Alanine

證據等級: L5

預測適應症: 1 個

ALANINE: From Amino Acid Supplement to Gastroparesis

One-Sentence Summary

Alanine (DB00160) is a non-essential amino acid involved in gluconeogenesis and energy metabolism, commonly used as a nutritional supplement component rather than a standalone therapeutic agent. The TxGNN model predicts it may have relevance for Gastroparesis, with 9 clinical trials and 3 publications identified — however, none of the clinical trials directly investigate Alanine as an intervention for this condition. The overall evidence base for this repurposing direction remains at a preliminary stage, warranting a Hold decision pending mechanistic clarification.

Quick Overview

Item	Content
Original Indication	Not established (amino acid nutritional component; no approved therapeutic indication on record)
Predicted New Indication	Gastroparesis
TxGNN Prediction Score	99.37%
Evidence Level	L5 — Model prediction only; no studies directly investigating Alanine in gastroparesis
Malaysia Market Status	✓ Marketed
Number of Registrations	36
Recommended Decision	Hold

Why is This Prediction Reasonable?

Currently, detailed mechanism of action data is not available for Alanine in this context. Based on known biochemistry, Alanine is a non-essential amino acid that plays a central role in the Glucose-Alanine Cycle — a metabolic shuttle between muscle and liver that maintains glucose homeostasis during fasting or physiological stress. It also participates in transamination reactions and serves as a gluconeogenic precursor.

The theoretical link to gastroparesis is indirect. Delayed gastric emptying involves dysfunction of autonomic innervation of the enteric nervous system, interstitial cells of Cajal, and enteroendocrine signalling (e.g., GLP-1, motilin). Amino acids including alanine are known to stimulate enteroendocrine cells in the gut and may influence gastric motility through nutrient-sensing mechanisms. There is also a metabolic rationale in diabetic gastroparesis, where impaired gluconeogenesis and autonomic neuropathy coexist — conditions where alanine metabolism is relevant.

However, these mechanistic links remain at the level of biological plausibility, not established pharmacology. No direct preclinical or clinical data supports Alanine as a gastroparesis therapeutic. The TxGNN high-confidence prediction (99.37%) likely reflects network proximity in the knowledge graph rather than a validated therapeutic relationship. Until mechanistic and in vivo data are available, this prediction should be treated as hypothesis-generating only.

Clinical Trial Evidence

All 9 trials identified study other drugs in gastroparesis; none involve Alanine as a primary intervention. They are listed here as contextual evidence of the therapeutic landscape.

Trial Number	Phase	Status	Enrollment	Key Findings
NCT03587142	Phase 2	Completed	96	Buspirone (anxiolytic) vs. placebo for early satiety and gastroparesis symptoms — not Alanine
NCT03941288	Phase 2	Completed	92	Cannabidiol (CBD) effects on gastric function in gastroparesis and functional dyspepsia — not Alanine
NCT07270939	Not Applicable	Not Yet Recruiting	150	Comparative study of 18h, 20h, and 24h enteral feeding cycles in critically ill ICU patients; Alanine may appear as a formula component but is not the focus
NCT01934192	Phase 2	Terminated	91	GSK962040 (motilin receptor agonist) for enteral nutrition adequacy in critical illness — terminated early
NCT01262898	Phase 2	Completed	79	Oral motilin receptor agonist GSK962040 in diabetic gastroparesis (Types I and II) — not Alanine
NCT01149369	Phase 2	Completed	126	Aprepitant (NK1 antagonist) for chronic nausea and vomiting of gastric origin — not Alanine
NCT01602549	Phase 2	Completed	58	Motilin receptor agonist effects on L-DOPA pharmacokinetics in Parkinson’s patients with delayed gastric emptying — not Alanine
NCT06452966	Not Applicable	Recruiting	350	Traditional Chinese medicine interventions for organ failure in ICU patients — multi-component intervention, no relation to Alanine
NCT02793154	Phase 4	Terminated	4	Albiglutide vs. exenatide on gastric motility in Type 2 diabetes — terminated very early (n=4 only), no usable conclusions

⚠️ Important Note: None of the above trials test Alanine as a therapeutic agent. All are graded Relevance C. The trials confirm that gastroparesis is an active area of clinical research with significant unmet need, but they provide no direct evidence for Alanine repurposing.

Literature Evidence

PMID	Year	Type	Journal	Key Findings
10926110	2000	Review	Advances in Renal Replacement Therapy	Reviews GI and hepatic disorders in end-stage renal disease; notes gastroparesis is more prevalent in chronic renal failure — contextual background only, not about Alanine
26315331	2016	Case Series / Observational	Diabetic Medicine	Describes diabetic hepatosclerosis as a microvascular complication; gastroparesis mentioned as a co-morbidity — tangential reference
33763324	2021	Case Report	Cureus	Case of glycogen hepatopathy in Type 1 diabetes with gastroparesis as a complication — Alanine not discussed

⚠️ Important Note: None of the 3 publications directly investigate Alanine in gastroparesis. All are tier-3 evidence (reviews or case reports) with only tangential relevance. No RCTs, meta-analyses, or mechanistic studies linking Alanine to gastroparesis were identified.

Malaysia Market Information

While 36 product registrations are recorded for Alanine in Malaysia (NPRA), the detailed product-level information (authorization numbers, product names, dosage forms, and approved indications) was not retrieved in the current data pack. Please refer to the NPRA official database for complete registration details.

Authorization Number	Product Name	Dosage Form	Approved Indication
—	—	—	—

36 registrations confirmed via NPRA query (2026-03-27). Product details pending retrieval.

Safety Considerations

Please refer to the package insert for safety information. No key warnings, contraindications, or drug interaction data were available in this evidence pack.

Conclusion and Next Steps

Decision: Hold

Rationale: The TxGNN model assigns a high prediction score (99.37%) to Alanine for gastroparesis, but this confidence is not supported by any direct clinical or preclinical evidence — all 9 identified trials involve other drugs, and the 3 literature references are tangential. The mechanistic hypothesis (enteroendocrine signalling, Glucose-Alanine Cycle) is biologically plausible but entirely speculative at this stage (Evidence Level L5). Additionally, Alanine lacks an established approved therapeutic indication, making repurposing context-setting particularly difficult.

To proceed, the following is needed:

Mechanism of Action data: Confirm whether Alanine has any documented direct or indirect effects on gastric motility, enteroendocrine signalling (GLP-1, motilin, ghrelin), or the enteric nervous system
Preclinical evidence: In vitro or animal model studies demonstrating Alanine’s effect on gastric emptying are prerequisite before any clinical hypothesis can be formed
NPRA package insert review: Download and parse product insert PDFs to identify any existing safety warnings and contraindications (currently a Blocking data gap)
DrugBank MOA retrieval: Query DrugBank API for DB00160 to populate pharmacological classification and mechanism detail (currently a High-severity data gap)
Dose and formulation assessment: Determine what dose, route, and formulation would be pharmacologically relevant for a gastroparesis indication, distinct from its nutritional use
Patient population definition: Clarify whether the target population is diabetic gastroparesis, post-surgical gastroparesis, or idiopathic — as mechanistic relevance may differ
Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.