CONTEXT:

Gastrointestinal disorders are common childhood complaints. Particular types of complementary and alternative medicine, such as herbal medicine, are commonly used among children. Research information on efficacy, safety, or dosage forms is still lacking.

OBJECTIVES:

To systematically summarize effectiveness and safety of different herbal treatment options for gastrointestinal disorders in children.

DATA SOURCES:

Medline/PubMed, Scopus, and the Cochrane Library were searched through July 15, 2016.

STUDY SELECTION:

Randomized controlled trials comparing herbal therapy with no treatment, placebo, or any pharmaceutical medication in children and adolescents (aged 0–18 years) with gastrointestinal disorders were eligible.

DATA EXTRACTION:

Two authors extracted data on study design, patients, interventions, control interventions, results, adverse events, and risk of bias.

RESULTS:

Fourteen trials with 1927 participants suffering from different acute and functional gastrointestinal disorders were included in this review. Promising evidence for effectiveness was found for Potentilla erecta, carob bean juice, and an herbal compound preparation including Matricaria chamomilla in treating diarrhea. Moreover, evidence was found for peppermint oil in decreasing duration, frequency, and severity of pain in children suffering from undifferentiated functional abdominal pain. Furthermore, evidence for effectiveness was found for different fennel preparations (eg, oil, tea, herbal compound) in treating children with infantile colic. No serious adverse events were reported.

LIMITATIONS:

Few studies on specific indications, single herbs, or herbal preparations could be identified.

CONCLUSIONS:

Because of the limited number of studies, results have to be interpreted carefully. To underpin evidence outlined in this review, more rigorous clinical trials are needed.

Functional gastrointestinal disorders like irritable bowel syndrome (IBS), functional abdominal pain, constipation, and infantile colic as well as acute gastrointestinal disorders like gastroenteritis are common childhood complaints that affect a large proportion of children and adolescents.1,4 Beside the painful impacts for the child, gastrointestinal disorders can lead to lower quality of life, school absenteeism, and a higher risk of depression and anxiety.5,6 Parents are also affected not only because they commiserate with their offspring but also because of the time needed to care for their child. Therefore, gastrointestinal disorders in children and adolescents may lead to both major reductions in quality of life for the child and parents and major socioeconomic impacts for the family and wider society.5,7 

The management of gastrointestinal disorders in children and adolescents, especially functional gastrointestinal disorders, can be challenging.8,9 Parents often visit different practitioners in search of a reliable diagnosis or therapy. Many available treatments are either effective but yield potential for undesirable adverse effects, or safe but might lack effectiveness.10 This may lead to conflicting advice, different prescribed treatments, and high direct and indirect costs.7,11,12 In this context, a high prevalence of complementary and alternative medicine (CAM) use can be observed among patients suffering from gastrointestinal disorders.13,16 Research suggests that parents often favor CAM products, such as herbal medicine, in the belief they are natural and therefore safe.17 In addition to this, evidence suggests some parents may also be dissatisfied or fear the side effects of conventional medication.18 As a result, parents often do not disclose the use of CAM to the attending pediatrician.19,23 

Whereas ∼52% of all children in Europe are using some kind of CAM, the use of particular types of CAM, such as herbal medicine, is increasingly common among children.20,24,27 Although herbal medicines are commonly used, research detailing information on efficacy, safety, dosage forms, and dose quantities is still lacking. In response, the scope of this review is to systematically summarize the effectiveness and safety of different herbal treatment options for gastrointestinal disorders in children and adolescents.

This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and recommendations of the Cochrane Collaboration.28,29 

Types of Studies

Randomized controlled trials (RCTs), randomized cross-over trials, and cluster-randomized trials were eligible. Trials were included if they were published in English or German.

Types of Participants

Only studies on children (0–12 years of age) or adolescents (13–18 years of age) were included if patients suffered from gastrointestinal complaints such as diarrhea, constipation, colic, IBS, inflammatory bowel diseases, and other disorders of the gastrointestinal tract.

Types of Interventions

Studies that compared herbal medicines with treatment-as-usual or other active comparators, placebo, or no treatment were eligible. If the herbal drug was applied only in homeopathic potency or if the herb is exclusively used in traditional Chinese medicine (so-called Chinese herbal medicine often includes ingredients of animal or mineral origin), the study was not included in this review. No other dosage restrictions were made.

Medline/PubMed, Scopus, and the Cochrane Central Register of Controlled Trials (Central) were searched from their inception dates to July 15, 2016. Embase was not searched separately because it is included in Scopus. Because this article is part of a major project to identify evidence for herbal therapy in children, the literature search was widely constructed around basic search terms for “children” and search terms for “herbal therapy.” The complete search strategy for PubMed/Medline is shown in Supplemental Information. For each database, the search strategy was adapted as necessary. Abstracts identified during the literature search were screened, and potentially eligible articles were read in full independently by 3 review authors (DA, HC, and RL) to determine if they met eligibility criteria. After identifying the literature in the field of interest, only these articles with children and adolescents suffering from gastrointestinal complaints as mentioned above were taken into account.

