Efficacy and Safety of Peppermint Oil in a Randomized, Double-Blind Trial of Patients With Irritable Bowel Syndrome

Zsa Zsa R.M. Weerts*, Ad A.M. Masclee, Ben J.M. Witteman, Cees H.M. Clemens, Bjorn Winkens, Jacobus R.B.J. Brouwers, Henderik W. Frijlink, Jean W.M. Muris, Niek J. De Wit, Brigitte A.B. Essers, Jan Tack, Johanna T.W. Snijkers, Andrea M.H. Bours, Annieke S. de Ruiter-van der Ploeg, Daisy M.A.E. Jonkers, Daniel Keszthelyi

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Scopus)

Abstract

Background & Aims: Peppermint oil is frequently used to treat irritable bowel syndrome (IBS), despite a lack of evidence for efficacy from high-quality controlled trials. We studied the efficacy and safety of small-intestinal–release peppermint oil in patients with IBS and explored the effects of targeted ileocolonic-release peppermint oil. Methods: We performed a double-blind trial of 190 patients with IBS (according to Rome IV criteria) at 4 hospitals in The Netherlands from August 2016 through March 2018; 189 patients were included in the intent-to-treat analysis (mean age, 34.0 years; 77.8% female; 57.7% in primary care), and 178 completed the study. Patients were randomly assigned to groups given 182 mg small-intestinal–release peppermint oil, 182 mg ileocolonic-release peppermint oil, or placebo for 8 weeks. The primary endpoint was abdominal pain response, as defined by the US Food and Drug Administration: at least a 30% decrease in the weekly average of worst daily abdominal pain compared with baseline in at least 4 weeks. The co-primary endpoint was overall relief of IBS symptoms, as defined by the European Medicines Agency. Secondary endpoints included abdominal pain, discomfort, symptom severity, and adverse events. Results: Abdominal pain response did not differ significantly between the peppermint oil and placebo groups: 29 of 62 patients in the small-intestinal–release peppermint oil group had a response (46.8%, P =. 170 vs placebo), 26 of 63 patients in the ileocolonic-release peppermint oil group had a response (41.3%, P =. 385 vs placebo), and 22 of 64 patients in the placebo group had a response (34.4%). We did not find differences among the groups in overall relief (9.7%, P =. 317 and 1.6%, P =. 351 vs 4.7% for placebo). The small intestinal peppermint oil did, however, produce greater improvements than placebo in secondary outcomes of abdominal pain (P =. 016), discomfort (P =. 020), and IBS severity (P =. 020). Adverse events, although mild, were more common in both peppermint oil groups (P <. 005). Conclusions: In a randomized trial of patients with IBS, we found that neither small-intestinal–release nor ileocolonic-release peppermint oil (8 weeks) produced statistically significant reductions in abdominal pain response or overall symptom relief, when using US Food and Drug Administration/European Medicines Agency recommended endpoints. The small-intestinal–release peppermint oil did, however, significantly reduce abdominal pain, discomfort, and IBS severity. These findings do not support further development of ileocolonic-release peppermint oil for treatment of IBS. Clinicaltrials.gov, Number: NCT02716285.

Original languageEnglish
Pages (from-to)123-136
Number of pages14
JournalGastroenterology
Volume158
Issue number1
DOIs
Publication statusPublished - 1 Jan 2020

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Irritable Bowel Syndrome
Safety
Abdominal Pain
Placebos
United States Food and Drug Administration
peppermint oil
Netherlands
Primary Health Care

