New secondary analysis confirms effective symptom relief

Functional gastrointestinal disorders are defined by Rome-IV as disorders of gut-brain interaction. Dyspeptic symptoms are often accompanied by typical irritable bowel symptoms, such as irregular bowel movements and flatulence. A recently published secondary analysis suggests that menthacarin – a proprietary combination of peppermint and cumin oils – is not only an effective and safe treatment option for functional dyspepsia, but can also benefit patients with concurrent irritable bowel symptoms.

The secondary analysis published in 2023 was based on a systematic search of PubMed, the Cochrane Library, and a database of clinical trials [1]. Five randomized-controlled trials (n=580) were identified in which menthacarin produced symptom relief in functional dyspepsia (FD) (Table 1) compared with placebo or a reference substance (cisapride) [1]. In seven other studies, the phytotherapeutic agent was also found to be effective in FD patients with concurrent irritable bowel syndrome (IBS) (Table 2) [1].

Menthacarin reduces pain and other FD symptoms

The results of clinical trials in FD patients support the efficacy of menthacarin (box) in the treatment of gastrointestinal symptoms and discomfort, especially epigastric and abdominal pain, flatulence, and bloating [1]. Three placebo-controlled studies with a total of 249 patients (full-analysis set, FAS) on menthacarin in FD were included in a meta-analysis [2–4]. Significant effects in favor of menthacarin were seen both in terms of pain intensity and in the Clinical Global Impression Scale. In the three studies, pain intensity was assessed using either a 6-point continuous scale or the visual analog scale (VAS). There was significantly better pain reduction from baseline to week 4 for menthacarin compared with placebo (standardized mean difference 0.80 [95% CI: 0.39-1.21]). In all three studies, overall improvement in patients’ condition was measured by the Clinical Global Impression Scale. This found that a significantly higher number of patients in the menthacarin group compared with placebo achieved a significant improvement in item 2 of the CGI at week 4 (RR 2.65 [95% CI: 1.81-3.87]).

• Rich et al. 2017 [2]: This prospective randomized-controlled multicenter study evaluated the effects of menthacarin (2× 1 capsule daily) on symptom intensity and disease-specific quality of life in 114 adult patients with FD that had been present for at least six months. Symptom intensity was assessed using the Nepean Dyspepsia Index (SF-NDI). This is a validated questionnaire developed specifically for FD patients, which contains 42 items (Likert ^scale$) on quality of life related to 17 key FD aspects and also allows assessment of the frequency, intensity and severity of disturbance of 15 upper GI tract symptoms. After four weeks of menthacarin treatment (n=58), the NDI subscores “pain” and “discomfort” as well as the total score improved significantly compared to placebo (n=56) (p<0.0001).
• May et al. 2000 [4]: This was a double-blind, randomized-controlled trial in which mean pain intensity according to the visual analog scale (VAS)** decreased by 2.60 ± 2.44 points (mean ± SD) and 40%, respectively, from baseline to day 29 with treatment with menthacarin (n=48; 2× 1 capsule daily) (mean VAS scores at baseline: 6.50 ± 1.40 points). In the placebo group (n=48), the corresponding pain reduction scores were 1.46 ± 1.77 points, or a 22% reduction (baseline scores: 6.71 ± 1.13 points). At the end of the study, 66.7% of patients in the menthacarin group had a very great or great improvement, operationalized by CGI item 2. In the placebo arm, the corresponding proportion was only 20.8%, which corresponded to a significant difference compared to the treatment arm (p=0.0001). Moreover, feelings of pressure and fullness improved significantly in patients treated with menthacarin compared with placebo (p<0.0005).
• May et al. 1996 [3]: This was a double-blind, placebo-controlled, multicenter study in FD patients. After four weeks of menthacarin treatment (3× 1 capsule daily), both pain intensity (6-point scale: 0=no pain, 5=very severe pain) and score in CGI item 2 significantly reduced in the menthacarin group (n=19) compared to placebo (n=20) (p=0.015 and p=0.008, respectively). Feelings of fullness, pressure and flatulence were also significantly reduced during the course of treatment.

