Evidence linking UPF exposure to cardiometabolic outcomes is primarily derived from prospective observational studies. Across multiple cohorts, higher UPF exposure is consistently associated with greater weight gain over time and increased risk of overweight and obesity, with several studies reporting dose-response relationships across exposure categories (Machado et al., 2020[95]; De Amicis et al., 2022[30]; Moradi et al., 2023[115]; Vitale et al., 2024[157]; Lane et al., 2024[79]). Effect sizes, however, vary across studies, potentially reflecting differences in dietary assessment methods and the operationalization of the Nova classification. UPF exposure is most commonly expressed as the proportion of total energy intake derived from UPFs, although alternative metrics such as weight-based measures or servings have also been used.

Associations between UPF intake and type 2 diabetes have also been reported. In three large US cohorts, higher UPF intake was associated with increased diabetes incidence, independent of body mass index (BMI) and overall diet quality (Chen et al., 2023[23]). Similarly, in the EPIC cohort, each 10 % increase in energy intake from UPFs was associated with a 17 % higher risk of incident type 2 diabetes during long-term follow-up (Dicken et al., 2024[34]). Comparable findings have been observed in the UK Biobank, where diabetes risk increased per 10 percentage-point increment in UPF consumption assessed as a proportion of food weight (Levy et al., 2021[87]). At the evidence-synthesis level, the umbrella review by Lane et al. classified the association between UPF intake and type 2 diabetes as convincing, and a recent meta-analysis reported a 13 % higher diabetes risk for each 10 % increase in UPF consumption (Lane et al., 2024[79]; Souza et al., 2025[144]).

For cardiovascular outcomes, meta-analyses indicate a higher risk of hypertension, overall cardiovascular disease, and cerebrovascular disease among individuals with greater UPF consumption (Juul et al., 2021[73]; Chen et al., 2022[22]; Wang et al., 2022[159]; Yuan et al., 2023[169]; Qu et al., 2024[130]). Evidence is considered convincing for increased cardiovascular disease mortality, with up to a 50 % higher risk among individuals with the highest UPF exposure, and highly suggestive for increased all-cause mortality, with approximately 20 % higher risk (Lane et al., 2024[79]). A recent American Heart Association scientific advisory interpreted these associations largely as reflecting high intake of nutritionally poor UPFs that overlap with foods rich in unhealthy fats, added sugars, and sodium, while noting the need for further research to disentangle the potential roles of additives and food matrix alterations (Vadiveloo et al., 2025[155]). Further, while the advisory also reinforced existing cardiovascular guidance favoring minimally processed, nutrient-dense foods within overall dietary patterns, they acknowledged heterogeneity within the UPF category, noting that some affordable UPFs with more favorable nutritional profiles may be compatible with healthy diets (Vadiveloo et al., 2025[155]). Consistent with this view, emerging evidence suggests that associations differ by UPF subgroups, with stronger positive associations observed for sugar-sweetened or artificially sweetened beverages and processed meats than for other UPFs (Mendoza et al., 2024[103]), although the conceptual basis and methodological approaches underlying UPF subgroup analyses have also been challenged (Rezende et al., 2026[132]). An important evidence gap in the literature is that most studies focus on disease incidence, whereas data on prognosis, recovery, and outcomes among individuals with established conditions remain scarce, limiting inference for secondary prevention.

Clinical experimental evidence remains limited but is gradually expanding. Overall, differences between ultra-processed and minimally processed diets appear more consistent for energy intake and adiposity than for short-term cardiometabolic biomarkers. In the first randomized controlled trial (RCT), Hall et al. showed that participants consumed approximately 500 kcal/day more and gained about 0.9 kg over two weeks during the ad libitum ultra-processed diet phase compared with the minimally processed diet (Hall et al., 2019[56]). Despite clear differences in energy intake and body weight, short-term changes in most cardiometabolic biomarkers were modest. Although between-diet biomarker analyses were not reported, within-diet analyses indicated that triglycerides and high-density lipoprotein cholesterol (HDL) cholesterol decreased relative to baseline after both diets. During the minimally processed diet only, the inflammatory marker high-sensitivity C-reactive protein (hsCRP) and the homeostasis model assessment of insulin resistance (HOMA-IR), an index of insulin resistance derived from fasting glucose and insulin concentrations, decreased, while fasting glucose and insulin tended to decline. Notably, although the two diets were matched for energy and nutrient composition, fiber in the ultra-processed diet was incorporated into beverages rather than provided through whole foods, a difference that may have affected food texture and eating behavior.

