Dominic P D'Agostino

Dominic P D'Agostino
University of South Florida | USF · Department of Molecular Pharmacology & Physiology

PhD

About

159
Publications
84,815
Reads
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Introduction
Our research program focuses on developing and testing metabolic therapies for CNS oxygen toxicity (seizures), epilepsy, neurodegenerative diseases, brain cancer and muscle wasting associated motorneuron diseases and cancer. We also study the physiology of extreme environments relevant to the undersea warfighter and astronaut. Current research projects include NASA NEEMO 22 and other space analog missions.
Additional affiliations
June 2006 - present
University of South Florida
Position
  • Professor (Associate)
Description
  • Classes include Medical Biochemistry, Physiology, Neuroscience, Neuropharmacology, Advanced Metabolism and Signaling
September 1999 - September 2004
Robert Wood Johnson University Hospital
Position
  • PhD Student

Publications

Publications (159)
Article
Full-text available
Glioblastoma (GBM), similar to most cancers, is dependent on fermentation metabolism for the synthesis of biomass and energy (ATP) regardless of the cellular or genetic heterogeneity seen within the tumor. The transition from respiration to fermentation arises from the documented defects in the number, the structure, and the function of mitochondri...
Article
Continuous glucose monitoring (CGM) is extensively used in diabetic populations but understudied in non-diabetic patients. Glycemic variability is a risk factor for cardiovascular disease, and emerging evidence suggests close monitoring of glycemic control may have a positive impact on chronic disease. CGM increases awareness of glycemic dysregulat...
Article
Elevated ketone levels have been shown to lead to improvement in diseased contexts including epilepsy, diabetes, obesity, cancer, Alzheimer's, and Parkinson's Disease. It can be difficult for many patients, especially children, to adhere to the strict and intense ketogenic diet necessary to achieve such elevation via dietary manipulation, hence why...
Article
Hyperbaric oxygen (HBO2 ) is used in hyperbaric oxygen therapy and in undersea and aerospace medicine. What limits the use of HBO2 is the risk of seizures, i.e. central nervous system oxygen toxicity (CNS-OT). In undersea medicine, the threat of CNS-OT is what limits the time that the warfighter remains at depth while breathing HBO2 . In addition,...
Article
Background: Kabuki Syndrome (KS) is a genetic disorder that affects multiple systems influencing learning and development. This project is focused on Type 1 KS, which is caused by a heterozygous loss-of-function mutation in the Lysine Methyltransferase 2D (KMT2D) gene. KMT2D encodes for kmt2d, a protein responsible for methylating histone 3 lysine...
Chapter
The ketone bodies β‎-hydroxybutyrate and acetoacetate are produced from fatty acids in the liver and serve as alternative energy sources for the brain, heart, skeletal muscle, and other peripheral tissues during prolonged fasting, calorie restriction, strenuous exercise, or adherence to a low-carbohydrate diet. Emerging evidence has revealed nutrit...
Chapter
Emerging evidence from numerous studies suggests that administration of exogenous ketone supplements, such as ketone salts and ketone esters, may have a therapeutic influence on several central nervous system disorders through neuroprotective and behavioral effects. Therefore, ketone supplementation is a potential therapeutic tool for epilepsy, neu...
Chapter
The physiologic state of ketosis is characterized by decreased blood glucose, suppression of insulin, and an increase in the blood ketones β‎-hydroxybutyrate (β‎HB) and acetoacetate (AcAc), which serve as alternative sources of ATP in the brain. Ketones are elevated by fasting, caloric restriction, exercise, or the ketogenic diet (KD), and until re...
Article
Full-text available
Diverse neurological disorders are associated with a deficit in brain energy metabolism, often characterized by acute or chronic glucose hypometabolism. Ketones serve as the brain's only significant alternative fuel and can even become the primary fuel in conditions of limited glucose availability. Thus, dietary supplementation with exogenous keton...
Article
Full-text available
Exogenous ketone esters have demonstrated the capacity to increase oxygen availability during acute hypoxic exposure leading to the potential application of their use to mitigate performance declines at high altitudes. Voluntary hypoventilation (VH) with exercise reliably reduces oxygen availability and increases carbon dioxide retention without al...
