Digestive Diseases and Sciences

, Volume 55, Issue 5, pp 1385–1390

The Effect of Enteric-Coated, Delayed-Release Peppermint Oil on Irritable Bowel Syndrome

Authors

  • Shahin Merat
    • Digestive Disease Research Center, Shariati HospitalTehran University of Medical Sciences
  • Shadi Khalili
    • Digestive Disease Research Center, Shariati HospitalTehran University of Medical Sciences
  • Pardise Mostajabi
    • Digestive Disease Research Center, Shariati HospitalTehran University of Medical Sciences
  • Anahita Ghorbani
    • Digestive Disease Research Center, Shariati HospitalTehran University of Medical Sciences
  • Reza Ansari
    • Digestive Disease Research Center, Shariati HospitalTehran University of Medical Sciences
    • Digestive Disease Research Center, Shariati HospitalTehran University of Medical Sciences
Original Article

DOI: 10.1007/s10620-009-0854-9

Cite this article as:
Merat, S., Khalili, S., Mostajabi, P. et al. Dig Dis Sci (2010) 55: 1385. doi:10.1007/s10620-009-0854-9

Abstract

Herbal remedies, particularly peppermint, have been reported to be helpful in controlling symptoms of irritable bowel syndrome (IBS). We conducted a randomized double-blind placebo-controlled study on 90 outpatients with IBS. Subjects took one capsule of enteric-coated, delayed-release peppermint oil (Colpermin) or placebo three times daily for 8 weeks. We visited patients after the first, fourth, and eighth weeks and evaluated their symptoms and quality of life. The number of subjects free from abdominal pain or discomfort changed from 0 at week 0 to 14 at week 8 in the Colpermin group and from 0 to 6 in controls (P < 0.001). The severity of abdominal pain was also reduced significantly in the Colpermin group as compared to controls. Furthermore, Colpermin significantly improved the quality of life. There was no significant adverse reaction. Colpermin is effective and safe as a therapeutic agent in patients with IBS suffering from abdominal pain or discomfort.

Keywords

Irritable bowel syndromePeppermint oilDelayed-action preparationsAbdominal pain

Introduction

Irritable bowel syndrome (IBS) consists of a group of functional bowel disorders [1] characterized by abdominal discomfort or pain accompanied by changes in bowel habits in the absence of any known mechanical, inflammatory, or biochemical explanation for these symptoms [2]. It can be accompanied by an array of symptoms including increased or decreased bowel movements, hard or loose stools, passage of mucus or extensive gas, urgency of defecation, straining during a bowel movement, feeling of incomplete evacuation and abdominal fullness or bloating [2].

Being common, it affects up to 20% of the general population [2]. IBS is a chronic troublesome condition [1] that puts both patients and the healthcare system into heavy expenses [3, 4] as a result of significant impairment in health-related quality of life [5] and work productivity [6].

As the underlying pathogenesis of IBS is not clear [7], current treatments are aimed at relieving the prominent symptoms of the disease. Among them, herbal remedies, particularly peppermint, are of great interest.

Peppermint is a plant that belongs to the mint family [8]. Its extract, peppermint oil, has been shown to have various therapeutic effects such as alleviating tension-type headaches [9], relieving non-ulcer dyspepsia, [10] reducing colonic spasm during barium examination, [11, 12] and antiviral activity against HSV-1 and HSV-2 [13] either alone or in combination. Peppermint oil, and its major constituent, menthol, also has relaxing effects on gastrointestinal smooth muscle by blocking Ca2+ channels in the gut, which may be useful in improving IBS symptoms [14, 15]. This finding has led medical researchers to investigate the effectiveness of peppermint oil in IBS treatment [16, 17]. Previous studies have suggested that an enteric-coated peppermint-oil formulation (Colpermin) might be helpful in relieving some symptoms of irritable bowel syndrome [18, 19].

Therefore, we conducted a randomized double-blind placebo-controlled clinical trial in outpatients with IBS in order to examine the effectiveness of Colpermin in terms of relieving symptoms and improving quality of life.

