Does keto diet help autism

Autism spectrum disorder (ASD) is a lifelong neurodevelopmental disorder that is characterized by stereotyped behavior and deficits in communication and social interaction. Autism spectrum disorder affects 3.4–6.7 per 1,000 children. Boys are four times more likely than girls to have Autism spectrum disorder. The core features of Autism spectrum disorder patients are social communication deficits and repetitive sensory–motor behaviors. According to the Diagnostic and Statistical Manual of Mental Disorders (DSM), patients who are diagnosed with Autism spectrum disorder must have persistent deficits in social communication and repetitive and unusual sensory–motor behaviors. Comorbidities in Autism spectrum disorder are common and include epilepsy, sleep disorders, gastrointestinal (GI) symptoms, and psychopathologies such as anxiety, depression, attention deficit hyperactivity disorder, and intellectual disability. Sleep disturbances occur in 50–80% Autism spectrum disorder children, and sleep disorder is associated with behavioral dysregulation. Epilepsy is also one of the most common comorbidities in Autism spectrum disorder children, and the average prevalence reaches 26%. Autism spectrum disorder individuals who have epilepsy are likely to exhibit more severe autism-related symptoms. GI symptoms, which range from 23 to 70% in ASD children, are related to the severity of Autism spectrum disorder. Approximately 31% of children with Autism spectrum disorder have intelligence quotient scores below 70. The cost of raising a child with Autism spectrum disorder is 1.4–3.6 million dollars according to the level of intellectual disability, and the largest expenses are special education costs and the loss of parental productivity. When children grow up, supportive living accommodations and the loss of individual productivity become the highest costs. Therefore, Autism spectrum disorder places a large burden on society and the affected families. There are no effective drugs for Autism spectrum disorder. Several interventions, such as special education and behavioral interventions, provide some benefits, but these interventions do not improve all core symptoms of Autism spectrum disorder and have less effects on comorbidities, including epilepsy. Therefore, new therapies are urgently needed to broaden the management options and improve the prognosis of these patients. Lower levels of disaccharidases and hexose transporters were found in Autism spectrum disorder patients with GI symptoms, which suggests carbohydrate digestion disorders as a physiopathological mechanism in Autism spectrum disorder patients. Therefore, a low-carbohydrate diet, such as a ketogenic diet (KD), is likely suitable for Autism spectrum disorder patients.

A ketogenic diet is a high-fat, appropriate-protein, and low-carbohydrate diet that has a positive effect on energy metabolism. For example, a ketogenic diet increases the levels of adenosine triphosphate (ATP) and enzymes associated with mitochondrial metabolic pathways and enhances mitochondrial biogenesis. Acetyl-CoA is converted to ketone bodies under the effects of d-β-hydroxybutyrate dehydrogenase, acetoacetate succinyl-CoA transferase, and acetoacetyl-CoA-thiolase. Ketone bodies, including β-hydroxybutyrate, acetoacetate, and acetone, function as fuels under fasting or starvation conditions and cross the blood–brain barrier (BBB) to feed the brain. These molecules also prevent mitochondrial permeability transition and attenuate reactive oxygen species (ROS). Therefore, ketone bodies have neuroprotective effects in the central nervous system (CNS). A ketogenic diet is a significantly effective treatment for epilepsy. Refractory epilepsy patients aged 1–18 years treated with a ketogenic diet for 4 months had a 56% reduction in mean seizure frequency. A ketogenic diet may also improve some core autistic features and comorbidities of Autism spectrum disorder, but data of clinical studies of a ketogenic diet as a treatment for Autism spectrum disorder are very limited. The present review examined the role of a ketogenic diet in Autism spectrum disorder treatment and discussed the underlying mechanisms.

