Peppermint Oil

證據等級: L5

預測適應症: 10 個

Peppermint Oil: Ten TxGNN-Predicted Indications — Cardiovascular Disease as the Only Evidence-Backed Candidate

One-Sentence Summary

Peppermint oil (DrugBank DB11198) has no recorded original indication in this evidence pack and is not currently marketed in Australia (0 ARTG entries). TxGNN generated 10 candidate new indications, but the highest-scoring prediction (leprosy, 99.8%) has zero supporting trials or literature, while the only candidate with real-world evidence — cardiovascular disease (rank 9, 99.1%) — is backed by 3 clinical trials and 8 publications, though all are small pilot studies rather than confirmatory RCTs.

Quick Overview

Item	Content
Original Indication	Not available — no approved indication recorded (drug not marketed in Australia)
Highest-Scoring Prediction	Leprosy (TxGNN score 99.80%), but no clinical trials or literature support it — likely model noise
Best-Evidenced Prediction	Cardiovascular Disease (TxGNN score 99.13%) — 3 trials, 8 publications
Evidence Level (Cardiovascular Disease)	L3
Evidence Level (other 9 candidates)	L5 (model prediction only)
Australia Market Status	Not Marketed
Number of ARTG Entries	0
Recommended Decision	Hold

All 10 Predicted Indications (Ranked by TxGNN Score)

Rank	Predicted Indication	TxGNN Score	Evidence	Evidence Level	Recommendation
1	Leprosy	99.80%	None	L5	Hold — no known mechanism, judged model noise
2	Pneumocystosis	99.58%	None	L5	Hold — no known antifungal mechanism
3	Coronary Artery Disease	99.35%	None	L5	Hold — mechanism purely inferential
4	Myocardial Ischemia	99.26%	None	L5	Hold — no preclinical/clinical validation
5	Echinococcus granulosus Infection	99.25%	None	L5	Hold — no specific antiparasitic mechanism
6	Polyp of Vocal Cord	99.14%	None	L5	Hold — no known mechanism
7	Uterine Polyp	99.14%	None	L5	Hold — no known mechanism
8	Polyp of Middle Ear	99.14%	None	L5	Hold — no known mechanism
9	Cardiovascular Disease	99.13%	3 trials, 8 papers	L3	Hold — research question, not yet actionable
10	Polyp of Frontal Sinus	99.12%	None	L5	Hold — sensory/decongestant effect only, not curative

The disconnect between TxGNN rank and evidence availability is notable: the model’s single highest-confidence prediction (leprosy) has no supporting data at all, while the only candidate with real trials and literature ranks 9th. This pattern is consistent with the mechanistic rationale text for each candidate, most of which explicitly flag “no known mechanism” or “model noise.”

Why is This Prediction Reasonable? (Cardiovascular Disease)

Detailed mechanism of action data for peppermint oil as a whole is not available in this evidence pack (marked as Data Gap). However, the evidence pack’s own mechanistic rationale for the cardiovascular disease candidate is informative: peppermint oil’s major constituent, menthol, is a known TRPM8 receptor agonist with calcium-channel-blocking activity. Menthol has documented effects on vagal (parasympathetic) tone, heart rate, and vascular smooth muscle, which provides a plausible physiological link to cardiovascular/cardiometabolic parameters such as blood pressure and heart rate variability.

This mechanism does not, however, establish disease-specific efficacy against “cardiovascular disease” as a clinical endpoint — it supports a narrower, symptomatic/parameter-level effect (e.g. blood pressure, autonomic tone) rather than a disease-modifying one. The related predictions for coronary artery disease and myocardial ischemia (ranks 3 and 4) rely on the same theoretical extrapolation but currently have no supporting trials or literature at all, so they should be treated as unproven hypotheses rather than corroborating evidence.

Clinical Trial Evidence (Cardiovascular Disease)

Trial Number	Phase	Status	Enrolment	Key Findings
NCT05071833	N/A (dietary intervention)	Completed	36	Small exploratory study of oral peppermint supplementation on cardiometabolic parameters; direct relevance but weak statistical power.
NCT05561543	N/A (dietary intervention)	Completed	40	Peppermint oil effects on cardiometabolic outcomes in mild-to-moderate hypertension; follows on from an earlier RCT showing improved systolic BP and lipids in healthy individuals.

One additional trial, NCT04966546 (subdural hematoma post-operative monitoring), was excluded from the table above — it was withdrawn (0 enrolled) and is mechanistically unrelated to peppermint oil or cardiovascular disease; it appears to be a search false-positive.

Neither remaining trial is a randomised, placebo-controlled Phase 2/3 trial with a formal phase designation — both are small, unblinded/exploratory dietary intervention studies.

Literature Evidence (Cardiovascular Disease)

PMID	Year	Type	Journal	Key Findings
40333716	2025	RCT (protocol)	PLoS One	Protocol for a placebo-controlled RCT of peppermint oil in pre-hypertension/stage 1 hypertension, citing menthol/flavonoid content as the rationale — trial not yet reporting results.
30070742	2018	Cohort	Experimental Physiology	Gastric cooling and menthol increase cardiac parasympathetic (vagal) activity and reduce heart rate in healthy volunteers — supports the autonomic mechanism cited above.
25037671	2014	Review	Explore (NY)	Brief review mentioning peppermint oil primarily for irritable bowel syndrome, not cardiovascular disease — low direct relevance.
19198983	2009	Review	Internal and Emergency Medicine	General internal/cardiovascular medicine update; no abstract available, relevance unclear.
17577363	2007	Case Report	Contact Dermatitis	Allergic contact dermatitis from peppermint foot spray — a safety signal, not an efficacy finding.

Three further records returned by the literature search — PMID 39139335 (lercanidipine nanoemulsion), 28889028 (candesartan nanoemulsion), and 27277875 (exhaled-breath menthol detection) — do not discuss peppermint oil’s cardiovascular effects and appear to be keyword-search false positives; they are excluded from the table above but flagged here for transparency rather than silently dropped.

Safety Considerations

Please refer to the TGA-approved Product Information (PI) for safety information. No drug interaction, contraindication, or warning data are currently available in this evidence pack, and drug–drug interaction lookups returned no results.

Conclusion and Next Steps

Decision: Hold

Rationale: Peppermint oil is not currently marketed in Australia, has no recorded original indication, and no TGA PI safety data — this alone is a blocking gap for any safety assessment. Of the 10 TxGNN-predicted indications, 9 have no supporting evidence whatsoever, and the one with genuine data (cardiovascular disease) is supported only by two small, non-randomised or protocol-stage studies (n=36–40), not a completed confirmatory RCT.

To proceed, the following is needed:

TGA Product Information (warnings, contraindications) — currently blocking (Severity: Blocking)
Original mechanism of action data from DrugBank (Severity: High)
Results from the ongoing/protocol-stage RCT (PMID 40333716) once completed
A larger, adequately powered RCT specifically testing cardiovascular disease outcomes before this indication can move beyond “Research Question” status
Re-verification of the leprosy and other L5 candidates against updated TxGNN model versions, given the complete absence of corroborating mechanism or evidence
Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.