Extraction of data on methods, patients (eg, age, sex, diagnosis), interventions (herbs, dose, etc), control interventions, and results was performed by 2 review authors (DA and RL) independently by using an a priori-developed data extraction form. Discrepancies were rechecked with a third reviewer (HC) and discussed until consensus was achieved.

By using the Cochrane risk of bias tool, the risk of bias of each included study was assessed by 2 authors (DA and HC) independently. This tool assesses risk of bias by using 7 criteria (rating: low, unclear, or high risk of bias): random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting, and other biases. Discrepancies were rechecked with a third reviewer and discussed until consensus was achieved. Trial authors were contacted for further details if necessary.

Literature search retrieved 10 083 nonduplicate records, of which 259 full texts were assessed for eligibility. Eighty-six of them were considered to be eligible for the whole field of herbal medicine in children and adolescents, whereas 173 full texts were excluded for the following reasons: they were not RCTs, the investigated herbs were exclusively used in traditional Chinese medicine, the herbal drug was applied only in homeopathic potency, or the study had no participants between 0 and 18 years exclusively. Finally, 14 full-text articles involving a total of 1927 participants suffering from gastrointestinal disorders were included in this review (Fig 1).

FIGURE 1

Flowchart of the results of the literature search.

FIGURE 1

Flowchart of the results of the literature search.

Detailed characteristics of samples sizes, interventions, outcome assessments, and results are shown in Table 1.

