Ketosis and ketone bodies.

What the evidence shows

Cahill's 2006 review (Annual Review of Nutrition), building on his classic starvation studies, describes how the body shifts to fat- and ketone-based fuel during fasting and how β-hydroxybutyrate becomes a major energy substrate for the brain — the adaptation that allows humans to tolerate prolonged food deprivation. This fuel-switching account is the settled core of the topic.

Two 2017 reviews extended the picture beyond fuel. Newman and Verdin (Annual Review of Nutrition) describe β-hydroxybutyrate not merely as an energy carrier but as a signalling metabolite — for example, acting as an endogenous inhibitor of histone deacetylases — linking the metabolic state to gene regulation. Puchalska and Crawford (Cell Metabolism) similarly map the multi-dimensional roles of ketone bodies across fuel metabolism, signalling, and potential therapeutics. The de Cabo and Mattson 2019 NEJM review places this ketone rise at the centre of the fasting "metabolic switch."

What's uncertain

Therapeutic applications are still largely preliminary. Both 2017 reviews discuss possible roles for ketone bodies in conditions ranging from epilepsy to metabolic and neurodegenerative disease, but they present these as areas of active investigation and mechanistic plausibility, not as established clinical treatments derived from fasting.

Depth and timing vary widely between people. How quickly and how deeply an individual enters ketosis depends on glycogen status, activity, diet, and prior fasting experience, so generic hour-by-hour claims about "entering ketosis" are approximations rather than fixed thresholds.

Fasting ketosis is not the same as ketoacidosis. The physiological ketosis described in these reviews is a regulated, low-level state; it should not be conflated with diabetic ketoacidosis, a dangerous uncontrolled condition. The reviews treat these as distinct.