The Metabolic Effects of β-hydroxybutyrate on Working Skeletal Muscle
AgingMetabolism Disorder2 moreThe goal of this clinical trial is to test ketone bodies in healthy elderly and young individuals. The main question it aims to answer are: • Do ketone bodies improve skeletal muscle function? Participants will ingest a ketone monoester and skeletal muscle function will then be evaluated by: Special magnetic imaging techniques Intravenous infusion of tracer-marked nutrients Performance tests on a ergometer bike and in a dynamometer Researchers will compare the outcomes between within the young and elderly groups and between the young and the elderly group to investigate if age has an effect on the outcomes.
Effects of Ketosis on Brain Function in Patients With T1DM
Type1diabetesThe scientific goal of this study is to examine the effects of a ketogenic diet on hypoglycemia tolerance and brain function in people with type 1 diabetes mellitus (T1D) and to clarify the mechanistic role of ketones in this process. Glycemic management of T1D is typified by alternating periods of hyper- and hypo-glycemia. Because brain metabolism under usual conditions depends on glucose, acute hypoglycemia leads to immediate complications including impaired cognitive function and a counter-regulatory hormone response. Recurrent hypoglycemia is associated with functional and structural changes in the brain and contributes to the cognitive decline observed in individuals with diabetes. The state of nutritional ketosis (as it occurs during fasting or when following a ketogenic [very low carbohydrate] diet) may protect against these acute and chronic complications. As the body relies on fat metabolism, ketone bodies build up and provide an alternative fuel for the brain. Studies during hypoglycemia have shown better cognitive function and less hypoglycemia symptoms in the setting of nutritional ketosis or with ketone administration. This physiological benefit may have special relevance for people with T1D who experience hypoglycemia frequently. To date, no mechanistic studies have examined brain effects of nutritional ketosis in T1D; nor have any trials explored the potential relevance of this for diabetes care.
Strategies to Augment Ketosis: Optimization of Ketone Delivery Strategies
KetosisOne important difference between KE compounds is the ketone-promoting components, which determines the circulating ratio of blood ketone bodies, BHB and AcAc, and may in turn lead to important metabolic and signaling differences. Whereas some actions of the ketone bodies BHB and AcAc are shared, R-BHB has a broad range of signaling functions that are distinct from AcAc, some of which are shared by the non-circulating, non-oxidizable enantiomer, S-BHB. AcAc also has metabolic and signaling actions that are independent of BHB and is selectively oxidized in some cells that cannot oxidize BHB. Furthermore, responses to different ketone bodies vary between tissue types. A second difference between KE arises from the balance between direct delivery of ketones compared to indirectly elevating ketone concentration via metabolism of non-classical or classical ketogenic precursors. Classical ketogenesis itself may drive adaptation and some of the functional benefits associated with ketosis. BDO is included in all of the KE compounds, but it is currently unknown how consumption of BDO alone, and its metabolism via non-classical ketogenesis acutely affects metabolism. Additionally, ketogenesis is now understood to occur in certain cells outside the liver with important local biological effects, for example ketogenesis driven by medium chain fatty acids has been reported in astrocytes in vitro. Provision of systemic BHB by a KE may elicit different biological effects in some tissues such as the brain versus promoting in situ ketogenesis in that tissue. Overall, not only are functional effects of KE incompletely defined, but also it is unknown which effects are common to all KE versus which are specific to an individual KE compound (i.e., BHB Monoester vs AcAc Diester) or which may be attributable to the BDO precursor common to all of the KE. This study will be the first comparative full crossover study of all available KE and the precursor BDO at two serving sizes. Outcomes will focus on established effects of the BHB Monoester (including the effects on ketones, glucose and acid-base balance) and compare these with the effects of the AcAc Diester, C8 Ketonef Diester and BDO.
The SHINE Study: Safety of Implant and Preliminary Performance of the SHINE SYSTEM in Diabetic Subjects...
Diabetes MellitusDiabetes Mellitus7 moreThe objectives of SHINE study are to confirm the safety aspects of the SHINE SYSTEM. Moreover, the goal of this clinical investigation is the initial evaluation of sensor's performance by assessing sensor's ability to qualitatively detect the appropriate analytes in subjects with diabetes of 18 years and older.
Evaluation of the Safety and Tolerability of Exogenous Ketosis Induced by Free Beta-hydroxybutyrate....
Exogenous KetosisThe goal of this clinical trial is to evaluate the safety and tolerability of free beta-hydroxybutyrate induced ketosis in healthy individuals. The main question it aims to answer is: Is free beta-hydroxybutyrate safe and well tolerated by adults? Participants will be asked to ingest 10 grams of beta-hydroxybutyrate, diluted in water and sweetened with Stevia, every morning between 9:00 and 11:00 for four weeks.
Assessment of BHB Concentration Agreement Among Sampling Locations and the Impact of Ketosis on...
Ketosishis study aims to address two key aspects - part 1: the suitability of selecting a specific sampling site for BHB measurement in patients and research, as well as potential differences between capillary and venous blood measurements. Additionally, the study will delve into the effects of ketosis on EPO concentrations, sex hormones levels, and hemodynamic markers and blood pressure - part 2. This investigation will utilize blood samples collected during part 1, including acute effects, as well as samples taken on day 7 and day 14 during which period participants are exposed to intermittent ketosis.