Keywords

  • Functional Gastrointestinal Disorder
  • PERSUADE Study
  • RCT
  • Treatment

Cite this

Weerts, Z. Z. R. M., Masclee, A. A. M., Witteman, B. J. M., Clemens, C. H. M., Winkens, B., Brouwers, J. R. B. J., ... Keszthelyi, D. (2020). Efficacy and Safety of Peppermint Oil in a Randomized, Double-Blind Trial of Patients With Irritable Bowel Syndrome. Gastroenterology, 158(1), 123-136. https://doi.org/10.1053/j.gastro.2019.08.026
Weerts, Zsa Zsa R.M. ; Masclee, Ad A.M. ; Witteman, Ben J.M. ; Clemens, Cees H.M. ; Winkens, Bjorn ; Brouwers, Jacobus R.B.J. ; Frijlink, Henderik W. ; Muris, Jean W.M. ; De Wit, Niek J. ; Essers, Brigitte A.B. ; Tack, Jan ; Snijkers, Johanna T.W. ; Bours, Andrea M.H. ; de Ruiter-van der Ploeg, Annieke S. ; Jonkers, Daisy M.A.E. ; Keszthelyi, Daniel. / Efficacy and Safety of Peppermint Oil in a Randomized, Double-Blind Trial of Patients With Irritable Bowel Syndrome. In: Gastroenterology. 2020 ; Vol. 158, No. 1. pp. 123-136.
@article{72985238c162444a824d18d396e08304,
title = "Efficacy and Safety of Peppermint Oil in a Randomized, Double-Blind Trial of Patients With Irritable Bowel Syndrome",
abstract = "Background & Aims: Peppermint oil is frequently used to treat irritable bowel syndrome (IBS), despite a lack of evidence for efficacy from high-quality controlled trials. We studied the efficacy and safety of small-intestinal–release peppermint oil in patients with IBS and explored the effects of targeted ileocolonic-release peppermint oil. Methods: We performed a double-blind trial of 190 patients with IBS (according to Rome IV criteria) at 4 hospitals in The Netherlands from August 2016 through March 2018; 189 patients were included in the intent-to-treat analysis (mean age, 34.0 years; 77.8{\%} female; 57.7{\%} in primary care), and 178 completed the study. Patients were randomly assigned to groups given 182 mg small-intestinal–release peppermint oil, 182 mg ileocolonic-release peppermint oil, or placebo for 8 weeks. The primary endpoint was abdominal pain response, as defined by the US Food and Drug Administration: at least a 30{\%} decrease in the weekly average of worst daily abdominal pain compared with baseline in at least 4 weeks. The co-primary endpoint was overall relief of IBS symptoms, as defined by the European Medicines Agency. Secondary endpoints included abdominal pain, discomfort, symptom severity, and adverse events. Results: Abdominal pain response did not differ significantly between the peppermint oil and placebo groups: 29 of 62 patients in the small-intestinal–release peppermint oil group had a response (46.8{\%}, P =. 170 vs placebo), 26 of 63 patients in the ileocolonic-release peppermint oil group had a response (41.3{\%}, P =. 385 vs placebo), and 22 of 64 patients in the placebo group had a response (34.4{\%}). We did not find differences among the groups in overall relief (9.7{\%}, P =. 317 and 1.6{\%}, P =. 351 vs 4.7{\%} for placebo). The small intestinal peppermint oil did, however, produce greater improvements than placebo in secondary outcomes of abdominal pain (P =. 016), discomfort (P =. 020), and IBS severity (P =. 020). Adverse events, although mild, were more common in both peppermint oil groups (P <. 005). Conclusions: In a randomized trial of patients with IBS, we found that neither small-intestinal–release nor ileocolonic-release peppermint oil (8 weeks) produced statistically significant reductions in abdominal pain response or overall symptom relief, when using US Food and Drug Administration/European Medicines Agency recommended endpoints. The small-intestinal–release peppermint oil did, however, significantly reduce abdominal pain, discomfort, and IBS severity. These findings do not support further development of ileocolonic-release peppermint oil for treatment of IBS. Clinicaltrials.gov, Number: NCT02716285.",
keywords = "Functional Gastrointestinal Disorder, PERSUADE Study, RCT, Treatment",
author = "Weerts, {Zsa Zsa R.M.} and Masclee, {Ad A.M.} and Witteman, {Ben J.M.} and Clemens, {Cees H.M.} and Bjorn Winkens and Brouwers, {Jacobus R.B.J.} and Frijlink, {Henderik W.} and Muris, {Jean W.M.} and {De Wit}, {Niek J.} and Essers, {Brigitte A.B.} and Jan Tack and Snijkers, {Johanna T.W.} and Bours, {Andrea M.H.} and {de Ruiter-van der Ploeg}, {Annieke S.} and Jonkers, {Daisy M.A.E.} and Daniel Keszthelyi",
year = "2020",
month = "1",
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doi = "10.1053/j.gastro.2019.08.026",
language = "English",
volume = "158",
pages = "123--136",
journal = "Gastroenterology",
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Weerts, ZZRM, Masclee, AAM, Witteman, BJM, Clemens, CHM, Winkens, B, Brouwers, JRBJ, Frijlink, HW, Muris, JWM, De Wit, NJ, Essers, BAB, Tack, J, Snijkers, JTW, Bours, AMH, de Ruiter-van der Ploeg, AS, Jonkers, DMAE & Keszthelyi, D 2020, 'Efficacy and Safety of Peppermint Oil in a Randomized, Double-Blind Trial of Patients With Irritable Bowel Syndrome', Gastroenterology, vol. 158, no. 1, pp. 123-136. https://doi.org/10.1053/j.gastro.2019.08.026

