Fructose-sweetened beverages induce diurnal redox dysregulation in pediatric MASLD

Plasma glutathione/glutathione disulfide (GSH/GSSG) and cysteine/cystine (Cys/CySS) redox couples undergo diurnal variation in adults and are more oxidized in obesity-related conditions, including metabolic dysfunction-associated steatotic liver disease (MASLD). There is limited research on redox in children and no data on redox responses to sugars, despite high sugar consumption in this population. This study aimed to describe the diurnal variation of redox couples in children, assess the impact of MASLD, and evaluate responses to fructose versus glucose beverages. In a 2-day randomized, controlled, crossover feeding study, 26 children (12 with MASLD, 14 controls; aged 10–18 years) consumed isocaloric meals with fructose beverages (FB) on one day and glucose beverages (GB) (set as control) on another, following a washout period. Blood was collected every 2 hours over 24 hours and analyzed for Cys/CySS and GSH/GSSG. Redox potentials, E h (Cys/CySS) and E h (GSH/GSSG), were calculated using the Nernst equation. Linear mixed models assessed diurnal variation and effects of MASLD and beverage type. Plasma E h (GSH/GSSG) and E h (CyS/CySS) varied significantly over time after both FB and GB (p < 0.05). With FB, E h (GSH/GSSG) was significantly more oxidized in children with MASLD (p = 0.034); this was not observed with GB. Among children with MASLD, FB also led to greater E h (GSH/GSSG) oxidation and lower GSH levels overnight (p < 0.05). While E h (Cys/CySS) showed a similar trend, differences did not reach statistical significance. Our findings demonstrate that plasma redox states vary diurnally in children and are more oxidized in those with MASLD. Fructose intake increased oxidation of the GSH/GSSG redox couple and lowered GSH concentrations overnight, indicating heightened oxidative stress. These results identify fructose as a driver of redox imbalance in pediatric MASLD and support fructose reduction and glutathione restoration as therapeutic targets. • Plasma redox couples (Cys/CySS, GSH/GSSG) show diurnal variation in children • Children with MASLD display more oxidized plasma redox states across the day • Fructose intake increases oxidation of the GSH/GSSG redox couple in MASLD • Lower overnight GSH suggests decreased antioxidant capacity after fructose intake • Findings highlight fructose as a driver of redox imbalance in pediatric MASLD