Intermittent fasting protocols involving prolonged fasting periods (≥16 hours) reduce the frequency of amino acid availability, impair muscle protein synthesis, increase muscle protein breakdown over 24 hours, and negatively affect net muscle protein balance and long-term muscle mass maintenance in populations with anabolic resistance such as older adults or those in energy deficit.

When a person goes without food for 16 hours or more, insulin levels drop and glucagon rises, causing muscles to break down more protein and release amino acids. These amino acids are not used to build new muscle because the body lacks the repeated signals from meals to trigger muscle building. Instead, the excess amino acids get burned for energy and lost from the body. Without frequent protein intake, the muscle-building signal shuts off after a few hours and does not restart until the next meal, leading to more muscle loss than gain over 24 hours.