Ultra-processed food consumption and the trajectory of cardio-renal-metabolic multimorbidity: insights from multi-state modelling.

Background: The global increase in ultra-processed food (UPF) consumption has been associated with individual cardio-renal-metabolic (CRM) diseases, but its role in multimorbidity progression remains unclear. Objective: This study aimed to examine the relationship between UPF intake and transitions across successive CRM disease stages. Methods: We included 115 745 UK Biobank participants free of CRM diseases at the baseline, each completing at least two 24-hour dietary assessments. Multi-state models were applied to estimate associations between UPF consumption and transitions from disease-free status to first, double, and triple CRM conditions. Substitution analyses were used to assess the impact of replacing UPFs with unprocessed or minimally processed foods (UNPFs). Results: Over a median follow-up of 13.7 years, 16 114 participants developed incident CRM disease, with 2274 progressing to double and 227 to triple multimorbidity. An interquartile range increase in UPF intake was linked to higher risks of developing a first CRM disease (HR: 1.16; 95% CI: 1.14-1.19), progressing to double disease (HR: 1.13; 95% CI: 1.08-1.20), and advancing to triple disease (HR: 1.22; 95% CI: 1.05-1.43). The associations were primarily driven by UPF beverages and processed fruits/vegetables, whereas yogurts and whole-grain cereals showed neutral or inverse associations. Replacing 15% of UPF intake with UNPFs was associated with a 13% reduction in the risk of developing a first CRM disease and a 17% reduction in the risk of progressing to triple disease, with the most significant benefits observed in lean individuals. Conclusions: UPF consumption is associated with CRM multimorbidity progression. Replacing UPFs with UNPFs may serve as a potential strategy for preventing the progression of CRM multimorbidity.