Ultra-processed food consumption is associated with increased risk of all-cause and cardiovascular mortality in the Moli-sani Study

Am J Clin Nutr. 2021 Feb 2;113(2):446-455. doi: 10.1093/ajcn/nqaa299.


Background: Consumption of ultra-processed food (UPF) is gaining growing attention in relation to disease/mortality risk, but less is known on the main nutritional factors or biological mechanisms potentially underlying such associations.

Objectives: We aimed to assess the association between UPF and mortality risk in a large sample of the Italian adult population and test which nutritional factors were on the pathway of this relation. Established risk factors for cardiovascular disease (CVD) were analyzed as potential biological mechanisms linking UPF to mortality.

Methods: Longitudinal analysis was conducted on 22,475 men and women (mean ± SD age: 55 ± 12 y) recruited in the Moli-sani Study (2005-2010, Italy) and followed for 8.2 y. Food intake was assessed using a semiquantitative FFQ. UPF was defined using the NOVA classification according to degree of processing, and UPF intakes were categorized as quartiles of the ratio (%) of UPF (g/d) to total food consumed (g/d).

Results: Individuals reporting the highest intake of UPF (Q4, >14.6% of total food), as opposed to the lowest (Q1, UPF < 6.6%), experienced increased risks of CVD mortality (HR: 1.58; 95% CI: 1.23, 2.03), death from ischemic heart disease (IHD)/cerebrovascular disease (HR: 1.52; 95% CI: 1.10, 2.09), and all-cause mortality (HR: 1.26; 95% CI: 1.09, 1.46). High sugar content explained 36.3% of the relation of UPF with IHD/cerebrovascular mortality, whereas other nutritional factors (e.g., saturated fats) were unlikely to be on the pathway. Biomarkers of renal function accounted for 20.1% of the association of UPF with all-cause mortality, and 12.0% for that of UPF with CVD mortality.

Conclusions: A high proportion of UPF in the diet was associated with increased risk of CVD and all-cause mortality, partly through its high dietary content of sugar. Some established biomarkers of CVD risk were likely to be on the pathway of such associations. These findings should serve as an incentive for limiting consumption of UPF, and encouraging natural or minimally processed foods, as several national nutritional policies recommend.

Keywords: cardiovascular disease risk factors; cardiovascular mortality; cerebrovascular mortality; mortality; sugar; ultra-processed food.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / mortality*
  • Cohort Studies
  • Female
  • Food Handling*
  • Humans
  • Italy / epidemiology
  • Male
  • Middle Aged
  • Nutritive Value
  • Risk Factors