Efficacy and Safety of Peppermint Oil in a Randomized, Double-Blind Trial of Patients With Irritable Bowel Syndrome. / Weerts, Zsa Zsa R.M.; Masclee, Ad A.M.; Witteman, Ben J.M.; Clemens, Cees H.M.; Winkens, Bjorn; Brouwers, Jacobus R.B.J.; Frijlink, Henderik W.; Muris, Jean W.M.; De Wit, Niek J.; Essers, Brigitte A.B.; Tack, Jan; Snijkers, Johanna T.W.; Bours, Andrea M.H.; de Ruiter-van der Ploeg, Annieke S.; Jonkers, Daisy M.A.E.; Keszthelyi, Daniel.

In: Gastroenterology, Vol. 158, No. 1, 01.01.2020, p. 123-136.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Efficacy and Safety of Peppermint Oil in a Randomized, Double-Blind Trial of Patients With Irritable Bowel Syndrome

AU - Weerts, Zsa Zsa R.M.

AU - Masclee, Ad A.M.

AU - Witteman, Ben J.M.

AU - Clemens, Cees H.M.

AU - Winkens, Bjorn

AU - Brouwers, Jacobus R.B.J.

AU - Frijlink, Henderik W.

AU - Muris, Jean W.M.

AU - De Wit, Niek J.

AU - Essers, Brigitte A.B.

AU - Tack, Jan

AU - Snijkers, Johanna T.W.

AU - Bours, Andrea M.H.

AU - de Ruiter-van der Ploeg, Annieke S.

AU - Jonkers, Daisy M.A.E.

AU - Keszthelyi, Daniel

PY - 2020/1/1

Y1 - 2020/1/1

N2 - Background & Aims: Peppermint oil is frequently used to treat irritable bowel syndrome (IBS), despite a lack of evidence for efficacy from high-quality controlled trials. We studied the efficacy and safety of small-intestinal–release peppermint oil in patients with IBS and explored the effects of targeted ileocolonic-release peppermint oil. Methods: We performed a double-blind trial of 190 patients with IBS (according to Rome IV criteria) at 4 hospitals in The Netherlands from August 2016 through March 2018; 189 patients were included in the intent-to-treat analysis (mean age, 34.0 years; 77.8% female; 57.7% in primary care), and 178 completed the study. Patients were randomly assigned to groups given 182 mg small-intestinal–release peppermint oil, 182 mg ileocolonic-release peppermint oil, or placebo for 8 weeks. The primary endpoint was abdominal pain response, as defined by the US Food and Drug Administration: at least a 30% decrease in the weekly average of worst daily abdominal pain compared with baseline in at least 4 weeks. The co-primary endpoint was overall relief of IBS symptoms, as defined by the European Medicines Agency. Secondary endpoints included abdominal pain, discomfort, symptom severity, and adverse events. Results: Abdominal pain response did not differ significantly between the peppermint oil and placebo groups: 29 of 62 patients in the small-intestinal–release peppermint oil group had a response (46.8%, P =. 170 vs placebo), 26 of 63 patients in the ileocolonic-release peppermint oil group had a response (41.3%, P =. 385 vs placebo), and 22 of 64 patients in the placebo group had a response (34.4%). We did not find differences among the groups in overall relief (9.7%, P =. 317 and 1.6%, P =. 351 vs 4.7% for placebo). The small intestinal peppermint oil did, however, produce greater improvements than placebo in secondary outcomes of abdominal pain (P =. 016), discomfort (P =. 020), and IBS severity (P =. 020). Adverse events, although mild, were more common in both peppermint oil groups (P <. 005). Conclusions: In a randomized trial of patients with IBS, we found that neither small-intestinal–release nor ileocolonic-release peppermint oil (8 weeks) produced statistically significant reductions in abdominal pain response or overall symptom relief, when using US Food and Drug Administration/European Medicines Agency recommended endpoints. The small-intestinal–release peppermint oil did, however, significantly reduce abdominal pain, discomfort, and IBS severity. These findings do not support further development of ileocolonic-release peppermint oil for treatment of IBS. Clinicaltrials.gov, Number: NCT02716285.