A ketogenic diet is a dietary intervention therapy in neurological disorders such as epilepsy and Autism spectrum disorder. A ketogenic diet may be an effective therapy for ASD because it might improve Autism spectrum disorder core symptoms and could benefit its comorbidities, including seizures. The efficiency of a ketogenic diet must be monitored using urinary ketones and serum beta-hydroxybutyrate (BHB). Some evidence showed that a ketogenic diet improved the core features of Autism spectrum disorder patients (Table 1). El-Rashidy et al. showed that a ketogenic diet improved autistic manifestations, which was demonstrated as improved scores on the Autism Treatment Evaluation Test (ATEC) scales and the Childhood Autism Rating Scale (CARS), especially sociability improvement. Lee et al. also reported that a modified ketogenic gluten-free diet with supplemental medium-chain triglycerides (MCTs) improved the social affect subdomain and total autism diagnostic observation schedule, 2nd edition (ADOS-2) scores, but it did not affect the restricted and repetitive behavior scores. A ketogenic diet improved social exploration and social interactions in an animal model of Autism spectrum disorder. It also ameliorates the comorbidities of Autism spectrum disorder more efficiently than the core symptoms of Autism spectrum disorder. A ketogenic diet improved the social communication of one of six Autism spectrum disorder patients, but it reduced the comorbidities of all six Autism spectrum disorder patients, including attention deficit hyperactivity disorder (ADHD), compulsive behavior, preoccupation with parts of objects, and abnormal sleep. It also decreased the frequency of seizures. A case report of an Autism spectrum disorder child found that a ketogenic diet improved the electroencephalogram results and increased the child's intelligence quotient. Although a ketogenic diet-induced decrease in seizures will lead to a better quality of life in patients with epilepsy, including Autism spectrum disorder, it is not associated with improvements in behaviors in Autism spectrum disorder patients. Antiepileptic drugs do not have a large effect on the behavioral symptoms in Autism spectrum disorder.

After ketogenic diet treatment, some blood parameters changed, such as an upregulation of beta-hydroxybutyrate, high-density lipoprotein (HDL), low-density lipoprotein, and cholesterol and a downregulation of eosinophils. Only the HDL increase, eosinophil percentage, and white blood cell count decrease predicted the effects of a modified ketogenic diet treatment in Autism spectrum disorder patients. Why the effects of ketogenic diet vary so much from patient to patient in Autism spectrum disorder is not clear. The pro-inflammatory condition at baseline was associated with an effective ketogenic diet treatment, which was demonstrated by a reduction in eosinophils.

A ketogenic diet seems effective in Autism spectrum disorder patients, but all of these clinical studies had small sample sizes, which is likely due to the difficulty of setting up randomized trials in Autism spectrum disorder children. Autism spectrum disorder patients also eat a narrower range of foods and exhibit more feeding problems. They refuse some food because of the presentation or the need for certain utensils. Therefore, it is difficult to introduce the ketogenic diet to Autism spectrum disorder children. The duration of these studies was 3–16 months, which is not sufficient to assess the side effects of ketogenic diet. In summary, more studies are needed to verify the precise role of ketogenic diet in Autism spectrum disorder patients.

The Neuroprotective Role of a ketogenic diet in the Central Nervous System A ketogenic diet contains abundant fat and induces the generation of acetyl-CoA in the mitochondria of the liver via fatty acid oxidation. Therefore, abundant acetyl-CoA is shunted to the formation of ketone bodies (acetoacetate, β-hydroxybutyrate, and acetone) in the liver. These ketone bodies enter into the circulation and are used to produce energy. One of the main ketones is acetone, which increases the seizure threshold and potentiates the anticonvulsant activity of some antiepileptic drugs. Therefore, fatty acids and ketone bodies exert neuroprotective effects in the brain. For example, ketone bodies improve the energy metabolism by enhancing ATP production and normalizing mitochondrial function via the stimulation of mitochondrial biogenesis and the reduction of oxidative stress, which reduces neuronal death. Ketone bodies regulate neurotransmitters, increase γ-aminobutyric acid (GABA) levels, and inhibit the activation of the mammalian target of rapamycin (mTOR) signaling pathway. However, the exact neuroprotective mechanisms of a ketogenic diet are not fully understood.

The Improvement of Energy Metabolism in the Central Nervous System Autism spectrum disorder individuals have impaired mitochondrial energy production due to the presence of abnormal mitochondrial markers in their plasma, such as elevated levels of lactic acid and pyruvate. Weissman et al. showed that Autism spectrum disorder patients had mitochondrial electron transport chain dysfunction, including complex I and complex III deficiencies. A ketogenic diet provides fuel sources in the human body, and the ketone bodies, including β-hydroxybutyrate, cross the blood-brain barrier and replace glucose as fuel for the brain. This molecule crosses the blood-brain barrier via proton symporters and a sodium-dependent monocarboxylate transporter, which is located in the blood-brain barrier, neurons, and astrocytes. Ketone bodies enhance adenosine triphosphate (ATP) production via the Krebs cycle to generate energy and balance metabolism. A ketogenic diet reduced seizures by enhancing brain metabolism via the regulation of transcripts encoding energy metabolism enzymes or mitochondrial proteins in rats with seizures.