How ultra-processed foods modulate cardiometabolic risk: A 2 × 2 factorial randomized controlled trial protocol in healthy adults

BACKGROUND: Despite growing evidence linking overconsumption of ultra-processed foods (UPFs) to numerous adverse health outcomes, there is still no consensus regarding whether all UPFs are equally concerning for cardiovascular health, regardless of their nutrient profile. OBJECTIVE: This 2 × 2 factorial randomized controlled trial aim to determine which feature(s) of UPFs, namely their poor nutrient profile or their underlying industrial processes, contribute to cardiometabolic risk. METHOD: 120 adults, men and women, are randomly assigned to one of the four experimental 6-week diets: 1- Low-UPF diet (5% total energy) low in saturated fats (SFAs), added sugars and sodium; 2- Low-UPF diet (5% total energy) rich in SFAs, added sugars and sodium; 3- High UPF diet (75% total energy) low in SFAs, added sugars and sodium; 4- High UPF diet (75% total energy) rich in SFAs, added sugars and sodium. All foods and beverages are provided to participants under isoenergetic conditions. The high UPF diets are largely comprised of commercial foods with variable amounts of SFAs, added sugars and sodium. The low UPF diets are custom prepared with varying amounts of SFAs, added sugars and sodium to match the nutrient values of the high UPFs diets. Primary outcomes measured at baseline and post treatment are fasting LDL-C concentrations, insulin sensitivity (HOMA-IR) and daytime systolic ambulatory blood pressure (dtSBP). CONCLUSION: This randomized controlled trial will be the first to use fully controlled feeding conditions to disentangle out the individual effects of the industrial processing techniques from the poor nutrient content of UPFs on cardiometabolic risk. TRIAL REGISTRATION: ClinicalTrials.gov (ID NCT06538831), registered July 31, 2024.