More recently, the UPDATE trial extended this evidence to a free-living, community-based setting aligned with national dietary guidance (Dicken et al., 2025[35]). In this crossover RCT, adults with overweight or obesity followed ultra-processed and minimally processed diets consistent with the UK Eatwell Guide for eight weeks each. Greater reductions in body weight, BMI, fat mass, body fat percentage, and visceral adiposity were observed during the minimally processed diet, but these did not translate into broadly superior cardiometabolic improvements compared with the ultra-processed diet. Among cardiometabolic biomarkers, between-diet differences were observed for triglycerides and low-density lipoprotein (LDL) cholesterol: triglycerides decreased more during the minimally processed diet, whereas LDL cholesterol decreased less during the minimally processed diet than during the ultra-processed diet. Similar patterns have been reported by Hamano et al., who observed greater increases in liver enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT], and gamma-glutamyl transpeptidase [γGTP]), markers of liver function and hepatocellular injury, during the UPF diet compared with the non-UPF diet (Hamano et al., 2024[57]). Between-diet differences were also observed in changes in total and HDL cholesterol, with greater increases during the UPF diet, whereas most other metabolic markers, including insulin resistance indices, did not differ between diets. Evidence from other community-based interventions is broadly consistent with these findings (Lopes et al., 2025[91]; Brandão et al., 2024[13]), and several ongoing RCTs are expected to further clarify effect sizes and relevance in real-world settings (Dinu et al., 2024[37]; Capra et al., 2024[15]; Lasschuijt et al., 2025[84]).

Observational evidence suggests that higher UPF consumption may be associated with increased cancer risk, although associations are generally site-specific and less consistent than those reported for cardiometabolic outcomes (DeVito and Sheean, 2026[33]). Early prospective evidence from the NutriNet-Santé cohort showed higher overall cancer incidence and breast cancer risk with increasing UPF exposure (Fiolet et al., 2018[46]). Subsequent analyses from the UK Biobank similarly identified positive associations between UPF intake and both overall cancer incidence and cancer mortality, with stronger signals for ovarian cancer incidence and for ovarian and breast cancer mortality (Chang et al., 2023[19]). In contrast, a more recent large pan-European analysis did not observe an association between UPF exposure and overall cancer mortality, highlighting substantial heterogeneity across populations, cancer sites, and exposure metrics (González-Gil et al., 2025[54]).

When examined specifically for breast cancer, findings are mixed. Several cohort studies reported higher breast cancer incidence and a trend toward increased breast cancer mortality with greater UPF intake, particularly among older women, alcohol consumers, and individuals with a family history of breast cancer (Chen et al., 2025[21]). However, evidence from meta-analyses indicates considerable variability. A recent meta-analysis reported a 25 % higher breast cancer risk associated with high consumption of fast foods and UPFs, although stronger associations were observed in case-control studies and in studies conducted in Latin America, where effect estimates ranged from approximately 65 % to 200 % higher risk. In contrast, associations did not reach statistical significance in prospective cohort studies or across menopausal strata (Karimi et al., 2025[75]). The meta-analysis also pooled studies assessing fast food consumption with those measuring UPF intake, which are related but conceptually distinct exposures and may contribute to heterogeneity in the pooled estimates.

For gastrointestinal cancers, a systematic review and meta-analysis of prospective cohort studies including more than 1.1 million participants found that the highest UPF exposure was associated with increased risk of colorectal cancer, colon cancer, and non-cardia gastric cancer (Meine et al., 2024[102]). In contrast, no associations were observed for hepatocellular, pancreatic, esophageal, gastric cardia, or rectal cancers (Meine et al., 2024[102]). Supporting a role in early colorectal carcinogenesis, a large prospective analysis within the Nurses' Health Study II reported a 45 % higher risk of early-onset conventional colorectal adenomas among participants with the highest UPF intake, independent of BMI and overall diet quality (Wang et al., 2026[158]). Indirect pathways may also contribute, as high UPF consumption is associated with obesity, a well-established risk factor for colorectal cancer (Tin et al., 2025[150]).

