Aspartic Acid

證據等級: L5

預測適應症: 1 個

Aspartic Acid: From Nutritional Amino Acid to Renal Tubular Acidosis

One-Sentence Summary

Aspartic acid (L-aspartic acid, DB00128) is a non-essential amino acid used primarily as a nutritional and metabolic substrate, registered under 23 product licences in Malaysia. The TxGNN model predicts it may have therapeutic relevance in Renal Tubular Acidosis (RTA) with a score of 99.47%, however the supporting evidence consists entirely of basic science and genetic background studies — no directly relevant clinical trials exist, and the sole clinical case dates to 1983.

Quick Overview

Item	Content
Original Indication	Nutritional amino acid supplement; registered indication details not available in current dataset
Predicted New Indication	Renal Tubular Acidosis
TxGNN Prediction Score	99.47%
Evidence Level	L4
Malaysia Market Status	✓ Marketed
Number of Registrations	23
Recommended Decision	Hold

Why is This Prediction Reasonable?

Aspartic acid (L-aspartic acid) is a non-essential amino acid that serves as a central metabolic hub — participating in the urea cycle, purine biosynthesis, and transamination reactions throughout the body. Detailed pharmacological MOA data is not currently available in this dataset; however, its biochemical roles in renal physiology are well-documented in the scientific literature.

The mechanistic connection to renal tubular acidosis is indirect but biologically plausible through three converging pathways. First, the SLC22A13 transporter has been shown to mediate unidirectional efflux of aspartate and glutamate at the basolateral membrane of type A intercalated cells in the renal collecting duct (PMID: 24147638) — the very cells responsible for proton secretion that is defective in distal RTA. Second, renal ammoniagenesis is the kidney’s primary compensatory mechanism in acid-base disorders, and aspartic acid contributes nitrogen to the glutamine synthesis pathway that fuels NH₄⁺ excretion. Third, animal studies demonstrate that metabolic acidosis alters the concentrations of aspartate and related intermediates in renal tubule cells (PMID: 5641145; PMID: 2884989), suggesting aspartate participates in the kidney’s adaptive metabolic response.

However, a critical caveat must be noted: RTA’s primary defect — whether impaired proton secretion in distal tubules or deficient proximal HCO₃⁻ reabsorption — is typically caused by mutations in genes such as SLC4A1, ATP6V1B1, or ATP6V0A4. Aspartic acid supplementation cannot directly repair these structural or genetic transporter defects. The high TxGNN score (0.9947) most likely reflects the broad connectivity of aspartate within the renal metabolic network, rather than a specific pharmacological mechanism. The only clinical case suggesting benefit (PMID: 6422151) involved a highly specific secondary RTA arising from pyruvate carboxylase deficiency — a scenario not representative of primary RTA.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT04725812	Phase 2	Terminated	2	[Database mismatch — not relevant] Investigated eculizumab (complement inhibitor) for preeclampsia at 23–30 weeks gestation. No connection to aspartic acid or renal tubular acidosis. Trial terminated early with only 2 participants enrolled; contributes zero evidence to this repurposing question.

⚠️ The sole retrieved trial (NCT04725812) is assessed Grade C relevance and represents a probable database mis-match. There are currently no registered clinical trials directly evaluating aspartic acid for the treatment of renal tubular acidosis.