Subjects and Methods

Subjects

Consecutive patients referred to an outpatient university clinic in Tehran during 2004 were evaluated. The diagnosis of IBS was made using the Rome II criteria. Physical examination, complete blood count, serum markers for celiac disease, liver function test, stool exam, and sigmoidoscopy were performed for all subjects. Additional studies were performed according to the patient’s age and prominent symptom. Patients over 40 years old underwent total colonoscopy or barium enema. In patients with predominant diarrhea or flatulence, lactase deficiency was ruled out by a 3-week lactose-free regimen and hydrogen breath test. Upper GI endoscopy was preformed for patients with frequent dyspepsia, and patients with predominant abdominal pain in the right upper quadrant underwent ultrasonographic evaluation of the biliary system. Patients with any abnormal result were excluded. Other exclusion criteria included progressive symptoms, nocturnal diarrhea, steatorrhea, onset of symptoms at age above 40, known malignancy, liver disease, lung disease, immunologic disease, neurological or psychological disease, pregnancy or lactation, inflammatory bowel disease, multiple or recent abdominal surgery, treatment with lactulose or other stimulating agents, treatment with other drugs used for IBS, and chronic use of analgesics or narcotics.

Sample Size Calculation

The possibility of placebo response (improvement in symptoms from baseline) was assumed to be 40% and improvement by Colpermin 75% [20, 21]. We calculated the sample size to detect this difference with a power of 85% at a significance level of 0.05. Assuming a loss of 20%, we calculated a sample size of 43 subjects in each group. We enrolled 90 patients.

Interventions

Patients were randomized into study or placebo groups using a computer-generated randomization table. Patients in the study group took one capsule of Colpermin (Tillotts Pharma, Ziefen, Switzerland) containing 187 mg or 0.2 ml peppermint oil, three times daily 30 min before each meal for 8 weeks. The placebo group received an identical-looking placebo. The medications were packaged in indistinguishable boxes and were labeled with numbers linked to the randomization table. Neither the researchers nor the patients were aware of the true contents of the packages.

Follow-Up

Participants were visited four times during the study; once at the beginning of the trial, then at weeks 1, 4, and 8 (visits 1 through 4).

Three questionnaires were used to evaluate patients during the study. The first was completed by the researchers at each visit (researcher questionnaire). The second was a report filled by the patients in person (patient questionnaire), and the third questionnaire, a validated Persian translation of the SF-36 form for assessment of quality of life, completed at visits 1 and 4 by the researcher [22]. The researcher questionnaire, which was not validated, included symptoms of abdominal pain, abdominal discomfort, heartburn, nausea and vomiting, abdominal distention and bloating, increased flatus, decreased or increased passage of stool, stool consistency, urgency, feeling of incomplete evacuation, and any new complaints. Based on its intensity and frequency, each symptom was scored on a scale of 0–3. Furthermore, adverse events were asked for and recorded on this questionnaire. Our primary outcome measure was absence of abdominal pain or discomfort at week 8 on this questionnaire.

The patient questionnaire, also not validated, included the ratings of six IBS symptoms and a general assessment of health and quality of life on a visual analogue scale (VAS). The IBS symptoms included abdominal pain, intestinal gas or bloating, constipation, diarrhea, incomplete evacuation, and urgency. The patient was asked to complete this questionnaire every night before going to sleep on the first week, then weekly for the rest of the study duration. For analysis, the patients’ mark on the VAS was converted to a number between 0 and 10.

Statistical Analysis

Chi-square and Mann–Whitney U was used to analyze results obtained by the researcher's questionnaire. Differences between groups in VAS and in parameters of SF-36 were studied using Student’s t-test. P-values of <0.05 were considered significant. Data was analyzed using SPSS 16.0 statistical software package for Windows (SPSS Inc, Chicago, IL, USA).

Ethics

All subjects were required to sign a written consent form and were free to withdraw anytime during the study. Patients not consenting were excluded. The study was approved by the institutional review board and medical ethics committee of the Digestive Disease Research Center of Tehran University of Medical Sciences.

Results

Ninety patients were included, 45 in each group. Sixty patients completed the study (Fig. 1). None had a history of alcohol or drug abuse. Except for sex, where the female proportion was significantly higher in the study group (P = 0.05), none of the parameters were significantly different between the two groups (Table 1).
https://static-content.springer.com/image/art%3A10.1007%2Fs10620-009-0854-9/MediaObjects/10620_2009_854_Fig1_HTML.gif
Fig. 1

Consort diagram

Table 1

Characteristics of patients included in the study

 

Placebo group

Colpermin group

Total

Number included

45

45

90

Completed study

27

33

60

Male/female

10/17

5/28

15/45

Age (year, mean ± SD)

37 ± 11

35 ± 13

36 ± 12

Married

23

22

45

Smoker

2

4

6

The most common presenting complaint was abdominal pain in 53 (88.3%) followed by distension in 52 (86.7%) and flatulence in 50 (83.3%). The presenting symptoms did not differ significantly between the two groups (Table 2).
Table 2