Evidence linking UPFs to liver cancer remains limited. Although higher UPF intake has been associated with increased long-term risk of metabolic dysfunction-associated steatotic liver disease, meta-analytic evidence does not support a clear association with primary liver cancer, including hepatocellular carcinoma or intrahepatic cholangiocarcinoma (Souza et al., 2025[143]). Additional site-specific evidence from the EPIC cohort indicates that higher UPF consumption is associated with increased risks of head and neck cancer and esophageal adenocarcinoma (Morales-Berstein et al., 2024[116]). Mediation analyses suggested that adiposity explained only a small proportion of these associations, pointing to the potential involvement of mechanisms beyond excess body fat.

Taken together, findings across cancer sites suggest that associations with UPF consumption are heterogeneous and appear to be site-specific rather than consistent across cancers. Some evidence also indicates stronger associations may be observed for specific UPF subgroups, such as sugar-sweetened beverages and ultra-processed meats, compared with the ultra-processed category as a whole (DeVito and Sheean, 2026[33]). Heterogeneity in exposure assessment, residual confounding, and the long latency of carcinogenesis continue to limit causal inference. These limitations underscore the need for mechanistic studies and long-term prospective research with improved characterization of UPF subtypes, processing-related exposures, and relevant intermediate pathways.

Interest is growing in the potential role of overall diet quality, including the degree of food processing, in mental health and cognitive function. Multiple cohort and cross-sectional studies report positive associations between higher UPF intake and depressive outcomes (Adjibade et al., 2019[1]; Gómez-Donoso et al., 2020[53]; Lane et al., 2023[81]; Leal et al., 2023[85]; Samuthpongtorn et al., 2023[138]; Sun et al., 2023[146]; Werneck et al., 2024[165]), as well as anxiety and psychological distress (Amadieu et al., 2021[3]; Bonaccio et al., 2022[10]; Coletro et al., 2022[25]; Noll et al., 2022[124]; Lopes Cortes et al., 2021[90]; Gomes Gonçalves et al., 2023[52]; Bhave et al., 2024[9]). Recent meta-analytic evidence indicates that high adherence to an ultra-processed dietary pattern is associated with increased risk across multiple mental health outcomes (Lane et al., 2022[80]). However, depression is among the outcomes showing the most consistent associations across studies, with a pooled relative risk of 1.23 (95 % CI 1.08 to 1.39) (Monteiro et al., 2025[113]). Other meta-analytic evidence from an umbrella review also reported convincing evidence that higher UPF consumption was associated with prevalent anxiety outcomes (OR 1.48, 95 % CI 1.37 to 1.59) and combined common mental disorder outcomes (OR 1.53, 95 % CI 1.43 to 1.63) (Lane et al., 2024[79]). Most studies assess depressive outcomes using validated symptom scales or clinical diagnoses, whereas evidence for other psychiatric endpoints remains more heterogeneous. Emerging intervention evidence suggests that reductions in UPF intake may be associated with improvements in depressive symptoms among adults with major depressive disorder. In a secondary analysis of the SMILES trial, each 10 % reduction in the dietary share of UPFs was associated with an additional 2.5-point improvement in MADRS scores (Lane et al., 2023[82]).

Related work has also explored disordered eating patterns and addictive-like eating behaviors, which may both increase vulnerability to UPF overconsumption and reinforce habitual intake. A recent systematic review of nine cross-sectional studies reported that higher UPF intake was associated with bulimic-type eating disorders, binge eating, other non-restrictive eating disorders, and food addiction, whereas no consistent associations were observed with restrictive eating disorders or body dissatisfaction (Pereira et al., 2024[126]). The lack of longitudinal studies represents a major gap in understanding the directionality of these relationships. Conceptually, UPFs have been proposed to have addictive potential. Drawing on evidence from 281 studies across 36 countries, pooled prevalence estimates of food addiction have been reported at approximately 14 % in adults and 12 % in children, levels comparable to those observed for some legal substances (Gearhardt et al., 2023[49]). Certain UPFs may be particularly likely to elicit addictive-like responses due to specific macronutrient combinations, altered food matrices that accelerate carbohydrate and fat delivery, and the use of sensory additives that enhance palatability and reinforce consumption.