Article
Full-text available
It has been previously demonstrated that KEKS food containing exogenous ketogenic supplement ketone salt (KS) and ketone ester (KE) decreased the lipopolysaccharide (LPS)-generated increase in SWD (spike-wave discharge) number in Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats, likely through ketosis. KEKS-supplemented food-generated ketosis may increa...
Article
Full-text available
Chronic Obstructive Pulmonary Disease (COPD) is a debilitating inflammatory respiratory condition that presents with worsening breathing difficulties and it is assumed to be progressive and incurable. As an inflammatory disease, COPD is associated with recruitment of immune cells to lung tissue and increased levels of pro-inflammatory cytokines, in...
Article
Hyperbaric oxygen (HBO 2 ) is breathing greater than 1 ATA (101.3 kPa) O 2 and is used in HBO 2 therapy and undersea medicine. What limits the use of HBO 2 is the risk of developing CNS oxygen toxicity (CNS-OT). A promising therapy for delaying CNS-OT is ketone metabolic therapy either through diet or exogenous ketone ester (KE) supplement. Previou...
Article
The use of hyperbaric oxygen (HBO2) in hyperbaric and undersea medicine is limited by the risk of seizures (i.e., CNS oxygen toxicity, CNS-OT) resulting from increased production of reactive oxygen species (ROS) in the CNS. Importantly, ketone supplementation has been shown to delay onset of CNS-OT in rats by ~600% in comparison to control groups (...
Article
To evaluate the neuroprotection exerted by ketosis against acute damage of the mammalian central nervous system (CNS). Search engines were interrogated to identify experimental studies comparing the mitigating effect of ketosis (intervention) vs non‐ketosis (control) on acute CNS damage. Primary endpoint was a reduction in mortality. Secondary endp...
Article
Full-text available
Both uridine and exogenous ketone supplements decreased the number of spike-wave discharges (SWDs) in a rat model of human absence epilepsy Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats. It has been suggested that alleviating influence of both uridine and ketone supplements on absence epileptic activity may be modulated by A1 type adenosine receptors...
Article
Full-text available
Human adaptation to extreme environments has been explored for over a century to understand human psychology, integrated physiology, comparative pathologies, and exploratory potential. It has been demonstrated that these environments can provide multiple external stimuli and stressors, which are sufficient to disrupt internal homeostasis and induce...
Article
Full-text available
In certain disease states, such as epilepsy, the elevation of blood ketone levels with ketogenic diets (KDs) has beneficial effects, while exogenous ketone supplements (EKSs) were shown to increase the level of blood ketone bodies (such as β-hydroxybutyrate, βHB) and decrease blood glucose levels without dietary restrictions. It has been suggested...
Article
Full-text available
The ketogenic diet (KD) is a low-carbohydrate, high-fat, adequate-protein diet proven to be effective for the reversal of obesity, metabolic syndrome and type 2 diabetes, and holding therapeutic potential for the prevention and treatment of other chronic diseases. Genetic and dynamic markers of KD response may help to identify individuals most like...
Article
Full-text available
Nutritional ketosis has been proven effective for neurometabolic conditions and disorders linked to metabolic dysregulation. While inducing nutritional ketosis, ketogenic diet (KD) can improve motor performance in the context of certain disease states, but it is unknown whether exogenous ketone supplements—alternatives to KDs—may have similar effec...
Preprint
Full-text available
Background: Interest into the health, disease, and performance impact of exogenous ketone bodies has rapidly expanded due to their multifaceted physiological and signaling properties but limiting our understanding is the isolated analyses of individual types and dose/dosing protocols. Methods: Thirteen recreational male distance runners (24.8±9.6y,...
Preprint
Full-text available
Background: Interest into the health, disease, and performance impact of exogenous ketone bodies has rapidly expanded due to their multifaceted physiological and signaling properties but limiting our understanding is the isolated analyses of individual types and dose/dosing protocols. Methods: Thirteen recreational male distance runners (24.8±9.6y,...
Preprint
Full-text available
Background: Interest into the health, disease, and performance impact of exogenous ketone bodies has rapidly expanded due to their multifaceted physiological and signaling properties but limiting our understanding is the isolated analyses of individual types and dose/dosing protocols. Methods: Thirteen recreational male distance runners (24.8±9.6y,...
