Does keto diet help autism: تفاوت میان نسخه‌ها

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 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.
 Anti-inflammatory Activity and Antioxidative Stress
 One of the risk factors for Autism spectrum disorder in children is abnormal maternal immune activation. For example, pregnant mice were injected with double-stranded RNA (dsRNA) poly (I: C) to mimic a viral infection, and the offspring of these mice had Autism spectrum disorder-like behaviors. Autism spectrum disorder patients also experience aberrant inflammation. Some cytokines and chemokines, such as interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), and monocyte chemotactic protein-1, are found at abnormal levels in brain samples and cerebrospinal fluid in Autism spectrum disorder patients. These cytokines activate the immune response via the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway. Young and colleagues found that the NF-κB protein was hyper-expressed in mature microglia in brain samples in Autism spectrum disorder patients, which indicates that immunity is activated in the brains of Autism spectrum disorder patients. Autism spectrum disorder patients also had higher levels of eight cytokines in plasma compared to control individuals. Autism spectrum disorder individuals also have associated oxidative stress level upregulation and antioxidant ability downregulation. Evidence showed that antioxidant enzymes, including superoxide dismutase and glutathione peroxidase, are altered in Autism spectrum disorder patients, which increases inflammation. In summary, there is a consensus that Autism spectrum disorder individuals have immune dysfunction.
 A ketogenic diet has powerful anti-inflammatory activity and antioxidative stress effects in the brain. Jeong et al. found that a ketogenic diet reduced neuroinflammation via the activation of the peroxisome proliferator-activated receptor gamma (PPARγ) and protected against excitotoxicity-induced neuronal cell death. Fatty acids activate PPARs and are critical regulators of lipid metabolism. Greco et al. found that ketone bodies decreased oxidative stress and improved the mitochondrial respiratory complex activity in a traumatic brain injury animal model. A ketogenic diet likely normalizes mitochondrial function by stimulating mitochondrial biogenesis, decreasing oxidative stress and the levels of pro-apoptotic factors, preventing changes in mitochondrial permeability, and decreasing the mitochondrial ROS production in neocortical neurons. Mirza et al. showed that rats treated with propionic acid exhibited social impairment and repetitive behavior. The cerebellum, brainstem, and prefrontal cortex of these rats had high levels of oxidative stress and inflammation, with increased IL-6 and TNF-α levels and decreased IL-10 levels. They also found that decreased levels of oxidative stress and inflammation improved neurobehavioral disorders in rats.
+The Regulation of Neurotransmitters in the Brain
+GABA is the main inhibitory neurotransmitter in the brain, and it originates from glutamate decarboxylation. Glutamate is the primary excitatory neurotransmitter in the Central Nervous System. Patients with autism exhibited abnormal levels of proteins and messenger RNAs (mRNAs) associated with the glutamate system in the cerebellum. The medium-chain fatty acids that are present during the consumption of a ketogenic diet directly inhibit glutamate receptors and reduce seizures. Other studies found that beta-hydroxybutyrate, which is produced from a ketogenic diet, inhibited GABA degradation in astrocytes. One study showed that children with Autism spectrum disorder had reduced GABA levels in sensorimotor function, and this phenomenon was associated with poor tactile performance compared to healthy children. Autism spectrum disorder patients had significantly lower GABA concentrations in the auditory cortex. Patients with Autism spectrum disorder also had abnormal maturation of the neuronal circuitry on magnetoencephalography (MEG) and edited magnetic resonance spectroscopy (MRS). In summary, a ketogenic diet may ameliorate Autism spectrum disorder behaviors via the modulation of neurotransmitters, such as increasing GABA levels.
+Modulation of the Gut Microbiota
+gastrointestinal symptoms, including constipation and diarrhea, are common in Autism spectrum disorder individuals and are associated with the severity of Autism spectrum disorder symptoms. Gorrindo et al. reported that constipation was associated with increased social impairment and language disorders. Patients with Autism spectrum disorder have different gut microbiome components and metabolic products. The gut microbiota communicates with the brain via the neuroendocrine, neuroimmune, and autonomic nervous systems, which is the so-called microbiota–gut-brain axis. Porphyromonadaceae, Prevotellaceae, Bacteroidales, and Lachnospiraceae were more abundant in the Autism spectrum disorder animal model. An increasing number of studies showed that gut microbiota disturbances were associated with Autism spectrum disorder patients, and modulation of the gut microbiota improved symptoms in Autism spectrum disorder patients.
+A ketogenic diet restored gut microbial composition and improved Autism spectrum disorder core features, including social communication and repetitive behaviors, in an Autism spectrum disorder animal model. A ketogenic diet increased the levels of Akkermansia, Parabacteroides, Bacteroides, and Desulfovibrio spp. in animal models of seizure, glucose transporter 1 deficiency syndrome, and Autism spectrum disorder. A ketogenic diet did not change locomotor activity, anxiety-related behaviors, recognition memory, or sociability in young male rats, which suggests that a ketogenic diet may be more effective in females in some cases. As mentioned above, a ketogenic diet likely modifies the composition of the gut microbiota in different animal disease models, including Autism spectrum disorder. However, there are few studies on alterations of the gut microbiota in humans treated with a ketogenic diet. In summary, modulation of the gut microbiota may be a new target for therapy in Autism spectrum disorder patients.
+The Side Effects of a Ketogenic Diet
+Autism spectrum disorder children have feeding problems because most of them are selective eaters. Therefore, it is difficult to apply a Ketogenic Diet to children with Autism spectrum disorder. There are also some side effects of the long-term implementation of a Ketogenic Diet in children. The main side effects of Ketogenic Diet treatment in children are constipation, vomiting, lack of energy, and hunger. Late-onset adverse effects include hyperuricemia, hyperlipidemia, and kidney stones. One serious side effect of a Ketogenic Diet in children is the suppression of physical development. Long-term Ketogenic Diet administration decreased growth, as indicated by height z-scores but growth, as indicated by weight z-scores, did not change. A Ketogenic Diet may cause height deceleration. However, these side effects do not occur often, and a Ketogenic Diet has been widely used in children with refractory epilepsy. In summary, although studies with larger samples of Autism spectrum disorder patients are lacking, Ketogenic Diet is a safe and effective treatment in people with Autism spectrum disorder.
+Autism spectrum disorder is a neurodevelopmental disease, and timely and effective treatment help improve the prognosis. There is no effective treatment for Autism spectrum disorder children. Many treatments are used for Autism spectrum disorder, but there are no curative treatments for all of the core features of Autism spectrum disorder. A  Ketogenic Diet may improve social behavior in Autism spectrum disorder via normalizing GABA, improving mitochondrial function, ameliorating inflammatory activity and oxidative stress in the brain, inhibiting the mTOR signaling pathway, and modulating the gut microbiota. However, the effects of  Ketogenic Diet vary widely between Autism spectrum disorder patients, and the underlying mechanisms are not known. Autism spectrum disorder children may also reject  Ketogenic Diet food because of their selective eating habits, which complicates the introduction of a  Ketogenic Diet to Autism spectrum disorder patients. Some studies showed that Autism spectrum disorder children have nutrient deficiencies, including vitamin D and folic acid. Long-term treatment of a  Ketogenic Diet likely aggravates the nutritional deficiency. The benefits of a long-term Ketogenic Diet treatment in Autism spectrum disorder children are not known. Therefore, more studies with larger samples and long-term Ketogenic Diet treatment are needed to demonstrate the beneficial effects of a Ketogenic Diet and its side effects in children with Autism spectrum disorder.