Emerging research has extended this literature to neurodevelopmental outcomes, with a focus on prenatal and early-life exposures. Higher maternal UPF intake has been associated with less favorable cognitive development in offspring (Zupo et al., 2024[170]; Mottis et al., 2025[117]), and some studies report positive associations between higher UPF consumption and attention-deficit/hyperactivity disorder (ADHD) in children and adolescents (Ferreira et al., 2024[45]; Yan et al., 2023[168]). However, this evidence base remains relatively sparse, relies almost exclusively on observational designs, and is therefore subject to residual confounding and limited causal inference.

Beyond psychiatric-related outcomes, several observational studies have examined cognitive function and neurodegenerative risk in relation to UPF intake. Higher consumption of UPFs has been associated with poorer cognitive performance and less favorable cognitive trajectories, although the evidence base remains limited and methodologically heterogeneous (Gomes Gonçalves et al., 2023[52]; Mottis et al., 2025[117]). Substantial variability exists in cognitive assessment tools and parameters, exposure metrics, and study populations, which are concentrated in a small number of geographic regions (Smith et al., 2025[140]). Associations with incident dementia, including Alzheimer's disease, have also been reported, suggesting a higher risk among individuals with greater UPF intake (Henney et al., 2024[60]; Weinstein et al., 2025[164]). Interpretation of these findings is complicated by the long preclinical phase of dementia and the potential for reverse causation, whereby early cognitive decline may influence dietary behaviors prior to clinical diagnosis.

Overall, the evidence linking UPF intake to mental and brain health is growing but remains predominantly observational. Residual confounding related to socioeconomic position and broader lifestyle factors, as well as bidirectional relationships between diet and mental health, remain key methodological challenges. Evidence is comparatively limited for psychiatric outcomes beyond depression and for endpoints other than binary measures of prevalence and incidence, such as analyses using continuous symptom measures, changes in symptom scores over time, clinical course, and long-term progression. Future research integrating longitudinal designs, repeated dietary and mental health assessments, and mechanistic approaches will be essential to clarify causal pathways and to better characterize the role of UPFs across the spectrum of mental and brain health.

In recent years, the range of health outcomes examined in relation to UPF exposure has expanded, often within the same large prospective cohorts. An updated dose-response meta-analysis of 18 cohort studies including more than 1.1 million participants reported a 15 % higher risk of all-cause mortality among individuals with the highest UPF intake, with a linear increase of approximately 10 % in mortality risk for each 10 % increment in UPF consumption (Liang et al., 2025[88]). Similarly, another dose-response meta-analysis estimated a 3 % increase in all-cause mortality per 10 % increase in dietary UPF share and suggested that a substantial proportion of premature deaths in countries with high UPF exposure may be attributable to these foods (Nilson et al., 2025[122]). Analyses from the UK Biobank further suggest that the association between UPF intake and mortality may be partly mediated by accelerated biological ageing, with differential effects observed across UPF subgroups, including beverages and products containing artificial sweeteners (Wang et al., 2025[161]).

Beyond mortality, evidence has also accumulated for gastrointestinal and renal outcomes. Meta-analytic data indicate that high UPF intake is associated with increased risk of inflammatory bowel disease, particularly Crohn's disease, with dose-response analyses supporting a positive linear association (Babaei et al., 2024[6]). A potential role of UPFs in irritable bowel syndrome has likewise been proposed, plausibly mediated by additive-related effects on gut microbiota composition, intestinal barrier function, and low-grade inflammation, although the current evidence base remains limited and largely observational (Dale et al., 2025[29]). For renal outcomes, systematic reviews and meta-analyses consistently report a higher risk of chronic kidney disease and declined renal function with greater UPF consumption, including dose-response relationships indicating increased risk with incremental UPF intake (Leonberg et al., 2025[86]; Hojjati Kermani et al., 2025[63]). These associations appear particularly relevant among vulnerable populations, such as older adults and individuals with pre-existing kidney disease (Kanbay et al., 2025[74]).

