ArticleNeurobiology of disease2015
Potent anti-seizure effects of D-leucine.
Article in Neurobiology of disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- Pooled it
- L-Leucine Upregulates Lysosomal Biogenesis and Autophagy to Lower Plaques in 5XFAD Mouse Model of Alzheimer's Disease.Journal of neurochemistry · 2026Article
- Cerebrospinal Fluid Neurotransmitters, Pterins, Folates and Amino Acids in Paediatric Onset Epilepsies: A Tertiary Centre Retrospective Cohort Study.Children (Basel, Switzerland) · 2025Article
- Detection and functional assessment of D-amino acids as potential biomarkers in neurological disorders.Molecular biology reports · 2025Review
- Promising Application of D-Amino Acids toward Clinical Therapy.International journal of molecular sciences · 2022Review
- DEPDC5-dependent mTORC1 signaling mechanisms are critical for the anti-seizure effects of acute fasting.Cell reports · 2022Article
- Circulating Metabolites as Biomarkers of Disease in Patients with Mesial Temporal Lobe Epilepsy.Metabolites · 2022Article
- d-Leucine protects oocytes from chronic psychological stress in mice.Reproductive medicine and biology · 2021Article
- Leucine-Enriched Essential Amino Acids Enhance the Antiseizure Effects of the Ketogenic Diet in Rats.Frontiers in neuroscience · 2021Article
- Personalised therapeutic management of epileptic patients guided by pathway-driven breath metabolomics.Communications medicine · 2021Article
- Advances in D-Amino Acids in Neurological Research.International journal of molecular sciences · 2020Review
- Effects of Branched-Chain Amino Acid Supplementation on Spontaneous Seizures and Neuronal Viability in a Model of Mesial Temporal Lobe Epilepsy.Journal of neurosurgical anesthesiology · 2019Article
- 2-Deoxyglucose and Beta-Hydroxybutyrate: Metabolic Agents for Seizure Control.Frontiers in cellular neuroscience · 2019Review
- Article
- d-Leucine: Evaluation in an epilepsy model.Epilepsy & behavior : E&B · 2018Article
- Non-ketogenic combination of nutritional strategies provides robust protection against seizures.Scientific reports · 2017Article
- d-Amino Acid Levels in Perfused Mouse Brain Tissue and Blood: A Comparative Study.ACS chemical neuroscience · 2017Article
- The changing face of dietary therapy for epilepsy.European journal of pediatrics · 2016Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
There are no effective treatments for millions of patients with intractable epilepsy. High-fat ketogenic diets may provide significant clinical benefit but are challenging to implement. Low carbohydrate levels appear to be essential for the ketogenic diet to work, but the active ingredients in dietary interventions remain elusive, and a role for ketogenesis has been challenged. A potential antiseizure role of dietary protein or of individual amino acids in the ketogenic diet is understudied. We investigated the two exclusively ketogenic amino acids, L-leucine and L-lysine, and found that only L-leucine potently protects mice when administered prior to the onset of seizures induced by kainic acid injection, but not by inducing ketosis. Unexpectedly, the D-enantiomer of leucine, which is found in trace amounts in the brain, worked as well or better than L-leucine against both kainic acid and 6Hz electroshock-induced seizures. However, unlike L-leucine, D-leucine potently terminated seizures even after the onset of seizure activity. Furthermore, D-leucine, but not L-leucine, reduced long-term potentiation but had no effect on basal synaptic transmission in vitro. In a screen of candidate neuronal receptors, D-leucine failed to compete for binding by cognate ligands, potentially suggesting a novel target. Even at low doses, D-leucine suppressed ongoing seizures at least as effectively as diazepam but without sedative effects. These studies raise the possibility that D-leucine may represent a new class of anti-seizure agents, and that D-leucine may have a previously unknown function in eukaryotes.
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What OpenQuestion holds
Registered trials
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.