Peppermint Oil
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
Peppermint Oil: From an Unspecified Original Indication to Cardiovascular Disease
One-Sentence Summary
Peppermint oil has no approved indication on record in the data compiled for this report, and all four of its US authorizations are cancelled. The TxGNN model ranks leprosy first, but the only prediction with any supporting evidence is Cardiovascular Disease, which is the one evaluated here. That prediction has 1 completed small trial and 2 directly relevant publications, both on hypertension rather than cardiovascular disease outcomes.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not available (no approved indication text in any authorization) |
| Predicted New Indication | Cardiovascular Disease (rank 9 of the top 10 predictions; the only one with any trial or literature support) |
| TxGNN Prediction Score | 99.13% |
| Evidence Level | L4 |
| US Market Status | Cancelled only |
| Number of NDAs | 4 (all cancelled) |
| Recommended Decision | Hold (research question only) |
Note on the top-ranked predictions: The nine other predictions (leprosy 99.80%, pneumocystosis 99.58%, coronary artery disease 99.35%, myocardial ischemia 99.26%, echinococcus granulosus infection 99.25%, and polyps of the vocal cord, uterus, middle ear and frontal sinus at 99.1%) have no clinical trials or publications. They are Level L5 (model prediction only) and are on Hold. Cardiovascular disease is reported here because it is the only prediction with supporting data.
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available. Based on known information, peppermint oil is a plant-derived essential oil rich in menthol and flavonoids. No approved indication is recorded, so the relationship to an original indication cannot be assessed.
Mechanistically, a link to blood pressure is plausible but unvalidated. Menthol may relax smooth muscle, possibly through calcium channel modulation. One physiological study in healthy volunteers (PMID 30070742) found that gastric cooling with menthol increased cardiac parasympathetic activity and lowered heart rate. These findings suggest a possible effect on blood pressure, but they do not show an effect on cardiovascular disease outcomes.
The evidence is also indirect. The available trial tested surrogate cardiometabolic markers in people with mild-to-moderate hypertension, not coronary events, stroke, or mortality. The high TxGNN score is a model prediction and should not be read as clinical proof.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT05561543 | Not applicable | Completed | 40 | Effects of peppermint oil on cardiometabolic outcomes in mild-to-moderate hypertension. It is small and uses surrogate markers, not cardiovascular disease events. |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 42024666 | 2026 | Placebo-controlled RCT | PLoS One | Twice-daily peppermint oil supplementation on cardiometabolic outcomes in pre- and stage 1 hypertension |
| 40333716 | 2025 | RCT protocol | PLoS One | Protocol for the same placebo-controlled trial in pre- and stage 1 hypertension |
| 30070742 | 2018 | Human physiological study | Exp Physiol | Gastric cooling and menthol increased cardiac parasympathetic activity in healthy adults |
The data compiled for this report also contained four publications that do not bear on peppermint oil efficacy. Two were formulation studies of other drugs (PMIDs 39139335 and 28889028), one was a breath-analysis methods paper (PMID 27277875), and one was a news digest (PMID 25037671). They are not listed above.
US Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| M005 | Gray Nail Essence Oil | Liquid | Not stated (cancelled) |
| M029 | Gray Nail Essence Oil | Liquid | Not stated (cancelled) |
| M017 | SINSINPAP COOL | Patch | Not stated (cancelled) |
| Not available | iShanCare | Patch | Not stated (cancelled) |
Safety Considerations
Please refer to the package insert for safety information. No warnings, contraindications, or drug interaction records were found in the data compiled for this report.
Conclusion and Next Steps
Decision: Hold (research question only)
Rationale: The prediction rests on one small, completed, non-phased trial and one related publication, both using surrogate hypertension endpoints. There is no approved indication, no mechanism data, and no safety data, and every US authorization is cancelled. Evidence is at Level L4 and is not enough to support a move forward.
To proceed, the following is needed:
- Published results from NCT05561543 and the 2026 placebo-controlled trial (PMID 42024666), including effect sizes on blood pressure
- Larger, adequately powered trials in hypertension, followed by studies on cardiovascular disease outcomes
- Mechanism of action data for peppermint oil, especially vascular and calcium channel effects
- Safety information from the FDA package insert (warnings, contraindications) and drug interaction data
- Clarification of the regulatory status and intended product type, since the cancelled authorizations are for topical liquids and patches, not oral formulations like those tested in the trials
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.