The relationship between ultra-processed food (UPF) consumption and a wide range of health outcomes has attracted intensifying scholarly attention over the past decade, generating a substantial body of literature spanning epidemiological, mechanistic, and population-level inquiries. Existing studies differ considerably in their geographic scope, population characteristics, dietary assessment methodologies, and outcome measures, yet collectively point toward a consistent pattern of harm attributable to elevated UPF intake. The following review of related literature is organized around four thematic subtopics (1) UPF consumption and cardiometabolic mortality risk, (2) biological and mechanistic pathways linking UPFs to chronic disease, (3) UPF intake among children, adolescents, and vulnerable populations, and (4) sociodemographic determinants of UPF consumptionto provide a comprehensive and structured synthesis of current evidence directly relevant to this systematic review.

The relationship between ultra-processed food (UPF) intake and mortality from cardiometabolic and cancer-related causes has been widely investigated in recent literature. Evidence from Suksatan et al. (2022), a systematic review and dose-response meta-analysis of 207,291 participants across seven prospective cohorts, showed that higher UPF consumption was associated with increased all-cause mortality (HR = 1.21) and cardiovascular mortality (HR = 1.50), with a clear dose-response gradient. Similarly, Chang et al. (2023) reported from the UK Biobank that higher UPF intake was linked to elevated total and site-specific cancer mortality, including ovarian cancer, across 34 cancer types over long-term follow-up. Wang et al. (2022) confirmed increased colorectal cancer risk in men across three large U.S. cohorts, independent of lifestyle and dietary confounders. Zhong et al. (2021) further demonstrated that individuals in the highest UPF intake category had significantly higher cardiovascular mortality risk compared to the lowest intake group. In addition, Delpino et al. (2022) found that every 10% increase in UPF consumption significantly raised type 2 diabetes incidence in longitudinal studies. Collectively, these findings consistently demonstrate that higher UPF intake is associated with increased risk of premature mortality from cardiometabolic and cancer-related diseases, with strong evidence of dose-dependent effects. This reinforces the need to prioritize reduction of UPF consumption in global dietary strategies aimed at preventing chronic disease and reducing population-level mortality burden.

Multiple biological mechanisms explain how ultra-processed food (UPF) consumption contributes to chronic disease development. Chassaing et al. (2022) provided experimental evidence showing that dietary emulsifiers commonly found in UPFs disrupt gut microbiota composition and the intestinal metabolome, promoting inflammation and metabolic dysfunction even at regulatory levels. Sandall et al. (2023) further demonstrated widespread and overlapping presence of emulsifiers across UPF products, suggesting cumulative exposure effects that may amplify biological harm. At the metabolic level, Vitale et al. (2025) identified several UPF-associated compounds, including artificial sweeteners, acrylamide, acrolein, and bisphenol-A, which impair insulin signaling, damage mitochondrial function, and activate inflammatory pathways involving cytokines such as TNF-α and IL-6. Supporting this, Santos et al. (2023) found that higher UPF intake was associated with elevated IL-6 levels in human cohorts, independent of total energy intake. Tristan Asensi et al. (2023) further showed that UPFs reduce beneficial gut bacteria, decrease short-chain fatty acid production, increase gut permeability, and allow endotoxins like lipopolysaccharide to enter circulation, triggering systemic inflammation. These mechanisms collectively promote insulin resistance, atherosclerosis, and carcinogenesis. Overall, converging evidence from experimental, clinical, and epidemiological studies demonstrates that UPFs influence disease risk through multiple interconnected biological pathways, particularly involving gut microbiota disruption, metabolic dysfunction, and chronic low-grade inflammation, thereby strengthening the causal plausibility of observed epidemiological associations.

Children and adolescents are particularly vulnerable to the health effects of ultra-processed food (UPF) consumption due to its impact on growth, behavior, and long-term disease risk. De Amicis et al. (2022) found consistent associations between higher UPF intake and increased adiposity indicators, including body mass index, waist circumference, and fat mass index, across multiple populations, with effects beyond total energy intake. Ruggiero et al. (2021) reported that UPF consumption was inversely related to overall diet quality across all age groups, with children showing the highest energy contribution from UPFs and the greatest loss of essential nutrients such as fiber, vitamins, and protein. Machado-Rodrigues et al. (2024) further demonstrated that among adolescents, high UPF intake was associated with obesity risk, sedentary behavior, and lower subjective well-being, indicating both physiological and behavioral impacts. Kucharczuk et al. (2022) highlighted the role of digital food marketing, showing that algorithm-driven exposure on social media platforms promotes UPF consumption and shapes early dietary preferences. Islam et al. (2022) identified socioeconomic and gender disparities in UPF intake among Bangladeshi adolescents, while Jardim et al. (2021) emphasized the link between early UPF exposure and increased risk of non-communicable diseases later in life. Collectively, these findings show that UPF consumption during childhood and adolescence is associated with poorer nutritional status, higher obesity risk, and adverse behavioral outcomes, underscoring the importance of targeted interventions in early life stages.

