Table 1.

Main preclinical and clinical evaluations of KD and treatments derived from the KD in diseases with motor dysfunction.

Disease	Pre-clinical evaluation			Clinical evaluation
	Type of study	Main findings	Reference	Type of study	Main findings	Reference
Amyotrophic lateral sclerosis (ALS)	KD, MCT, or DP in SOD1-G93A transgenic ALS mouse model	Longer maintenance of motor function Decrease in motor neuron death Delay onset of motor symptoms	Zhao et al., 2006, 2012; Ari et al., 2014; Tefera et al., 2016	Clinical trial of KD use, phase III NCT01016522	No result provided	Not published
Angelman syndrome (AS)	KE-treated AS mouse model	Improvement of motor coordination No effect on locomotor activity	Ciarlone et al., 2016	Case reports (KD and low glycemic index diet in AS patients)	Decrease in seizures	Evangeliou et al., 2010; Thibert et al., 2012
Mitochondrial myopathy	KD in mouse model	Delayed disease progression	Ahola-Erkkila et al., 2010	Pilot study KD in patients	Improvement of muscle strength and delayed disease progression	Ahola et al., 2016
Alzheimer’s disease	KD in APP/PS1 and Tg4510 mouse models KE in Alzheimer mouse models	Improvement of motor function Improvement in energy metabolism and reduction in amyloid deposition	Beckett et al., 2013; Brownlow et al., 2013 Zhang J. et al., 2013; Pawlosky et al., 2017	Pilot study for assessment of MCT tolerance in Alzheimer patients KE in a case of Alzheimer’s disease	Good tolerance No improvement in cognitive function No assessment of motor function Gain in cognitive function and daily motor activity	Ohnuma et al., 2016 Newport et al., 2015
Spinal cord injury (SCI)	KD in rats with SCI	Improvement of functional forelimb	Streijger et al., 2013	Clinical trial of KD use	Safety and feasibility in patients with acute SCI	Guo et al., 2014
Parkinson’s disease	KD or βOHB in rodents models	Protection of dopaminergic neurons from degeneration Improvement of motor function	Tieu et al., 2003; Cheng et al., 2009; Yang and Cheng, 2010; Shaafi et al., 2016	Feasibility study of KD use	Improvement of unified Parkinson’s disease rating scale score, including motor function	Vanitallie et al., 2005
Rett syndrome	Restricted KD or MCT in Rett syndrome (Mecp2 KO) mice	Improvement of motor behavior and reduction in anxiety Augmented survival, improvement in mitochondrial morphology	Mantis et al., 2009; Park et al., 2014	Cases reports (KD)	Improvement of motor function	Haas et al., 1986; Liebhaber et al., 2003
GLUT 1 deficiency				Case report KD use in GLUT1 patients Evaluation of KD short effect in GLUT1 patients	Improvement of motor function Mainly improvement of cognitive function, with improvement of language and physical endurance Moderate improvement of motor disorder	Friedman et al., 2006 Ramm-Pettersen et al., 2014 Bertoli et al., 2015

ALS, amyotrophic lateral sclerosis; AS, Angelman syndrome; βOHB, β-hydroxybutyrate; DP, Deanna protocol; KD, ketogenic diet; KEs, ketone esters; MCTs, medium-chain triglycerides.