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Liver glycogen is depleted within the first day of fasting, after which gluconeogenesis helps maintain glucose supply using substrates such as alanine, lactate, and glycerol. With continued fasting, muscle-sparing mechanisms reduce reliance on amino acids, while low insulin and increased counter-regulatory hormones support lipolysis and fatty-acid oxidation. The liver produces ketone bodies from excess acetyl-CoA; their use by the brain reduces its glucose requirement. The heart, skeletal muscle, and renal cortex can use fatty acids or ketones, whereas red blood cells still require glucose. Prolonged starvation also involves reduced energy expenditure and nitrogen loss, alongside depletion of intracellular electrolytes that can matter during refeeding. If fat stores become exhausted, rapid muscle breakdown can lead to severe organ injury.