Combination of a traditional Mediterranean Diet with ultra-processed food consumption in relation to all-cause and cause-specific mortality: Prospective findings from the Moli-sani Study

Background & aims: Ultra-processed foods (UPFs) are increasingly displacing traditional diets with threatening health impacts. We therefore aimed to examine the association between different combinations of adherence to a traditional Mediterranean Diet (MD) and ultra-processed food (UPF) consumption with all-cause and cause-specific mortality amongst adult Italians. Methods: We prospectively analysed data from 22,939 men and women (mean age 55 ± 12 years) followed for 15.0 years (median). Food intake was assessed by a 188-item FFQ. UPF was defined following the Nova classification and calculated as a weight ratio. The Mediterranean Diet Score (MDS; range 0-9) was used to assess adherence to MD. Low/High MD adherence (i.e. MDS <6 or ≥6, respectively) was combined with low/high UPF consumption (i.e. <9.4 or ≥9.4, i.e. population median intake) to obtain a 4-level dietary variable resulting in the following dietary combinations: 1) low MD/high UPF; 2) High MD/high UPF; 3) Low MD/low UPF; and 4) High MD/low UPF. Results: When compared to the low MD/high UPF category, a high adherence to a traditional MD combined with low UPF consumption emerged as the optimal dietary pattern for reducing the risk of all-cause mortality (HR = 0.76; 95%CI 0.68-0.85), as well as cardiovascular (HR = 0.80; 95%CI 0.67-0.96) and non-cardiovascular/non-cancer mortality (HR = 0.57; 95%CI 0.47-0.70). An interaction between these two dietary factors was observed for ischemic heart disease (IHD)/cerebrovascular and non-cardiovascular/non-cancer mortality outcomes (p values for multiplicative interaction = 0.050 and 0.0011, respectively), indicating that these two dietary factors work synergistically. No association was found with cancer-related mortality. Conclusions: In a large cohort of adult Italians, a high adherence to a traditional MD combined with low consumption of UPFs was the optimal dietary combination for improved survival rates and lower non-cancer-related mortality. Dietary guidelines should emphasize the importance of reducing UPF consumption alongside following an MD to fully maximize its health benefits.