Peppermint oil has been considered a remedy for bothersome gastrointestinal symptoms for centuries. While a recent meta-analysis suggested that peppermint oil was a safe and effective short-term treatment of irritable bowel syndrome (IBS) [Khanna R et al. J Clin Gastroenterol. 2014], oral ingestion of single-unit, liquid-filled enteric-coated peppermint oil can be associated with adverse effects such as heartburn, dyspepsia, or anal burning. These adverse effects likely occur due to the unpredictability of peppermint oil release in the gastrointestinal tract with these older formulations. [Epstein MS et al. DDW 2015 (poster 314)].

A novel, targeted-release formulation of peppermint oil appeared to significantly reduce 4 self-reported symptoms of severe abdominal symptoms associated with IBS, according to research presented in a poster by Brooks D. Cash, MD, University of South Alabama, Mobile, Alabama, USA.

The IBREST trial was a randomized, placebo-controlled, double-blinded study to compare the safety and efficacy of a proprietary, targeted-release formulation of peppermint oil compared with an identical placebo in a US population. This formulation consists of ultra-purified, solid-state microspheres triple-coated to facilitate oral ingestion and rapid delivery of the peppermint oil directly to the small intestine.

Inclusion criteria were the Rome III criteria for IBS with mixed symptoms or diarrhea, Total IBS Symptom Score (TISS) > 2 on a scale of 0 to 4, and persistent levels of abdominal pain ≥ 4 on a scale of 0 to 10. Patients were excluded if they had any other type of IBS, if they had organic gastrointestinal disease, or if they were unwilling to stop any restricted medications prior to enrolling in the study.

Three weeks before enrollment, patients were required to undergo laboratory testing and washout of all prohibited medicines; rescue medications were not allowed. Patients were also instructed to keep a 2-week baseline system diary. Patients were then randomized to either 2 capsules (each containing 90 mg) of peppermint oil TID (treatment group; n = 35) or to 2 identical placebo capsules TID (placebo; n = 37). The majority of patients were white and were women, with a mean age of 40.7 years (Table 1).

The primary outcomes were self-reported differences after 4 weeks of therapy between the 2 groups on the TISS and the frequency and intensity of the 8 symptoms that customarily constitute IBS: abdominal discomfort, bloating or distention, diarrhea, constipation, feeling of incomplete evacuation, urgency, pain on evacuation, and gas or mucus.

At baseline, there was no significant difference between the placebo and treatment groups with regard to the TISS or any of its 8 individual components. At week 4, patients in the treatment group achieved a significant reduction in the TISS (P = .0246), as well as in 4 of the 8 individual components—abdominal discomfort, abdominal bloating, pain at evacuation, and urgency of bowel movement (P < .05, Table 2).

There were 6 treatment-emergent adverse events (TEAEs): 2 in the treatment group and 4 in the placebo group. One TEAE above grade 1 was reported, and no serious TEAEs or deaths were reported. No patients dropped out of the study because of a TEAE.

In conclusion, patients with nonconstipated IBS randomized to a novel formulation of peppermint oil designed to release in the small intestine showed improvement in the TISS, a global IBS symptom score, as well as many of the common individual IBS symptoms, after 4 weeks of therapy compared with placebo. This formulation of peppermint oil was well tolerated and no safety signals were noted.