One of the most important sources of fuel is ketone bodies for all evolutionary realms of life. Ketone is the name for a particular type of elemental structure in organic chemistry, that is made up of a single bond between two CH3 or R groups and a double bond with an oxygen molecule. Acetone, 3-B-hydroxybutyrate (3HB), and acetoacetate are all ketone group compounds that are highly soluble in bodily tissues. Due to their solubility, these ketones can be transported throughout the body to numerous tissues. Lipase (HSL), succinyl CoA-oxoacid transferase (SCOT), acetyl CoA carboxylase, and HMG CoA synthase are enzymes that help in metabolism with the use of ketones as fuel. Insulin inhibits and glucagon increases production of HSL, HMG CoA synthase and acetyl CoA carboxylase. All three enzymes produce the same effect: they slow down ketone synthesis when insulin is present and increase it when glucagon is present.
Simply put, in the absence of a carbohydrate source, the body uses fatty acids, which are converted to ketones, as its energy source. They account for 5% to 20% of total energy consumption in the human body. Ketone bodies are produced in the liver and then transported throughout the body. This procedure is especially critical when a person’s blood glucose level has dropped and they need to maintain an energy supply for organs like the brain. The oxidation and consumption of ketone bodies by mitochondria, particularly in organs with high energy demands, constitute ketone metabolism. This mechanism generates NADH and FADH2 for the electron transport chain while also supplying acetyl CoA for gluconeogenesis.
Long periods of fasting or strenuous activity may result in an excess of ketones from ketosis. Diabetic individuals often resort to ketosis for their insulin requirements. But when diabetic patients do not receive enough insulin, either naturally or by supplementation, they enter ketosis incorrectly, resulting in diabetic ketoacidosis (DKA).
Nutrition intake before and during exercise increases efficiency by delaying weariness and facilitating muscle recovery via refilling endogenous substrate storage. Adequate food consumption is essential for physical activity, and delaying exhaustion. This is true for endurance activities that require a large amount of energy expenditure. Alternative energy boosters that require a low-carb diet encourages fat oxidation during exercise. It also helps to save the body’s limited glycogen resources.
While fat-based diets increase fat oxidation potential during workout, carb restriction (e.g., 50 g/day) boosts ketone body production, which improves the energy substrate for skeletal muscle tissues.
Tissue type, exercise status, ketone body concentrations, and skeletal muscle fiber type all influence body metabolism. When entirely oxidized, ketones have a pulmonary quotient akin to glucose (AcAc = 1.0, β-OHB = 0.89). Ketone bodies, by acting as an alternate source, lessens dependency on glucose use and free up endogenous glycogen stores. As a result, while a low carb diet may increase endurance performance, ketone body supplementation during exercise limits glucose oxidation, decreasing the capacity to sustain higher intensity efforts. The great majority of Olympic sports thus require relatively brief, high-intensity workouts. Acetoacetate and D-ß-hydroxybutyrate are metabolites that are commonly produced when the body goes through stress like an injury or carb/nutrient deficiency.
Some of the ketones circulating in the blood have been converted from acetyl-CoA that the hepatocyte mitochondria gets from fatty acids. These are then transferred to the extrahepatic tissues for terminal oxidation. Emerging evidence suggests that each ketone body has distinct cell-specific roles, including intracellular signaling and roles in lipogenic and cholesterologenic pathways. AcAc and its redox partner D-ßOHB, the principal circulating ketone bodies, exchange in near balance.
Despite the fact that sports rely heavily on carb metabolism to maintain high-intensity exercise performance, glycogen stores are unlikely to be depleted due to the brief period of competition. Carb limitation highly limits performance in some sports like triathlon and cycling, which are often regarded as endurance events with high levels of oxidative metabolism. That is why ketone bodies are so helpful in such endurance workouts. Cycling races, on the other hand, contain periods of elevated workload that long surpass an athlete’s maximal power. These phases of increasing intensity of workouts influence the outcome of the competition. There is a decrease in glycolytic capability which can jeopardize an athlete’s specific energy requirements. Ketone bodies modify acute exercise metabolism. It improves post-exercise recovery by speeding up muscle glycogen replacement. A ketone-ester beverage resulted in plasma β-OHB concentrations of 5.3 mol/L, enhanced glucose removal by 33%, and muscle glycogen content by 50% when compared to a control beverage. Ingestion of combined ketone esters and carbohydrate reduced the respiratory quotient during exercise and intramuscular triacylglycerol content after 2 hours of intense training. A larger dependence on endogenous fat sources for energy provision during prolonged exercise preserves endogenous glycogen stores, boosting performance capability. However, ketone bodies have been demonstrated to diminish circulatory FFA availability by blocking catecholamine lipolysis and/or stimulating hyperinsulinemia, which reduces lipolysis.
Studies reported an intravenous injection of ketone bodies during exercise reduced the activity-mediated rise in circulating FFA and glycerol availability, implying that ketone bodies may have repressed exercise’s lipolytic impact. β–OHB has been shown to block adipocyte lipolysis in vitro via the nicotinic acid receptor protein (PUMA-G/HM74a), which is activated in macrophages by interferon. Ketone body intake as a whole, is in itself, an alternative fuel source for working skeletal muscle and modify fuel choices during exercise. It is not known for sure if ketone bodies are the actual reason behind the liver not using the carb as fuel source during workouts. It is also not clear if ketone bodies can boost IMTAG consumption as a fuel or reduce lipolysis and FFA availability during exercise.