Efficacy and safety of a food supplement with standardized menthol, limonene, and gingerol content in patients with irritable bowel syndrome: A double-blind, randomized, placebo-controlled trial

Abstract

Background: Irritable bowel syndrome (IBS) affects 9,2% of the global population and places a considerable burden on healthcare systems. Most medications for treating IBS, including spasmolytics, laxatives, and antidiarrheals, have low efficacy. Effective and safe therapeutic treatments have yet to be developed for IBS.

Purpose: This study assessed the efficacy and safety of a food supplement containing standardized menthol, limonene, and gingerol in human participants with IBS or IBS/functional dyspepsia (FD).

Design: A double-blind, randomized, placebo-controlled trial.

Methods: We randomly assigned 56 patients with IBS or IBS/FD to an intervention group (Group 1) or control group (Group 2) that were given supplement or placebo, respectively, in addition to the standard treatment regimen for 30 d. Three outpatient visits were conducted during the study. Symptom severity was measured at each visit using a 7×7 questionnaire. Qualitative and quantitative composition of the intestinal microbiota were assessed at visits 1 and 3 based on 16S rRNA gene sequencing.

Results: At visit 1 (before treatment), the median total 7×7 questionnaire score was in the moderately ill range for both groups, with no difference between the groups (p = 0.1). At visit 2, the total 7×7 score decreased to mildly ill, with no difference between the groups (p = 0.4). At visit 3, the total score for group 1 indicated borderline illness and for group 2 remained indicated mild illness (p = 0.009). Even though we observed some variations in gut microbiota between the groups, we did not find any statistically significant changes.

Conclusion: The food supplement with standardized menthol, limonene, and gingerol content increased the efficacy of standard therapy in IBS and FD patients. The use of the supplement did not cause any obvious side effects.

Registration: ClinicalTrials.gov Identifier: NCT04484467.

Fig 1. CONSORT flow diagram.

Fig 2. Total 7×7 questionnaire scores in group 1 and group 2 at visits 1, 2, and 3.

Fig 3. Qualitative and quantitative composition of the intestinal microbiota genera in patients of groups 1 and 2 at visit 1.

Columns 2 and 3 present the relative bacterial content of a given genus (r.c., represents the normalized number of reads annotated to the current genus) averaged over all samples of a group. The color brightness reflects the average content, whereas the color hue (blue to orange) indicates the difference between the groups. The heatmaps in columns 4 and 5 show the bacterial content profiles of the genera for individual samples. The genera are sorted by a scoring factor, which reflects the magnitude of differences between groups 1 and 2, statistical significance (based on the Mann-Whitney test), and the average bacterial content across all samples.

Fig 4. Relative content in the metagenome of genes involved in fatty acid biosynthesis (FAB) in patients of groups 1 and 2 at visit 1 (inferred from taxonomic data).

Columns 5 and 6 show the average content of FAB genes in each group. The heatmaps in columns 3 and 4 demonstrate the relative gene abundance per sample. Samples are re-arranged according to the similarity of gene abundance profiles.

Fig 5. Statistically significant differences in the composition of intestinal microbiota genera between groups 1 and 2 at visit 3.

Columns 2 and 3 present the relative content (r.c.) of bacterial genera averaged over all samples in each group. The heatmaps in columns 4 and 5 show the bacterial content profiles for individual samples.

Fig 6. The relative content in the metagenome of genes participating in FAB in patients of groups 1 and 2 at visit 3 (inferred from taxonomic data).

Columns 5 and 6 show the average content of FAB genes in each group. The heatmaps in columns 3 and 4 demonstrate the relative gene abundance per sample. The samples are re-arranged according to the similarity of gene abundance profiles.