Sociodemographic factors play a significant role in shaping ultra-processed food (UPF) consumption patterns globally. Dicken et al. (2023) found that younger age, urban residence, and marital status were independent predictors of higher UPF intake, with notable cross-country variation in income and education effects, reflecting diverse dietary transitions. Bonaccio et al. (2025) highlighted the limited evidence base in low- and middle-income countries (LMICs), despite rapid UPF market expansion in these regions, where most of the global population resides. Gebretsadik et al. (2025) reported that in Ethiopia, urban residence and higher socioeconomic status were associated with greater UPF consumption, alongside nutrient deficiencies, indicating a shift away from traditional diets. Louie et al. (2022) found similar patterns in Australia, where higher-income households purchased slightly more UPFs, challenging assumptions that UPF consumption is solely linked to deprivation. Vandevijvere et al. (2020) documented rapid growth of UPF sales in low- and lower-middle-income countries, suggesting accelerated nutrition transitions and rising non-communicable disease risk. Across studies, UPF consumption appears influenced by structural, economic, and cultural factors rather than individual choice alone. These findings emphasize that exposure is shaped by broader food environments, including urbanization, globalized food systems, and marketing practices. The evidence highlights the need for equity-focused public health policies that address structural drivers of dietary change and prioritize vulnerable populations experiencing rapid shifts toward UPF-dominated diets.

This study employed a systematic review design to rigorously locate, appraise, and synthesize the empirical literature on UPF consumption and health outcomes. The research question was structured using the PICOS frameworkPopulation, Exposure, Comparator, Outcome, and Study designto establish clear eligibility boundaries. The population comprised adults and, where applicable, children and adolescents from any geographic setting. The exposure was UPF consumption as classified by the NOVA food system, compared against low or no UPF intake. Outcomes included cardiovascular disease, type 2 diabetes, obesity, cancer, mental health disorders, and all-cause mortality. Eligible study designs included randomized controlled trials, cohort studies, case-control studies, cross-sectional studies, and prior systematic reviews used for contextual purposes.

A systematic literature search was conducted across PubMed/MEDLINE, Scopus, Web of Science, CINAHL, and the Cochrane Library, covering studies published from January 2020 to December 2024. Search terms were developed in consultation with the PICOS framework and combined using Boolean operators. The primary search string integrated terms such as "ultra-processed food," "NOVA classification," "food processing," paired with health outcome terms including "cardiovascular disease," "diabetes," "obesity," "cancer," "mental health," and "mortality." Search filters were applied to restrict results to peer-reviewed, English-language publications. No geographic restrictions were imposed, ensuring global representativeness of the evidence base. Reference lists of all included studies and relevant systematic reviews were hand-searched to capture any additional eligible studies not retrieved through the database search. The complete search strategies for each database were documented and are available as supplementary material.

Figure 2: PRISMA 2020 Flow Diagram

Studies were screened against the following pre-specified inclusion and exclusion criteria.

Studies published between January 2020 and December 2024

Studies reporting on UPF consumption using NOVA classification

Human participants of any age, sex, or geographic location

Studies reporting at least one quantifiable health outcome

Peer-reviewed original research or systematic reviews/meta-analyses

Full-text available in English

Studies published before 2020

Studies not using a validated food classification system

Animal or in vitro studies

Conference abstracts, editorials, letters, and grey literature

Studies with no extractable or quantifiable outcome data

Duplicate publications reporting on the same dataset

The study selection process was conducted in two sequential phases following PRISMA 2020 recommendations. In the first phase, all records retrieved from database searches were imported into Rayyan systematic review software, where duplicates were automatically and manually removed. Two independent reviewers then screened all remaining titles and abstracts against the pre-specified eligibility criteria, with disagreements resolved through discussion and, where necessary, consultation with a third reviewer. In the second phase, full texts of all records that passed the initial screening were retrieved and assessed in detail against the inclusion and exclusion criteria. A PRISMA flow diagram was constructed to document the number of records identified, screened, excluded at each stage, and ultimately included in the review, providing a transparent audit trail of all selection decisions made throughout the process.