Preprint
Full-text available
Background: Interest into the health, disease, and performance impact of exogenous ketone bodies has rapidly expanded due to their multifaceted physiological and signaling properties but limiting our understanding is the isolated analyses of individual types and dose/dosing protocols. Methods: Thirteen recreational male distance runners (24.8±9.6y,...
Article
Objective The aim of this study was to examine the effects of a ketone ester (KE)‐supplemented diet on energy expenditure (EE) and adiposity in mice housed at 23 °C versus thermoneutrality (30 °C), in which sympathetic nervous system activity is diminished. Methods Thirty‐two 10‐week‐old male C57BL/6J mice were assigned to 1 of 4 groups (n = 8 per...
Article
Full-text available
The ability to switch between glycolysis and ketosis promotes survival by enabling metabolism through fat oxidation during periods of fasting. Carbohydrate restriction or stress can also elicit metabolic switching. Keto-adapting from glycolysis is delayed in aged rats, but factors mediating this age-related impairment have not been identified. We m...
Article
Full-text available
Background Cancer Anorexia Cachexia Syndrome (CACS) is a distinct atrophy disease negatively influencing multiple aspects of clinical care and patient quality of life. Although it directly causes 20% of all cancer‐related deaths, there are currently no model systems that encompass the entire multifaceted syndrome, nor are there any effective therap...
Article
The objective of this study was to measure potential changes in cognitive function in response to living in an extreme underwater habitat. Chronic high stress and intense workload can affect individual and team cognition. As such, associated variables were monitored during the NASA Extreme Environment Mission Operation (NEEMO) 23 mission at the Aqu...
Article
Full-text available
Background: It has been demonstrated that administration of exogenous ketone supplement ketone salt (KS) and ketone ester (KE) increased blood ketone level and delayed the onset of isoflurane-induced anesthesia in different rodent models, such as Wistar Albino Glaxo Rijswijk (WAG/Rij) rats. The modulatory effect of adenosinergic system may have a...
Preprint
Full-text available
Background: It has been demonstrated that administration of exogenous ketone supplement ketone salt (KS) and ketone ester (KE) increased blood ketone level and delayed the onset of isoflurane-induced anesthesia in different rodent models, such as Wistar Albino Glaxo Rijswijk (WAG/Rij) rats. The modulatory effect of adenosinergic system may have a r...
Article
Full-text available
Numerous oral ketone supplements are marketed with the claim that they will rapidly induce ketosis and improve exercise performance. The purpose of this study was to assess exercise performance time and related physiological, metabolic and perceptual responses of recreational endurance runners after ingestion of a commercially available oral ketone...
Article
Full-text available
Background: Ketogenic and low-glycemic-index diets are effective in treating drug-resistant seizures in children with Angelman syndrome. Cognition, mobility, sleep, and gastrointestinal health are intrinsically linked to seizure activity and overall quality of life. Ketogenic and low-glycemic diets restrict carbohydrate consumption and stabilize b...
Preprint
Full-text available
The ability to switch between glycolysis and ketosis promotes survival by enabling metabolism through fat oxidation during periods of fasting. Carbohydrate restriction or stress can also elicit metabolic switching. Keto-adapting from glycolysis is delayed in aged rats, but factors mediating this age-related impairment have not been identified. We m...
Preprint
Background It has been demonstrated that administration of exogenous ketone supplement ketone salt (KS) and ketone ester (KE) increased blood ketone level and delayed the onset of isoflurane-induced anesthesia (immobility) in different rodent models, such as Wistar Albino Glaxo Rijswijk (WAG/Rij) rats. The modulatory effect of adenosinergic system...
Data
Video abstract for the paper: Ari, C.; Murdun, C.; Koutnik, A.P.; Goldhagen, C.R.; Rogers, C.; Park, C.; Bharwani, S.; Diamond, D.M.; Kindy, M.S.; D’Agostino, D.P.; Kovács, Z. Exogenous Ketones Lower Blood Glucose Level in Rested and Exercised Rodent Models. Nutrients 2019, 11, 2330.
