Valine
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
Valine: From Parenteral Nutrition Amino Acid Component to Sclerosing Cholangitis
One-Sentence Summary
Valine is an essential branched-chain amino acid (BCAA) used as a component of amino acid infusions and parenteral nutrition products. The TxGNN model predicts it may be relevant to sclerosing cholangitis, but there are 0 clinical trials and only 2 publications (one observational study, one Mendelian randomization study), and neither tests valine as a treatment. This is a research question, not a therapeutic candidate.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not stated in the Singapore registration data. The products are amino acid and parenteral nutrition formulations. |
| Predicted New Indication | Sclerosing cholangitis |
| TxGNN Prediction Score | 99.42% |
| Evidence Level | L4 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 19 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available. Based on known information, valine is a branched-chain amino acid and a component of amino acid infusion and parenteral nutrition products. Its role in providing nutritional amino acids is well established.
In chronic cholestatic liver disease, amino acid metabolism is altered, including imbalances between branched-chain and aromatic amino acids. These changes may relate to fatigue and hepatic metabolic dysfunction. The retrieved literature shows a metabolic association between amino acids and primary biliary cirrhosis/primary sclerosing cholangitis. It does not show that giving valine treats the disease.
The TxGNN score is high, but it is a graph-based prediction. The supporting papers describe associations, not therapeutic effects of valine supplementation.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 39015781 | 2024 | Mendelian randomization | Frontiers in Medicine | Examines the causal relationship between blood metabolites and the risk of primary biliary cholangitis and primary sclerosing cholangitis. |
| 15790420 | 2005 | Cohort | BMC Gastroenterology | Studies abnormal amino acid patterns (plasma tyrosine) and their relation to fatigue in PBC and PSC. It does not test valine as a treatment. |
Singapore Market Information
All 19 registrations are valid single-ingredient licences. The data compiled for this report contains no approved indication text. The five below are examples.
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN16337P | AMINOVEN SOLUTION FOR INFUSION 15% | Infusion, solution | Not available |
| SIN11682P | AMINOVEN SOLUTION FOR INFUSION 5% | Injection | Not available |
| SIN11829P | AMINOVEN SOLUTION FOR INFUSION 10% | Injection | Not available |
| SIN06299P | NEPHROSTERIL FOR INTRAVENOUS INFUSION | Injection | Not available |
| SIN08352P | AMINOPLASMAL-15% INFUSION | Injection | Not available |
The other registrations include Trophamine, Nutrineal PD4, Vaminolact, Aminoplasmal B.Braun 10% E, Oliclinomel, SmofKabiven (several variants) and Nutriflex Omega (several variants). Dosage forms are infusion solutions, injections and emulsions.
Safety Considerations
Please refer to the package insert for safety information.
Other Predicted Indications (For Reference)
None of the other top predictions has real therapeutic support:
- Hyperthyroidism (99.32%): Observational studies link BCAAs, including valine, to thyroid function and metabolism. Many other retrieved papers concern thyroid-stimulating hormone receptor mutations that substitute a valine residue in the protein. These are name-matching artifacts, not evidence for valine as a drug. Hold.
- Resistance to thyroid hormone (99.21%) and hyperthyroxinemia (99.07%): All retrieved papers are genetic reports of receptor mutations with valine residue substitutions. Supplementation cannot correct a genetic cause. Hold.
- Angle-closure, traumatic and neovascular glaucoma, glaucomatous optic disc atrophy, and aqueous misdirection (99.23% to 99.39%): No relevant evidence or plausible mechanism. The one paper retrieved, a pedigree report on angle-closure glaucoma, does not involve valine. The scores likely reflect network proximity to other glaucoma terms. Hold.
- Obsolete bundle branch block (99.19%): An obsolete ontology term, not a valid repurposing target. Hold.
Conclusion and Next Steps
Decision: Hold
Rationale: The sclerosing cholangitis prediction rests on two papers showing a metabolic association. No clinical trial tests valine as a treatment, and no mechanism is established. The evidence level is L4 (mechanism and association studies only). Valine is widely marketed in Singapore as a nutritional component, but that gives no support for a new indication.
To proceed, the following is needed:
- Mechanism of action data and a plausible pathway from valine or BCAA supplementation to cholestatic liver disease
- Preclinical studies, or prospective studies of BCAA supplementation in primary sclerosing cholangitis
- Package insert warnings and contraindications, including safety in liver impairment, since amino acid loads can be hazardous in hepatic dysfunction
- Approved indication text for the Singapore registrations, and a check that the infusion routes suit the target patients
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.