Hepcidin Levels Peak in the Afternoon and Evening Hours
Hepcidin concentrations display a clear diurnal rhythm, with levels being lowest in the early morning and steadily increasing throughout the day before declining during the evening hours. 1 This pattern makes afternoon to evening the time when hepcidin levels typically reach their peak.
Diurnal Variation of Hepcidin
Hepcidin is a 25-amino acid peptide considered to be the principal iron-regulatory hormone in the body. It plays a crucial role in iron homeostasis through the following mechanisms:
- Binds to ferroportin (found in macrophages and on the basolateral surface of enterocytes)
- When bound, causes ferroportin to be internalized and degraded
- Inhibits iron export from macrophages and enterocytes 2
The diurnal rhythm of hepcidin has been well-documented using sensitive and specific measurement techniques:
- Morning: Lowest levels
- Afternoon/Evening: Progressive increase throughout the day, reaching peak levels
- Night: Begins to decline 1
This pattern appears to be independent of food intake, suggesting an intrinsic circadian regulation rather than a response to meals.
Factors Affecting Hepcidin Levels
Several factors can influence hepcidin concentrations beyond the natural diurnal variation:
Physiological Regulators
- Iron status: Increased iron stores and plasma iron stimulate hepcidin production 2
- Erythropoiesis: Increased erythropoietic activity suppresses hepcidin 3
- Inflammation: Inflammatory states upregulate hepcidin expression 2, 3
- Hypoxia: Decreases hepcidin expression 2
External Factors
- Fasting: Prolonged fasting (3 days) can increase hepcidin concentrations approximately 3-fold 1
- Growth hormone: Administration decreases hepcidin concentrations by approximately 65%, likely by stimulating erythropoiesis 1
Clinical Implications
Understanding the diurnal variation of hepcidin has important clinical implications:
- Timing of measurements: For accurate assessment of iron status, hepcidin measurements should ideally be taken at consistent times of day
- Interpretation of results: Clinicians should consider the time of day when interpreting hepcidin levels
- Iron supplementation: Theoretically, iron supplements might be more effectively absorbed in the morning when hepcidin levels are lowest
Measurement Considerations
When measuring hepcidin levels, several methodological considerations are important:
- Various assay types exist, including radioimmunoassays, ELISAs, and mass spectrometry methods 4
- Mass spectrometry methods are more specific for the biologically active hepcidin-25 but are more complex and costly 4
- Standardization of hepcidin assays remains challenging, which can affect the comparability of results between different studies 2
In conclusion, for accurate assessment of hepcidin levels, samples should ideally be collected at consistent times of day, with the understanding that levels will naturally be higher in the afternoon and evening compared to early morning.