Objective: To evaluate the existing meta-analytic evidence of associations between exposure to ultra-processed foods, as defined by the Nova food classification system, and adverse health outcomes. Design: Systematic umbrella review of existing meta-analyses. Data Sources: MEDLINE, PsycINFO, Embase, and the Cochrane Database of Systematic Reviews, as well as manually searching reference lists from 2009 to June 2023. Inclusion Criteria: Systematic reviews and meta-analyses of cohort, case-control, and/or cross-sectional study designs that evaluated the associations between exposure to ultra-processed foods and adverse health outcomes in humans across the lifespan. Results: The search identified 45 unique pooled analyses, including 13 dose-response and 32 non-dose-response associations (n=9,888,373). Overall, direct associations were found between exposure to ultra-processed foods and 32 (71%) health outcome domains spanning cardiometabolic, gastrointestinal, and respiratory conditions, cancer, mental health, and mortality. Based on a pre-specified evidence classification criteria, convincing evidence (Class I) supported direct associations between greater ultra-processed food exposure and higher risks of incident cardiovascular disease-related mortality (RR: 1.50; 95%CIs: 1.37 to 1.63), type two diabetes (dose-response RR: 1.12; 95%CIs: 1.11 to 1.13), and depressive outcomes (HR: 1.21; 95%CIs: 1.16 to 1.28), as well as higher risks of prevalent anxiety outcomes (OR: 1.48; 95%CIs: 1.37 to 1.59) and combined common mental disorder outcomes (OR: 1.53; 95%CIs: 1.43 to 1.63). Highly suggestive (Class II) evidence indicated that greater exposure to ultra-processed foods was directly associated with higher risks of incident all-cause mortality (RR: 1.21; 95%CIs: 1.15 to 1.27), heart disease-related mortality (dose-response HR: 1.66; 95%CIs: 1.51 to 1.84), and type two diabetes (OR: 1.40; 95%CIs: 1.23 to 1.59), together with higher risks of prevalent obesity (OR: 1.55; 95%CIs: 1.36 to 1.77), adverse sleep-related outcomes (OR: 1.41; 95%CIs: 1.24 to 1.60), and wheezing (RR: 1.40; 95%CIs: 1.27 to 1.55). Out of the remaining 34 pooled analyses, 21 were graded as suggestive or weak strength (Class III-IV) and 13 were graded as no evidence (Class V). Using the GRADE framework, 22 pooled analyses were rated as "Low" quality, with 19 rated as "Very Low” and four rated as "Moderate" quality. Conclusions: Higher exposure to ultra-processed food was associated with a greater risk of adverse health outcomes, especially cardiometabolic, common mental disorder, and mortality outcomes. These findings provide a rationale to evaluate the effectiveness of using population-based measures to target and reduce dietary exposure to ultra-processed foods for improved human health. Systematic Review Registration: PROSPERO CRD42023412732.

Background/Objectives: Ultra-processed food consumption has been shown to be linked with clinical cardiovascular disease. This study aims to examine the associations of ultra-processed food consumption with biomarkers for subclinical-level myocardial damage [high-sensitivity cardiac troponin I and T (hs-cTnI and hs-cTnT)] and myocardial stretch (NT-proBNP) in U.S. adults. Methods: We used data from 6615 U.S. adults aged ≥20 years without prevalent cardiovascular disease from the National Health and Nutrition Examination Survey 2001–2004. We identified ultra-processed food by applying the Nova classification to dietary recall data, and we divided participants into quartiles based on their consumption, expressed as a proportion of total daily energy (%kcal) and gram intakes (%grams). We defined elevated cardiac biomarkers as hs-cTnI > 12 ng/L in men and >10 ng/L in women, hs-cTnT ≥ 14 ng/L for all participants, and NT-proBNP ≥ 125 pg/mL for age < 75 y and ≥450 pg/mL for age ≥ 75 y. We used multivariable logistic regression with adjustment for socio-demographic, total energy intake, behavioral, and clinical characteristics. Results: Higher ultra-processed food intake in %grams was associated with elevated NT-proBNP [odds ratio (OR) for quartile 4 vs. 1: 1.27, 95% CI: 1.00–1.61] when socio-demographic characteristics and total energy intake were adjusted for, but this was not the case with hs-cTnI or hs-cTnT. Further adjusting for clinical characteristics attenuated the association with NT-proBNP (OR: 1.26, 95% CI: 0.98, 1.61). There was no consistent association between ultra-processed food in %kcal and elevated NT-proBNP, hs-cTnT, or hs-cTnI. Conclusions: Ultra-processed food consumption is associated with subclinical myocardial stretch, a precursor to early heart failure. This supports the potential risks of subclinical cardiovascular disease associated with consuming ultra-processed food.