AB - Background & Aims: Peppermint oil is frequently used to treat irritable bowel syndrome (IBS), despite a lack of evidence for efficacy from high-quality controlled trials. We studied the efficacy and safety of small-intestinal–release peppermint oil in patients with IBS and explored the effects of targeted ileocolonic-release peppermint oil. Methods: We performed a double-blind trial of 190 patients with IBS (according to Rome IV criteria) at 4 hospitals in The Netherlands from August 2016 through March 2018; 189 patients were included in the intent-to-treat analysis (mean age, 34.0 years; 77.8% female; 57.7% in primary care), and 178 completed the study. Patients were randomly assigned to groups given 182 mg small-intestinal–release peppermint oil, 182 mg ileocolonic-release peppermint oil, or placebo for 8 weeks. The primary endpoint was abdominal pain response, as defined by the US Food and Drug Administration: at least a 30% decrease in the weekly average of worst daily abdominal pain compared with baseline in at least 4 weeks. The co-primary endpoint was overall relief of IBS symptoms, as defined by the European Medicines Agency. Secondary endpoints included abdominal pain, discomfort, symptom severity, and adverse events. Results: Abdominal pain response did not differ significantly between the peppermint oil and placebo groups: 29 of 62 patients in the small-intestinal–release peppermint oil group had a response (46.8%, P =. 170 vs placebo), 26 of 63 patients in the ileocolonic-release peppermint oil group had a response (41.3%, P =. 385 vs placebo), and 22 of 64 patients in the placebo group had a response (34.4%). We did not find differences among the groups in overall relief (9.7%, P =. 317 and 1.6%, P =. 351 vs 4.7% for placebo). The small intestinal peppermint oil did, however, produce greater improvements than placebo in secondary outcomes of abdominal pain (P =. 016), discomfort (P =. 020), and IBS severity (P =. 020). Adverse events, although mild, were more common in both peppermint oil groups (P <. 005). Conclusions: In a randomized trial of patients with IBS, we found that neither small-intestinal–release nor ileocolonic-release peppermint oil (8 weeks) produced statistically significant reductions in abdominal pain response or overall symptom relief, when using US Food and Drug Administration/European Medicines Agency recommended endpoints. The small-intestinal–release peppermint oil did, however, significantly reduce abdominal pain, discomfort, and IBS severity. These findings do not support further development of ileocolonic-release peppermint oil for treatment of IBS. Clinicaltrials.gov, Number: NCT02716285.

KW - Functional Gastrointestinal Disorder

KW - PERSUADE Study

KW - RCT

KW - Treatment

U2 - 10.1053/j.gastro.2019.08.026

DO - 10.1053/j.gastro.2019.08.026

M3 - Article

VL - 158

SP - 123

EP - 136

JO - Gastroenterology

JF - Gastroenterology

SN - 0016-5085

IS - 1

ER -