Peppermint oil (PO) has intrinsic properties that may benefit patients with irritable bowel syndrome (IBS) symptoms. The study objective was to determine the effect of peppermint oil in the treatment of the IBS.

Methods

We systematically searched MEDLINE (PubMed), Cochrane Central Register of Controlled Trials (Cochrane CENTRAL), ClinicalTrials.gov, EMBASE (Ovid), and Web of Science for randomized controlled trials (RCTs) of PO for IBS. We appraised the eligible studies by the Cochrane risk of bias tool. We performed random-effects meta-analysis on primary outcomes including global improvement in IBS symptoms and abdominal pain. A PRISMA-compliant study protocol is registered in PROSPERO Register [2016, CRD42016050917]. Irritable Bowel Syndrome and Peppermint Oil Essay.

Results

Twelve randomized trials with 835 patients were included. For global symptom improvement, the risk ratio (RR) from seven RCTs for the effect of PO (n = 253) versus placebo (n = 254) on global symptoms was 2.39 [95% confidence interval (CI): 1.93, 2.97], I² = 0%, z = 7.93 (p < 0.00001). Regarding abdominal pain, the RR from six RCTs for the effect of PO (n = 278) versus placebo (n = 278) was 1.78 [95% CI: 1.43, 2.20], I² = 0%, z = 5.23 (p < 0.00001). Overall, there were no differences in the reported adverse effects: PO (32 events, 344 total, 9.3%) versus placebo (20 events, 327 total, 6.1%) for eight RCTs; RR 1.40 [95% CI: 0.87, 2.26] I² = 0%, z = 1.39 (p = 0.16). The number needed to treat with PO to prevent one patient from having persistent symptoms was three for global symptoms and four for abdominal pain.

Conclusions

In the most comprehensive meta-analysis to date, PO was shown to be a safe and effective therapy for pain and global symptoms in adults with IBS.

The irritable bowel syndrome (IBS) is a chronic, functional gastrointestinal syndrome characterized by relapsing abdominal pain and altered bowel habits, with either predominant symptoms of diarrhea (IBS-D), constipation (IBS-C), both (IBS-M), or undetermined (IBS-U), and is categorized according to the Rome IV criteria [1]. As a common digestive tract disorder, IBS affects an estimated 5–15% of Western populations [2]. Irritable Bowel Syndrome and Peppermint Oil Essay. Lovell and Ford conducted a meta-analysis of the world’s literature and reported that, on a global scale, IBS is seen predominantly in females, and the age of onset is typically under 50 years-of-age [3]. In their research, Lovell and Ford found the global prevalence of IBS to be 11.2% (95% confidence interval [CI], 9.8–12.8%) [3]. IBS accounts for a significant number of annual visits to primary care physicians, health-care utilization, quality of life, and adverse economics owing to absenteeism from work [4].

The pathophysiology of IBS is complex and involves an interaction of various factors, which includes, but is not limited to, genetic predisposition, gut-brain axis, visceral sensitivity, gastrointestinal motility, gut dysbiosis, neurotransmitters, food reactions, intestinal permeability, bile acids, inflammatory mediators, early-life stressors, psychosocial maladaptation, and somatization, among others [5]. IBS patients with mild and intermittent symptoms usually benefit from lifestyle and dietary modification, which includes a diet low in fermentable oligo-, di-, and monosaccharides and polyols (FODMAPs) [6]; and in some cases, lactose and gluten avoidance [7]. Smooth muscle relaxants and antispasmodics can also be used to help with IBS symptoms, especially abdominal pain and bloating [8].

Peppermint oil (PO) (Mentha Piperita) is a naturally-occurring carminative herb containing monoterpene compounds that target the pathophysiology of IBS. PO contains L-menthol, which blocks calcium channels in smooth muscle, thus producing antispasmodic effects on the gastrointestinal tract [9]. PO possesses antimicrobial, anti-inflammatory, antioxidant, immunomodulating, and anesthetic activities, all of which may be relevant for the treatment of IBS [10,11,12]. Several case reports, observational studies, and randomized clinical trials (RCTs) with methodological inconsistencies and heterogeneous outcomes have been reported since the research conducted by Rees et al. Irritable Bowel Syndrome and Peppermint Oil Essay. in 1979 [8, 13,14,15,16,17,18,19,20]. Earlier systematic reviews of RCTs of PO for IBS treatment revealed trial design flaws (e.g., no washout period for crossover trials), short follow-up duration, and conflicting trial results [14, 21]. Some more recent systematic reviews of RCTs of PO for IBS treatment were limited in the lack of evidence for adverse events [8, 18]. In addition, the risk-benefit profile of PO has been evolving as new RCTs continue to arise.