Variations in Ketone Metabolism
KetosisThis outcome of this study will elucidate how the phenotype of the individual modulates the KE metabolic effect. Most studies of KE have been in homogenous populations, usually young, male athletes. However, two striking experiments using identical, body weight adjusted KE doses in healthy and obese individuals found that BHB area under the curve (AUC) and removal was reduced by obesity and poor metabolic health. Similarly, ketone infusion experiments found that diabetes, obesity, and insulin resistance alter BHB metabolism. It is important to determine how obesity affects KE 'sensitivity' (i.e., breakdown and oxidation) because the increasing prevalence of obesity as a function of age. Age may be another important source of variation in ketone metabolism. The genes that control the ketone system are regulated by a cascade of transcription factors and hormones including PPARα and FGF21, which are themselves known to be affected by aging and dietary status, and the cellular protein sensor target of rapamycin (TOR). Aberrant hyperactivation of TOR with aging may reduce ketogenesis, while it was observed that a long-term ketogenic diet specifically up-regulated PPARα activity. Preliminary work revealed substantial changes across mouse lifespan in the expression of ketone-related genes in the liver such as Hmgcs2 (rate limiting for ketone production) and Bdh1 (rate limiting for BHB oxidation) between young, middle-aged, and old mice, with a nadir of gene expression in middle age before increasing again late in life. Substantial age differences were found in response to matched doses of oral KE in mice and in rats. These data may have important implications for treating people of different ages and for translating KE technologies into the Department of VA. Therefore, this project plans to study individual responses to KE ingestion across the lifespan, against the background of varying metabolic health
The Effect of Different Ketone Supplements on Blood β-OHB and Blood Glucose in Healthy Individuals...
KetosisBlood GlucoseKetone bodies are a fuel source and signaling molecule that are produced by your body during prolonged fasting or if you consistently eat at low-carbohydrate diet. Blood ketones can be used as a source of energy during fasting and are used by your brain as an alternative source of fuel to glucose. Previous studies have found that ketones, when consumed in form of a supplement drink, can increase blood ketone levels and lower blood glucose, the amount of sugar in your blood. This is of potential interest for individuals with high blood sugar, such as people living with type 2 diabetes. However, there are different types of ketone supplements that differ in how they are metabolized in the body. Little is known about how these supplements affect blood ketone and blood glucose levels. The main objective of this study is to determine the effect of three different ketone supplements on blood ketones and blood glucose. The results of this pilot study will be used to guide future research for larger and more extensive studies on ketone supplements.
Modulation of Circulating Levels of the Ketone Body 3-hydroxybutyrate in Patients With Chronic Heart...
Heart FailureKetosis1 moreThe ketone body 3-hydroxybutyrate (3-OHB) is a naturally occurring energy substrate, and is associated with increased life span and improved health. We have previously shown that intravenous 3-OHB treatment increases myocardial blood flow > 70% in healthy humans and data from our group show that 3-OHB increases cardiac output by 40 % in patients with heart failure. In this study the investigators aim to investigate: If this effect is reproducible with a commercially available oral ketone supplements The safety of commercially available ketone supplements in heart failure patients
Clinical and Laboratory Parameters Associated With Different Degrees of Dehydration Among Children...
Diabetic KetoacidosisDiabetic ketoacidosis (DKA) is a common acute complication of type 1 diabetes mellitus (T1DM). DKA is characterized by hyperglycemia, metabolic acidosis, increased levels of ketone bodies in blood and urine. This leads to osmotic diuresis and severe depletion of water and electrolytes from both the intra- and extracellular fluid (ECF) compartments. Estimation of the degree of dehydration for children admitted with DKA is of great clinical importance. The calculation of the amount of deficit therapy depends on the estimated degree of dehydration. However, the degree of dehydration present during DKA is difficult to be clinically assessed. Hyperosmolality tends to preserve intravascular volume with maintenance of peripheral pulses, blood pressure, and urine output until extreme volume depletion occurs. Metabolic acidosis leads to hyperventilation and dry oral mucosa as well as decreased peripheral vascular resistance and cardiac function . consequently, hyper-osmolality may lead to an underestimation of the degree of dehydration, whereas metabolic acidosis may lead to an overestimation of the degree of dehydration. This makes the physical findings unreliable in this setting. Several clinical and biochemical markers were suggested to assess and stage the degree of dehydration at hospital admission. The blood urea nitrogen , hematocrit , plasma albumin are useful markers of the degree of ECF contraction.However, Several previous studies demonstrated that there was no agreement between assessed and measured degree of dehydration which is calculated according to change in body weight at admission and after correction of dehydration. there were tendencies to overestimated or underestimate the degree of dehydration between different physicians. The assessment of the magnitude of dehydration in DKA is of major interest and continues to be a subject of research. This study aims to assess the association between different clinical and laboratory parameters in children with diabetic ketoacidosis and the degree of dehydration at hospital admission among those children.