When we say ketones, we are referring to the primary circulating fatty acid metabolites beta-hydroxybutyrate (βOHB) and acetoacetate (AcAc).
Hepatic (liver) production of these 4-carbon molecules increases when insulin levels are low and glucagon is high enough to result in accelerated lipolysis (release of fatty acids from adipose tissue triglycerides) and their transport via the bloodstream to the liver. Ketones are synthesized from the controlled cleavage of fatty acids in the liver, a process called ‘ketogenesis.’ Release of fatty acid-derived ketones into the circulation results in a metabolic state of ‘ketosis.’
The liver produces ketones all the time, but the rate of ketogenesis and magnitude of ketosis depends primarily on dietary carbohydrate and protein intake. If you consume enough carbohydrate and protein to elevate the hormone insulin to levels that inhibit fat breakdown (and make glucose the predominant fuel), then ketogenesis operates at idle, translating into blood ketone concentrations about 0.1 mmol/L. Most people following official dietary guidelines that emphasize carb-rich foods, be it ‘low fat’ or ‘Mediterranean,’ rarely experience ketones higher than 0.3 mmol/L. Nevertheless, the ketogenic process is always idling in the background, so they are always present in the circulation. At these low levels however, ketones don’t have much of a role in providing fuel nor do they exert signaling effects.
Read more in our deep dive on ketone basics here.