Article
Full-text available
Diseases involving inflammation and oxidative stress can be exacerbated by high blood glucose levels. Due to tight metabolic regulation, safely reducing blood glucose can prove difficult. The ketogenic diet (KD) reduces absolute glucose and insulin, while increasing fatty acid oxidation, ketogenesis, and circulating levels of β-hydroxybutyrate (βHB...
Article
Full-text available
The ketogenic diet (KD) is a high-fat, low-carbohydrate treatment for medically intractable epilepsy. One of the hallmark features of the KD is the production of ketone bodies which have long been believed, but not yet proven, to exert direct anti-seizure effects. The prevailing view has been that ketosis is an epiphenomenon during KD treatment, mo...
Article
Objectives: 70.7% of Americans over 20 years of age are overweight or obese. Currently, the main strategy for weight loss is caloric restriction. Ketone bodies have been shown to facilitate voluntary caloric restriction through altering the appetite stimulating hormone ghrelin. However, these non-toxic ketone bodies have not been evaluated as weig...
Article
Full-text available
Globally, psychiatric disorders, such as anxiety disorder, bipolar disorder, schizophrenia, depression, autism spectrum disorder, and attention-deficit/hyperactivity disorder (ADHD) are becoming more prevalent. Although the exact pathological alterations are not yet clear, recent studies have demonstrated that widespread changes of very complex met...
Article
Full-text available
Objectives: Exogenous ketones may provide therapeutic benefit in treatment of obesity. Administration of the ketone ester (KE) R,S-1,3-butanediol acetoacetate diester (BD-AcAc2) decreases body weight in mice, but effects on energy balance have not been extensively characterized. The purpose of this investigation was to explore concentration-depende...
Article
Full-text available
An increasing amount of evidence suggests that migraines are a response to a cerebral energy deficiency or oxidative stress levels that exceed antioxidant capacity. The ketogenic diet (KD), a diet mimicking fasting that leads to the elevation of ketone bodies (KBs), is a therapeutic intervention targeting cerebral metabolism that has recently shown...
Article
The ketone bodies acetoacetate (AcAc) and β-hydroxybutyrate (βHB) are the subject of renewed interest given recently established pleiotropic effects regulating inflammation, oxidative stress, and gene expression. Anticatabolic effects of β-hydroxybutyrate have recently been demonstrated in human skeletal muscle under inflammatory insult, thereby ex...
Cover Page
Full-text available
An increasing amount of evidence points towards migraine being a response to cerebral energy deficiency or oxidative stress levels that exceed antioxidant capacity. The ketogenic diet (KD), a diet mimicking fasting that leads to the elevation of ketone bodies (KBs), is a therapeutic intervention targeting cerebral metabolism that has recently shown...
Article
Full-text available
It has been demonstrated previously that exogenous ketone supplements such as ketone ester (KE) decreased absence epileptic activity in a well-studied animal model of human absence epilepsy, Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats. It is known that lipopolysaccharide (LPS)-generated changes in inflammatory processes increase absence epileptic a...
Article
Full-text available
The overall goal of this study is to describe the methodology of the elevated plus maze (EPM) test in combination with a video tracking software. The purpose of the method is to document the effect of various potential anxiolytic treatments on laboratory rodent models. The EPM test is based on the rodents' proclivity toward protected, enclosed dark...
Article
Full-text available
Central nervous system oxygen toxicity (CNS‐OT) manifests as tonic‐clonic seizures and is a limitation of hyperbaric oxygen therapy (HBOT), as well as of recreational and technical diving associated with elevated partial pressure of oxygen. A previous study showed that ketone ester (1,3‐butanediol acetoacetate diester, KE) administration delayed la...
Article
Full-text available
INTRODUCTION: While the KD holds promise as a therapeutic option for brain cancer patients, stringency of the diet impacts compliance. We have previously demonstrated that a high fat/low carbohydrate diet, similar to the Ketogenic Diet [KD], can reduce tumor progression and enhance survival in an orthotopic xenograft model. However, while this diet...
Article
Full-text available
Background: Ketogenic diet (KD) and exogenous ketone supplements can evoke sustained ketosis, which may modulate sleep and sleep-like effects. However, no studies have been published examining the effect of ketosis on the onset of general isoflurane induced anesthesia. Therefore, we investigated the effect of the KD and different exogenous ketogen...