This 2018 review describes the “metabolic switch” — the shift from glucose dependence and fat storage to fatty acid mobilization and ketone production that occurs once liver glycogen is depleted (typically after 12–36 hours without food). Frequent eating keeps insulin elevated and suppresses fat oxidation, whereas fasting lowers insulin and restores access to stored fuel. The authors argue that many benefits attributed to intermittent fasting — including improved insulin sensitivity, reduced inflammation, enhanced cardiovascular and cognitive function, and preservation of lean mass — stem from periodically entering this fat-burning state. They suggest inconsistent human results may reflect failure to actually achieve the switch, emphasizing that metabolic flexibility, not simply calorie reduction, is the true mechanism.

https://onlinelibrary.wiley.com/doi/10.1002/oby.22065