TABLE 1

Characteristics of Included Studies

AuthorStudy populationExperimental group age, medianControl group age, medianIntervention(s)Control condition(s)Measurement(s)Outcome measure(s)Results
Gastroenteritis 
Diarrhea 
Akşit et al30  Patients with acute diarrhea, N = 80; age: 4–48 mo 15 ± 13 mo 18 ± 14 mo WHO-ORS and CBJ 20 mL/kg body weight and breast milk or cows’ milk-yoghurt-mix WHO-ORS 20 mL/kg body weight and breast milk or cows’ milk-yoghurt-mix Initial visit, then regularly until diarrhea stopped Primary outcome Significant group differences after therapy 
 1. Duration of diarrhea (d) Primary outcome 
 2. Stool output (g/kg body weight)  1. Duration of diarrhea (d) 
Secondary outcomes  2. Stool output (g/kg body weight) 
 1. WHO-ORS intake (mL/kg body weight) Secondary outcomes 
 2. Weight gain in percent  1. WHO-ORS intake (mL/kg body weight) 
 3. Serum sodium (mmol/L)  2. Serum sodium (mmol/L) 
 4. Serum potassium (mmol/L)  3. Serum potassium (mmol/L 
Subbotina et al31  Patients with rotavirus diarrhea, N = 40; age: 3 mo–7 y 23.5 mo 22.5 mo WHO-ORS 20 mL/kg body weight; 3 drops P erecta elixir (1 part of dried root with 10 parts of 40% ethyl alcohol) per year of life, 3 times daily until discontinuation of diarrhea or maximum of 5 d WHO-ORS 20 mL/kg body weight; 3 drops placebo elixir per year of life, 3 times daily until discontinuation of diarrhea or maximum of 5 d Initial visit, then daily until diarrhea ceased, or stool output was <10 mL/kg/d, stool consistency was normalized, and symptoms of dehydration were corrected Primary outcome Significant group differences after therapy 
 1. Duration of diarrhea (d) Primary outcome 
Secondary outcomes  1. Duration of diarrhea (d) 
 1. Duration of abnormal stool (d) Secondary outcomes 
 2. Duration of hospitalization (d)  1. Duration of abnormal stool (d) 
 3. Stool output (mL/kg/d)  2. Duration of hospitalization (d) 
 4. Oral rehydration volume (mL/kg/d)  3. Stool output (mL/kg/d) 
Becker et al32  Patients with acute diarrhea, N = 225; age: 6 mo–6 y 33.76 ± 22.99 mo 33.02 ± 22.77 mo Oralpädon and Diarrhoesan (apple pectin, M chamomilla) dosage: Diarrhoesan up to 40–80 mL/d depending on age; Oralpädon within the first 24 h: 1 sachet after each stool over 5 d Oralpädon and placebo in same dosage Initial visit, and at day 3 and day 5 of intervention Primary outcome Significant group differences after therapy 
 1. Duration of diarrhea (h) Primary outcome 
 2. Stool frequency  1. Duration of diarrhea (h) 
 3. Consistency of stool  2. Stool frequency 
Secondary outcomes 
 1. Therapeutic response 
 2. General condition 
 3. Existence of abdominal cramps 
 4. Efficacy 
De la Motte et al33  Patients with acute diarrhea, N = 79; age: 6 mo–5.5 y — — Diarrhoesan 5 mL per dose bag, maximum dose 12 bags a day depending on age Placebo in same dosage Diary assessed by parents: Initial, then 2 times/d until diarrhea ceased Primary outcome Significant group differences after therapy 
 1. Duration of diarrhea (h) Primary outcome 
Secondary outcomes  1. Duration of diarrhea (h) 
 1. Consistency of stool 
 2. Well-being 
Dehydration 
Freedman et al34  Patients with mild gastroenteritis, N = 647; age: 6–60 mo 28 ± 15.4 mo 29 ± 16.5 mo Half-strength apple juice, 5 mL aliquots every 2–5 min up to 2 L, and preferred other liquids (juices or milk) Apple-flavored, sucralose-sweetened pediatric electrolyte solution, in same dosage Initial visit, then daily telephone assessment by parents for 7 d of intervention Primary outcome Significant group differences after therapy 
 1. Treatment failure, defined as a composite score of intravenous rehydration or hospitalization, subsequent unscheduled physician encounter, protracted symptoms or significant weight loss occurring within 7 d of enrollment Primary outcome 
 1. Treatment failure 
Secondary outcomes Secondary outcomes 
 1. Intravenous rehydration  1. Intravenous rehydration 
 2.Hospitalization 
 3. Frequency of diarrhea and vomiting 
 4. Percentage of weight change 
Functional gastrointestinal disorders 
Infantile colic 
Alexandrovich et al35  Patients with infantile colic, N = 125; age: 2–12 wk 29.7 ± 8.2 d 30.5 ± 6.9 d Emulsion of 0.1% of fennel seed oil (F vulgare) and 0.4% polysorbate-80 in water, a minimum of 5 mL and a max of 20 mL up to 4 times a day Emulsion of 0.4% polysorbate-80 in water in same dosage Diary assessed by parents. Diaries were entered for 21 d (7 d before the trial, during the 7-d trial, 7 d after the trial). Visits before, during, and after intervention Primary outcome Significant group differences after therapy 
 1. Relief of colic symptoms (defined as <9 h cumulative crying h/wk) Primary outcome 
Secondary outcomes  1. Relief of colic symptoms (defined as <9 h cumulative crying h/wk) 
 1. Cumulative crying at the end of treatment (h/wk) Secondary outcomes 
 2. Consumed emulsion/placebo (mL/d)  1. Cumulative crying at the end of treatment (h/wk) 
 3. No. doses per day  2. Consumed emulsion/placebo (mL/d) 
 3. No. doses/d 
