Trial reportPloS one2015
L-Arginine Affects Aerobic Capacity and Muscle Metabolism in MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-Like Episodes) Syndrome.
Trial report in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01603446 (Pilot Study to Investigate the Efficacy of L-arginine Therapy on Endothelium-dependent Vasodilation & Mitochondrial Metabolism in MELAS Syndrome.), which is not on this map. Cited by 16 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Pilot Study to Investigate the Efficacy of L-arginine Therapy on Endothelium-dependent Vasodilation & Mitochondrial Metabolism in MELAS Syndrome.
Who cites it
16 citing papers in PubMed, 39 citations in OpenAlex.
- Therapeutic regimen of L-arginine for MELAS: 9-year, prospective, multicenter, clinical research.Journal of neurology · 2018Trial
- Mitochondrial disease management through phytochemical interventions.Molecular and cellular biochemistry · 2025Review
- Mitochondrial diseases: from molecular mechanisms to therapeutic advances.Signal transduction and targeted therapy · 2025Review
- Arginine Supplementation in MELAS Syndrome: What Do We Know about the Mechanisms?International journal of molecular sciences · 2024Review
- The Research Progress of Mitochondrial Transplantation in the Treatment of Mitochondrial Defective Diseases.International journal of molecular sciences · 2024Review
- Mitochondrion-targeted RNA therapies as a potential treatment strategy for mitochondrial diseases.Molecular therapy. Nucleic acids · 2022Review
- Molecular Mechanisms Underlying Qi-Invigorating Effects in Traditional Medicine: Network Pharmacology-Based Study on the Unique Functions of Qi-Invigorating Herb Group.Plants (Basel, Switzerland) · 2022Article
- Reversal of Stroke-Like Episodes With L-Arginine and Meticulous Perioperative Management of Renal Transplantation in a Patient With Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-Like Episodes (MELAS) Syndrome. Case Report.The Neurohospitalist · 2022Article
- Exercise Testing, Physical Training and Fatigue in Patients with Mitochondrial Myopathy Related to mtDNA Mutations.Journal of clinical medicine · 2021Review
- Optimising therapeutic strategies for acute stroke-like lesions in MELAS.eNeurologicalSci · 2020Article
- Emerging therapies for mitochondrial diseases.Essays in biochemistry · 2018Review
- Nutritional Interventions for Mitochondrial OXPHOS Deficiencies: Mechanisms and Model Systems.Annual review of pathology · 2018Review
- ALDH2 Activity Reduces Mitochondrial Oxygen Reserve Capacity in Endothelial Cells and Induces Senescence Properties.Oxidative medicine and cellular longevity · 2018Article
- Monitoring clinical progression with mitochondrial disease biomarkers.Brain : a journal of neurology · 2017Review
- Toward a therapy for mitochondrial disease.Biochemical Society transactions · 2016Review
- Mitochondrial disorders in children: toward development of small-molecule treatment strategies.EMBO molecular medicine · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveTo study the effects of L-arginine (L-Arg) on total body aerobic capacity and muscle metabolism as assessed by (31)Phosphorus Magnetic Resonance Spectroscopy ((31)P-MRS) in patients with MELAS (Mitochondrial Encephalomyopathy with Lactic Acidosis and Stroke-like episodes) syndrome.
methodsWe performed a case control study in 3 MELAS siblings (m.3243A>G tRNA(leu(UUR)) in MTTL1 gene) with different % blood mutant mtDNA to evaluate total body maximal aerobic capacity (VO(2peak)) using graded cycle ergometry and muscle metabolism using 31P-MRS. We then ran a clinical trial pilot study in MELAS sibs to assess response of these parameters to single dose and a 6-week steady-state trial of oral L-Arginine.
resultsAt baseline (no L-Arg), MELAS had lower serum Arg (p = 0.001). On 3(1)P-MRS muscle at rest, MELAS subjects had increased phosphocreatine (PCr) (p = 0.05), decreased ATP (p = 0.018), and decreased intracellular Mg(2+) (p = 0.0002) when compared to matched controls. With L-arginine therapy, the following trends were noted in MELAS siblings on cycle ergometry: (1) increase in mean % maximum work at anaerobic threshold (AT) (2) increase in % maximum heart rate at AT (3) small increase in VO(2peak). On (31)P-MRS the following mean trends were noted: (1) A blunted decrease in pH after exercise (less acidosis) (2) increase in Pi/PCr ratio (ADP) suggesting increased work capacity (3) a faster half time of PCr recovery (marker of mitochondrial activity) following 5 minutes of moderate intensity exercise (4) increase in torque. SIGNIFICANCE: These results suggest an improvement in aerobic capacity and muscle metabolism in MELAS subjects in response to supplementation with L-Arg. Intramyocellular hypomagnesemia is a novel finding that warrants further study. CLASSIFICATION OF EVIDENCE: Class III evidence that L-arginine improves aerobic capacity and muscle metabolism in MELAS subjects.
trial registrationClinicalTrials.gov NCT01603446.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.