Combination Therapy with Pyridoxine and Arginine Supplementations along with a Lysine-Restricted Diet in Individuals with Pyridoxine-Dependent Epilepsy: A Comprehensive Systematic Review.

2025-08
Current developments in nutrition 9(8)
- Ali Jafari
- Mohammad Mehdi Abbasi
- Hamid Abbasi
- Sama Rahnemayan
- Farnush Bakhshimoghaddam
- Saeid Doaei

PubMed: 40800672
DOI: 10.1016/j.cdnut.2025.107504

Study Design

Type: Review
Population: individuals diagnosed with PDE
Methods: extensive search across Scopus, Embase, Web of Science, PubMed, and Google Scholar; methodological quality assessment using Newcastle-Ottawa Scale and Joanna Briggs Institute tool

Background

Pyridoxine-dependent epilepsy (PDE) is identified as a rare neurometabolic disease marked by biallelic pathogenic mutations of the ALDH7A1 gene. A combination therapy involving pyridoxine, arginine supplementation (AS), and a lysine-restricted diet (LRD) was frequently reported to effectively improve PDE through reducing neurotoxic lysine metabolites, improving seizure management, and enhancing neurodevelopmental outcomes.

Objectives

The study sought to investigate the effects of mono-(pyridoxine), dual- (pyridoxine combined with AS or LRD), and triple-therapy approaches in individuals diagnosed with PDE.

Methods

An extensive search was carried out across international databases, comprising Scopus, Embase, Web of Science, PubMed, and Google Scholar, to find relevant publications published before 12 November, 2024. The methodological quality assessment of chosen articles was evaluated utilizing the Newcastle-Ottawa Scale and the Joanna Briggs Institute tool.

Results

Among 2097 studies reviewed, 38 met inclusion criteria, covering treatment methods for individuals with PDE including monotherapy (22 articles), dual therapy (9 articles), and triple therapy (7 articles). The results indicated that pyridoxine monotherapy is a highly effective first-line treatment in PDE that improves seizure control with minimal cognitive decline. Combining pyridoxine with an LRD or AS targets metabolic issues, reducing neurotoxic metabolites and enhancing cognitive and motor functions. Early triple therapy, within the first 6 months of life, exhibited significant benefits for seizure management and cognitive performance in patients with PDE.

Conclusions

In summary, administration of pyridoxine is highly effective, particularly when combined with AS and an LRD. Triple therapy illustrates promise for improved seizure control and cognitive function, especially when initiated early. Further research is warranted.

Research Insights

L-Arginine→Improved Cognitive Function
Combining pyridoxine with an LRD or AS targets metabolic issues, reducing neurotoxic metabolites and enhancing cognitive and motor functions.
Effect
Beneficial
Effect size
Moderate
L-Arginine→Improved Motor Function
Combining pyridoxine with an LRD or AS targets metabolic issues, reducing neurotoxic metabolites and enhancing cognitive and motor functions.
Effect
Beneficial
Effect size
Moderate
L-Arginine→Improved Seizure Control
pyridoxine monotherapy is a highly effective first-line treatment in PDE that improves seizure control with minimal cognitive decline.
Effect
Beneficial
Effect size
Moderate
Vitamin B6→Improved Cognitive Function
Combining pyridoxine with an LRD or AS targets metabolic issues, reducing neurotoxic metabolites and enhancing cognitive and motor functions.
Effect
Beneficial
Effect size
Moderate
Vitamin B6→Improved Motor Function
Combining pyridoxine with an LRD or AS targets metabolic issues, reducing neurotoxic metabolites and enhancing cognitive and motor functions.
Effect
Beneficial
Effect size
Moderate
Vitamin B6→Improved Seizure Control
pyridoxine monotherapy is a highly effective first-line treatment in PDE that improves seizure control with minimal cognitive decline.
Effect
Beneficial
Effect size
Moderate