A Ketogenic Diet and the Treatment of Autism Spectrum Disorder

Abstract

Autism spectrum disorder (ASD) is characterized by stereotyped behavior and deficits in communication and social interaction. There are no curative treatments for children with ASD. The ketogenic diet (KD) is a high-fat, appropriate-protein, and low-carbohydrate diet that mimics the fasting state of the body and is proven beneficial in drug-resistant epilepsy and some other brain diseases. An increasing number of studies demonstrated that a KD improved autistic behavior, but the underlying mechanisms are not known. We reviewed the neuroprotective role of a KD in ASD, which is likely mediated via improvements in energy metabolism, reductions in antioxidative stress levels, control of neurotransmitters, inhibition of the mammalian target of rapamycin (mTOR) signaling pathway, and modulation of the gut microbiota. A KD is likely a safe and effective treatment for ASD.

Keywords: autism spectrum disorder; blood-brain barrier; gut microbiota; ketogenic diet; neuroprotection.

Figure 1

Ketone bodies have neuroprotective effects in the brain. Ketone bodies containing acetoacetate, β-hydroxybutyrate, and acetone generated from a ketogenic diet cross the blood–brain barrier. Firstly, ketone bodies improve the energy metabolism and enhance adenosine triphosphate (ATP) production. Secondly, they normalize mitochondrial function by stimulating mitochondrial biogenesis and reducing oxidative stress, which reduces neuronal death. Thirdly, ketone bodies regulate neurotransmitters and increase γ-aminobutyric acid (GABA) levels. Fourthly, they also inhibit the activation of the mammalian target of rapamycin (mTOR) signaling pathway and decrease seizures. Lastly, ketone bodies modulate the gut microbiota.