Riboflavin intake and kidney health: population evidence and mechanistic insights from NHANES and molecular docking analyses

Chronic kidney disease (CKD) constitutes a significant global public health challenge, with emerging evidence suggesting that riboflavin may confer renoprotective effects. However, the association between dietary riboflavin intake and CKD risk remains inadequately elucidated. To investigate this, we analyzed National Health and Nutrition Examination Survey (NHANES) 2005-2018 datasets using weighted multivariate logistic regression, interaction testing, stratified subgroup analyses, and curve fitting. Additionally, network pharmacology and molecular docking simulations were employed to identify and validate potential therapeutic targets. Our results showed that patients with CKD exhibited significantly lower riboflavin intake than their non-CKD counterparts (1.98 vs. 2.21 mg/d, <i>p</i> < 0.001). After full adjustment, each 1 mg/d increment in riboflavin intake was associated with an 18.8% reduced risk of CKD (adjusted OR = 0.812, 95% CI: 0.686-0.962). Individuals in the highest intake quartile had a 42.7% lower risk compared to the lowest quartile (adjusted OR = 0.573, 95% CI: 0.400-0.822). A non-linear dose-response relationship was observed, characterized by an inflection point at 1.66 mg/d, indicating a more pronounced protective effect at lower intake levels. Mechanistic investigations suggested that riboflavin's benefits may be mediated through interactions with key targets like caspase-3 (CASP3), Erb-B2 receptor tyrosine kinase 2 (ERBB2), and matrix metallopeptidase 9 (MMP9), implicating apoptotic and metabolic pathways. In conclusion, dietary riboflavin intake is inversely associated with CKD risk, particularly at lower concentrations, and strategic augmentation of intake represents a promising dietary intervention for CKD prevention and management.