Consider phytotherapeutics as a therapeutic option

Functional dyspepsia (FD) is a heterogeneous disorder in terms of both pathophysiology and symptomatology. Accordingly, there is hardly any intervention that is effective for all patients. In the context of a multimodal therapy, the combination of drug and non-drug treatment measures can be useful. The advantages of phytotherapeutics lie in particular in the fact that they develop their efficacy according to the multitarget principle and are generally well tolerated.

Recurrent upper abdominal discomfort is a common symptom in family practice. In patients who test positive for Helicobacter pylori, H. pylori eradicationis considered first-line therapy. For the remaining patients with appropriate symptoms, acid inhibitors and prokinetics are the first-line treatment options. If adequate symptom control cannot be achieved by monotherapy, the second-line approach is to combine acid inhibitors and prokinetics. The data situation on both groups of drugs is controversial and the exact mechanisms of action have not yet been elucidated. Low-dose neuromodulators are often used in the third line. In light of ample evidence from placebo-controlled trials, phytotherapeutics are now recommended for functional dyspepsia and irritable bowel syndrome by national and international guidelines [1,2]. Herbal medicines and non-pharmacological treatment options, such as psychotherapy or acupuncture, can be used in a complementary manner in any thereapy line.

Heterogeneous disorder – individual treatment

Evaluations of a secondary analysis by Masuy et al. (box) revealed the following [3]: acid inhibitory therapy resulted in symptom reduction in 30-70% of patients, with proton pump inhibitors (PPIs) proving more effective than H2 antagonists for epigastric pain. Prokinetics used mainly to treat postprandial distress syndrome showed the following outcomes in terms of efficacy: 59-81% response rate for dopamine receptor antagonists, 32-91% for serotonin receptor agonists, and 31-80% for muscarinic receptor antagonists. Eradication of H. pylori, which is recommended in infected patients, proved effective in 24-82%. Refractory symptoms are usually treated with neuromodulators. However, the authors of the secondary analysis point out that their efficacy in functional dyspepsia has not yet been fully elucidated. Available data show symptom reduction in 27-71% of patients. Among phytotherapeutic agents, peppermint oil reduced symptoms in 66-91%, rikkunshito in 29-34%, and iberogast in 20-95%. Last, but not least, acupuncture, cognitive behavioral therapy, and hypnotherapy may also contribute to symptom control, but there is limited research on their effectiveness. In the following, the findings obtained from the secondary analysis concerning the effects of peppermint oil and caraway oil (Tab. 1) are discussed in some detail.

Peppermint oil: relaxing effects on the intestinal muscles

Herbal-based medicines have been used for many decades to treat gastrointestinal complaints. In recent years, the research of phytotherapeutics in the context of the limited efficacy and sometimes unfavorable side effect profile of standard therapies, has experienced an upsurge [3]. Preparations from the leaves of peppermint (Mentha × piperita) have been used for many years to treat digestive complaints. An essential oil is extracted from the leaves, which contains menthol and other monoterpenes, as well as labiate tannins, flavonoids and triterpenes. Peppermint oil exhibits a relaxing effect on intestinal smooth muscle cells, which can be explained, among other things, by the influence of calcium influx into the cell similar to calcium antagonists from the class of dihydropyridines [4,5].

Peppermint/caraway oil combination: proven to relieve FD symptoms

Peppermint oil has been shown to lead to a reduction in intragastric pressure and gastroduodenal motility shortly after ingestion [5,7]. The best documented studies are on the use of peppermint oil in combination with caraway oil. This combination showed therapeutic efficacy comparable to cisapride in FD patients [8–10]. In three placebo-controlled randomized trials, the peppermint/caraway oil combination was found to be superior to placebo in reducing FD symptoms (Table 1) . May et al reported significant improvement in 66% of patients treated with peppermint/caraway oil versus 20.9% on placebo [8]. Moreover, Rich et al. demonstrated greater than 10% improvement in FD symptoms in 88% of patients who received the peppermint/caraway oil combination. Under placebo, this proportion was only 55.4% [11]. In a study by Chey et al. symptom improvement was achieved in 78% of patients with PDS and in 72% of those with EPS compared to 50% and 40%, respectively, on placebo [10]. The symptom-relieving effects are attributed to synergistic and additive actions of the two essential oils. A proprietary active ingredient combination of peppermint and caraway oil is Carmenthin® (Menthacarin®) [13].

Literature:

1. Stanghellini V, et al: Rome IV – Gastroduodenal Disorders. Gastroenterology 2016 pii: S0016-5085(16)00177-3.
2. Talley NJ, Walker MM, Holtmann G: Functional dyspepsia. Curr Opin Gastroenterol 2016; 32: 467-473.
3. Masuy I, Van Oudenhove L, Tack J: Review article: treatment options for functional dyspepsia. Aliment Pharmacol Ther 2019; 49(9): 1134-1172.
4. Hills JM, Aaronson PI: The mechanism of action of peppermint oil on gastrointestinal smooth muscle. An analysis using patch clamp electrophysiology and isolated tissue pharmacology in rabbit and guinea pig. Gastroenterology 1991; 101: 55-65.
5. Papathanasopoulos A, et al. Effect of acute peppermint oil administration on gastric sensorimotor function and nutrient tolerance in health. Neurogastroenterol Motil 2013; 25: e263-271.
6. Chey WD, et al: Long-term tegaserod treatment for dysmotility-like functional dyspepsia: results of two identical 1-year cohort studies. Dig Dis Sci 2010; 55: 684-697.
7. Micklefield G, et al: Effects of intraduodenal application of peppermint oil (WS(R) 1340) and caraway oil (WS(R) 1520) on gastroduodenal motility in healthy volunteers. Phytother Res 2003; 17: 135-140.
8. May B, Kohler 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: 1671-1677.
9. Madisch A, et al.: Treatment of functional dyspepsia with a fixed peppermint oil and caraway oil combination preparation as compared to cisapride. A multicenter, reference-controlled double-blind equivalence study. Drug Research 1999; 49: 925-932.
10. Chey WD, et al: Sa1619 – efficacy of caraway oil/l-menthol plus usual care vs placebo plus usual care, in functional dyspepsia patients with post-prandial distress (PDS) or epigastric pain (EPS) syndromes: results from a us RCT. Gastroenterology 2017; 152:S307.
11. 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. https://doi.org/10.1111/nmo.13132
12. Madisch A, et al: The Diagnosis and Treatment of Functional Dyspepsia. Dtsch Arztebl Int 2018; 115(13): 222-232.
13. Swiss Drug Compendium: www.compendium.ch (last accessed 11.10.2022)

HAUSARZT PRAXIS 2022, 17(10): 30-31