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Formation and Utilization of Ketone Bodies; Ketoacidosis

In fasting and starvation conditions, the liver creates ketones in a process called gluconeogenesis, which produces glucose.

Formation and Utilization of Ketone Bodies

In fasting and starvation conditions, the liver creates ketones in a process called gluconeogenesis, which produces glucose. The liver produces three kinds of ketone bodies. This group of compounds consists of acetoacetate, beta-hydroxybutyrate, and acetone. Healthy individuals use these compounds when glucose levels are low or absent from their diets to provide energy to their cells.

In the figure above, you can see the three ketone bodies. The left picture shows acetone, the middle shows acetoacetate, and the right picture shows beta-hydroxybutyrate.


The body stores excess glucose as fat builds proteins, and in general, grows when glucose levels are high. The process is called "absorption." During fasting or starvation, your blood glucose levels rapidly decline. After absorption, our bodies enter a state called post-absorption. It then begins converting fat into fatty acids, glycogen into glucose, and even amino acids into energy as a result of this process. Glycogen, while a storage product of glucose, can be converted back to glucose within the body quickly, but only a limited amount is stored in the body (mainly in the liver). Upon depletion of these stores, energy must be retrieved from another breakdown product. Fat is broken down in the body into fatty acids, which are necessary to survive. The liver and brain, though, cannot survive off of fatty acids. Their preferred energy source is glucose. For the brain to receive glucose, the liver needs to make glycerol, pyruvate, lactate, amino acids, and glycerol into glucose. In addition to gluconeogenesis, acetoacetate and beta-hydroxybutyrate are also produced as ketone bodies. The brain is fuelled by ketone bodies and glucose released into the bloodstream. It is at this point that the muscles and other organs are mainly reliant on fatty acids for energy, leaving the brain with glucose. This is known as glucose sparing and is very beneficial to animals that are forced to fast or starve for extended periods. After about 4 days of starvation, the brain will switch to ketone bodies as a source of energy. A body may be able to go for longer periods without food, but there may be adverse side effects. Ketone bodies build up when the glucose supply is not replenished. However, if the kidneys are overworked with too many ketone bodies, they may not be able to clear them out.

Acetate is formed when the additional ketone bodies in the blood spontaneously break down. Acetone is a volatile and reactive chemical. When it builds up in the body, this substance lowers blood pH, causing acidosis. Nearly all body tissues are affected by acidosis, reducing their functionality and interfering with enzymes, which rely on a specific pH balance. A coma or death will result from ketoacidosis, which is an acidosis caused by excessive ketone bodies.


The diabetic ketoacidosis (DKA) is a serious complication in both type 1 and type 2 diabetes. Ketones are acidic substances that build up in your body when your blood sugar is very high. It's important to distinguish ketoacidosis from ketosis, which is harmless. Among the various ways to induce ketosis is to follow a low carbohydrate diet, or to fast. Diabetes ketoacidosis is a condition caused by low levels of insulin in your body. Insulin levels are less likely to drop so low in type 2 diabetics; however, it can still occur. Diabetics with type 1 diabetes cannot produce their insulin, so DKA may be the first sign of the disease.


You may notice these symptoms quickly if you have DKA:
  • Confusion
  • Abdominal pain
  • Fatigue
  • Frequent urination
  • Rapid breathing
  • Dry mouth as well as skin
  • Vomiting and nausea


In diabetic ketoacidosis, insulin levels are low as well as blood sugar levels as high as they can go. High blood sugar levels result in low insulin levels. A high blood sugar level causes DKA since glucose cannot enter the cells. By doing so, the body starts transforming fat into a fuel that requires no insulin. Ketones are that fuel. When the blood is high in ketones, it becomes acidic. The condition is known as diabetic ketoacidosis.

DKA is typically caused by:
  • (For those who use an insulin pump) a clog in it
  • Missing an insulin injection or not injecting enough insulin
  • Infection or illness
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Ankur Choudhary is India's first professional pharmaceutical blogger, author and founder of, a widely-read pharmaceutical blog since 2008. Sign-up for the free email updates for your daily dose of pharmaceutical tips.
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