Large secondary analysis on peppermint oil

A total of 157 publications were analyzed according to the PRISMA protocol, including randomized controlled trials, meta-analyses and case series. The authors conclude that peppermint oil is well suited as a complementary and alternative treatment component for the relief of functional gastrointestinal disorders. In addition to an overview of the evidence from clinical studies, study findings on mechanisms of action are also discussed in detail.

The secondary analysis by Scarpellini et al. was published in the journal Current Pharmaceutical Design in 2023 [1]. Functional gastrointestinal disorders (FGID) such as functional dyspepsia or irritable bowel syndrome are widespread in adults [1–3]. Recent studies have shown that interactions between food intake, gut microbiota and the central and peripheral nervous system play an important role in pathogenesis [4,5]. The use of peppermint oil as part of a phytotherapeutic treatment is becoming increasingly popular, as the risk-benefit profile is very favorable [6,7]. Menthol, the main active ingredient in peppermint oil, has been shown to have analgesic properties (box).

What are the main mechanisms of action of peppermint oil?
In addition to a relaxation of the smooth intestinal muscles (inhibition of the voltage-dependent Ca++ channels), peppermint oil leads to a reduction in the sensation of pain in the digestive system. Several studies have shown a reduction in visceral pain with applications containing peppermint oil [8,9,13]. The reduction of visceral pain is achieved by modulating TRPM8 and/or TRPA1 receptors, which are localized near dendritic cells and nerve endings. In addition to menthone (20-31%) and menthyl acetate (3-10%), peppermint oil contains the stereoisomer menthol (35-55%) [16].
Menthol is the most important active ingredient. This has an inhibitory effect on pain-transmitting nerves by binding to the cold receptor (TRPM8) [1]. The mechanisms of action were analyzed in more detail in animal experiments. In vitro studies on ileal smooth muscle in guinea pigs indicate that menthol has calcium channel blocking properties [9,17]. In addition, menthol significantly reduced contractile responses to acetylcholine, histamine, 5-hydroxy-tryptamine and substance P in Taenia coli – three muscle strips running along the ileum – in guinea pigs [9,18]. In the mouse model, menthol induced a concentration-dependent membrane depolarization in a cell culture of interstitial Cajal cells [9,19]. Cajal cells form a complex cell system that acts as a mediator between the autonomic nerves and the smooth muscle cells of the gastrointestinal tract; they are the “pacemakers” of the GI tract, so to speak.

Functional dyspepsia

In the indication functional dyspepsia (FD), the clinical evidence is limited to peppermint oil in combination with caraway oil. The combination of these two essential oils in appropriate medicines has been shown to reduce visceral hyperalgesia [8,9]. In a randomized controlled trial (RCT) by Liu et al. showed a significant reduction in symptoms and an improvement in quality of life (p<0.05) in 114 outpatients with FD after four weeks of treatment with a fixed combination of peppermint and caraway oil [10]. And in an RCT by Chey et al. a new formulation of L-menthol and caraway oil was used to achieve a significant reduction in postprandial distress symptoms in FD patients as early as 24 hours after ingestion. In addition, approximately 75% of patients with a more severe symptom expression in the placebo comparison showed a substantial global improvement after 4 weeks, although interestingly this was significant in patients with EPS**, while in contrast a trend towards significance was observed in those with PDS** [11].

** According to the current Rome IV criteria, the two leading symptoms of FD are epigastric pain (EPS) and postprandial distress syndrome (PDS).

Irritable Bowel Syndrome

For the indication irritable bowel syndrome (IBS), there are also several RCTs that prove the symptom-relieving effects of peppermint oil. In a study by Asao et al. RDS symptom reduction ≥50% was achieved in 64% of the included patients (n=57) after four weeks of treatment with a peppermint oil preparation, compared to 34% with placebo [12]. And Karashima et al. report an RCT (n=90) in which 42.5% of patients in the treatment arm were free of abdominal pain after eight weeks of treatment, while this proportion was 22.2% in the placebo group [13]. Cash et al. tested a newer formulation of peppermint oil, which proved to be significantly superior to placebo after four weeks with a 40% reduction in IBS symptom scores (p<0.05) [14]. Weerts et al. conducted one of the largest RCTs to date on peppermint oil in IBS, with a total of 178 patients completing the study [15]. After four weeks, no significant difference was found between verum and placebo in terms of reduction in abdominal pain and overall IBS score, but greater improvements were achieved in various secondary endpoints (e.g. discomfort, IBS severity) in the treatment group than with placebo.

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