Frequency of symptoms in placebo and Colpermin groups at the beginning of the study (n (%))

Symptom

Placebo (n = 27)

Colpermin (n = 33)

P-value

Abdominal pain

22 (81.5%)

31 (93.9%)

0.226

Abdominal discomfort

7 (25.9%)

16 (48.5%)

0.074

Heartburn

13 (48.1%)

14 (42.4%)

0.657

Nausea and vomiting

12 (44.4%)

17 (51.5%)

0.614

Abdominal distension

22 (81.5%)

30 (90.9%)

0.448

Flatulence

21 (77.8%)

29 (87.9%)

0.322

Loose stool

16 (59.3%)

21 (63.6%)

0.793

Hard stool

18 (69.2%)

23 (69.7%)

1.00

Urgency

12 (44.4%)

22 (68.8%)

0.071

Incomplete evacuation

23 (85.2%)

24 (72.7%)

0.348

Researcher Questionnaire

In the data collected by the researcher questionnaire, all individuals had either abdominal pain or discomfort associated with a change in bowel habit on the first visit. The number of patients free from abdominal pain or discomfort increased to 14 (42.5%) vs. 6 (22.2%) at visit 4 (week 8, P < 0.001) in the Colpermin and placebo groups, respectively (Table 3). Furthermore, the intensity of abdominal pain or discomfort was significantly reduced in the Colpermin group as compared to controls at week 8 (P < 0.001, Table 3). Other factors recorded in the researcher questionnaire did not show significant difference between groups throughout the study.
Table 3

Frequency and severity of abdominal pain or discomfort in patients receiving Colpermin or placebo throughout the study. (n(%))

Abdominal pain or discomfort

Week 0

Week 1

Week 4

Week 8

None

    Placebo

0 (0%)

9 (33%)

11 (41%)

6 (22%)

    Colpermin

0 (0%)

6 (18%)

14 (42%)

14 (42%)

Occasional

    Placebo

17 (63%)

15 (56%)

10 (37%)

7 (26%)

    Colpermin

15 (46%)

18 (55%)

11 (33%)

14 (42%)

Persistent

    Placebo

9 (33%)

3 (11%)

6 (22%)

14 (52%)

    Colpermin

14 (42%)

8 (24%)

7 (21%)

5 (15%)

Severe

    Placebo

1 (4%)

0 (0%)

0 (0%)

0 (0%)

    Colpermin

4 (12%)

1 (3%)

1 (3%)

0 (0%)

Patient Questionnaire

None of the eight variables reported in the patient questionnaire was significantly different among the two groups at the beginning of the study. But quality of life on VAS was significantly improved in the Colpermin group as compared to placebo. The mean value for quality of life before treatment was 4.1 and 5.8 in the Colpermin and placebo groups, respectively. This changed to 4.8 and 4.4 at week one (P = 0.007 for difference in improvements) and to 4.7 and 4.0 at week eight (P = 0.016). Other variables showed no significant difference between groups throughout the study.

SF-36

Quality of life in the two groups did not differ significantly at the beginning of the trial (Table 4a), but after eight weeks, the patients on Colpermin, as compared to controls, showed statistically significant improvement in the SF-36 domains of bodily pain, general health, social functioning, and role limitations due to emotional problems. The summary scores, however, were not significantly different (Table 4b).
Table 4

SF-36 results at the beginning and at the end of the trial

SF-36 domains

Mean (SD)

P-value

Placebo

Colpermin

a. Beginning of trial

    Physical functioning

74.1 (28.8)

80.4 (23.5)

0.358

    Role limitations due to physical health

31.6 (40.4)

51.6 (40.4)

0.06

    Bodily pain

47.6 (24.7)

48.8 (22.7)

0.839

    General health

41.1 (23.8)

50.2 (22.1)

0.135

    Physical health summary

48.6 (30.2)

57.8 (28.2)

0.230

    Vitality

55.1 (21.8)

53.6 (18.7)

0.772

    Social functioning

54.1 (32.2)

64.6 (30.4)

0.204

    Role limitations due to emotional problems

37.7 (37.8)

47.7 (41.6)

0.335

    Mental health

49.7 (23.1)

57.1 (25.7)

0.253

    Mental health

49.2 (29.5)

55.8 (30.3)

0.399

    Overall summary

48.9 (29.8)

57.8 (29.3)

0.308

b. End of trial

    Physical functioning

81.6 (18.2)

78.9 (23.7)

0.628

    Role limitations due to physical health

42.5 (40.5)

62.5 (39.2)

0.057

    Bodily pain

51.2 (26.0)

64.2 (19.5)

