Association between night fasting duration and inflammatory biomarkers in European children and adolescents: a cross-sectional analysis within the I.Family study

Abstract Background Night fasting has been proposed as a potential modulator of inflammatory processes, yet evidence in pediatric populations is scarce. Moreover, individual metabolic status may influence inflammatory responses to fasting. The objective of the study was to explore the association between night fasting duration and circulating inflammatory biomarkers in children and adolescents, and to determine if weight status modulates this relationship, using data from the I.Family study. Methods This cross-sectional analysis (years: 2013–2014) included 1027 participants (mean age 11.4 years, SD 1.8) from the I.Family study. Night fasting duration was calculated as the interval between the last caloric intake prior to blood sampling (reported by parents/participants at the examination visit) and the time of venipuncture. Circulating inflammatory biomarkers, specifically high-sensitivity C-reactive protein (hs-CRP), interferon gamma-induced protein 10 (IP-10), interleukins (IL-15, IL-6, IL-8), tumor necrosis factor-alpha (TNF- $$\:\alpha\:$$ ), and interleukin-1 receptor antagonist (IL-1Ra), were quantified in fasting blood samples. Associations between fasting duration and biomarkers were examined using linear regression models, adjusted for age, sex, country of residence, physical activity, sleep duration, daily energy intake, fasting insulin, and body mass index (BMI) z-score. Stratified analyses by BMI status were performed. Sensitivity analyses excluded sleep duration and were restricted to participants fasting ≥ 6 h. Results The analytical sample comprised 44% females, presenting a mean BMI z-score of 0.41 (SD 1.09). In normal-weight participants, longer night fasting was associated with higher interleukin-1 receptor antagonist (IL-1Ra) concentrations ( β = 5.34, 95% CI: 0.80, 9.87) and lower interleukin-6 (IL-6) concentrations ( β = -0.01, 95% CI: -0.02, -0.00). Interleukin-15 (IL-15) showed a consistent decrease with longer fasting duration in the overall sample and in participants fasting ≥ 6 h. Conversely, no consistent linear associations were observed in participants with overweight or obesity. Conclusions Prolonged night fasting in normal-weight youth was associated with a favourable, albeit subclinical, anti-inflammatory profile characterized by higher IL-1Ra and lower IL-6 concentrations. IL-15 concentrations showed a uniform, modest linear decline with extended fasting across the study population. These exploratory results suggest that obesity may blunt the basal immune-metabolic adaptation to nocturnal catabolism. Further longitudinal research is required to establish causality and determine the long-term clinical implications. Clinical trial number The IDEFICS/I.Family cohort is registered under ISRCTN62310987 ( https://www.isrctn.com/ISRCTN62310987 ).