In the context of declining fertility rates in most industrialized countries, reproductive outcomes have begun to receive increasing attention in relation to UPF exposure (GBD 2021 Fertility and Forecasting Collaborators, 2024[48]). The current evidence remains limited and is derived predominantly from cross-sectional observational studies, which report associations between higher UPF intake and infertility, with BMI frequently identified as a potential mediating factor (Ceretti et al., 2024[17]; Evans et al., 2025[41]; Su et al., 2025[145]; Soltani et al., 2025[142]). Importantly, experimental evidence is now emerging. In a recently published randomized controlled 2-by-2 crossover feeding trial, consumption of an ultra-processed diet for 3 weeks resulted in adverse changes in body weight, lipid profiles, and endocrine markers, along with trends toward impaired sperm quality, despite equivalent energy intake across dietary conditions. Although preliminary, these findings provide experimental support for the possibility that UPFs may influence metabolic and reproductive health through mechanisms that extend beyond excess caloric intake alone (Preston et al., 2025[129]).

A major critique is that the Nova system aggregates a highly heterogeneous range of foods into a single “ultra-processed” category, which may be overly broad and conceptually imprecise (Petrus et al., 2021[127]; Louie, 2025[92]). This concern relates primarily to the qualitative and descriptive nature of the Nova definition, which relies on criteria for the extent and purpose of industrial processing rather than quantitative thresholds. Consequently, the classification may introduce subjectivity and potential misclassification, particularly when detailed information on ingredients, formulation, brand names, or processing methods is lacking in dietary datasets (Monteiro et al., 2025[113]). This limitation is especially relevant for mixed dishes and multi-ingredient products and may contribute to between-study heterogeneity (Jung et al., 2025[72]). At the same time, more recent evaluations have reported acceptable construct validity and strong inter-coder agreement for the Nova classification system. Empirical assessments indicate that the system's definitions and examples allow classification of more than 70 % of food items reported in food frequency questionnaires from US cohorts and over 90 % of food items recorded in 24-hour dietary recalls from participants in a national Brazilian dietary survey (Khandpur et al., 2021[77]; Sneed et al., 2023[141]; Louzada et al., 2023[93]). In parallel, recent initiatives, including the development of best practice guidelines, have focused on improving the efficiency and transparency of Nova food group categorization, with the aim of enhancing the accuracy of effect estimates (Martinez-Steele et al., 2023[99]).

In addition, UPFs vary widely in composition, nutrient profiles, and food matrices, and treating them as a homogeneous exposure may obscure meaningful differences in underlying biological mechanisms (Wang et al., 2024[160]; Messina et al., 2023[106]; Visioli et al., 2025[156]). For example, sugar-sweetened beverages and processed meats are clearly ultra-processed and consistently associated with obesity, diabetes, and cardiovascular disease. In contrast, other UPFs, including certain plant-based or mixed products such as probiotic yogurts that may contain additives or added micronutrients, have shown neutral or even beneficial associations in some observational studies (Cordova et al., 2023[27]; Louie, 2025[92]). These contrasts suggest that UPFs with different nutrient compositions and ingredient origins may exert health effects through distinct pathways, and that pooling such products may conflate the effects of processing with those of nutritional quality (Louie, 2025[92]; Visioli et al., 2025[156]). In this context, others have argued that the primary relevance of the UPF construct lies in its role as a marker of dietary patterns characterised by industrial formulations, high energy density, and displacement of minimally processed foods, making comparisons between ultra-processed products themselves less informative than comparisons between UPF and minimally processed alternatives within similar food categories (Monteiro et al., 2026[114]). Indeed, to better isolate potential effects of ultra-processing, appropriate counterfactual comparisons would ideally contrast the same food type across different processing levels, for example, a fruit-flavored yoghurt drink versus plain yoghurt with fresh fruit (Rezende et al., 2026[132]).

More broadly, critics argue that research and policy should focus primarily on specific nutrients or ingredients of concern, such as added sugars, trans fats, and sodium, as well as on overall dietary patterns, rather than on the less clearly defined concept of ultra-processing. Proponents of the Nova framework counter that it should be viewed as a complementary analytical tool rather than a replacement for established nutrient- and pattern-based approaches. From this perspective, foods, nutrients, additives, and food matrices are all relevant determinants of health, and the contribution of UPFs reflects not only their nutrient profiles but also shared characteristics related to industrial formulation, altered food matrices, sensory engineering, and marketing practices that promote overconsumption (Monteiro et al., 2025[113]; Rezende et al., 2026[132]; Monteiro et al., 2026[114]). This debate remains active, and a notable exchange of viewpoints published in the American Journal of Clinical Nutrition highlights the persistent divide among nutrition scientists regarding the scope, limitations, and utility of the Nova classification (Astrup and Monteiro, 2022[5]; Monteiro and Astrup, 2022[111]).