0.035

    General health

45.7 (20.3)

58.0 (25.6)

0.046

    Physical health summary

55.3 (27.7)

65.9 (28.0)

0.146

    Vitality

59.0 (14.8)

53.9 (22.5)

0.307

    Social functioning

57.1 (27.9)

70.8 (24.2)

0.046

    Role limitations due to emotional problems

32.2 (36.6)

56.6 (46.4)

0.028

    Mental health

60.1 (13.2)

59.2 (22.1)

0.844

    Mental health summary

52.1 (25.1)

60.1 (28.4)

0.256

    Overall summary

53.7 (26.4)

63.0 (28.2)

0.194

Adverse Events

Adverse events were mild, transient, and well tolerated. A total of 33 patients reported one or more adverse events, 19 in the Colpermin group and 14 in controls. The most frequently observed adverse events were heartburn (four in the Colpermin group, five in controls), headache (six in Colpermin, three in controls), and dizziness (three in Colpermin, five in controls). Other less frequent events included belching, dry mouth, and increased appetite seen in less than 10% of subjects. The frequency of adverse events was not significantly different between the two groups.

Discussion

The chronic nature of IBS symptoms can adversely affect patients’ quality of life by interfering with their normal everyday life [5, 23]. Former studies have suggested peppermint oil as a possible treatment for IBS symptoms [18, 21].

In one randomized placebo-controlled clinical study, a 4-week treatment with Colpermin improved the overall abdominal symptoms in patients with IBS [19]. Another study demonstrated that Colpermin could alleviate the severity of abdominal pain in 79% of patients [21]. The role of Colpermin on abdominal pain can be attributed to its calcium-channel-blocking properties, which relaxes gastrointestinal smooth muscle [14, 15, 24]. We did not find improvement in other symptoms of our IBS patients taking Colpermin.

Patients with IBS have impaired health-related quality of life on SF-36 scales in comparison to the general population [5, 6, 25]. Adverse impacts of IBS on life quality are even greater than many important chronic diseases such as gastroesophageal reflux disease, diabetes, or even end stage renal disease in some particular scales [5]. At the beginning of our trial, there were no statistically significant differences between the two groups in SF-36 scales. After 8 weeks of treatment with Colpermin, our study participants showed significant enhancement in some scales of health-related quality of life including role limitation due to emotional problems, social functioning, general health, and bodily pain. Given that abdominal pain is the most troublesome symptom, [26] improvements in abdominal pain may account for this improvement in quality of life. Abdominal pain, among other symptoms of IBS, exerts the strongest influence on health-related quality of life [26]. It is interesting to note that patients taking Colpermin reported improvement in general quality of life on the VAS as early as week 1; whereas significant improvement in abdominal pain was observed on week 8. This probably indicates that there are other variables effecting quality of life that are not accounted for by the symptoms we have studied. This has also been suggested by other researchers [27].

We observed that Colpermin improves abdominal pain and discomfort, but not diarrhea, constipation, or bloating. This underscores the already established fact that IBS patients should be treated according to their prominent symptom and a single treatment cannot be expected to be effective in all IBS patients.

The major limitation of our study is the number of participants who were lost to follow-up. Almost 30% of our subjects did not refer for follow-up. We believe that the main reason for such a high loss rate is that many of our patients did not live in Tehran and probably their symptoms were not severe enough to justify traveling to Tehran four times in 8 weeks. Unfortunately, in the presence of high loss rates, an intention-to-treat analysis would not be meaningful and thus was not performed [28]. This large loss rate should be taken into account when interpreting our results.

Another limitation of our study is that the researcher and patient questionnaires were not validated. Since the researcher questionnaire was completed by a trained physician in a direct interview with the subject, not being validated does not impose an important drawback. In the case of the patient’s questionnaire, however, the lack of validation is a concern. Our results are primarily based on the SF-36 and researcher questionnaire and none are based solely on the patient questionnaire. The patient questionnaire only confirmed the findings of the SF-36 questionnaire, so we believe that the validity of our findings is not affected by the lack of validation.

Conclusions

We conclude that treatment with Colpermin may be effective in alleviating abdominal pain and discomfort and improving some aspects of quality of life in patients with IBS. This is especially true for patients in whom abdominal pain or discomfort is the dominant symptom.

Acknowledgments

This study was supported by a grant from the Digestive Disease Research Center of Tehran University of Medical Sciences. The study medication (Colpermin) and placebo was kindly provided by Tillotts Pharma, Ziefen, Switzerland.

Copyright information

© Springer Science+Business Media, LLC 2009