Table 4.

Diseases and mortality as outcomes.

Study Details			UPF Exposure			Outcomes		Results
Publication Author(s) Year	Study Type (Year) Setting	Population (Number)	Extraction Level	Relative exposure [UPF reference year]	Data Collection Method	Health Outcome	Data Collection Method	Key Findings
Cancer
Queiroz 2018 [81]	Case control study (2015) Brazil	Adult women Mean 53.1 years (n = 118)	Individual	UPF ≥ 5 day/week {NOVA.2010] [25]	98-item FFQ, 12-month recall	Breast cancer (BC)	Diagnosed BC	Regular consumption UPF (≥5 day/week) identified as risk factors for BC (OR = 2.35, 95% CI 1.08–5.12).
Fiolet 2018 [84]	Prospective Cohort (2017), 5 years median follow-up France	Adults ≥ 18 years Mean 42.8 (n = 104,980)	Individual	UPF % g (quartiles) [NOVA 2018] [30]	3 × 24-h records	Overall, breast, prostate, and colorectal cancer	Self-report or/physician contact	UPF contribution in proportion of grams ranged from 18.7% lowest quartile to 32.3% in highest. A 10% increase in proportion of UPF consumption associated with a significant increase in overall (HR = 1.12; 95% CI 1.06; 1.18; p for trend <0.001) and BC risk (HR = 1.11; 95% CI 1.02; 1.22, P trend = 0.02). No significant associations were found for prostate and colorectal cancers (p = 0.8 and p = 0.2, respectively).
Cardiovascular disease (CVD)
Srour 2019 [83]	Prospective cohort (2019), 5.2 years median follow-up France	Adults ≥18 years (n = 105,109)	Individual	UPF % grams (quartiles) [NOVA.2018] [30]	3 × 24 h records	Cardiovascular (CVD), coronary heart (CHD), cerebrovascular disease	Medical records, committee of doctors	UPF contribution averaged 17. 4% of total grams. A 10% increase in proportion of UPF consumption was associated with significant higher risk of overall CVD (HR = 1.12; 95% CI 1.05; −1.20, p < 0.001); CHD (HR = 1.13; 95% CI 1.10; −1.24, p = 0.02); and cerebrovascular disease (HR = 1.11; 95% CI 1.01–1.21; p = 0.02).
Type 2 Diabetes (T2D)
Srour 2019 [87]	Prospective cohort (2017), 6.0 years median follow-up France	Adults ≥ 18 Mean 42.7 years (n = 104,707)	Individual	UPF % g [NOVA.2018] [30]	3 × 24 h records	Type 2 Diabetes (T2D)	ICD-10 code or T2D medication	Mean UPF contribution was 17.3% by weight, and 29.95% by % E intake. A 10% increase in the proportion of UPF consumption was associated with a significant higher risk of T2D (HR = 1.15; 95% CI 1.06; 1.25; p = 0.001).
Mortality
Kim 2019 [94]	Prospective cohort (2011), 19 years median follow-up USA	Adults ≥20 years (n = 11,898)	Individual	UPF frequency (times/day) (quartiles) [NOVA.2018] [30]	81-item FFQ, and 24-h recall	All-cause mortality (ACM) CVD mortality	National death index. CVD items 100–169 ICD-10	Participants consumed UPF a mean 4 times/day. Individuals in the highest quartile of frequency of UPF consumption had significantly higher risk of ACM, (HR = 1.31; 95% CI 1.09; 1.58, p-trend = 0.001). No significant association was observed with CVD mortality.
Schnabel 2019 [86]	Prospective Cohort (2017), (median follow-up 7.1 years) France	Adults ≥ 45 years (n = 44,551)	Individual	UPF % g [NOVA 2018] [30]	3 × 24-h food record	ACM	National death registries. Causes by ICD-10	UPF contributed 14.4% total weight, and 29.9% total E intake. A 10% increase in the proportion of UPF consumption was associated with a significant higher risk of ACM 1.14 (95% CI, 1.04–1.27; p = 0.008).
Rico-Campà 2019 [91]	Prospective Cohort (2014), (median follow-up 10.4 years) Spain	Adults 20−91 years (n = 19,899)	Individual	UPF servings/day (quartiles) [NOVA.2016] [22]	136-item FFQ	ACM CVD mortality Cancer mortality	Next of kin/Registries	UPF consumption ranged from 1.4 servings a day in lowest quintile to 5.3 servings a day in highest quintile. Individuals in the highest quartile of UPF consumption were at higher risk of ACM (HR = 1.62; 95% CI 1.13; 2.33) than those in the lowest quartile. No significant associations were found for cardiovascular and cancer mortality.
Blanco-Rojo 2019 [92]	Prospective Cohort (2016), (mean follow-up 7.7 years) Spain	Adults Mean 46.9 years (n = 11,898)	Individual	UPF % total E intake (quartiles) [NOVA.2018] [30]	880-item FFQ	ACM	National Death Index	UPF contributed 24.4% total E intake. Individuals in the highest quartile of UPF consumption were at higher risk of ACM (HR = 1.46; 95% CI 1.04-2.05; P trend = 0.03), than those in the lowest quartile.

Results are presented for adjusted associations for potential confounders and statistically significant associations. NOVA refers to the food classification system [21] or earlier versions, as referenced; UPF: ultra-processed food (includes food and beverages); E:energy in calories or kilojoules; OR: odds ratio; FFQ: food frequency questionnaire; CI: confidence interval; HR: hazards ratio; food = food and beverages; BC = breast cancer; ICD-10:International Classification of Disease; CVDL cardiovascular disease, CHD: coronary heart disease; T2D:Type 2 diabetes; ACM: all-cause mortality.