What Are Ketones?
Ketones are important respiratory fuel created from fatty acids and act as the main reserve fuel for the brain when glucose is low or in times of very high energy demand, such as a low-carbohydrate diet, prolonged exercise, or lactation. In fact, when ketones are abundant in the blood, such as during caloric restriction or a ketogenic diet, the brain can obtain up to 60% of its energy from their oxidation. This condition, known as nutritional ketosis, can be maintained for years, and is quite different from metabolic acidosis/pathological ketosis, which can arise in type I diabetes due to severe insulin deficiency.
Ketones do cross the blood-brain barrier and have been shown to be neuroprotective, promoting oxidative defense, NAD+/NADH ratio, and enhancing mitochondrial respiration. In addition to acting as an energy source for the brain, ketones also enhance cerebral blood flow. In a human intervention study involving 20 elderly subjects and young controls, administration of 30 grams MCT (Medium Chain Triglycerides) to increase ketone concentration resulted in an increased overall brain energy metabolism by 3%, without altering brain glucose consumption.
It has been shown in animals that ketone bodies can also replace glucose as a cellular signal in the central nervous system. Fasting in humans is associated with an increase in ketones. Conversely, administering ketones directly into the brain of rats results in body weight loss without changing food intake, nor affecting blood glucose levels or liver glycogen levels. Subcutaneous injections result in decreased food intake, specifically targeting a decrease in meal frequency and the time between meals.
In a randomized, controlled, crossover trial involving 15 healthy subjects, consumption of ketogenic esters after an overnight fast resulted in significantly decreased ghrelin, glucagon-like peptide 1 (GLP-1), and peptide tyrosine (PYY) compared to a dextrose control. Subjects also reported decreased hunger and desire to eat. Research studies involving athletes indicate that ketones also increase fat oxidation in the muscle during exercise, acting as an alternative fuel, even in the presence of carbohydrate and insulin. Additionally, they result in decreased plasma lactate concentrations, suggesting support for athletic endurance and muscle comfort.