Dominic P D'Agostino

University of South Florida | USF · Department of Molecular Pharmacology & Physiology

Heavy reliance on glucose metabolism and a reduced capacity to use ketone bodies makes glioblastoma (GBM) a promising candidate for ketone-based therapies. Ketogenic diet (KD) is well-known for its promising effects in controlling tumor growth in GBM. Moreover, synthetic ketone ester (KE) has demonstrated to increase blood ketone levels and enhance...

Purpose Acute ingestion of a ketone monoester with co-ingestion of a carbohydrate (KME + CHO) compared to carbohydrate (CHO) was investigated on cycling performance and cognitive performance in trained females. Methods Using a two condition, placebo-controlled, double-blinded and crossover design, twelve trained females (mean ± SD: age, 23 ± 3 y...

Exogenous ketones have shown potential to mitigate cognitive decrements in states of fatigue, but studies in females are limited. Following a familiarization session and a baseline session without a mental fatiguing protocol (MF), 12 females completed two experimental sessions, consisting of a battery of cognitive tests (psychomotor vigilance test...

Amyotrophic lateral sclerosis (ALS) is a progressive disease of neuronal degeneration in the motor cortex, brainstem, and spinal cord, resulting in impaired motor function and premature demise as a result of insufficient respiratory drive. ALS is associated with dysfunctions in neurons, neuroglia, muscle cells, energy metabolism, and glutamate bala...

In exercise science, the crossover effect denotes that fat oxidation is the primary fuel at rest and during low-intensity exercise with a shift towards an increased reliance on carbohydrate oxidation at moderate to high exercise intensities. This model makes four predictions: First, >50% of energy comes from carbohydrate oxidation at ≥60% of maximu...

Rucksack marches (‘rucks’) are strenuous, military‐relevant exercises that may benefit from pre‐event fuelling. The purpose of this investigation was to explore whether acute ingestion of carbohydrate‐ or lipid‐based nutritional bars before rucking can elicit unique advantages that augment exercise performance. Recreationally active and healthy mal...

Background It has been suggested that administration of exogenous ketone supplements (EKSs) not only increases blood ketone body levels but also decreases blood glucose level and modulates isoflurane-induced anesthesia in different rodents, such as Wistar Albino Glaxo Rijswijk (WAG/Rij) rats. Thus, we investigated whether administration of EKSs can...

High carbohydrate, low fat (HCLF) diets have been the predominant nutrition strategy for athletic performance, but recent evidence following multi-week habituation has challenged the superiority of HCLF over low carbohydrate, high fat (LCHF) diets, along with growing interest in the potential health and disease implications of dietary choice. Highl...

Highlights • Lean mass hyper-responders exhibit extreme increases in LDL-c on ketogenic diets. • LDL-c increases in LMHRs are dependent on carbohydrate restriction. • Other cardiometabolic risk factors are normal to optimal in LMHRs. • A prudent clinical approach is required for managing LDL-c in LMHR patients. • Research is warranted to assess mec...

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...

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...

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...

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,...

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...

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...

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...

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...

Ketogenic diets have been treating epilepsy for over 100 years, and in recent decades the awareness and applications of ketogenic therapies have expanded dramatically. The second edition of Ketogenic Diets and Metabolic Therapies: Expanded Roles in Health and Disease honors the major milestone of entering the second century of metabolic therapies....

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...

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...

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...

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...

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...

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 (...

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) versus non‐ketosis (control) on acute CNS damage. Primary endpoint was a reduction in mortality. Secondary...

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...

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...

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...

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...

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...

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,...

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,...

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,...

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,...

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...

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...

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...

Oxygen acts as a drug at increased atmospheric pressures, such as occurs during exposure to hyperbaric oxygen (HBO) during hyperbaric and undersea medicine. Use of HBO is limited by the risk of developing CNS oxygen toxicity (CNS‐OT) which manifests as seizures. The ketogenic diet (KD) is used clinically as an anticonvulsant therapy for refractory...

Background Tumors can be viewed as populations of cells which may succumb to eradication principles observed in nature. For example, population reduction or eradication occurs when populations are exposed to simultaneous press and pulse pressures. Press disturbances are pressures which produce chronic stress in populations, while pulse disturbances...

Background Kabuki Syndrome is a rare genetic disorder that leads to many developmental abnormalities, and is caused by a heterozygous mutation in either KMT2D (Type 1) or KDM6A (Type 2) that leads to a loss of function. Both genes play a role in gene regulation via histone modification. KMT2D is a gene that codes for the protein kmt2d , a lysine me...

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...

The present challenges of long duration spaceflight and other missions in extreme environments include changes of sensory functions, including vision impairment and changes in taste perception. In order to monitor and improve astronaut health and performance during long duration spaceflight and future spaceflight missions we studied sensory functio...

Understanding changes in individual motor function and how it relates to workload, personality types, and shared knowledge is vital to the success of team‐based missions. Such changes may present a challenge in long duration spaceflight and other missions in extreme environments. Therefore, we studied grip strength, dexterity, stress level, task lo...

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...

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...

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...

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...

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...

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...

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...

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.

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...

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...

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...

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...

Objectives: To compare the perioperative and short-term outcomes of robotic pyelolithotomy (RP) and laparoscopic pyelolithotomy (LP) for the treatment of renal stones. Materials and methods: We retrospectively evaluated 39 patients who underwent robotic or laparoscopic pyelolithotomy from January 2015 to December 2018. Results: The preoperativ...

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...

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...

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...

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...