Despite consistent epidemiological associations between UPF exposure and adverse health outcomes, causal inference remains limited, and further mechanistic studies and RCTs are needed to clarify whether and how UPFs directly contribute to disease risk (Forde, 2023[47]; Visioli et al., 2025[156]). The current evidence base is dominated by observational studies, which are inherently vulnerable to residual confounding, as high UPF intake often co-occurs with other unhealthy behaviors and socioeconomic disadvantage. Although most studies adjust for a wide range of covariates, residual and unmeasured confounding cannot be excluded and may partially account for the observed associations. In this context, recent analyses suggest that unmeasured confounding of sufficient magnitude to account for associations between UPF intake and weight gain in longitudinal cohort studies is at least plausible, underscoring the need for more robust causal study designs (Robinson and Jones, 2024[134]).

Dietary assessment represents an additional and important source of uncertainty. Although some questionnaires have been specifically developed to assess the consumption of foods according to their level of processing (Dinu et al., 2021[38]; Neri et al., 2023[121]), commonly used tools such as food frequency questionnaires and 24-hour dietary recalls were not originally designed to capture the degree or purpose of food processing. Many also predate the development of the Nova classification, increasing the risk of exposure misclassification (Jung et al., 2025[72]). This raises some methodological questions. On one hand, misclassification has been suggested to be largely non-differential with respect to outcomes and would therefore be expected to bias associations toward the null. On the other hand, measurement error may disproportionately affect analyses of specific UPF subgroups compared with analyses of overall ultra-processed dietary patterns, as attempts to distinguish finer product categories using imperfect instruments may amplify instability and misclassification (Rezende et al., 2026[132]). Consistent with this interpretation, studies using dietary assessment tools specifically designed to capture food processing according to the Nova framework have generally reported stronger associations between UPF consumption and health outcomes (Werneck et al., 2024[165]).

Methodological innovations are beginning to address some of these limitations. Machine learning and artificial intelligence approaches are increasingly applied to automate and standardize Nova coding across large datasets, including efforts to leverage Food Composition Tables to incorporate more detailed product information, with the potential to improve reproducibility and reduce inter-researcher variability (Menichetti et al., 2023[104]; Campbell et al., 2026[14]; Cattem et al., 2026[16]). In addition, linking dietary intake data with food purchase and retail transaction datasets offers opportunities to quantify UPF exposure more objectively over time and across populations. Related approaches have already been implemented in large prospective cohorts such as the French NutriNet-Santé, where repeated 24-hour dietary records capturing branded food products are dynamically linked to multiple composition databases and laboratory assays to estimate individual-level exposure to food additives and other processing-related components (Chazelas et al., 2021[20]). However, such approaches may incompletely capture foods consumed outside the home or in informal food environments and do not fully resolve broader conceptual challenges related to heterogeneity within the ultra-processed category (Campbell et al., 2026[14]).

Selective reporting and publication bias may further bias the body of published evidence, as studies identifying harmful associations are more likely to attract attention (Louie, 2025[92]). Another important limitation is the scarcity of long-term intervention trials explicitly targeting UPF and clinical endpoints, mainly due to ethical, logistical, and financial constraints. Consequently, critics argue that the current evidence does not definitively establish UPFs as independent causal agents and that public health strategies focusing on established nutritional targets such as added sugars, sodium, and unhealthy fats may capture much of the observed risk without requiring a distinct ultra-processing framework (Astrup and Monteiro, 2022[4]; Braesco et al., 2022[12]; Visioli et al., 2025[156]). Finally, although several plausible biological mechanisms have been proposed, direct evidence linking specific UPF components to particular disease outcomes remains limited. Ongoing research examining additives such as emulsifiers and non-nutritive sweeteners, as well as processing-related byproducts such as advanced glycation end-products, and packaging-related chemicals aims to clarify their individual and combined contributions (Muncke et al., 2025[118]; Hasenböhler et al., 2026[58]; Salame et al., 2024[137]).