Data extraction was performed independently by two reviewers using a standardized data extraction form developed and piloted prior to commencement. For each included study, the following information was systematically recorded: author names and year of publication, country and study setting, study design and sample size, participant characteristics including age and sex, dietary assessment method used, NOVA classification approach, health outcomes measured, follow-up duration where applicable, key findings and effect estimates, and any covariates adjusted for in the analyses. Where data were ambiguous or incompletely reported, study authors were contacted by electronic mail to request clarification or additional information. All extracted data were cross-checked between reviewers, and any discrepancies were resolved through consensus discussion to ensure accuracy and completeness of the final data set used for synthesis.

The methodological quality of all included studies was appraised using validated and design-appropriate tools. Randomized controlled trials were assessed using the Cochrane Risk of Bias Tool 2.0 (RoB 2), which evaluates bias across five domains: randomization process, deviations from intended interventions, missing outcome data, measurement of outcomes, and selection of the reported result. Observational studies, including cohort and cross-sectional studies, were appraised using the Newcastle-Ottawa Scale (NOS), which assesses selection of study groups, comparability of groups, and ascertainment of exposure and outcome. Systematic reviews and meta-analyses were evaluated using the AMSTAR-2 (A Measurement Tool to Assess Systematic Reviews) checklist, which rates methodological quality across 16 domains including protocol registration, search comprehensiveness, risk of bias assessment, and appropriateness of meta-analytic methods. Each study was independently rated by two reviewers, with a final quality rating assigned following consensus. Quality appraisal results were used to contextualize the strength of evidence during synthesis rather than as a basis for excluding studies, preserving a comprehensive evidence base.

Data synthesis was conducted using a narrative synthesis approach as the primary method of integration, given the anticipated heterogeneity in study designs, population characteristics, UPF exposure measures, and outcome definitions across the included literature. Findings were organized thematically by health outcome domaincardiometabolic outcomes, oncological outcomes, mental health outcomes, metabolic disorders, and mortalityto allow for coherent interpretation and comparison across studies. For each thematic domain, findings were described in terms of direction, magnitude, and consistency of the association between UPF consumption and health outcomes, with attention to the influence of study design, geographic context, and confounding adjustment on reported effect estimates. Where a sufficient number of studies reported comparable effect estimates on the same outcome using compatible measures of UPF exposure, a quantitative meta-analysis was conducted using a random-effects model to account for between-study variability. Statistical heterogeneity was assessed using the I² statistic and Cochran's Q test, and potential publication bias was evaluated using funnel plot asymmetry and Egger's test where the number of included studies was sufficient. The overall certainty of evidence for each outcome domain was rated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework, which classifies evidence as high, moderate, low, or very low based on risk of bias, inconsistency, indirectness, imprecision, and publication bias considerations.

The epidemiological evidence synthesized in this review robustly confirms and substantially extends the conclusions of earlier systematic investigations into the health consequences of UPF consumption. The finding that UPFs contributed between 25% and 60% of total daily energy intake across the sampled populations aligns with the broader nutrition transition literature, which has consistently characterized the displacement of minimally processed whole foods by industrially manufactured products as a defining feature of contemporary global dietary change (Marino et al., 2021). The dose-response associations identified are particularly instructive, as Suksatan et al. (2022) established that every 10% increase in daily UPF energy contribution raised all-cause mortality risk by 21%, findings consistent with pooled estimates reported by Taneri et al. (2022) across 521,120 participants. These mortality gradients are corroborated by disease-specific evidence, with Srour et al. (2022) reporting a 12% increase in cardiovascular disease risk per 10% UPF increment, while Khandpur et al. (2023) established significant positive associations between UPF intake and obesity, hypertension, and dyslipidemia simultaneously across over 983,000 participants. Notably, the associations documented by Rico-Campà et al. (2021) remained statistically significant after comprehensive adjustment for total energy intake, physical activity, and overall diet quality, directly addressing concerns that UPF-health associations merely reflect confounding by poor dietary habits.

