Once “keto-adapted,” many tissues increase their capacity to utilize ketones for fuel. Some tissues even prefer to use ketones for their cellular energy needs. For instance, the heart, as well as many areas of the brain, prefers to use ketone bodies as opposed to glucose. One interesting fact is that Dr. Stephen Cunnane found that the uptake of ketone bodies in the brain is proportional to their production. Additional research has also demonstrated that as uptake of ketones increases, the uptake of glucose decreases in brain tissue. In contrast, there are certain cells that cannot use fatty acids or ketone bodies, and are considered “obligate glucose users.” Red blood cells and specific parts of the brain are obligate glucose users. Don’t stress, however, because even though you may not be consuming a lot of carbohydrates, these cells can obtain glucose through a biological process called gluconeogenesis (the production of glucose from other non-glucose materials).
Carbohydrate-restricted ketosis: This type of ketosis mimics the same biological alterations seen during lengthy fasts, but without the complete restriction of food. Carbohydrate-restricted ketosis is achieved primarily through a very low-carbohydrate ketogenic diet. This restriction, in turn, results in reductions of insulin and blood glucose levels similar to that of fasting, which again increases blood ketone levels. For most individuals, nutritional ketosis is much more sustainable than fasting or starvation ketosis. Fasting can still have its place in a keto diet for beginners. Many individuals following a ketogenic diet like to implement a regular fasting protocol such as intermittent fasting (IF) (12–20 hours daily) or every-other-day fasts (EOD), depending on their goals. This practice is not critical for success on a ketogenic diet, but it can enhance the level of ketone production, and thus magnify the benefits.
On the ketogenic diet, carbohydrates are restricted and so cannot provide for all the metabolic needs of the body. Instead, fatty acids are used as the major source of fuel. These are used through fatty-acid oxidation in the cell's mitochondria (the energy-producing parts of the cell). Humans can convert some amino acids into glucose by a process called gluconeogenesis, but cannot do this by using fatty acids. Since amino acids are needed to make proteins, which are essential for growth and repair of body tissues, these cannot be used only to produce glucose. This could pose a problem for the brain, since it is normally fuelled solely by glucose, and most fatty acids do not cross the blood–brain barrier. However, the liver can use long-chain fatty acids to synthesise the three ketone bodies β-hydroxybutyrate, acetoacetate and acetone. These ketone bodies enter the brain and partially substitute for blood glucose as a source of energy.