Literature Evidence

PMID	Year	Type	Journal	Key Findings
6422151	1983	Case Report	J Inherited Metab Dis	Patient with pyruvate carboxylase deficiency, proximal RTA, and cystinuria showed clinical improvement after dietary aspartic acid supplementation — the most direct (though highly disease-specific) clinical evidence available
990372	1976	Clinical Loading Study	Biomedicine	IV ornithine-aspartate loading in children with familial neurological syndrome, RTA, and cystinuria; examined amino acid metabolic interplay, indirect relevance
24147638	2014	Basic Science	Biochemical Journal	SLC22A13 mediates unidirectional aspartate/glutamate efflux at basolateral membrane of type A intercalated cells in renal collecting duct — directly links aspartate transport to the cell type responsible for proton secretion in dRTA
2884989	1987	Animal Study	Biochemical Journal	¹³C-NMR and GC-MS study showing glutamate/aspartate carbon metabolism is significantly altered in rat renal tubules under chronic metabolic acidosis
5641145	1968	Animal Study	Nature	Concentrations of metabolic intermediates, including aspartate-related substrates, are shifted in kidneys of rats with metabolic acidosis
26208211	2015	Genetic Diagnostic Study	Jornal de Pediatria	Whole-exome sequencing as diagnostic tool for distal RTA in 4 children; establishes genetic underpinning, no therapeutic relevance to aspartic acid
20068363	2010	Genetic Study / Case Series	Nephron Physiology	SLC4A1 mutations causing distal RTA in Filipino children; genetic characterisation only
12087557	2002	Genetic Case Study	Am J Kidney Dis	G701D mutation in AE1/SLC4A1 causes autosomal recessive dRTA by disrupting Cl⁻/HCO₃⁻ exchange; mechanistic context for RTA pathophysiology
23053187	2013	Case Report	Ann Hematol	SLC4A1/AE1 A858D homozygote presenting with dRTA, thrombocytopenic purpura, and acanthocytosis; disease characterisation only
14301365	1965	Basic Science	Am J Physiology	Foundational study on the relationship between tubular cell PNH₃ and renal ammonia production — background physiology for understanding ammoniagenesis in RTA

Malaysia Market Information

⚠️ 23 product registrations for Aspartic Acid are confirmed in Malaysia (NPRA query, 2026-03-27), however individual licence details — including authorization numbers, product names, dosage forms, and approved indication texts — are not available in the current dataset. Full NPRA licence retrieval is recommended as a priority next step.

Authorization Number	Product Name	Dosage Form	Approved Indication
—	Details pending retrieval	—	—

23 licences confirmed active; individual records require direct retrieval from the NPRA database.

Safety Considerations

Detailed key warnings and contraindications for aspartic acid are not yet available in this dataset and represent a Blocking data gap that must be resolved before any formal safety screening can proceed. No drug-drug interactions were identified in this evaluation.

Please refer to the package insert and NPRA/TFDA official product monographs for complete safety information.

Conclusion and Next Steps

Decision: Hold

Rationale: The evidence base for aspartic acid in renal tubular acidosis does not yet support a repurposing investment decision. Supporting evidence is limited to preclinical mechanistic studies, foundational animal physiology (some dating to 1965–1987), and a single 1983 case report from a highly atypical secondary RTA scenario. The one retrieved clinical trial is a confirmed database mismatch. While the metabolic biology connecting aspartate to renal acid-base regulation is scientifically coherent, it falls well short of a pharmacologically actionable mechanism, and the root cause of primary RTA (genetic transporter defects) is not addressable by amino acid supplementation.

To proceed, the following is needed:

Retrieve NPRA licence details — authorization numbers, dosage forms, and approved indication texts for all 23 registered aspartic acid products (priority action)
Resolve MOA data gap — query DrugBank API to obtain pharmacological mechanism, pharmacokinetics, and drug class classification for DB00128
Retrieve package insert safety data — download and parse NPRA/TFDA official product inserts to address the Blocking DG001 data gap (key warnings and contraindications)
Conduct a targeted literature review — specifically on ornithine-aspartate in renal acid-base disorders and on aspartate supplementation in metabolic acidosis subtypes, to determine whether any clinical signals exist beyond the 1983 case report
Expert consultation — engage a nephrologist to assess whether any RTA subtype (particularly secondary or metabolic RTA) could plausibly benefit from aspartate supplementation and, if so, whether a preclinical proof-of-concept study is warranted before any clinical investment is considered
Disclaimer

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