Alves et al36  Patients with infantile colic, N = 30; age: 8–56 d (m = 33 ± 11.1 d) — — Peppermint oil drops (1 drop/kg body weight). Simethicone drops (2.5 mg/kg body weight) Initial visit, and at day 7 and day 17 of intervention Primary outcome Significant group differences after therapy 
 1. Responses to treatment No significant group differences for responses to treatment. No other results reported 
 2. Daily episodes of colic  
 3. Crying time (h)  
Secondary outcomes  
 1. Milk regurgitation  
 2. Vomiting  
 3. Diarrhea  
 4. Constipation  
 5. Drowsiness  
Arikan et al37  Patients with infantile colic, N = 175; age: 4–12 wk 2.24 ± 0.69 mo contr grp 1: 2.29 ± 0.75 mo Fennel tea (F vulgare) 3 times a day 35 mL up to 150 mL Grp. 1: massage 2 times 25 min/d; grp. 2: 12% sucrose solution 2 times a day 2 mL; grp. 3: hydrolyzed formula; grp. 4: treatment as usual Diary assessed by parents, 7 d during the intervention Primary outcome Significant group differences after therapy 
 contr grp 2: 1.97 ± 0.75 mo  1. Crying time (h) Primary outcome 
 contr grp 3: 1.97 ± 0.71 mo Secondary outcomes  1. Crying time (h) when compared with treatment as usual. No comparison of fennel tea to the other interventions was performed 
 contr grp 4: m = 2.28 ± 0.61 mo  No secondary outcomes  
Savino et al38  Patients with infantile colic, N = 93; age: 21–60 d 4.2 ± 1.4 wk 4.4 ± 1.6 wk ColiMil (F vulgare, M chamomilla, M officinalis) 2 mL/kg (body weight) Placebo in same dosage Initial visit, and after intervention period (7 d). Diary assessed by parents, 7 d during the intervention and 14 d after intervention Primary outcome Significant group differences after therapy 
 1. Crying time (mean min/d) Primary outcome 
Secondary outcomes  1. Crying time (mean min/d) 
 1. Treatment responding Secondary outcomes 
  1. Treatment responding 
Weizmann et al39  Patients with infantile colic, N = 68; age: 2–8 wk 21.1 ± 9.3 d 24.6 ± 7.6 d Herbal tea preparation (M chamomilla, V officinalis, G glabra, F vulgare, M officinalis); every episode of colic, up to 150 mL/dose, not more than 3 times a day Placebo tea preparation: instant powder of glucose and natural flavors in same dose Diaries assessed by parents: 7 d with no therapy, and 7 d of treatment. Initial examination by pediatrician, and at day 7, and day 14 1. No. of night wakings requiring parental response Significant group differences after therapy 
2. Elimination of colic  1. Elimination of colic 
3. Colic improvement  2. Colic improvement 
No primary outcome defined  
Irritable bowel syndrome 
Kline et al40  Patients with irritable bowel syndrome, N = 42; age: (8–17 y) Total: m = 12 y — — Colpermin capsules (pH-dependent peppermint oil 187 mg), 3 times/d 1–2 capsules depending on weight Placebo capsules with peanut oil in same dosage Initial visit, and at day 14 of intervention Primary outcome Significant group differences after therapy 
 1. Gastrointestinal symptom rating No significant group differences 
Shulman et al41  Patients with irritable bowel syndrome N = 103; age: 7–18 y 13.1 ± 0.4 y 13.5 ± 0.4 y Psyllium fiber powder, 6–12 g depending on age per day Maltodextrin powder in same dosage 2 wk baseline measurement, 6 wk treatment period, final assessment within the last 2 wk of treatment period Primary outcome Significant group differences after therapy 
 1. Number abdominal pain episodes Primary outcome 
 2. Severity of abdominal pain episodes  1. Number abdominal pain episodes 
 3. Percentage of normal stools  
Secondary outcomes  
 1. Changes in breath hydrogen/methane production  
 2. Gut permeability  
Functional abdominal pain 
Asgarshirazi et al42  Patients with functional abdominal pain, N = 120; age: 4–13 y 7.06 ± 2.38 y contr grp 1: 7.42 ± 2.49 y Colpermin capsules (pH-dependent peppermint oil 187 mg), 3 times/d 1–2 capsules depending on weight Grp 1: Folic acid tablet 1 mg, daily 30 min before breakfast or lunch; grp 2: Lactol tablets (150 million spores of Bacillus coagulans + Fructooligosaccharide), 3 times/d after meals Questionnaire before, and after 4 wk intervention. Periodic visits during intervention period 1. Duration of pain (min/d) Significant group differences after therapy 
contr grp 2: 7.44 ± 2.44 y 2. Frequency of pain, per week Compared with Placebo 
 3. Severity of pain  1. Duration of pain (min/d) 
 No primary outcome defined  2. Frequency of pain, per week 
   3. Severity of pain 
  Compared with Lactol 
   1. Duration of pain (min/d) 
   2. Severity of pain 
Constipation 
Quitadamo et al43  Patients with chronic functional constipation, N = 100; age: 4–10 y 6.5 ± 2.6 y 6.7 ± 2.8 y Mixture of Acacia fiber, Psyllium, and fructose powder 16.8 g/d + 0.5 g/kg body weight Polyethylene glycol 3350 with electrolytes 16.8 g/d + 0.5 g/kg body weight Initial visit, daily stool diary assessed by parents, and follow-up-visits 1, 2, 4 and 8 wk after enrollment Primary outcome Significant group differences after therapy 
 1. Improvement of constipation No significant differences between both groups 
Secondary outcomes  
 1. Improvement of other associated gastrointestinal symptoms  
