Arginine
| Evidence Level: L5 | Predicted Indications: 1 |
Table of Contents
Arginine: From Parenteral Nutrition (Amino Acid Supply) to Gastroparesis
One-Sentence Summary
Arginine is an amino acid. In South Africa it is registered mainly as a component of infusion products such as parenteral nutrition and peritoneal dialysis solutions. The TxGNN model predicts it may be useful for Gastroparesis, but this rests on 0 relevant clinical trials and only preclinical animal studies (3 with a plausible mechanistic link). No human study of arginine in gastroparesis was identified.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not stated in the registration records. Product names suggest use as an amino acid component of parenteral nutrition and dialysis solutions (inferred, not confirmed). |
| Predicted New Indication | Gastroparesis |
| TxGNN Prediction Score | 99.42% |
| Evidence Level | L4 (preclinical and mechanism studies only) |
| South Africa Market Status | Marketed |
| Number of SAHPRA Registrations | 11 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data for arginine is not available in this record. The rationale below comes from the published literature.
L-arginine is the substrate of neuronal nitric oxide synthase (nNOS), which produces the nitric oxide (NO) needed for nitrergic relaxation of the stomach (fundus) and pylorus. When this pathway is impaired, gastric emptying can slow, which is the hallmark of gastroparesis.
Three preclinical findings support the link:
- Glucocorticoid-induced gastroparesis in mice was linked to depletion of L-arginine (PMID 25057793).
- Tetrahydrobiopterin (BH4) deficiency, which impairs the nNOS cofactor, induced gastroparesis in newborn mice (PMID 23639814).
- Impaired nitrergic relaxation of the pyloric sphincter was found in a rat model of Parkinson’s disease with delayed gastric emptying (PMID 35380456).
This gives a biologically plausible story. However, the evidence is all animal data, and none of these studies tested arginine as a treatment in people. The high TxGNN score is a computational prediction and does not count as clinical evidence. The relationship between arginine’s registered nutritional use and gastroparesis is also unclear, because they are different therapeutic areas.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT01702051 | N/A | Unknown | 150 | Observational study of autologous pancreatic islet cell transplantation for glycaemic control after pancreatectomy. It does not involve arginine and does not study gastroparesis, so it provides no evidence for this pairing. |
No SANCTR or PACTR registrations were identified.
Literature Evidence
All publications are preclinical or case-level. No RCTs, reviews or human studies of arginine in gastroparesis were found.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 25057793 | 2014 | Preclinical (mouse) | Endocrinology | Glucocorticoids induced gastroparesis in mice through depletion of L-arginine. The most directly relevant study. |
| 23639814 | 2013 | Preclinical (mouse) | Am J Physiol Gastrointest Liver Physiol | BH4 deficiency (an nNOS cofactor) induced gastroparesis in newborn mice. |
| 35380456 | 2022 | Preclinical (rat) | Am J Physiol Gastrointest Liver Physiol | Impaired nitrergic relaxation of the pyloric sphincter in a Parkinson’s disease rat model that shows gastroparesis. |
| 18312542 | 2008 | Preclinical (rat) | Neurogastroenterol Motil | Myenteric neuropathy and nNOS in the jejunum of diabetic BB-rats, relevant to diabetic gastroparesis mechanisms. |
| 21193530 | 2011 | Preclinical (animal) | Am J Physiol Gastrointest Liver Physiol | Hyperglycaemia inhibits gastric motility via nodose ganglia KATP channels. Indirect relevance. |
| 18322959 | 2008 | Preclinical (mouse) | World J Gastroenterol | Gastric motor effects of ghrelin and GHRP-6 in diabetic mice with gastroparesis. Does not involve arginine. |
| 19023028 | 2009 | Preclinical (dog, device) | Am J Physiol Gastrointest Liver Physiol | Synchronized gastric electrical stimulation improved vagotomy-induced impairment of gastric accommodation via the nitrergic pathway. |
| 31984783 | 2020 | Preclinical (rat, device) | Am J Physiol Gastrointest Liver Physiol | Sacral nerve stimulation increased gastric accommodation in rats. Does not involve arginine. |
| 8194696 | 1994 | Preclinical (rat) | Gastroenterology | Delayed gastric emptying after food-protein-induced anaphylaxis. Indirect relevance. |
| 33867519 | 2021 | Case report | Am J Case Rep | Lifestyle changes normalised serum lactate in an m.3243A>G (MELAS) carrier. Limited relevance to this pairing. |
South Africa Market Information
Showing 5 of 11 registrations. The registration records do not include approved indication text or manufacturer.
| Registration Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| Reg. No. 37/34/0243 | Nutrineal PD4 with 1.1% amino acids 2.5L | Infusion | Not stated in the record |
| Reg. No. 33/10.2.1/0271 | Adco-ipratropium (ni201) | Vial | Not stated in the record. The product name suggests an ipratropium product, so the link to arginine should be verified. |
| Reg. No. 37/25.2/0503 | Oliclinomel N6 900E 2000ml | Infusion | Not stated in the record |
| Reg. No. 41/25/0757 | Nutriflex Lipid Peri | Infusion | Not stated in the record |
| Reg. No. 52/25/0739 | Numeta G13E | Infusion | Not stated in the record |
All listed forms are parenteral (infusion or vial). No oral formulation was identified in the records reviewed.
Safety Considerations
No drug-specific safety data (warnings, contraindications) was available in this record, and a drug interaction query returned no records.
Please refer to the SAHPRA-approved Professional Information (PI) for safety information. Report adverse drug reactions to SAHPRA.
Conclusion and Next Steps
Decision: Hold
Rationale:
- The prediction has a plausible nitric oxide (nNOS) mechanism, but the evidence is animal-only (L4). No human study of arginine in gastroparesis exists in this evidence pack, and the single registered trial is unrelated.
- Safety information from the SAHPRA Professional Information has not been obtained, which is a blocking gap for any further screening.
- All registered products in the record are parenteral, so route compatibility with a gastroparesis use is unresolved.
To proceed, the following is needed:
- SAHPRA package insert warnings and contraindications for the arginine-containing products (blocking).
- Mechanism-of-action data for arginine from DrugBank.
- Confirmed original approved indications for the registered products.
- Human evidence, such as pilot or exploratory studies of arginine or NO-pathway modulation in gastroparesis.
- An assessment of whether an appropriate route or formulation exists for this use.
This report is for research reference only and does not constitute medical advice. Repurposing candidates require clinical validation before any clinical use.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.