TABLE 2.

Randomized controlled trials evaluating the efficacy peppermint oil in IBS patients with diarrhea.

Study	Population (n), Rome criteria	Period (weeks)	Dose	Main outcome, significant difference compared to placebo	Adverse events
Liu et al. (1997), Taiwan	IBS (n = 101, 52 PO), No Rome criteria	4	187 mg t.i.d. or b.i.d	Alleviation of the severity in abdominal pain (RR: 79% vs. 43%)	Heartburn and mild transit skin rash
Cappello et al. (2007), Italy	IBS (n = 57, 28 PO), Rome II	4	450 mg b.i.d	Decrease >50% in total IBS symptom scores (RR: 75% vs. 38%)	Prolonged heartburn
Merat et al. (2010), Iran	IBS (n = 90, 33 PO), Rome II	8	187 mg t.i.d	Significant difference in the number of abdominal pain free patients (RR: 42% vs. 22%)	Heartburn, headache, and dizziness
Cash et al. (2016), United States	IBS-M and IBS-D (n = 72, 35 PO), Rome III	4	180 mg t.i.d	Reduction of the total IBS symptom scores (RR: 40% vs. 24%)	Dyspepsia, gastroesophageal reflux, flatulence
Weerts et al. (2020), The Netherlands	IBS (n = 189, 62 SBR-PO 63 ICR-PO Rome IV	8	182 mg t.i.d	No significant differences in abdominal pain	SBR-PO: heartburn, GERD, belching, headache; ICR-PO: Altered anal sensation or sensitive urethra, headache, abdominal cramps

b.i.d., twice daily; GERD, gastro-esophageal reflux disease; ICR-PO, ileo-colonic release-peppermint oil; IBS, irritable bowel syndrome; IBS-D, IBS with predominant diarrhea IBS-M, IBS with mixed bowel habits; o. d., once daily; PO: peppermint oil; RR, response rate; SBR-PO: small-bowel release-peppermint oil; t. i.d., thrice daily.