Ketonemia variability through menstrual cycle in patients undergoing classic ketogenic diet

Ketogenic dietary therapies (KDT) are well-established, safe, non-pharmacologic treatments used for children and adults with drug-resistant epilepsy and other neurological disorders. Ketone bodies (KBs) levels are recognized as helpful to check compliance to the KDT and to attempt titration of the diet according to the individualized needs. KBs might undergo inter-individual and intra-individual variability and can be affected by several factors. Possible variations in glycemia and ketone bodies blood levels according to the menstrual cycle have not been systematically assessed yet, but this time window deserves special attention because of hormonal and metabolic related changes.This study aims at searching for subtle changes in KBs blood level during menstrual cycle in female patients undergoing a stable ketogenic diet, by analyzing 3-months daily measurement of ketone bodies blood levels and glucose blood levels throughout the menstrual cycle.We report the preliminary results on six female patients affected by GLUT1DS or drug resistant epilepsy, undergoing a stable classic ketogenic diet. A significant increase in glucose blood levels during menstruation was found in the entire cohort. As far as the ketone bodies blood levels, an inversely proportional trend compared to glycemia was noted.Exploring whether ketonemia variations might occur according to the menstrual cycle is relevant to determine the feasibility of transient preventive diet adjustments to assure a continuative treatment efficacy and to enhance dietary behavior support.clinicaltrials.gov, identifier NCT05234411.

[1]  Priyanka Madaan,et al.  Efficacy and Safety of Dietary Therapies for Childhood Drug-Resistant Epilepsy: A Systematic Review and Network Meta-analysis. , 2023, JAMA pediatrics.

[2]  E. Kossoff,et al.  Does the ketogenic ratio matter when using ketogenic diet therapy in pediatric epilepsy? , 2022, Epilepsia.

[3]  E. Felton,et al.  The Feasibility and Tolerability of Medium Chain Triglycerides in Women with a Catamenial Seizure Pattern on the Modified Atkins Diet , 2021, Nutrients.

[4]  A. Tagliabue,et al.  Families’ Perception of Classic Ketogenic Diet Management in Acute Medical Conditions: A Web-Based Survey , 2020, Nutrients.

[5]  A. Tagliabue,et al.  Comment on: Ketogenic diet therapy provision in the COVID-19 pandemic: Dual-center experience and recommendations , 2020, Epilepsy & Behavior.

[6]  A. Tagliabue,et al.  Use of Remote Monitoring by E-mail for Long-Term Management of the Classic Ketogenic Diet , 2020, Nutrients.

[7]  L. Pirola,et al.  Modulation of Cellular Biochemistry, Epigenetics and Metabolomics by Ketone Bodies. Implications of the Ketogenic Diet in the Physiology of the Organism and Pathological States , 2020, Nutrients.

[8]  A. Tagliabue,et al.  Quality of Life in Chronic Ketogenic Diet Treatment: The GLUT1DS Population Perspective , 2019, Nutrients.

[9]  I. Scheffer,et al.  Optimal clinical management of children receiving dietary therapies for epilepsy: Updated recommendations of the International Ketogenic Diet Study Group , 2018, Epilepsia open.

[10]  S. Friedman,et al.  β-Hydroxybutyrate Detection with Proton MR Spectroscopy in Children with Drug-Resistant Epilepsy on the Ketogenic Diet , 2018, American Journal of Neuroradiology.

[11]  J. Rho,et al.  Do ketone bodies mediate the anti-seizure effects of the ketogenic diet? , 2018, Neuropharmacology.

[12]  A. Tagliabue,et al.  The changing face of dietary therapy for epilepsy , 2016, European Journal of Pediatrics.

[13]  W. Han,et al.  Pancreatic regulation of glucose homeostasis , 2016, Experimental & Molecular Medicine.

[14]  Michael R Sperling,et al.  Distribution of seizures across the menstrual cycle in women with epilepsy , 2015, Epilepsia.

[15]  A. Herzog Catamenial epilepsy: Update on prevalence, pathophysiology and treatment from the findings of the NIH Progesterone Treatment Trial , 2015, Seizure.

[16]  P. Veggiotti,et al.  GLUT1 deficiency syndrome 2013: Current state of the art , 2013, Seizure.

[17]  P. Aggarwal,et al.  Catamenial diabetic ketoacidosis--a diagnostic dilemma in ED. , 2013, The American journal of emergency medicine.

[18]  A. Tagliabue,et al.  Effects of the ketogenic diet on nutritional status, resting energy expenditure, and substrate oxidation in patients with medically refractory epilepsy: a 6-month prospective observational study. , 2012, Clinical nutrition.

[19]  R. Browne,et al.  Longitudinal study of insulin resistance and sex hormones over the menstrual cycle: the BioCycle Study. , 2010, The Journal of clinical endocrinology and metabolism.

[20]  A. Bosch,et al.  The Effect of the Menstrual Cycle on Exercise Metabolism , 2010, Sports medicine.

[21]  G. Mathern,et al.  Definition of drug resistant epilepsy: Consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies , 2009, Epilepsia.

[22]  J. Klepper Glucose transporter deficiency syndrome (GLUT1DS) and the ketogenic diet , 2008, Epilepsia.

[23]  M. Rickels,et al.  Menstrual cycle effects on insulin sensitivity in women with type 1 diabetes: a pilot study. , 2007, Diabetes technology & therapeutics.

[24]  W. Sivitz,et al.  Cyclic changes in glycemia assessed by continuous glucose monitoring system during multiple complete menstrual cycles in women with type 1 diabetes. , 2004, Diabetes technology & therapeutics.

[25]  G. Mitchell,et al.  Pathways and control of ketone body metabolism: on the fringe of lipid biochemistry. , 2004, Prostaglandins, leukotrienes, and essential fatty acids.

[26]  D. Gilbert,et al.  The Ketogenic Diet: Seizure Control Correlates Better With Serum β-Hydroxybutyrate Than With Urine Ketones , 2000, Journal of child neurology.

[27]  M. Diamond,et al.  Alterations in Glucose Metabolism During Menstrual Cycle in Women With IDDM , 1992, Diabetes Care.

[28]  P. Solli,et al.  Longitudinal studies. , 2015, Journal of thoracic disease.

[29]  M. Majoie,et al.  Blood beta-hydroxybutyrate correlates better with seizure reduction due to ketogenic diet than do ketones in the urine , 2010, Seizure.