Exogenous ketone bodies and the ketogenic diet as a treatment option for neurodevelopmental disorders.

Background: Despite being the most prevalent neurodevelopmental disorders, there are comparatively few treatment options available to patients presenting with autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). The ketogenic diet has historically shown therapeutic utility in treating refractory epilepsy, an adjacent neuropsychiatric condition, in children, adolescents and adults. The following review explores preclinical and clinical literature focusing on the therapeutic potential of the ketogenic diet and exogenous ketone body supplementation in treating common neurodevelopmental disorders.

Exploring the role of ketone bodies in the diagnosis and treatment of psychiatric disorders.

In recent times, advances in the field of metabolomics have shed greater light on the role of metabolic disturbances in neuropsychiatric conditions. The following review explores the role of ketone bodies and ketosis in both the diagnosis and treatment of three major psychiatric disorders: major depressive disorder, anxiety disorders, and schizophrenia. Distinction is made between the potential therapeutic effects of the ketogenic diet and exogenous ketone preparations, as exogenous ketones in particular offer a standardized, reproducible manner for inducing ketosis.

Exogenous Ketones and Lactate as a Potential Therapeutic Intervention for Brain Injury and Neurodegenerative Conditions.

Metabolic dysfunction is a ubiquitous underlying feature of many neurological conditions including acute traumatic brain injuries and chronic neurodegenerative conditions. A central problem in neurological patients, in particular those with traumatic brain injuries, is an impairment in the utilization of glucose, which is the predominant metabolic substrate in a normally functioning brain. In such patients, alternative substrates including ketone bodies and lactate become important metabolic candidates for maintaining brain function.

Ketones for Post-exercise Recovery: Potential Applications and Mechanisms.

Ketogenic diet has been introduced in therapeutic areas for more than a century, but the role of ketones in exercise performance has only been explored in the past decade. One of the main reasons that allows the investigation of the role of ketones in exercise performance is the emergence of exogenous ketones, allowing athletes to achieve the state of ketosis acutely, and independent of their metabolic states. While there are mixed results showing either exogenous ketones improve exercise performance or no effect, the mechanisms of action are still being heavily researched.

Assessing the effect of hypoxia on cardiac metabolism using hyperpolarized C magnetic resonance spectroscopy.

Hypoxia plays a role in many diseases and can have a wide range of effects on cardiac metabolism depending on the extent of the hypoxic insult. Noninvasive imaging methods could shed valuable light on the metabolic effects of hypoxia on the heart in vivo. Hyperpolarized carbon-13 magnetic resonance spectroscopy (HP C MRS) in particular is an exciting technique for imaging metabolism that could provide such information.

Inhibition of sarcolemmal FAT/CD36 by sulfo-N-succinimidyl oleate rapidly corrects metabolism and restores function in the diabetic heart following hypoxia/reoxygenation.

Aims: The type 2 diabetic heart oxidizes more fat and less glucose, which can impair metabolic flexibility and function. Increased sarcolemmal fatty acid translocase (FAT/CD36) imports more fatty acid into the diabetic myocardium, feeding increased fatty acid oxidation and elevated lipid deposition. Unlike other metabolic modulators that target mitochondrial fatty acid oxidation, we proposed that pharmacologically inhibiting fatty acid uptake, as the primary step in the pathway, would provide an alternative mechanism to rebalance metabolism and prevent lipid accumulation following hypoxic stress.

Increased oxidative metabolism following hypoxia in the type 2 diabetic heart, despite normal hypoxia signalling and metabolic adaptation.

Key Points: Adaptation to hypoxia makes the heart more oxygen efficient, by metabolising more glucose. In contrast, type 2 diabetes makes the heart metabolise more fatty acids. Diabetes increases the chances of the heart being exposed to hypoxia, but whether the diabetic heart can adapt and respond is unknown.

Cardiac metabolism in a new rat model of type 2 diabetes using high-fat diet with low dose streptozotocin.

Background: To study the pathogenesis of diabetic cardiomyopathy, reliable animal models of type 2 diabetes are required. Physiologically relevant rodent models are needed, which not only replicate the human pathology but also mimic the disease process. Here we characterised cardiac metabolic abnormalities, and investigated the optimal experimental approach for inducing disease, in a new model of type 2 diabetes.