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 Original paper

What was studied?

This trial evaluated whether adding a menthol, limonene, and gingerol supplement for IBS symptom improvement to standard care could reduce symptom burden and remain safe in adults with irritable bowel syndrome (IBS), including those with overlapping functional dyspepsia (FD). In a double-blind, randomized, placebo-controlled design, participants received either one daily capsule of the standardized supplement (peppermint oil providing menthol/limonene plus ginger oil providing gingerol, in an olive-oil base) or an olive-oil placebo for 30 days, alongside guideline-concordant symptomatic therapy tailored to IBS subtype and FD overlap. Symptom severity was tracked at baseline, mid-treatment, and end-treatment using the validated 7×7 questionnaire, while gut microbiota composition was measured at baseline and day 30 using 16S rRNA (V3–V4) sequencing with downstream taxonomic and predicted functional profiling.

Who was studied?

Fifty-six adults (18–59 years) treated in outpatient settings in Moscow, Russia, met Rome IV criteria for IBS, with organic disease excluded through clinical evaluation, labs, stool testing, and colonoscopy with biopsies when indicated. Participants were randomized evenly: 28 to supplement and 28 to placebo. Baseline characteristics were similar between groups, including mean age (about early 30s), sex distribution (approximately half female), disease duration (median 48 months), and baseline symptom severity (moderately ill range by 7×7 score). Diagnoses included IBS alone (about two-thirds) and IBS with FD overlap (about one-third), reflecting the common clinical coexistence of upper and lower functional GI symptoms.

Most important findings

Both groups improved by mid-treatment, but by day 30 the supplement group showed a significantly greater reduction in total 7×7 score, reaching “borderline ill,” while placebo remained “mildly ill” (between-group p = 0.009). Specific symptoms (including epigastric pain, “nuts”/hard stool, abdominal pain relieved by bowel movement, and bloating) decreased in more supplement-treated patients. Microbiome analyses showed heterogeneity and no statistically significant FDR-adjusted taxonomic shifts attributable to the supplement, despite nominal differences in certain genera (e.g., higher Oscillibacter in supplement; higher Veillonella, Collinsella, and Gemmiger in placebo at visit 3). Importantly for microbiome-signature interpretation, symptom severity correlated most robustly (after FDR correction) with Fusobacterium/Fusobacteriaceae (positive association), although this taxon was low-abundance and present in a minority of samples. Predicted functional signals suggested a weak, non-FDR-significant relationship between severity and an inferred short-chain fatty acid transporter gene (atoE), aligning with mechanistic links between SCFA ecology, barrier function, and visceral sensitivity. Safety assessments found no meaningful lab abnormalities and no additional complaints in either group.

Key implications

Clinically, this study supports that a standardized peppermint/ginger-derived supplement may enhance symptom relief when layered onto usual IBS/FD management over 30 days, with reassuring short-term tolerability. From a microbiome-signature perspective, the key actionable signal is not a treatment-driven microbiome “shift,” but the identification of Fusobacterium-related taxa as a severity-associated marker (albeit low-prevalence), alongside suggestive links to Veillonellaceae and Coriobacteriaceae. For clinicians and database builders, the data argue for cautious interpretation: symptom improvement occurred without robust compositional change, implying that benefits may be mediated through neuromuscular, sensory, anti-inflammatory, or metabolomic pathways rather than large-scale microbiota remodeling, and that future trials need larger samples and longitudinal follow-up to confirm microbial predictors of response.

Citation

Ivashkin VT, Kudryavtseva AV, Krasnov GS, Poluektov YM, Morozova MA, Shifrin OS, et al. 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. PLoS One. 2022;17(6):e0263880. doi:10.1371/journal.pone.0263880