AuthorStudy populationExperimental group age, medianControl group age, medianIntervention(s)Control condition(s)Measurement(s)Outcome measure(s)Results
Gastroenteritis 
Diarrhea 
Akşit et al30  Patients with acute diarrhea, N = 80; age: 4–48 mo 15 ± 13 mo 18 ± 14 mo WHO-ORS and CBJ 20 mL/kg body weight and breast milk or cows’ milk-yoghurt-mix WHO-ORS 20 mL/kg body weight and breast milk or cows’ milk-yoghurt-mix Initial visit, then regularly until diarrhea stopped Primary outcome Significant group differences after therapy 
 1. Duration of diarrhea (d) Primary outcome 
 2. Stool output (g/kg body weight)  1. Duration of diarrhea (d) 
Secondary outcomes  2. Stool output (g/kg body weight) 
 1. WHO-ORS intake (mL/kg body weight) Secondary outcomes 
 2. Weight gain in percent  1. WHO-ORS intake (mL/kg body weight) 
 3. Serum sodium (mmol/L)  2. Serum sodium (mmol/L) 
 4. Serum potassium (mmol/L)  3. Serum potassium (mmol/L 
Subbotina et al31  Patients with rotavirus diarrhea, N = 40; age: 3 mo–7 y 23.5 mo 22.5 mo WHO-ORS 20 mL/kg body weight; 3 drops P erecta elixir (1 part of dried root with 10 parts of 40% ethyl alcohol) per year of life, 3 times daily until discontinuation of diarrhea or maximum of 5 d WHO-ORS 20 mL/kg body weight; 3 drops placebo elixir per year of life, 3 times daily until discontinuation of diarrhea or maximum of 5 d Initial visit, then daily until diarrhea ceased, or stool output was <10 mL/kg/d, stool consistency was normalized, and symptoms of dehydration were corrected Primary outcome Significant group differences after therapy 
 1. Duration of diarrhea (d) Primary outcome 
Secondary outcomes  1. Duration of diarrhea (d) 
 1. Duration of abnormal stool (d) Secondary outcomes 
 2. Duration of hospitalization (d)  1. Duration of abnormal stool (d) 
 3. Stool output (mL/kg/d)  2. Duration of hospitalization (d) 
 4. Oral rehydration volume (mL/kg/d)  3. Stool output (mL/kg/d) 
Becker et al32  Patients with acute diarrhea, N = 225; age: 6 mo–6 y 33.76 ± 22.99 mo 33.02 ± 22.77 mo Oralpädon and Diarrhoesan (apple pectin, M chamomilla) dosage: Diarrhoesan up to 40–80 mL/d depending on age; Oralpädon within the first 24 h: 1 sachet after each stool over 5 d Oralpädon and placebo in same dosage Initial visit, and at day 3 and day 5 of intervention Primary outcome Significant group differences after therapy 
 1. Duration of diarrhea (h) Primary outcome 
 2. Stool frequency  1. Duration of diarrhea (h) 
 3. Consistency of stool  2. Stool frequency 
Secondary outcomes 
 1. Therapeutic response 
 2. General condition 
 3. Existence of abdominal cramps 
 4. Efficacy 
De la Motte et al33  Patients with acute diarrhea, N = 79; age: 6 mo–5.5 y — — Diarrhoesan 5 mL per dose bag, maximum dose 12 bags a day depending on age Placebo in same dosage Diary assessed by parents: Initial, then 2 times/d until diarrhea ceased Primary outcome Significant group differences after therapy 
 1. Duration of diarrhea (h) Primary outcome 
Secondary outcomes  1. Duration of diarrhea (h) 
 1. Consistency of stool 
 2. Well-being 
Dehydration 
Freedman et al34  Patients with mild gastroenteritis, N = 647; age: 6–60 mo 28 ± 15.4 mo 29 ± 16.5 mo Half-strength apple juice, 5 mL aliquots every 2–5 min up to 2 L, and preferred other liquids (juices or milk) Apple-flavored, sucralose-sweetened pediatric electrolyte solution, in same dosage Initial visit, then daily telephone assessment by parents for 7 d of intervention Primary outcome Significant group differences after therapy 
 1. Treatment failure, defined as a composite score of intravenous rehydration or hospitalization, subsequent unscheduled physician encounter, protracted symptoms or significant weight loss occurring within 7 d of enrollment Primary outcome 
 1. Treatment failure 
Secondary outcomes Secondary outcomes 
 1. Intravenous rehydration  1. Intravenous rehydration 
 2.Hospitalization 
 3. Frequency of diarrhea and vomiting 
 4. Percentage of weight change 
Functional gastrointestinal disorders 
Infantile colic 
Alexandrovich et al35  Patients with infantile colic, N = 125; age: 2–12 wk 29.7 ± 8.2 d 30.5 ± 6.9 d Emulsion of 0.1% of fennel seed oil (F vulgare) and 0.4% polysorbate-80 in water, a minimum of 5 mL and a max of 20 mL up to 4 times a day Emulsion of 0.4% polysorbate-80 in water in same dosage Diary assessed by parents. Diaries were entered for 21 d (7 d before the trial, during the 7-d trial, 7 d after the trial). Visits before, during, and after intervention Primary outcome Significant group differences after therapy 
 1. Relief of colic symptoms (defined as <9 h cumulative crying h/wk) Primary outcome 
Secondary outcomes  1. Relief of colic symptoms (defined as <9 h cumulative crying h/wk) 
 1. Cumulative crying at the end of treatment (h/wk) Secondary outcomes 
 2. Consumed emulsion/placebo (mL/d)  1. Cumulative crying at the end of treatment (h/wk) 
 3. No. doses per day  2. Consumed emulsion/placebo (mL/d) 
 3. No. doses/d 
