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General introduction 19 1 its usage and have demonstrated a reduction in abdominal pain and overall symptoms. 101-104 Similarly, meta-analyses indicate that peppermint oil has a treatment effect compared to placebo of approximately 30%. 105,106 Although these findings are highly favorable compared to other treatments 107 , the results are based on studies with methodological shortcomings, impeding the ability to draw firm conclusions about the effectiveness of peppermint oil in patients with IBS and limiting the incorporation in treatment guidelines. Therefore, there is a need for a well-designed randomized controlled trial conducted according to Food and Drug Administration (FDA) and European Medicines Agency (EMA) guidelines on trials in IBS. Another factor hindering application in daily clinical practice is that conventional small-intestinal release peppermint oil is associated with bothersome upper GI adverse events such as heartburn, belching, and a peppermint oil taste 101-103,108 , which impair treatment adherence. It is likely that a colonic release and therefore more distal gastrointestinal exposure to peppermint oil would decrease these adverse events. This could also induce a more colonic anti-spasmodic effect as colonic application of peppermint oil has been found to inhibit colonic motor activity and peristalsis. 93 Furthermore, it can be envisaged that an ileocolonic release of peppermint oil enhances the local exposure of the ileocolonic nociceptive afferents to the oil and thereby increases its analgesic effects. Therefore, in addition to conducting a well-designed randomized controlled trial with small-intestinal release peppermint oil, it is worth exploring a colonic delivery system of peppermint oil as this may result in fewer adverse events and increased efficacy.