This contrasts with ketoacidosis, an uncontrolled production of ketones that occurs in pathologic states and causes a metabolic acidosis, which is a medical emergency.

[2] This occurs during states of increased fatty acid oxidation such as fasting, starvation, carbohydrate restriction, or prolonged exercise.

[3] The liver itself cannot utilize these molecules for energy, so the ketone bodies are released into the blood for use by peripheral tissues including the brain.

[2] Ketoacidosis is distinct from physiological ketosis as it requires failure of the normal regulation of ketone body production.

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.

Propensity for ketone production in neonates is caused by their high-fat breast milk diet, disproportionately large central nervous system and limited liver glycogen.

Once inside the mitochondrion, the bound fatty acids are used as fuel in cells predominantly through beta oxidation, which cleaves two carbons from the acyl-CoA molecule in every cycle to form acetyl-CoA.

This utilization of oxaloacetate in gluconeogenesis can make it unavailable to condense with acetyl-CoA, preventing entrance into the TCA cycle.

[18] The counter-argument is that there is no physiological requirement for dietary carbohydrates, as adequate energy can be made via gluconeogenesis and ketogenesis indefinitely.

[19] Alternatively, the switching between a ketotic and fed state has been proposed to have beneficial effects on metabolic and neurologic health.

SGLT2 inhibitor medications have been associated with cases of euglycemic ketoacidosis – a rare state of high ketones causing a metabolic acidosis with normal blood glucose levels.

[21] Additionally, medications used to directly lower blood glucose including insulin and sulfonylureas may cause hypoglycemia if they are not titrated prior to starting a diet that results in ketosis.

[22] These may include headache, fatigue, dizziness, insomnia, difficulty in exercise tolerance, constipation, and nausea, especially in the first days and weeks after starting a ketogenic diet.

[7] Most adverse effects of long-term ketosis reported are in children because of its longstanding acceptance as a treatment for pediatric epilepsy.

[23] Ketosis induced by a ketogenic diet should not be pursued by people with pancreatitis because of the high dietary fat content.

Ketosis is also contraindicated in pyruvate carboxylase deficiency, porphyria, and other rare genetic disorders of fat metabolism.

[24] In dairy cattle, ketosis commonly occurs during the first weeks after giving birth to a calf and is sometimes referred to as acetonemia.

The elevated β-hydroxybutyrate concentrations can depress gluconeogenesis, feed intake and the immune system, as well as have an impact on milk composition.