Alves et al36  Patients with infantile colic, N = 30; age: 8–56 d (m = 33 ± 11.1 d) — — Peppermint oil drops (1 drop/kg body weight). Simethicone drops (2.5 mg/kg body weight) Initial visit, and at day 7 and day 17 of intervention Primary outcome Significant group differences after therapy 
 1. Responses to treatment No significant group differences for responses to treatment. No other results reported 
 2. Daily episodes of colic  
 3. Crying time (h)  
Secondary outcomes  
 1. Milk regurgitation  
 2. Vomiting  
 3. Diarrhea  
 4. Constipation  
 5. Drowsiness  
Arikan et al37  Patients with infantile colic, N = 175; age: 4–12 wk 2.24 ± 0.69 mo contr grp 1: 2.29 ± 0.75 mo Fennel tea (F vulgare) 3 times a day 35 mL up to 150 mL Grp. 1: massage 2 times 25 min/d; grp. 2: 12% sucrose solution 2 times a day 2 mL; grp. 3: hydrolyzed formula; grp. 4: treatment as usual Diary assessed by parents, 7 d during the intervention Primary outcome Significant group differences after therapy 
 contr grp 2: 1.97 ± 0.75 mo  1. Crying time (h) Primary outcome 
 contr grp 3: 1.97 ± 0.71 mo Secondary outcomes  1. Crying time (h) when compared with treatment as usual. No comparison of fennel tea to the other interventions was performed 
 contr grp 4: m = 2.28 ± 0.61 mo  No secondary outcomes  
Savino et al38  Patients with infantile colic, N = 93; age: 21–60 d 4.2 ± 1.4 wk 4.4 ± 1.6 wk ColiMil (F vulgare, M chamomilla, M officinalis) 2 mL/kg (body weight) Placebo in same dosage Initial visit, and after intervention period (7 d). Diary assessed by parents, 7 d during the intervention and 14 d after intervention Primary outcome Significant group differences after therapy 
 1. Crying time (mean min/d) Primary outcome 
Secondary outcomes  1. Crying time (mean min/d) 
 1. Treatment responding Secondary outcomes 
  1. Treatment responding 
Weizmann et al39  Patients with infantile colic, N = 68; age: 2–8 wk 21.1 ± 9.3 d 24.6 ± 7.6 d Herbal tea preparation (M chamomilla, V officinalis, G glabra, F vulgare, M officinalis); every episode of colic, up to 150 mL/dose, not more than 3 times a day Placebo tea preparation: instant powder of glucose and natural flavors in same dose Diaries assessed by parents: 7 d with no therapy, and 7 d of treatment. Initial examination by pediatrician, and at day 7, and day 14 1. No. of night wakings requiring parental response Significant group differences after therapy 
2. Elimination of colic  1. Elimination of colic 
3. Colic improvement  2. Colic improvement 
No primary outcome defined  
Irritable bowel syndrome 
Kline et al40  Patients with irritable bowel syndrome, N = 42; age: (8–17 y) Total: m = 12 y — — Colpermin capsules (pH-dependent peppermint oil 187 mg), 3 times/d 1–2 capsules depending on weight Placebo capsules with peanut oil in same dosage Initial visit, and at day 14 of intervention Primary outcome Significant group differences after therapy 
 1. Gastrointestinal symptom rating No significant group differences 
Shulman et al41  Patients with irritable bowel syndrome N = 103; age: 7–18 y 13.1 ± 0.4 y 13.5 ± 0.4 y Psyllium fiber powder, 6–12 g depending on age per day Maltodextrin powder in same dosage 2 wk baseline measurement, 6 wk treatment period, final assessment within the last 2 wk of treatment period Primary outcome Significant group differences after therapy 
 1. Number abdominal pain episodes Primary outcome 
 2. Severity of abdominal pain episodes  1. Number abdominal pain episodes 
 3. Percentage of normal stools  
Secondary outcomes  
 1. Changes in breath hydrogen/methane production  
 2. Gut permeability  
Functional abdominal pain 
Asgarshirazi et al42  Patients with functional abdominal pain, N = 120; age: 4–13 y 7.06 ± 2.38 y contr grp 1: 7.42 ± 2.49 y Colpermin capsules (pH-dependent peppermint oil 187 mg), 3 times/d 1–2 capsules depending on weight Grp 1: Folic acid tablet 1 mg, daily 30 min before breakfast or lunch; grp 2: Lactol tablets (150 million spores of Bacillus coagulans + Fructooligosaccharide), 3 times/d after meals Questionnaire before, and after 4 wk intervention. Periodic visits during intervention period 1. Duration of pain (min/d) Significant group differences after therapy 
contr grp 2: 7.44 ± 2.44 y 2. Frequency of pain, per week Compared with Placebo 
 3. Severity of pain  1. Duration of pain (min/d) 
 No primary outcome defined  2. Frequency of pain, per week 
   3. Severity of pain 
  Compared with Lactol 
   1. Duration of pain (min/d) 
   2. Severity of pain 
Constipation 
Quitadamo et al43  Patients with chronic functional constipation, N = 100; age: 4–10 y 6.5 ± 2.6 y 6.7 ± 2.8 y Mixture of Acacia fiber, Psyllium, and fructose powder 16.8 g/d + 0.5 g/kg body weight Polyethylene glycol 3350 with electrolytes 16.8 g/d + 0.5 g/kg body weight Initial visit, daily stool diary assessed by parents, and follow-up-visits 1, 2, 4 and 8 wk after enrollment Primary outcome Significant group differences after therapy 
 1. Improvement of constipation No significant differences between both groups 
Secondary outcomes  
 1. Improvement of other associated gastrointestinal symptoms  

