Treating Irritable Bowel Syndrome: A Fresh and Minty Approach to an Old Therapy.

At the hairdresser’s the other day, the beautician applied a conditioner that contained peppermint oil (PO). My scalp felt cooled and soothed, and the scent was very calming. As I contemplated writing this editorial, it occurred to me that even my hairdresser was aware of the wisdom of the ages that PO is used to soothe and calm. In fact, the Internet touts 21 uses for PO, five of which are for digestive issues, with the number one indication being the treatment for irritable bowel syndrome (IBS). IBS is defined as a chronic disorder of altered bowel function characterized by symptoms of diarrhea, constipation, or alternating bowel habits accompanied by pain or discomfort and may include a constellation of other symptoms, e.g., bloating, urgency, and incomplete evacuation. The pathophysiology of this disorder has been attributed to gut inflammation, altered visceral sensitivity, food sensitivities, gene susceptibility, and changes in the gut–host microbiome, and altered brain–gut signaling [1, 2]. The heterogeneity of this disorder has long presented challenges in developing treatments since it is unlikely that one intervention will treat all causes and relieve all symptoms. That being said, the characteristics of PO make it an interesting choice as a therapeutic agent. The active ingredient of PO is the cyclic terpene L-menthol. The compound has anti-inflammatory, antioxidant, and anti-apoptotic activity as reported in animal studies in which PO was stated to heal gastric ulcers induced by either 1 ml 96 % ethanol or indomethacin (100 mg/kg) [3, 4], doses higher than typically ingested by humans. The reduction in average ulcer area produced corresponded to a gastroprotective effect for PO of 92 % for alcohol and 73 % for indomethacin. In these rat studies, L-menthol (50 mg/kg, lowest effective dose), a dose higher than in clinical use, induced mucus secretion maintained the production of prostaglandin E2, decreased concentrations of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-a and interleukin (IL)-6, and increased concentrations of the anti-inflammatory cytokine interleukin10. Additionally, the antispasmodic activity of PO is thought to be due to inhibition of smooth muscle voltagegated Ca channels [5, 6]. Carrying this research one step further, a recent study has also reported the L-menthol can also inhibit 5-HT3 receptors in vitro, which may explain the decrease in the frequency and amplitude of gut contractions associated with PO [7]. This laboratory research notwithstanding, the clinical effects of PO have been mixed. The authors of a recent meta-analysis concluded that PO was safe and effective for the short-term treatment for the treatment of IBS [8]. Using the Cochrane bias tool, they identified nine studies involving 726 patients where the risk of bias was low for most of the factors assessed. PO was significantly superior to placebo for global relief of IBS symptoms in five studies (N = 392 patients, RR 2.23, 95 % confidence interval 1.78–2.81) and for improving abdominal pain in five studies (N = 357 patients, RR 2.14, 95 % confidence interval 1.64–2.79). Even the recent American College of Gastroenterology guidelines, which gave PO a weak recommendation, reported that the level of evidence was moderate and stated, ‘‘Peppermint oil is superior to placebo in improving IBS symptoms. The risk of adverse events is no greater with PO than with placebo’’ [9]. The clinical trials on which these recommendations were based were & Lucinda A. Harris Harris.Lucinda@mayo.edu