^$5 Likert scale (1=not at all, 5=extremely)
** VAS: 0=absent, 10=maximum intensity

IBS symptoms also improve significantly

In summary, several analyses indicate that menthacarin improves both FD and IBS symptoms:

In about one third (n=111) of the FD patients in the three studies mentioned above [2–4], IBS symptoms were also present at the same time as functional dyspepsia. Data from this patient subpopulation were included in a pooled analysis [5]. IBS symptoms such as feelings of pressure, flatulence or diarrhea were reduced approximately twice as much with menthacarin treatment compared to placebo.

In a randomized controlled trial, 200 IBS patients each received 1 capsule of menthacarin or placebo twice daily for a period of two months [6]. This was followed by a one-month sequence in which all study participants received menthacarin. Abdominal pain as well as discomfort, cramps, bloating and fullness improved after four and eight weeks of treatment, respectively. However, due to the heterogeneous study samples, the statistical significance level was not reached. According to the authors, IBS patients of the diarrhea subtype in particular benefit from menthacarin. The 12-week treatment was found to be well tolerated and safe [6].

A four-week open-label multicenter study investigated the treatment effects of menthacarin in 2148 patients (mean age 48.4 ± 16.1 years) with dyspeptic symptoms in the primary care setting (448 practices participated) [7]. At baseline, 53% of patients reported suffering from postprandial pain. This proportion decreased to 7% by week 4 under menthacarin treatment. Regarding nocturnal abdominal pain, the rate decreased from 41% to 3%. While 60% suffered from dyspepsia at baseline, only 1% did so at week 4. Regarding irregular bowel movements and flatulence, the proportion decreased from 22% to 1% and from 51% to 1.5%, respectively.

Literature:

1. Madisch A, et al.: Menthacarin, a Proprietary Peppermint Oil and Caraway Oil Combination, Improves Multiple Complaints in Patients with Functional Gastrointestinal Disorders: A Systematic Review and Meta-Analysis. Dig Dis 2023; 41(3): 522–532.
2. Rich G, et al: A randomized placebo-controlled trial on the effects of Menthacarin, a proprietary peppermint and caraway-oil preparation, on symptoms and quality of life in patients with functional dyspepsia. Neurogastroenterol Motil 2017; 29(11): e13132.
3. May B, et al: Efficacy of a fixed peppermint oil/caraway oil combination in non-ulcer dyspepsia. Drug Research 1996; 46(12): 1149-1153.
4. May B, Köhler S, Schneider B: Efficacy and tolerability of a fixed combination of peppermint oil and caraway oil in patients suffering from functional dyspepsia. Aliment Pharmacol Ther 2000; 14(12): 1671-1677.
5. Madisch A, et al: Effectiveness of menthacarin on symptoms of irritable bowel syndrome. Wien Med Wochenschr 2019; 169(5-6): 149-155.
6. Madisch A, et al.: Wirksamkeit und Verträglichkeit von Menthacarin bei Patienten mit Reizdarmsyndrom: Ergebnisse einer randomisierten, doppelblinden, placebo-kontrollierten Studie. Z Gastroenterol 2019(57): e379.
7. Senf K, Laux P, Friedland T: Therapie mit Arzneipflanzen: funktionelle Dyspepsie im Visier. Der Bayerische Internist 1998(3): 1–4.
8. Lacy BE, Patel NK: Rome Criteria and a Diagnostic Approach to Irritable Bowel Syndrome. J Clin Med 2017 Oct 26; 6(11).
9. Stanghellini V, et al.: Rome IV – Gastroduodenal Disorders. Gastroenterology 2016 pii: S0016–5085(16)00177–3.
10. Medix: www.medix.ch/wissen/guidelines, (letzter Abruf 28.06.2023)
11. Deutsche Apothekerzeitung (DAZ): DAZ 2018 (9): 73, 01.03.2018.

HAUSAZT PRAXIS 2023; 18(7): 18–19
GASTROENTEROLOGIE PRAXIS 2023; 1(1): 34–35