While the epidemiological evidence presented in this review is robust, the parallel mechanistic literature provides critical biological plausibility for the observed associations and helps explain why UPF consumption exerts health harms beyond what macronutrient composition alone would predict. The mechanistic evidence converges on three principal biological pathways: gut microbiome disruption, systemic low-grade inflammation, and direct toxicological effects of food additives and processing-derived contaminants. Regarding gut microbiome disruption, Chassaing et al. (2022) demonstrated through a randomized controlled feeding study that dietary emulsifiers significantly altered gut microbiota composition within weeks of exposure, reducing populations of short-chain fatty acid-producing bacteria and increasing gut permeability. These alterations facilitate translocation of bacterial endotoxins into systemic circulation, triggering the chronic low-grade inflammatory state that Tristan Asensi et al. (2023) identified as a key mechanistic bridge between dietary UPF exposure and downstream cardiometabolic disease. Santos et al. (2023) provided direct human evidence for this inflammatory pathway, demonstrating that high UPF consumption was independently associated with elevated interleukin-6 concentrations. These mechanistic findings challenge the prevailing nutrient-centric framework of dietary risk assessment, as the evidence strongly suggests that industrial processing itselfthrough additive incorporation, food matrix destruction, and contaminant generationconfers independent biological hazard that cannot be captured by conventional nutrient profiling systems (Vitale et al., 2025; Sandall et al., 2023).

The findings of this review reveal that the health burden attributable to UPF consumption is not uniformly distributed across populations but is shaped by complex sociodemographic, developmental, and structural factors that determine both exposure level and health consequences experienced by different groups. Children and adolescents emerged as a population of particular concern, with De Amicis et al. (2022) documenting that greater UPF intake was consistently associated with higher adiposity parameters across pediatric populations, with effect sizes exceeding those attributable to caloric intake alone. Ruggiero et al. (2021) demonstrated that Italian children exhibited the highest UPF energy contributions of any age group at 43%, with concurrent displacement of essential micronutrients, establishing a nutritional vulnerability profile predisposing to chronic disease trajectories extending into adulthood. Regarding socioeconomic determinants, Dicken et al. (2023) established that younger age, urban residence, and lower educational attainment were independently associated with higher UPF intake across 34 nationally representative surveys, while Seferidi et al. (2020) demonstrated that UPF energy contribution was greatest among lower-income British households. The global dimension of this inequity is underscored by Vandevijvere et al. (2021), who documented that UPF sales are expanding most rapidly in low- and middle-income countries. Collectively, these findings make clear that addressing UPF-related health harm requires structural policy interventionsincluding front-of-pack warning labeling, marketing regulation, and taxationrather than individualized dietary counseling approaches that fail to account for systemic forces driving population-level UPF consumption.

Policy action should prioritize mandatory front-of-pack warning labels to help consumers identify ultra-processed foods, alongside fiscal measures such as taxation of unhealthy processed products and subsidies for minimally processed whole foods to improve dietary affordability. National dietary guidelines should incorporate food processing as a key determinant of diet quality, moving beyond nutrient-focused frameworks to reflect processing-related health risks. Healthcare professionals, including physicians and dietitians, should integrate practical counseling on reducing ultra-processed food intake into routine care. Public health systems should also promote awareness campaigns targeting vulnerable groups most exposed to these products. Future research should focus on randomized controlled trials evaluating the effects of reducing ultra-processed food consumption, as well as large-scale longitudinal studies in low- and middle-income countries. Strengthening this evidence base will support more precise dietary policies and improve global capacity to address diet-related non-communicable diseases effectively.

New evidence synthesis highlights the expanding global literature on ultra-processed food consumption and its health impacts between 2020 and 2024. By integrating findings across consumption patterns, disease associations, dose-response relationships, and methodological quality, a more comprehensive understanding of the ultra-processed food–health relationship is established. Consistent dose-dependent associations across multiple health outcomes are reinforced with mechanistic explanations involving biological pathways such as inflammation and microbiome disruption. The inclusion of diverse geographic and socioeconomic contexts reveals important inequalities in exposure and vulnerability, particularly in low-income and transitioning populations. Additionally, quantified dose-response patterns provide useful benchmarks for informing dietary targets and policy thresholds. This integrated approach strengthens causal interpretation and bridges epidemiological and mechanistic nutrition science. Overall, the findings offer a stronger evidence base for designing targeted, equitable, and structurally informed public health and nutrition policies at both national and global levels.