Elevated blood ketone levels are most often caused by accelerated ketone production but may also be caused by consumption of exogenous ketones or precursors.
When glycogen and blood glucose reserves are low, a metabolic shift occurs in order to save glucose for the brain which is unable to use fatty acids for energy. This shift involves increasing fatty acid oxidation and production of ketones in the liver as an alternate energy source for the brain as well as the skeletal muscles, heart, and kidney. Low levels of ketones are always present in the blood and increase under circumstances of low glucose availability. For example, after an overnight fast, 2–6% of energy comes from ketones and this increases to 30–40% after a 3-day fast.
The amount of carbohydrate restriction required to induce a state of ketosis is variable and depends on activity level, insulin sensitivity, genetics, age and other factors, but ketosis will usually occur when consuming less than 50 grams of carbohydrates per day for at least three days.
Neonates, pregnant women and lactating women are populations that develop physiological ketosis especially rapidly in response to energetic challenges such as fasting or illness. This can progress to ketoacidosis in the setting of illness, although it occurs rarely. Propensity for ketone production in neonates is caused by their high-fat breast milk diet, disproportionately large central nervous system and limited liver glycogen.