Cbj, carob bean juice; contr: control; grp, group; m, median; max, maximum; WHO-ORS, World Health Organization-oral rehydration solution; —, not applicable.

The risk of biased judgment in individual studies is shown in Figs 2 and 3. Researchers for 8 studies had reported adequate random sequence generation, whereas for 6 RCTs the randomization procedure remained unclear. Researchers for only 5 of the included studies reported adequate allocation concealment. Researchers for 3 of the included trials did not report blinding of patients and personnel, and 2 studies did not reveal adequate blinding of outcome assessment. Three of the 14 trials had high risk of attrition bias, and 2 were not free of suspected selective reporting. Because of multiple primary outcomes without performing an α-correction, a high risk of other bias has to be suspected for 2 RCTs.

FIGURE 2

Risk of bias assessment: using the Cochrane risk of bias tool and generated with Review Manager 5 software (version 5.2; The Nordic Cochrane Centre, Copenhagen, Denmark).

FIGURE 2

Risk of bias assessment: using the Cochrane risk of bias tool and generated with Review Manager 5 software (version 5.2; The Nordic Cochrane Centre, Copenhagen, Denmark).

FIGURE 3

Risk of bias graph: presented as percentages across all included studies and generated with Review Manager 5 software (version 5.2; The Nordic Cochrane Centre, Copenhagen, Denmark).

FIGURE 3

Risk of bias graph: presented as percentages across all included studies and generated with Review Manager 5 software (version 5.2; The Nordic Cochrane Centre, Copenhagen, Denmark).

Diarrhea

Researchers in 4 studies with a total of 424 participants researched the efficacy of herbal medicine for the treatment of acute diarrhea in children. Two studies observed an herbal compound preparation (Diarrhoesan) containing apple pectin and M chamomilla.32,33 Both studies demonstrated a significant reduction in the duration of diarrhea compared with placebo. Additionally, Becker et al32 showed that the herbal compound significantly reduced stool frequency in comparison with placebo.

Subbotina et al31 investigated the effectiveness of P erecta in treating children with diarrhea due to a rotavirus infection. The duration of diarrhea, abnormal stool, and hospitalization, as well as stool output was decreased significantly compared with placebo.

Researchers in another study observed carob bean juice as an add-on therapy compared with standard therapy alone.30 The duration of diarrhea, stool output, and the intake of a standard rehydration solution was decreased significantly if carob bean juice was given additionally.

Researchers for only 2 of the 4 studies reported adverse events,32,33 with a total of 12 adverse events being registered. None of these were regarded as related to the trial medication.

Dehydration due to Gastroenteritis

Freedman et al34 investigated the effectiveness of half-strength apple juice as a rehydration strategy in 647 children with mild gastroenteritis. The results revealed that apple juice intake provoked significantly fewer treatment failures, defined as a composite score of intravenous rehydration or hospitalization, subsequent unscheduled physician encounter, and protracted symptoms or significant weight loss occurring within 7 days of enrollment when compared with a standard rehydration solution.

Freedman et al34 reported that 2 children were hyponatremic at the time of intravenous insertion (1 in the apple juice group and 1 in the usual care group). No other serious adverse events were reported.

Infantile Colic

Researchers in 5 studies with a total of 491 participants investigated the efficacy of herbal medicine in infants suffering from colic. One study37 demonstrated that a tea of Foeniculum vulgare could significantly decrease the crying time (hours) when compared with usual care, whereas an herbal tea preparation containing M chamomilla, Verbena officinalis, Glycyrrhiza glabra, F vulgare, and Melissa officinalis was superior in elimination of colic and colic improvement in comparison with a placebo tea preparation.39 Similar results were shown by Alexandrovich et al35 for an emulsion of 0.1% of fennel (F vulgare) seed oil. After a 7-day trial, a significant improvement in colic symptoms and cumulative crying time could be observed when compared with placebo. Also, an herbal compound preparation (ColiMil) containing F vulgare, M chamomilla, and M officinalis could reduce the crying time significantly compared with placebo.38 However, no significant group differences for treatment response, daily episodes of colic, and crying time could be shown for peppermint oil drops in comparison with usual care (Simethicone drops).36 

Researchers for 4 of the 5 studies reported that no side effects or adverse events were observed during the study period,35,37,39 whereas Savino et al38 reported side effects such as vomiting, sleepiness, and constipation. None of these side effects were severe, and there was no significant difference between the herbal compound preparation and placebo in the occurrence of side effects.

Irritable Bowel Syndrome

Two RCTs with a total of 145 participants were conducted to research herbal medicine for the treatment of IBS in children and adolescents. Although capsules of peppermint oil (Colpermin) did not show any significant differences when compared with the placebo,40 psyllium fiber powder41 significantly reduced the number of abdominal pain episodes in comparison with the placebo (maltodextrin powder).

The authors of both trials reported that no side effects or adverse events were observed by investigators or parents during the treatment period.

Functional Abdominal Pain

Asgarshirazi et al42 investigated the efficacy of peppermint oil in the treatment of functional abdominal pain disorders. A total of 120 participants were treated either with Colpermin capsules or probiotic tablets, or folic acid tablets as the placebo. When compared with the placebo, peppermint oil significantly reduced the duration of pain (minutes/day), frequency of pain (episodes per week), and severity of pain. In comparison with probiotics, peppermint oil significantly reduced the duration of pain (minutes/day) and the severity of pain.

Asgarshirazi et al42 stated that no adverse events or side effects occurred as a result of peppermint oil use and probiotics during the study period.

Constipation

Quitadamo et al43 studied an herbal compound of acacia fiber and psyllium fiber versus a solution of polyethylene glycol and electrolytes in the treatment of constipation in 100 children. Compliance rates were significantly higher in children treated with the solution of polyethylene glycol and electrolytes (96%) compared with children treated with the herbal compound (72%). No significant differences between both groups were observed in primary or secondary study outcomes.

No serious side effects or adverse events were observed by the authors during the study period.

