Patients with irritable bowel syndrome (IBS) are some of the most frequently encountered by gastroenterologists. IBS can be defined using the Rome IV criteria which state that a patient must have recurrent abdominal pain on average for at least 1 day per week for the preceding 3 months and associated with at least 2 or more of these symptoms: a relation to defecation, and an association with a change in stool form and/or frequency.1

Prevalence can vary based on location and country, with some studies reporting rates ranging from 1.1% to 45%.2 Patients with IBS can present with chronic, crampy abdominal pain, altered bowel habits (constipation or diarrhea) and tenesmus.1 IBS is typically considered a diagnosis of exclusion after other etiologies and their symptoms have been ruled out.

Once a diagnosis of IBS is made, choosing a treatment option can be challenging. Depending on the type of IBS, there may be limited options. A commonly used over-the-counter treatment for IBS is peppermint oil. The exact mechanism of action in IBS is not entirely known; however, it has been postulated that it may be mediated through smooth muscle relaxation, antimicrobial effects, modulation of pain receptors, and 5-hydroxytryptamine antagonism.3

Despite its frequency of use, there have been limited randomized, well-controlled clinical trials with lack of confounders to support its use. In the 2018 American College of Gastroenterology (ACG) guidelines on the management of IBS, the authors reported a total of 7 randomized controlled trials (RCTs) using peppermint oil with a relative risk of remaining symptomatic compared with placebo of 0.54 (95% CI, 0.39-0.76).4 The number needed to treat was reported as 4 (95% CI, 3-6) and the studies were considered relatively heterogeneous. These ACG guidelines do recommend peppermint oil for overall symptom improvement in patients with IBS, although the recommendation and quality of evidence is considered weak and low, respectively.

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Based on the lack of well-controlled RCTs, a group led by Weerts, et al recently conducted a multicenter, randomized, placebo-controlled study titled, Peppermint Oil for the Treatment of Irritable Bowel Syndrome: Optimizing Therapeutic Strategies Using Targeted Delivery (PERSUADE), which evaluated the safety and efficacy of enteric-coated peppermint oil capsules in patients with IBS.3 The PERSUADE study enrolled patients between 18 and 75 years with IBS based on Rome IV criteria from 4 Dutch hospitals. Patients received either 182 mg of small intestinal- or ileocolonic-release peppermint oil capsules or placebo.

Under the study protocol, the patients were not allowed to make lifestyle changes, including diet or exercise routines. Adjunct pain medications were allowed if they were first cleared by one of the study investigators. The authors used the Food and Drug Administration definition of abdominal pain responders as their primary endpoint: at least 30% decrease in the weekly average of worst daily abdominal pain compared with baseline for at least 50% of the treatment period (at least 4 of the 8 weeks). Global relief of symptoms was used as a coprimary efficacy endpoint with a global relief responder defined as a patient with a weekly relief of threshold 6 or 7 on the numerical rating scale in at least 50% of the treatment period (at least 4 weeks). Secondary endpoints included assessment of symptomatic improvement as well as safety data.

A total of 190 patients were randomly assigned in the trial. There was no statistically significant difference in the primary outcomes between the placebo and small intestinal-release and ileocolonic-release peppermint oil. The response rates ranged from 34.4% in the (placebo) to 46.8% (small intestinal-release peppermint oil). There were significant differences, albeit minimal, in several secondary outcomes when comparing small intestinal-release of peppermint oil with placebo: abdominal pain, discomfort, and IBS severity.

With respect to safety data, there was significantly more mean total adverse events (AEs) in both the small intestinal release and ileocolonic release (4.26 and 4.45, respectively) when compared with placebo (2.78, P =.012). The most commonly experienced AEs varied based on the formulation. In the small intestinal-release group, the most common AEs included heartburn, belching, and headache. For the ileocolonic release, the most common AEs were headache, abdominal cramps, sensitive urethra, and altered anal sensation. Belching was found to mostly subside by 2 weeks posttreatment in the small intestinal-release group. Only 11 patients withdrew from the study, of which 9 did so secondary to AEs. This was more common in the peppermint oil groups which represented 8 of these 9 patients.

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The authors concluded neither formulation of peppermint oil was found to significantly improve the primary endpoints compared with placebo. They did state that the small intestinal-release formulation had very mild statistically significant improvements in certain secondary outcomes, and could therefore be considered as a treatment option in patients with IBS. The ileocolonic-release formulation did not show any statistical benefits in the efficacy endpoints and was associated with more significant lower abdominal symptoms; therefore, its routine use was not supported by this trial.

When reviewing this study, it is important to note several limitations. The patient population was only derived from Dutch hospitals; therefore, it may not be possible to generalize the results to all patients with IBS. The blinding was challenging based on the aroma and taste associated with peppermint oil. In addition, the study was relatively short; therefore, long-term data could prove useful in the future. It would have been interesting to evaluate if the peppermint oil had any statistical benefit on any of the IBS subtypes such as IBS-diarrhea or constipation predominant.

Based on this study, peppermint oil can still be considered as a treatment option by gastroenterologists, especially based on the lack of treatment options for certain patients with IBS, relative cost, and widespread availability. A detailed discussion should be had with the patient, however, to discuss the potential AEs and the expected modest improvement in symptoms.


1. Lacy BE, Mearin F, Mearin F, Chang L, et al. Bowel disorders. Gastroenterology. 2016;150(6):1393-1407.e5.

2. Lovell RM, Ford AC. Global prevalence of and risk factors for irritable bowel syndrome: a meta-analysis. Clin Gastroenterol Hepatol. 2012;10(7):712-721.e4.

3. Weerts ZZRM, Masclee AAM, Witteman BJM, et al. Efficacy and safety of peppermint oil in a randomized, double-blind trial of patients with irritable bowel syndrome. Gastroenterology 2020;158(1):123-136.

4. Ford AC, Moayyedi P, Chey WD; and the ACG Task Force on Management of Irritable Bowel Syndrome, et al. American College of Gastroenterology monograph on management of irritable bowel syndrome. Am J Gastroenterol. 2018;113(suppl 2):1-18.