Nutrition, Diet, and Anti-aging: Ketogenic Diet and Anti-aging

A ketogenic diet is one where the daily intake of protein is ensured, carbohydrate intake is usually kept below 50 g/day, and about 60–80% of the total energy intake comes from fats. The main energy source shifts from carbohydrates to fats, leading to an increase in the production of ketone bodies (acetoacetic acid, acetone, and β-hydroxybutyric acid (βOHB)). This is why it is generally referred to as a ketogenic diet. Under a ketogenic diet, the increased dietary fat and decreased carbohydrate intake lead to low insulin levels, which in turn increase fat breakdown (lipolysis) in fat cells. The resulting fatty acids flow into the liver, undergo β-oxidation, and are converted to acetyl-CoA. This is then converted to HMG-CoA by mitochondrial hydroxymethylglutaryl (HMG)-CoA synthase 2 (HMGCS2), and further to β-OHB via acetoacetic acid. The βOHB produced in the liver is released into the circulating blood by the specific transporter SLC16A (Fig. 96.1). Therefore, most of the ketone bodies in circulation are βOHB. The ketogenic diet is thought to work through the effects of this increased βOHB and the effects based on low insulin levels due to carbohydrate restriction. In a state where a balanced diet is being consumed, the blood concentration of ketone bodies is several to tens of μM, but it is said to increase to 200–300 μM after about half a day of fasting, up to 6–8 mM after about 2 days of fasting, and up to 2–3 mM in a ketogenic diet.