In 2016, Cash et al. reported the findings of a 4-week double blinded, placebo controlled RCT which tested a novel, proprietary, enteric-coated peppermint formulation (IBgard®) for its potential efficacy in reducing IBS symptoms in 72 patients with IBS-M or IBS-D [22]. The specialized enteric-coating utilized in their trial consisted of a solid-state matrix that was triple-coated and designed to deliver PO with sustained release to the small intestine with fewer potential adverse effects. After 24 h. of treatment, there was a reduction in the total IBS symptom score over baseline (mean change − 0.55, SD ± 0.613) vs. placebo (mean change − 0.27, SD ± 0.342) (p = 0.0092). At trial completion, there was a 40% reduction in the total IBS symptom score in the PO group compared to baseline (mean change − 1.16, SD ± 0.807) vs. 24.3% (mean change − 0.70, SD ± 0.737) with placebo (P = 0.0246). There was an increased improvement in both multiple and individual gastrointestinal symptoms, as well as in severe or unbearable symptoms compared to the placebo.

Given the recent findings by Cash et al. [22] and the potential limitations of previous meta-analyses, we conducted a systematic review and meta-analysis of available RCTs to determine the effect of peppermint oil in reducing the abdominal pain and global symptoms of irritable bowel syndrome and to evaluate the possible side effects of PO as compared to the placebo. Irritable Bowel Syndrome and Peppermint Oil Essay.

Identification and retrieval of primary studies

We conducted this systematic review and meta-analysis as per the PRISMA guidelines (i.e., the preferred reporting items of systematic reviews and meta-analysis) [23]. An experienced medical informationist (JN) developed and executed the research strategy in collaboration with the co-authors. There were no restrictions placed on publication dates. A preliminary search was executed on October 10, 2016, and repeated on October 10, 2017, and April 11, 2018, using the following databases: MEDLINE (PubMed), Cochrane Central Register of Controlled Trials (Cochrane CENTRAL), ClinicalTrials.gov, EMBASE (Ovid), and Web of Science. Controlled vocabulary terms for each concept were identified and combined with keyword synonyms. Web of Science was searched using keyword terms only (please see Additional file 1. Medical Literature Search Results for full search strategies). All results were downloaded to Endnote X8 (Thompson and Reuters, Philadelphia, Pennsylvania) and duplicate citations were identified and removed. The protocol is registered in PROSPERO Register [2016:CRD42016050917; (http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42016050917)].

Study selection and data extractions

The titles and abstracts of the studies were carefully reviewed by two of the authors (GM, NA) independently to include RCTs that evaluated the influence of enteric-coated PO on IBS, based on the inclusion and exclusion criteria (Table 1). When there was a disagreement, a third reviewer (BS) determined whether the study qualified for inclusion. Irritable Bowel Syndrome and Peppermint Oil Essay. We also reviewed the bibliography of prior meta-analyses, review articles, and studies that underwent full-text screening for additional studies (reverse snowballing) to maximize the yield [24].

Once the articles met the criteria, the full text was reviewed and data extraction performed by four independent reviewers (GM, BS, GH, LW) based on data quality, sufficiency, and relevance. Disagreements were resolved by a third reviewer to reach a consensus. Our primary outcomes are proportion of patients with improvement in global symptoms and proportion of patients with improvement in abdominal pain. Extracted data included last name of the first author, year of publication, country of origin, study setting, demographic information of patients, publication year, population, sample size, study design, subtype(s) of IBS (if specified), criterion used for the IBS diagnosis, peppermint oil dose, preparation of peppermint oil, and patients enrolled and completed, and quantitative results. For RCTs with cross-over design, we only extracted data from the first stage before the wash-out period to account for intra-patient correlation of outcomes.

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Risk of bias, quality assessment, and data synthesis

We used the modified Cochrane Collaboration’s risk of bias assessment tool for RCTs. Bias was assessed as a judgment (high, low, or unclear) for individual elements from five domains (selection, performance, attrition, reporting, and other) [25]. Any disagreements were then discussed with a third reviewer (BS) with an agreement to be reached by consensus [25]. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) analysis was utilized to rate the evidence of our review, whereby very low = 1, low = 2, moderate = 3, high = 4. The strength of recommendations were 1 (strong) or 2 (weak) [26].

Statistical analysis

We pooled the results from included studies by random-effects meta-analysis with inverse variance weighting to determine the risk ratio (RR) and the 95% confidence interval (95% CI) for each outcome in RevMan 5.3.5 [27]. Q statistics, I-squared (I²), and tau-squared (τ²) were calculated to assess statistical heterogeneity. For Q statistics, a critical value of 0.1 was used to determine statistical significance. We considered an I² greater than 0.75 as a cutoff for considerable heterogeneity across studies. We planned to use funnel plots and Egger’s test [28] to examine publication bias if the number of studies for an outcome is larger than ten. We conducted sensitivity analyses by removing studies with a high risk of bias per the Cochrane risk of bias tool. Irritable Bowel Syndrome and Peppermint Oil Essay.

Study selection

A literature search conducted from inception to April 11, 2018, identified 759 studies. After duplicates were removed, a total of 427 studies remained for a review of titles and abstracts, from which 22 trials were identified that underwent full text screening. A total of ten studies were excluded (Additional file 2: Table of Excluded Studies), and twelve randomized studies (835 patients) that met the inclusion criteria were identified and underwent systematic review and data synthesis. A flow diagram of the study selection is summarized in Fig. 1.  Irritable Bowel Syndrome and Peppermint Oil Essay.