Table 6.

Peppermint Oil (PMO) Randomized Double Blind Controlled Trials for Adult Irritable Bowel Syndrome (IBS)

Reference	Population	Design	Findings	Adverse Events
Rees (1979)89	Adults with IBS (n=18); 2 withdrawals	Double blind cross-over trial comparing PMO 0.2 mL 1-2 caps TID vs placebo × 3 weeks Primary objective: Overall symptoms graded from on 5-point scale (+2 to −2 being excellent to terrible)	More subjects had excellent or good outcomes while on PMO vs. placebo [ 9 (50%) vs. 2 (12.5%)], P< 0.01	PMO with heartburn, n=2
Dew (1984)90	Adults with IBS (n=29)	Double blind crossover multicenter study comparing PMO 0.2 mL 3-6 caps/day vs placebo × 2 weeks Primary objective: Severity of daily abdominal symptoms (graded 0-3; asymptomatic to severe)	More subjects (12/29) on PMO vs. Placebo (3/29) with excellent or good overall abdominal symptoms (P<0.001)	Not reported
Nash (1986)66	Adults with IBS (n=41) with pain as a major symptom; 8 withdrawals: 6 failed to complete diary cards and 2 because of nausea and vomiting with PMO	Double blind crossover study: PMO 0.2 mL 2 caps TID vs placebo × 2 weeks each Primary outcome: Daily pain recorded on visual analogue scale and 4 category scale (0-3; “no pain” to “a great deal of pain”)	No difference in primary outcomes (raw data not presented)	PMO with nausea/vomiting, n=2 PMO with heartburn, n=6
Wildgrube (1988)56	Adult IBS patients (n=40) 1 placebo dropout	Double-blind randomized study PMO vs. placebo × 2 weeks Primary outcome: Compared fullness, flatulence, bowel sounds, abdominal pain from the 1st to 2nd week	Median scores for fullness decreased from 39.0 to 27.5 vs. placebo 42 to 44; flatulence from 50 to 28.5 vs. placebo 46 to 47; bowel sounds from 34.0 to 22.5 vs. placebo 34 to 33; and abdominal pain from 25.0 to 16.5 vs. placebo 24 to 30; all (P<0.05) See also Wildgrube in Table 3	“Heartburn or belching either did not occur or if it did was minimal” (unclear which group) Slight burning during defecation, n= 5 (unclear which group)
Liu (1997)91	Adults with IBS (n=110); 9 withdrawals	Double-blind parallel group study: PMO 187 mg TID to QID (n=52) or placebo (n=49) × 4 weeks Primary Objective: Response in 5 symptoms graded on 4-point scale (+2 marked improvement to −1 worsening of symptoms) at one month	Higher proportion of subjects with PMO vs. placebo with a marked or moderate improvement in pain [41 (79%) vs. 21 (43%)], distention [43 (83%) vs. 14 (29%)], stool frequency [43 (83%) vs. 16 (33%)], borborygmi [38 (73%) vs. 15 (31%)], and flatulence [41 (79%) vs. 11 (22.5%)], all comparisons P < 0.05.	PMO with heartburn, n=1; skin rash, n=1
Capanni (2005)92	Adult IBS (n=178); 5 withdrawals	Double-blind parallel group study PMO 225 mg 2 cap bid (n= 91) vs. placebo (n=87) × 12 weeks Primary objective: Global improvement in IBS symptoms	Proportion with global IBS symptom improvement greater in PMO (73/91) vs. placebo (31/87), P<0.02	Placebo drop out for ‘non-IBS related reasons,’ n=2 PMO drop out for ‘non-IBS related reasons,’ n=1; heartburn, n=2
Cappello (2007)93	Adults with Rome II IBS (n=57)	Double-blind parallel group study: PMO 225 mg 2 caps BID (n=24) vs. placebo (n=26) × 4 weeks Primary objective: Remission of IBS symptoms (>50% improvement of the overall IBS symptom score from baseline to 4 and 8 weeks).	18 (75%) of the patients in the PMO group vs. 10 (38%) placebo had a >50% reduction of total IBS symptoms score at week 4 (P<0.01). 13 (54%) PMO subjects vs. 3 (11%) placebo subjects had a >50% reduction in total IBS symptoms score at week 8 (P<0.01).	PMO with prolonged heartburn, n=1
Merat (2010)94	Adults with Rome II IBS (n=90); 30 withdrawals	Double-blind parallel group study of PMO 187 mg (0.2 mL) TID (n=27) vs. placebo (n=33) × 8 weeks Primary objective: Number of patients free from abdominal pain or discomfort	Greater proportion free from abdominal pain or discomfort at week 8 in PMO group (14/33) vs placebo (6/27) (P < 0.001).	No significant adverse events reported No differences in adverse event frequency between groups
Alam (2013)95	Adults with Rome II IBS (n=74); 9 withdrawals	Double-blind parallel group study of PMO 2 mL TID (n=33) vs. placebo (n=32) × 6 weeks Primary objective: Assess changes in symptoms and quality of life at 3 week intervals and 2 weeks after treatment completed	No significant difference at 3 weeks PMO improved abdominal pain (4.94 ± 1.30; mean ± SD) vs. placebo (6.15 ± 1.93; P<0.001) at 6 weeks. No significant difference 2 weeks after treatments ended No improvements in quality of life	No significant adverse events occurred
Cash (2016)96	Adults with Rome III IBS-diarrhea or IBS-mixed (n=72)	Randomized double blind trial PMO 180 mg TID (n=35) vs placebo (n=37) × 4 weeks Primary objective: Change from baseline in the Total IBS Symptom Score after 4 weeks of therapy	Total IBS Symptom Score decreased more relative to baseline in PMO vs. placebo (40.0% vs 24.3%, P=0.025)	No significant differences between groups

Unless otherwise indicated data are presented as mean ± standard deviation.