The ketogenic diet increases in vivo glutathione levels in patients with epilepsy

Antonio Napolitano, Daniela Longo, Martina Lucignani, Luca Pasquini, Maria Camilla Rossi-Espagnet, Giulia Lucignani, Arianna Maiorana, Domenica Elia, Paola De Liso, Carlo Dionisi-Vici, Raffaella Cusmai

Research output: Contribution to journalArticlepeer-review


The Ketogenic Diet (KD) is a high-fat, low-carbohydrate diet that has been utilized as the first line treatment for contrasting intractable epilepsy. It is responsible for the presence of ketone bodies in blood, whose neuroprotective effect has been widely shown in recent years but remains unclear. Since glutathione (GSH) is implicated in oxidation-reduction reactions, our aim was to monitor the effects of KD on GSH brain levels by means of magnetic resonance spectroscopy (MRS). MRS was acquired from 16 KD patients and seven age-matched Healthy Controls (HC). We estimated metabolite concentrations with linear combination model (LCModel), assessing differences between KD and HC with t-test. Pearson was used to investigate GHS correlations with blood serum 3-B-Hydroxybutyrate (3HB) concentrations and with number of weekly epileptic seizures. The results have shown higher levels of brain GSH for KD patients (2.5 ± 0.5 mM) compared to HC (2.0 ± 0.5 mM). Both blood serum 3HB and number of seizures did not correlate with GSH concentration. The present study showed a significant increase in GSH in the brain of epileptic children treated with KD, reproducing for the first time in humans what was previously observed in animal studies. Our results may suggest a pivotal role of GSH in the antioxidant neuroprotective effect of KD in the human brain.

Original languageEnglish
Article number504
Pages (from-to)1-9
Number of pages9
Issue number12
Publication statusPublished - Dec 2020


  • Glutathione
  • Ketogenic diet
  • Magnetic resonance spectroscopy

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology


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