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Review
. 2022 Dec 19;14(12):e32709.
doi: 10.7759/cureus.32709. eCollection 2022 Dec.

Arginine for the Treatment of Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-Like Episodes: A Systematic Review

Jennifer M Argudo  1 , Olga M Astudillo Moncayo  1 , Walter Insuasti  2 , Gabriela Garofalo  3 , Alex S Aguirre  4 , Sebastian Encalada  5 , Jose Villamarin  3 , Sebastian Oña  4 , Maria Gabriela Tenemaza  4 , Ahmed Eissa-Garcés  6 , Sakina Matcheswalla  7 , Juan Fernando Ortiz  8
Affiliations
Review

Arginine for the Treatment of Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-Like Episodes: A Systematic Review

Jennifer M Argudo et al. Cureus. .

Abstract

Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a mitochondrial disease that lacks a definitive treatment. Lately, there has been an increased interest in the scientific community about the role of arginine in the short and long-term settings of the disease. We aim to conduct a systematic review of the clinical use of arginine in the management of MELAS and explore the role of arginine in the pathophysiology of the disease. We used PubMed advanced-strategy searches and only included full-text clinical trials on humans written in the English language. After applying the inclusion/exclusion criteria, four clinical trials were reviewed. We used the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol for this systematic review. We used the Cochrane Collaboration risk-of-bias tool to assess the bias encountered in each study. Overall, IV arginine seems to be effective in improving symptoms during acute attacks of MELAS, while oral arginine supplementation increases endothelial function, preventing further stroke-like episodes.

Keywords: l-arginine; lactic acidosis; melas; melas syndrome; mitochondrial disease; mitochondrial encephalopathy; stroke.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. PRISMA flow chart showing the results of the research conducted
PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses.
Figure 2
Figure 2. Bias analysis of this systematic review
References [4,16-18].
Figure 3
Figure 3. Process of synthesis of glutamine, citrulline, arginine, and NO
NO: nitric oxide; P5C: pyrroline-5-carboxylic acid; NADP: nicotinamide adenine dinucleotide phosphate (oxidase form); NADPH: nicotinamide adenine dinucleotide phosphate (reduced form).
Figure 4
Figure 4. Pathophysiology of MELAS
Part A: Pathophysiology of MELAS. Part B: Effects of decreased NO levels in MELAS. Low levels of arginine, citrulline, and NO lead to negative repercussions over the endothelial system. MELAS: mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes; NO: nitric oxide; ATP: adenosine 5′-triphosphate; PCR: phosphocreatine.
See this image and copyright information in PMC

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