Background: Circadian rhythms govern endocrine, metabolic, and immunological homeostasis. Early morning wakefulness, particularly between 04:00–05:00 AM, coincides with a transitional hormonal window that may influence systemic physiology and gene expression. Objective: This study aimed to evaluate the biochemical and molecular effects of early morning wakefulness on circadian hormone regulation, metabolic synchronization, and human systemic health. Methods: A randomized experimental study was conducted from August 2023 to September 2024 in five Indonesian regions with 210 healthy adults. Participants were randomized into an intervention group (early wakefulness at 04:00–05:00 AM for 4 weeks) and a control group (usual sleep patterns). Outcome measures included serum cortisol, melatonin, insulin, fasting glucose, β-hydroxybutyrate (BHB), and expression of core clock genes (BMAL1 (Brain and Muscle ARNT-Like 1) , PER2 (Period Circadian Regulator 2), CLOCK (Circadian Locomotor Output Cycles Kaput), CRY1 (Cryptochrome Circadian Regulator 1)) assessed via qRT-PCR (Quantitative Reverse Transcription Polymerase Chain Reaction) Results: The early wakefulness group exhibited a 45% increase in morning cortisol levels and a 30% reduction in melatonin (p < 0.001). Fasting glucose and insulin decreased significantly, while BHB levels increased (p < 0.05), indicating a metabolic shift. Clock gene expression showed significant upregulation of BMAL1 and PER2 (1.5-fold, p < 0.01), correlating inversely with HOMA-IR scores. Conclusion: Consistent early morning wakefulness positively modulates circadian hormonal dynamics, enhances metabolic flexibility, and upregulates key circadian genes, suggesting potential health benefits in metabolic and endocrine regulation. These findings provide molecular evidence supporting early wakefulness as a non-pharmacological intervention for circadian and metabolic alignment.
Agussalim Agussalim (2025) studied this question.