From Autophagy to Clinical Practice: Fasting and Caloric Restriction

Fasting and caloric restriction (CR) are increasingly used to improve weight control and metabolic health, and they may also engage cellular maintenance pathways such as autophagy. Their clinical value, however, depends on whether patients can safely sustain the intervention. This narrative review synthesizes human evidence on practical factors that may improve fasting adherence or reduce ad libitum energy intake, including protein, hydration, dietary fiber, prebiotics, exogenous ketones, and caffeine. It also examines the relationship between fasting/CR and autophagy, disease-specific applications, measurement limitations, and clinical implementation.

Across human studies, protein, pre-meal water, viscous fiber, selected prebiotics, and replacement of caloric beverages show the most consistent potential to support satiety or reduce subsequent intake. Exogenous ketone esters may transiently reduce hunger when substantial ketonemia is achieved, whereas ketone salts and caffeine have less consistent behavioral effects. Fasting and CR activate nutrient-sensing pathways associated with autophagy, but direct evidence of tissue-specific autophagic flux in humans remains limited. The clinical meaning of autophagy is also context-dependent: enhancement may be favorable in some metabolic or neurodegenerative settings, while established tumors may use autophagy for survival.

Fasting and CR should therefore be viewed as selective therapeutic tools rather than universal prescriptions. Their responsible use requires a clear indication, individualized dosing, support for adherence, explicit contraindication screening, and ongoing monitoring of patient-centered outcomes.

Keywords: Fasting, caloric restriction, autophagy, time-restricted eating, appetite, energy intake, aging, metabolic health, autophagic flux