 1 0 1 3
(2012)
Nimrouzi [32] 1 1 0 1 3
(2015)
Esmaeilidooki [33] 1 1 0 1 3
(2016)
Shahamat [34] 1 1 0 1 3
(2016)
Tajik [35] 1 1 0 1 3
(2018)
Dehghani [36] 1 1 1 1 1 5
(2019)
Mali [37] 0 0 1 1
(2016)
Cai [38] 1 1 1 1 1 5
(2018)
Manipulations Broide [39] 0 0 1 1
(2001)
Gordon [40] 1 1 1 1 1 5
(2007)
Tarsuslu [42] 0 0 0 0
(2009)
Silva [43] 1 1 0 1 3
(2013)
Bromley [44] 0 0 1 1
(2014)
Orhan [45] 1 1 0 1 3
(2016)
Elbasan [46] 1 1 0 1 3
(2018)
Canbulat Sahiner 1 0 0 1 2
[47]
(2017)
824 DARU J Pharm Sci (2019) 27:811–826

Table 4 Quality assessment of included case series Author contributions MK made the main themes of the study. MSP
searched databases and selected articles. MSP, MSM and SB assessed
First author (year) Risk of bias papers for eligibility, read full texts, filled a form for each one and
assessed their quality. MSP created the table of results and wrote review
Filho [49] Moderate risk of bias draft. MK and PK reviewed the draft critically. MK was the guarantor of
(2005) the study.
Alcantara [41] Moderate risk of bias
(2008)
Zollars [48] Moderate risk of bias Compliance with ethical standards
(2018)
Conflict of interest None

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