Long-term follow-up of nutritional status in children with GLUT1 Deficiency Syndrome treated with classic ketogenic diet: a 5-year prospective study

Ramona De Amicis; Alessandro Leone; Marta Pellizzari; Andrea Foppiani; Alberto Battezzati; Chiara Lessa; Anna Tagliabue; Cinzia Ferraris; Valentina De Giorgis; Sara Olivotto; Roberto Previtali; Pierangelo Veggiotti; Simona Bertoli

doi:10.3389/fnut.2023.1148960

Long-term follow-up of nutritional status in children with GLUT1 Deficiency Syndrome treated with classic ketogenic diet: a 5-year prospective study

Front Nutr. 2023 May 24:10:1148960. doi: 10.3389/fnut.2023.1148960. eCollection 2023.

Authors

Ramona De Amicis^{1

2}, Alessandro Leone¹, Marta Pellizzari^{1

2}, Andrea Foppiani¹, Alberto Battezzati^{1

3}, Chiara Lessa¹, Anna Tagliabue^{4

5}, Cinzia Ferraris^{4

5}, Valentina De Giorgis⁶, Sara Olivotto⁷, Roberto Previtali^{7

8}, Pierangelo Veggiotti^{7

8}, Simona Bertoli^{1

2}

Affiliations

¹ ICANS-DIS, Department of Food Environmental and Nutritional Sciences, University of Milan, Milan, Italy.
² Obesity Unit and Laboratory of Nutrition and Obesity Research, Department of Endocrine and Metabolic Diseases, IRCCS Istituto Auxologico Italiano, Milan, Italy.
³ Clinical Nutrition Unit, Department of Endocrine and Metabolic Medicine, IRCCS Istituto Auxologico Italiano, Milan, Italy.
⁴ Human Nutrition and Eating Disorder Centre, University of Pavia, Pavia, Italy.
⁵ Ketogenic Metabolic Therapy Laboratory, Department of Public Health, Experimental and Forensic Medicine University of Pavia, Pavia, Italy.
⁶ Department of Child Neurology and Psychiatry, IRCCS "C. Mondino" National Neurological Institute, Pavia, Italy.
⁷ Pediatric Neurology Unit, "V. Buzzi" Hospital, Milan, Italy.
⁸ Biomedical and Clinical Sciences Department, University of Milan, Milan, Italy.

Abstract

Introduction: The classic ketogenic diet (cKD) is an isocaloric, high fat, low-carbohydrate diet that induces the production of ketone bodies. High consumption of dietary fatty acids, particularly long-chain saturated fatty acids, could impair nutritional status and increase cardiovascular risk. The purpose of this study was to evaluate the long-term effects of a 5-year cKD on body composition, resting energy expenditure, and biochemical parameters in children affected by Glucose Transporter 1 Deficiency Syndrome (GLUT1DS).

Methods: This was a prospective, multicenter, 5-year longitudinal study of children with GLUT1DS treated with a cKD. The primary outcome was to assess the change in nutritional status compared with pre-intervention, considering anthropometric measurements, body composition, resting energy expenditure, and biochemical parameters such as glucose and lipid profiles, liver enzymes, uric acid, creatinine, and ketonemia. Assessments were conducted at pre-intervention and every 12 months of cKD interventions.

Results: Ketone bodies increased significantly in children and adolescents, and remained stable at 5 years, depending on the diet. No significant differences were reported in anthropometric and body composition standards, as well as in resting energy expenditure and biochemical parameters. Bone mineral density increased significantly over time according to increasing age. Body fat percentage significantly and gradually decreased in line with the increase in body weight and the consequent growth in lean mass. As expected, we observed a negative trend in respiratory quotient, while fasting insulin and insulin resistance were found to decrease significantly after cKD initiation.

Conclusion: Long-term adherence to cKD showed a good safety profile on anthropometric measurements, body composition, resting energy expenditure, and biochemical parameters, and we found no evidence of potential adverse effects on the nutritional status of children and adolescents.

Keywords: GLUT1-Deficiency Syndrome; body composition; energy expenditure; ketogenic diet; long-term effect; nutritional status.