Circadian-oriented intermittent versus continuous enteral feeding is associated with differential circadian clock...

Circadian rhythm disruption is highly prevalent in critically ill patients and may be modulated by feeding patterns and environmental factors. This study aimed to investigate the effects of circadian-oriented intermittent versus continuous enteral feeding, implemented under different feeding-fasting timing and nocturnal light conditions, on circadian gene expression in critically ill patients. This single-center randomized controlled study was conducted in the anesthesiology and reanimation ICU of Ankara Training and Research Hospital between November 2023 and September 2025. Twenty-four patients who initiated enteral nutrition within 48 h of ICU admission were randomized to a circadian-oriented intermittent feeding protocol with reduced nocturnal light exposure (IF, n = 12) or continuous feeding under standard ICU conditions (CF, n = 12). Peripheral blood samples were collected on day 1 and day 7 at 08:00, 16:00, and 00:00 to assess BMAL1, CRY1, and PER2 gene expression. Circadian rhythmicity was analyzed using Fourier-based cosinor modeling to determine mesor, amplitude, and acrophase. Baseline demographic and clinical characteristics were comparable between groups. BMAL1 expression and its rhythmic parameters remained stable in both groups over time. In the IF group, CRY1 expression decreased at 08:00 with a reduction in mesor, without significant phase shift. In contrast, the CF group demonstrated a significant 6-h delay in CRY1 acrophase (p = 0.038), indicating altered circadian timing. PER2 expression showed modest reductions in the IF group, whereas it was significantly suppressed across all time points in the CF group, accompanied by decreased mesor values. No significant differences were observed in clinical outcomes, including ICU length of stay and 7-day mortality. Both feeding strategies were associated with alterations in circadian gene expression; however, continuous enteral feeding under standard ICU conditions was associated with greater disruption in circadian timing and suppression of negative feedback clock genes. Aligning enteral nutrition delivery with physiological feeding-fasting cycles may help preserve circadian rhythm organization, potentially acting as a peripheral zeitgeber. Larger studies are warranted to confirm these exploratory findings.Trial registration: Registered on 05/06/2025 at ClinicalTrials.gov (NCT07063303).