Manganese
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
Manganese: From Trace-Element Parenteral Nutrition to Sclerosing Cholangitis
One-Sentence Summary
Manganese is an essential trace element, marketed in Singapore as a concentrate for infusion (a parenteral nutrition additive). The TxGNN model predicts it may be relevant to sclerosing cholangitis, but the 0 clinical trials and 6 publications compiled for this report mostly describe manganese accumulating because of the disease, not treating it. The prediction is best read as a disease-association signal rather than a therapeutic lead.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not stated in the registration data (the approved indication text is empty; the product is a trace-element concentrate for infusion) |
| Predicted New Indication | Sclerosing cholangitis |
| TxGNN Prediction Score | 85.41% |
| Evidence Level | L4 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 1 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data is not available for this drug. Manganese is an essential micronutrient and a cofactor for metalloenzymes, including manganese superoxide dismutase (MnSOD). It is excreted mainly through the liver and bile.
The link to sclerosing cholangitis appears to be an association, not a therapeutic effect. When bile flow is impaired, manganese is retained. Studies in cholestatic patients report raised blood manganese, and a case report describes neurological symptoms from manganese overload in a patient with sclerosing cholangitis (PMID 39815815). Giving additional manganese could worsen this toxicity. The high TxGNN score most likely reflects this disease-causation or biomarker relationship.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 33428478 | 2021 | Cohort | Scand J Clin Lab Invest | Manganese and copper blood levels in patients with primary biliary cirrhosis and primary sclerosing cholangitis; long-term cholestasis can lead to accumulation of both elements |
| 10499363 | 1999 | Cohort | Neurotoxicology | Iron and manganese homeostasis in chronic liver disease, related to pallidal MRI signal hyperintensity |
| 39815815 | 2025 | Case report | Haematologica | Manganese overload as a co-factor of neurological symptoms in a patient with sclerosing cholangitis due to Langerhans cell histiocytosis |
| 7944963 | 1993 | Histology study | Arkhiv Patologii | Liver morphology in 9 men with primary sclerosing cholangitis; mild cholestasis with a marked rise in copper |
| 12612912 | 2003 | Preclinical | Gastroenterology | Cytokine-stimulated nitric oxide inhibits cAMP-dependent secretion in cholangiocytes (indirect relevance) |
| 23917144 | 2013 | Cohort | Free Radic Biol Med | Inflammation-related DNA damage in cholangiocarcinoma; sclerosing cholangitis noted as a risk factor (indirect relevance) |
None of these studies tests manganese as a treatment.
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN14341P | Nutritrace Concentrate for solution for infusion (B. Braun Melsungen AG) | Infusion, solution concentrate | Not stated in the registration data |
Safety Considerations
- Toxicity in cholestasis: The literature compiled for this report consistently identifies manganese retention and overload when biliary excretion is impaired. Reported consequences include neurological symptoms and brain accumulation visible on MRI. Parenteral nutrition guidelines cited in the literature recommend reducing or monitoring manganese supplementation in cholestatic patients.
No drug interaction records were found. For other safety information, please refer to the package insert.
Conclusion and Next Steps
Decision: Hold
Rationale: No clinical trials exist, and the literature shows manganese as a consequence or possible aggravating factor of sclerosing cholangitis, not as a therapy. Because impaired biliary excretion causes manganese retention, giving more manganese to these patients carries a real toxicity risk.
Other predictions reviewed (all Hold):
- Dry eye syndrome (L4): only animal and in vitro studies using manganese-based SOD mimetics or bacterial MnSOD, not elemental manganese.
- Drug-induced osteoporosis (L4): a single general review of trace elements.
- Cholestasis (L4) and intrahepatic biliary atresia (L4): the evidence points toward toxicity, not benefit.
- Vitamin deficiency disorder (L4): broad nutrition and toxicity literature, not a repurposing indication.
- Biotin metabolic disease (L4): the one relevant study shows biotin rescuing manganese toxicity, the reverse of the predicted direction.
- Respiratory syncytial virus infection, esotropia, and non-syndromic visceral malformation (L5): prediction only, with no trials or literature.
To proceed, the following is needed:
- Package insert warnings and contraindications from the HSA, which are currently unavailable
- Detailed mechanism-of-action data
- Evidence that manganese has therapeutic benefit, rather than merely accumulating, in cholestatic or biliary disease
- A toxicity risk assessment and a manganese blood-level monitoring plan for patients with impaired biliary excretion
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.