ULTRA-PROCESSED FOODS:FROM NUTRITIONAL CHARACTERISTICS TO THE IMPACT ON HUMAN HEALTH

Historically, nutritional science has focused on individual nutrients or bioactive compounds as determinants of health. While this reductionist approach led to major discoveries, such as the prevention of nutrient deficiencies, it proved inadequate for addressing complex chronic diseases, where the effects of foods depend on the interactions between multiple components and the broader dietary context. Consequently, the field has shifted toward studying whole foods, and more recently the overall dietary pattern, intended as adequate portion and frequencies of consumption of foods. It has been argued that the issue from the point of human health is not nutrients nor foods, as the type, degree and purpose of processing. In this context, the NOVA classification introduced the concept of “ultra-processed foods”. Although this framework has been widely adopted, its scientific robustness and reproducibility remain under debate. This PhD thesis aimed to explore the role of food processing, serving sizes, and UPFs in shaping food-based dietary guidelines (FBDGs) and influencing human health. The research comprised four main components. The first section of the work included a global scoping review of 100 national FBDGs. This first review revealed large variability in how countries define serving sizes and consumption frequencies, ranging from quantitative to purely qualitative formats, with limited harmonization. These inconsistencies hinder effective public health communication and cross-country comparability. The second review of this first section consisted in the analysis of terminology and wording related to food processing in worldwide FBDGs. In total, 75 national guidelines were investigated. Among the 89% of documents referring to processing, 25% mention UPFs and fewer cite the NOVA system, reflecting conceptual ambiguity and uneven integration of processing-related terminology in policy documents. In view to the fact that industrial foods are often perceived with a lower nutritional quality and safety with respect to home-made preparations, the second section of this work is a comparative experimental analysis of home-made versus industrially produced foods (plum cake, fish sticks, tomato sauce, cereal bars). This study demonstrated that when the same ingredients and methods are used, nutritional composition and contaminants levels (e.g., acrylamide) are largely comparable. These findings challenge the assumption that industrial foods are intrinsically less healthy or less safe than home-made equivalents. Moreover, based on the consideration that most current evidence on UPF derives from observational studies, in the third section of this thesis a systematic review of randomized controlled trials on UPF consumption was performed. The analysis revealed heterogeneous methodologies and inconclusive results, though some studies suggested higher energy intake and adverse changes in body composition with UPF-rich diets supporting that nutritional quality of diet play a pivotal role in determining the effect on human health. Finally, in the last section, the PROMENADE randomized controlled crossover trial evaluated the inclusion of five daily UPF servings within an isocaloric Mediterranean diet (MD) in overweight adults. Preliminary data showed no adverse effects on anthropometric, or lipid parameters after 12 weeks, suggesting that moderate UPF inclusion in a balanced MD does not impair short-term cardiometabolic health. In conclusion, this thesis highlights that the health impact of a diet cannot be fully explained by the degree of processing alone. Instead, the overall dietary context, quality, and balance play a pivotal role. Therefore, further well-designed and rigorously conducted research is essential to inform future food policies, as relying solely on broad or unobjective classifications of food processing risks fostering confusion and misinterpretation rather than promoting clear, evidence-based public health guidance.