Hormonal Dynamics Across Fasting and Feeding Phases

Endocrine System Responses to Fasting and Feeding

The endocrine system orchestrates comprehensive hormonal adjustments in response to feeding and fasting states, directing energy storage, mobilisation, and utilisation. This article examines key hormonal changes occurring during transitions between fed and fasted conditions, presented for educational understanding of endocrine regulation during intermittent fasting.

Insulin: The Storage Hormone

Fed-State Function: During feeding, elevated blood glucose stimulates pancreatic beta cells to secrete insulin. Insulin promotes glucose uptake into cells, glycogen synthesis (anabolism), protein synthesis, and lipid storage whilst inhibiting catabolic processes.

Fasting-State Suppression: As blood glucose declines during fasting, insulin secretion falls sharply. Low insulin levels signal the transition from anabolic (storage) to catabolic (mobilisation) metabolism.

Insulin Sensitivity: Research examining intermittent fasting and insulin sensitivity shows variable outcomes. Some studies report improved fasting insulin levels and insulin sensitivity measures following intermittent fasting protocols, though improvements often correlate with weight loss rather than the eating pattern per se.

Duration Dependence: Insulin suppression during fasting becomes progressively more pronounced as fasting extends beyond 4–6 hours, with minimal insulin secretion maintained beyond 12–16 hours to prevent hypoglycemia.

Glucagon: The Mobilisation Hormone

Counter-Regulatory Role: Glucagon, secreted by pancreatic alpha cells, rises in response to declining blood glucose and elevated sympathetic nervous system activity during fasting. Glucagon opposes insulin actions.

Hepatic Effects: Glucagon stimulates hepatic glycogenolysis (glycogen breakdown) and gluconeogenesis (glucose synthesis), maintaining blood glucose during fasting periods and preventing hypoglycemia.

Adipose Tissue Activation: Glucagon promotes lipolysis in adipose tissue, facilitating free fatty acid release into circulation for utilisation by muscles and other organs.

Fasting Duration Response: Glucagon levels increase progressively during fasting, with more pronounced elevations during extended fasting periods (16+ hours).

Growth Hormone (GH): Metabolic Adaptation

Fasting-State Elevation: Growth hormone secretion typically increases during fasting periods, particularly with extended fasting (12+ hours). GH release is stimulated by declining insulin, elevated amino acid ratios, and sleep-wake cycles.

Metabolic Effects: Growth hormone promotes lipolysis, inhibits insulin action (contributing to insulin resistance during fasting), and may support lean tissue preservation during energy restriction.

Protein Sparing: Some research suggests that elevated GH during fasting may reduce protein catabolism, potentially preserving muscle mass during prolonged energy deficit. However, this hypothesis remains incompletely tested in humans engaged in resistance training.

Individual Variation: Growth hormone responses to fasting vary substantially between individuals based on age, fitness level, sleep patterns, and baseline metabolic characteristics.

Catecholamines: Sympathetic Activation

Norepinephrine and Epinephrine: Fasting periods trigger increased sympathetic nervous system activity, elevating circulating norepinephrine and epinephrine (catecholamines). These hormones promote lipolysis, increase heart rate and blood pressure, and enhance metabolic rate.

Duration-Dependent Activation: Catecholamine elevations are typically modest during short-term fasting (4–8 hours) but increase during extended fasting periods. Some studies report catecholamine elevation during the transition into fasting (first 12–24 hours of time-restricted eating).

Metabolic Rate Impact: Elevated catecholamines during fasting may produce modest increases in metabolic rate, partially offsetting the caloric deficit created by reduced food intake. However, this effect is typically small (10–15% elevation at most) and diminishes with prolonged or repeated fasting.

Habituation: With repeated fasting practice, catecholamine responses may diminish as the body adapts to recurrent fasting periods, reducing the metabolic rate elevation observed with novel fasting.

Cortisol: Stress Hormone Response

Fasting-State Elevation: Cortisol, the primary glucocorticoid hormone, typically increases during fasting periods, particularly with extended fasting (16+ hours). Cortisol supports gluconeogenesis and mobilises amino acids from muscle protein.

Circadian Interaction: Cortisol exhibits a strong circadian rhythm, with peak levels early morning and nadir levels at night. Fasting timing relative to circadian phase influences cortisol response patterns.

Chronic Elevation Concern: Persistently elevated cortisol from chronic fasting or caloric restriction may have metabolic and immunological consequences. However, research on intermittent fasting protocols suggests cortisol elevations remain modest and intermittent rather than chronically elevated.

Appetite Hormones: Ghrelin and Leptin

Ghrelin (Hunger Promoter): Ghrelin, secreted primarily by gastric mucosa, increases during fasting and promotes appetite signalling to the brain. Ghrelin levels typically peak during expected meal times and decline during eating windows.

Ghrelin Adaptation: Interestingly, ghrelin elevation during intermittent fasting is often temporary. Some research suggests that habitual practitioners of time-restricted eating show reduced ghrelin responses after several weeks of practice, potentially facilitating hunger adaptation.

Leptin (Satiety Signal): Leptin, produced by adipose tissue, declines during fasting and energy restriction. Lower leptin signalling to the brain reduces satiety perception and increases appetite drive. Leptin reduction during caloric deficit persists over time, creating a sustained appetite pressure during prolonged energy restriction.

Individual Variation: Responses to ghrelin and leptin changes vary substantially. Some individuals experience reduced hunger despite rising ghrelin and falling leptin, whilst others report sustained or increasing appetite regardless of hormonal changes.

Temporal Hormone Patterns in Time-Restricted Feeding