Methionine
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
Methionine: From Maple Syrup Urine Disease to Acne
One-Sentence Summary
Methionine (marketed as Maapliv) was originally authorised in the EU for acute decompensation episodes of maple syrup urine disease (MSUD). The TxGNN model predicts it may be effective for acne, but there are 0 clinical trials and only 2 loosely related publications, neither of which tests methionine as a treatment. This is a model prediction with very weak supporting evidence.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Maple syrup urine disease (MSUD) presenting with an acute decompensation episode, in patients from birth who are not eligible for an oral or enteral BCAA-free formulation |
| Predicted New Indication | Acne (disease) |
| TxGNN Prediction Score | 99.9996% |
| Evidence Level | L4 |
| EU Market Status | Cancelled only (no currently valid authorisation) |
| Number of Authorizations | 1 (cancelled) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available. Methionine is an essential sulfur-containing amino acid and the precursor of homocysteine through the methionine cycle. Its use in MSUD is metabolic and nutritional, not anti-inflammatory or dermatological.
The link to acne is indirect. The only acne-related paper (PMID 11277950) found elevated plasma homocysteine in patients taking isotretinoin for cystic acne. This is an association with methionine metabolism, not evidence that methionine treats acne. The second paper (PMID 39357918) is a case report of an MTHFR mutation with neonatal encephalopathy, in which neonatal acne was one of several skin findings. It does not support a therapeutic role either.
The very high TxGNN score reflects a computational prediction from network features. Supplying more methionine could also raise homocysteine, so a mechanistic rationale for benefit in acne has not been established.
Other high-scoring predictions for this drug are mostly eye conditions (cataract subtypes and diabetic retinopathy). They have the same limitation: the literature describes methionine oxidation in lens proteins as pathology, not methionine as a treatment.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 11277950 | 2001 | Cohort | Int J Dermatol | Plasma homocysteine was elevated in patients on isotretinoin therapy for cystic acne. This is an indirect link to methionine metabolism. |
| 39357918 | 2024 | Case report | BMJ Case Reports | A novel MTHFR mutation in a neonate with encephalopathy, hair loss, marfanoid features and neonatal acne. It is not evidence for methionine as an acne treatment. |
EU Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| EMEA/H/C/005557 (cancelled) | Maapliv | Not specified | Maple syrup urine disease (MSUD) presenting with an acute decompensation episode in patients from birth who are not eligible for an oral and enteral branched-chain amino acids free (BCAA-free) formulation. |
Safety Considerations
- Drug Interactions (5 recorded, mostly minor):
- Activated charcoal: Moderate
- Ephedrine, pseudoephedrine, mexiletine, flecainide: Minor
- Disease associations flagged in the knowledge graph (derived from the TxGNN knowledge graph, not from label text): hypertension, kidney disease (including chronic and end-stage renal failure and nephrolithiasis), diabetes and diabetic ketoacidosis, heart disease and cardiovascular disease, hyperlipidaemia, hypercalcaemia and nephrocalcinosis, sarcoidosis, and phenylketonuria. These should be reviewed against the SmPC.
Please refer to the SmPC for the official warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The acne prediction rests on a computational score alone. There are no clinical trials, and the two papers are indirect associations that do not test methionine as a treatment. The only EU authorisation is cancelled, and the possibility that methionine raises homocysteine is a safety concern for new uses.
To proceed, the following is needed:
- Mechanism of action data for methionine and a plausible biological rationale for acne
- Preclinical or early clinical evidence that methionine supplementation improves acne
- Official safety information (warnings and contraindications) from the SmPC, which is not yet available
- A review of homocysteine-related cardiovascular and renal risks in the target population
- Clarification of the cancelled EU authorisation status and available formulations and routes
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.