This analysis indicates an emerging evidence base for the use of certain herbal medicines for conditions such as diarrhea, dehydration, infantile colic, IBS, and functional abdominal pain. P erecta, carob bean juice, and an herbal compound preparation including M chamomilla and apple pectin (Diarrhoesan) were shown to significantly reduce the duration of symptoms in children suffering from diarrhea. This review also demonstrated that peppermint oil (Colpermin) can decrease duration, frequency, and severity of pain in children suffering from undifferentiated functional abdominal pain, whereas Colpermin showed no effects in treating children and adolescents with IBS exclusively. Furthermore, evidence was found for different fennel preparations (eg, oil, tea, herbal compound ColiMil) in treating children with infantile colic. This review also found that psyllium fiber may be a useful adjunct in treating children with constipation and in decreasing pain episodes in patients with IBS. However, research evaluating the efficacy and safety of herbal medicine for gastrointestinal disorders in children is in its infancy. Because the number of included RCTs for the different herbs and indications was small, future rigorous RCTs might change the existing conclusions.

Two previously conducted systematic reviews failed to locate any systematic reviews on the use of herbal medicine for gastrointestinal disorders in children.44,45 A previous literature review of herbal medicine use in children included 90 clinical studies, of which one-third were conducted in China in children with respiratory disorders.46 A further 18 studies were located that investigated the use of herbal medicine for gastrointestinal disorders, however only 2 clinical studies of garlic for diarrhea were mentioned in the results. Although the review found that RCTs are feasible with children, the authors noted that few high-quality trials were identified.46 

There are several limitations to this systematic review. Although aligning our methodology with guidelines from the Cochrane Collaboration strengthens rigor overall and decreases risk of bias, it also means that early-stage, non-RCTs of herbal medicines were not captured. Although this was the intent, it was designed to exclude trial designs that may give preliminary insights into an understudied area and emerging field of research. Secondly, many RCTs that were included in this systematic review were small trials with between 30 and 100 participants and larger trials are warranted to further examine efficacy and safety of herbal medicine for gastrointestinal disorders in the pediatric population. Thirdly, most of the studies revealed no adverse events, calling into question the way that adverse events information was collected and recorded. A number of studies did not indicate whether information on adverse events was collected.

It is difficult to make a strong recommendation for the use of herbal medicine for gastrointestinal disorders in children when the evidence base is only just emerging. Large-scale trials are needed to further investigate early positive results presented here; however, research in herbal medicine faces many challenges when compared with the study of synthetic drugs. Many herbal medicines are not standardized with batch-to-batch and label-to-label variations because of various elements such as growing conditions, manufacturing processes, and differing formulations. In addition to this, there are many ethical47 and clinical hurdles involved in studying the use of herbal medicine in children. Despite these challenges, additional well-designed trials are required to build an adequate evidence base and give accurate information on dosing to assist clinical decision-making and ensure the safe use of herbal medicine for children.

A recent study found that over two-thirds of children attending gastroenterology outpatient clinics at a tertiary pediatric hospital were using complementary medicine including herbal medicine.48 The vast majority of parents surveyed (80%) felt that medical professionals should support the use of CAM.48 Medical professionals could recommend the use of herbal medicines that have been shown to be safe and effective as a first-line measure to parents who have expressed interest in trying CAM for their children. Herbal medicines such as P erecta (tormentil), carob bean juice, and Diarrhoesan for diarrhea; peppermint oil (Colpermin) for functional abdominal pain; fennel preparations (eg, oil, tea, herbal compound ColiMil) for treating infantile colic; and psyllium fiber can be used as an adjunct while treating constipation in children with IBS. Currently, most herbal medicine used by children is parent initiated and often not disclosed to a primary health care professional, leading to concerns about safety, herb–drug interactions and inadequate treatment.49 This revelation underscores the need to have open and nonjudgmental conversations with parents about the use of herbal medicine to ensure safe, coordinated patient care.

     
  • CAM

    complementary and alternative medicine

  •  
  • IBS

    irritable bowel syndrome

  •  
  • RCT

    randomized controlled trial

Mr Anheyer conceptualized and designed the study, conducted the literature review, collected the data, created the tables and figures, and drafted the initial manuscript; Drs Cramer and Lauche participated in conceptualizing and designing the review, participated in collecting the data, and reviewed and revised the manuscript; Dr Frawley and Ms Koch participated in drafting the initial manuscript, and reviewed and revised the manuscript; Drs Dobos and Langhorst critically reviewed the manuscript; and all authors approved the final manuscript as submitted.

FUNDING: This review was supported by a grant from the Karl and Veronica-Carstens Foundation and the Rut- and Klaus-Bahlsen Foundation. The funding sources had no influence on the design or conduct of the review; the collection, management, analysis, or interpretation of the data; or in the preparation, review, or approval of the manuscript.

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Competing Interests

POTENTIAL CONFLICT OF INTEREST: Dr Langhorst has received grants from Schwabe Pharma, Steigerwald and Repha; the other authors have indicated they have no potential conflicts of interest to disclose.

FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.

Supplementary data