J Compr Ped. 2017 August; 8(3):e12609. Published online 2017 August 31. doi: 10.5812/compreped.12609. Research Article The Inﬂuence of Ketogenic Diet on Liver Function in Children and Adolescents with Intractable Epilepsy Shahabeddin Rezaei, 1,2 Mona Kavoosi, 1 Reza Shervin Badv, 3 Mahmoud Mohammadi, 3 Gholam Reza Zamani, 3 Mahmoud Reza Ashraﬁ, 3 Mir Saeed Yekaninejad, 4 and Maryam Mahmoudi 1,5,6, * 1 Department of Cellular Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran 2 Students’ Scientiﬁc Research Center, Tehran University of Medical Sciences, Tehran, Iran 3 Paediatrics Centre of Excellence, Department of Paediatric Neurology, Children’s Medical Centre, Tehran University of Medical Sciences, Tehran, Iran 4 Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences (TUMS), Tehran, Iran 5 Pediatric Gastroenterology and Hepatology Research Center, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran 6 Dietetics and Nutrition Experts Team (DiNET), Universal Scientiﬁc Education and Research Network (USERN), Tehran, Iran * Corresponding author: Maryam Mahmoudi, Associate Professor of Nutrition, Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran. P.O. Box: 14155-6447. Tel: +98-2188955698, E-mail: m-mahmoudi@sina.tums.ac.ir Received 2017 April 13; Revised 2017 May 04; Accepted 2017 July 23. Abstract Background: High-fat content and carbohydrate restriction of the ketogenic diet (KD) increases the workload of some organs, especially the liver. Moreover, most of the antiepileptic drugs (AEDs) are metabolized in the liver; therefore, the function of the liver could be inﬂuenced during the treatment with KD. This study was undertaken to investigate the inﬂuence of the ketogenic diet on liver function. Methods: A prospective, open-label study was carried out. A total of 28 patients with intractable epilepsy initiated the diet. All pa- tients were children and adolescents who did not respond to at least 2 AEDs. Liver function tests including Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were analyzed before and after 3 months on the KD. Results: Fourteen patients with the median age of 4.12 (2.31 - 9.70) years completed the study. The serum levels of ALP and AST did not diﬀer signiﬁcantly before and after 3 months on the diet (P value > 0.05). There was a signiﬁcant diﬀerence in the serum level of ALT before and after 3 months of treatment (13 vrs 20, P = 0.014). Conclusions: Albeit, it seems that KD did not have any inﬂuence on the serum levels of AST and ALP; however, it had a signiﬁcant eﬀect on the serum level of ALT. More investigations with a larger sample size and longer follow-up duration are needed to approve abovementioned results. Keywords: Ketogenic Diet, Epilepsy, Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase, Child, Adolescent 1. Background The ketogenic diet (KD) is a low-carbohydrate, high fat, adequate-protein diet. Primarily, KD was introduced to treat intractable epilepsy in 1921 (1), however, in the recent years, use of KD expanded to the other diseases including inherent metabolic diseases (2), autism (3), and glioblas- toma (4). The diet initially used was the classical KD, which long chain triglycerides are the primary energy source of the diet (90%) (5). The diet is calculated based on fat to car- bohydrate plus protein ratio (ketogenic ratio). The ratio in the classical ketogenic diet is 4:1 or 3:1, 4 g (or 3 gram) of fat to 1 g of combined protein and carbohydrate (5). Under the KD treatment, the body mimics the metabolic conditions found during fasting (6). Fat be- comes predominant energy sources during KD treatment instead of glucose (6). In the liver, long-chain fatty acids converted to ketone bodies including β-hydroxybutyrate, acetoacetate, and acetone through the β-oxidation path- way (6). Generally, patients with intractable epilepsy need long- term treatment with antiepileptic drugs (AEDs) (7). Most of the AEDs are predominantly metabolized by the liver, in- cluding valproate (VPA), carbamazepine, lamotrigine, phe- nobarbital, oxcarbazepine, phenytoin, felbamate, ethosux- imide, and benzodiazepines (8). Additionally, some are AEDs partially metabolized by the liver including levetirac- etam, topiramate, and zonisamide (8). It seems that the combination of the KD and AEDs could inﬂuence the liver function. Several studies reported the short- and long-term adverse eﬀects of KD (9, 10). Yet, the inﬂuence of KD on the liver function is ambiguous. Therefore, this study was conducted to investigate the in- ﬂuence of classical KD on the serum levels of liver enzymes in epileptic children and adolescents. Copyright © 2017, Journal of Comprehensive Pediatrics. 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