Isoleucine
| 證據等級: L5 | 預測適應症: 10 個 |
目錄
Isoleucine: From Essential Amino Acid Supplementation to Gastroparesis
One-Sentence Summary
Isoleucine is an essential branched-chain amino acid (BCAA) with established roles in protein synthesis, energy metabolism, and gut hormone signalling, used clinically as a nutritional supplement. The TxGNN model predicts it may be effective for Gastroparesis, with 0 clinical trials and 0 publications directly supporting this therapeutic direction — making this a hypothesis-only finding at present.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Essential amino acid / nutritional supplementation (no formal regulatory indication registered in Singapore) |
| Predicted New Indication | Gastroparesis |
| TxGNN Prediction Score | 99.32% |
| Evidence Level | L5 |
| Singapore Market Status | Not marketed |
| Number of Registrations | 0 |
| Recommended Decision | Hold (Research Question) |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available for Isoleucine in the context of gastroparesis. Based on known biochemistry, Isoleucine is a branched-chain amino acid (BCAA) — along with leucine and valine — that serves as a structural protein building block and plays a role in energy metabolism and gut endocrine signalling.
The mechanistic rationale proposed by TxGNN centres on the gut hormone axis: BCAAs, including Isoleucine, are known to stimulate intestinal K cells and L cells to secrete cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), and peptide YY (PYY). These gut hormones directly regulate gastric emptying rate and antral contractility — both of which are impaired in gastroparesis. Isoleucine may therefore modulate gastric motility via intestinal nutrient-sensing mechanisms involving the mTOR and calcium-sensing receptor (CaSR) pathways.
However, this mechanistic chain remains indirect and largely speculative. No clinical intervention study has tested Isoleucine as a treatment for gastroparesis, and the causal direction of BCAA–gut motility interactions in disease states has not been established. The prediction plausibility is rated moderate (indirect).
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
Currently no related literature directly studying Isoleucine as a treatment for gastroparesis.
Note: Related mechanistic evidence exists for Dyspepsia (TxGNN rank #4), a condition with overlapping gastric motility pathophysiology. A 2016 rat model study (PMID 27558952) demonstrated that branched-chain amino acids influence gastric adaptive relaxation (accommodation) — a core dyspepsia mechanism potentially shared with gastroparesis. This indirect evidence provides limited but non-zero biological plausibility for the gastroparesis prediction.
Singapore Market Information
Isoleucine (DB00167) has no product registrations with the Health Sciences Authority (HSA) in Singapore. It is not currently marketed as a pharmaceutical product in this jurisdiction.
Safety Considerations
Please refer to the package insert for safety information.
Important safety signal identified from mechanistic analysis: Patients with methylmalonic acidemia (MMA) or beta-ketothiolase deficiency carry a known contraindication-equivalent risk. Isoleucine catabolism proceeds through Propionyl-CoA → Methylmalonyl-CoA → Succinyl-CoA; in patients with MUT/MMAA/MMAB gene mutations, excess Isoleucine intake accelerates accumulation of toxic methylmalonic acid, which can cause distal renal tubular damage. This population-specific safety concern must be screened for in any future study design.
Conclusion and Next Steps
Decision: Hold (Research Question)
Rationale: The TxGNN model assigns a high prediction score (99.32%), but there is zero direct clinical or preclinical evidence supporting Isoleucine as a treatment for gastroparesis. The mechanistic hypothesis — gut BCAA sensing → CCK/GLP-1/PYY secretion → improved gastric motility — is biologically plausible but entirely unvalidated in this indication. The evidence level is L5 (model prediction only), which does not support clinical advancement without foundational studies.
To proceed, the following is needed:
- Mechanistic proof-of-concept studies: In vitro and animal studies directly measuring the effect of Isoleucine on gastric emptying rates and antral contractility in gastroparesis models
- Biomarker analysis: Plasma BCAA profiling in gastroparesis patient cohorts to determine whether Isoleucine dysregulation is present and causally relevant
- Safety screening protocol: Identification and exclusion of patients with methylmalonic acidemia or related BCAA catabolic enzyme deficiencies from any future study cohort
- Dose-response characterisation: Determination of pharmacologically active Isoleucine doses that achieve gut hormone effects without systemic metabolic perturbation
- Comparison with established GLP-1 pathway agents: Contextualise potential Isoleucine effects against approved gastroparesis or gastric motility treatments (e.g., metoclopramide, domperidone) to assess whether the BCAA mechanism adds clinical value
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.