Concerns have also been raised about the practical and social implications of stigmatizing UPF consumption. As discussed above, UPFs are typically inexpensive, convenient, and shelf-stable, characteristics that make them especially relevant for lower-income groups and for individuals facing time, financial, or resource constraints (Coyle et al., 2022[28]; Baker et al., 2025[7]). These consumption patterns are linked with persistent gender inequalities, as women continue to bear a disproportionate share of responsibility for food provisioning and meal preparation in many settings, even when engaged in paid work (Njuki et al., 2023[123]). Time scarcity, caregiving demands, and unequal access to resources may therefore increase household reliance on ready-to-eat products, particularly in families with young children or dependent members. In this context, public health recommendations that broadly discourage all UPFs risk being unrealistic and potentially counterproductive if not accompanied by policies that improve access to affordable, nutritious alternatives (Forde, 2023[47]; Scrinis et al., 2025[139]). In food-insecure or highly urbanized environments, UPFs may partially compensate for limited food availability by providing low-cost calories that require minimal preparation. Discouraging their consumption without parallel structural changes to food systems may inadvertently increase the risk of inadequate dietary intake (Scrinis et al., 2025[139]).

Importantly, not all forms of food processing have been detrimental to public health. Within the Nova framework, fortification strategies aimed at restoring nutrients lost during processing, such as enrichment of wheat or corn flour with iron and folic acid, have been widely used in processed staple foods to prevent micronutrient deficiencies. Several successful public health interventions have relied on processed or fortified foods, including ultra-processed fortified cereals, to prevent or reduce micronutrient deficiencies at the population level (Hoffman et al., 2020[62]; Hossain et al., 2025[64]). While the presence of fortification alone does not determine whether a food is classified as ultra-processed within the Nova framework, concerns have been raised that overly restrictive interpretations of UPF reduction could inadvertently discourage the use of fortified or nutritionally enhanced products that play an important role in food security, particularly for women of reproductive age, children, and other nutritionally vulnerable groups (Forde, 2023[47]).

There is also a cultural dimension to consider. UPFs have become embedded in many contemporary food practices and culinary traditions, such as instant noodles in parts of Asia or packaged breads in Western diets. Strategies aimed at reducing UPF exposure must therefore account for cultural acceptability and feasibility and are more likely to be effective if they promote gradual, context-sensitive transitions rather than abrupt dietary shifts. Overall, policies targeting UPFs should be carefully designed to avoid stigmatizing lower-income groups and to ensure that healthier dietary patterns are both accessible and culturally appropriate (Popkin et al., 2021[128]; Scrinis et al., 2025[139]).

In light of these debates, several experts have argued for refining the UPF framework rather than abandoning it altogether (Sadler et al., 2021[136]; Ahrné et al., 2025[2]; Medin et al., 2025[101]; Bernstein et al., 2026[8]). Monteiro and colleagues have likewise acknowledged key limitations of the framework. In the recent Lancet series, they recognized the need for additional RCTs and mechanistic studies, as well as the heterogeneity within the UPF category and the fact that not all UPFs have equivalent nutritional value (Monteiro et al., 2025[113]). At the same time, they and others have argued that the current body of evidence is sufficiently robust to justify population-level actions to reduce UPF exposure and that placing emphasis on unresolved scientific uncertainties may delay policies with the potential to mitigate obesity and other chronic diseases (Baker et al., 2025[7]; Scrinis et al., 2025[139]).

From a policy perspective, this debate implies different strategic emphases. If processing-related characteristics exert effects independent of nutrient profile, food-based and processing-oriented recommendations may be warranted. Conversely, if UPFs primarily function as markers of poor nutrient quality and unhealthy dietary patterns, nutrient-focused or hybrid approaches may capture much of the relevant risk. Balancing timely action based on consistent but imperfect evidence with the need for stronger causal resolution therefore remains central to ongoing discussions surrounding UPFs.

Conceptualization: M.D., D.M., W.M.; Methodology: M.D., S.L., F.A., D.J.Z., W.M.; Data curation: S.L., F.A., D.J.Z., B.C., S.G.; Writing - original draft preparation: M.D., S.L., F.A., D.J.Z., S.G., W.M.; Writing - review and editing: All authors; Visualization: S.L., B.C.; Supervision: M.D., D.M., W.M.; Project administration: M.D. All authors have read and agreed to the published version of the manuscript.

This research did not receive any specific grant from funding agencies in the public, commercial, or non-for-profit sectors. S.G. is funded by NHMRC Synergy Grant SOLVE CHD (#GNT1182301).

M.D. and D.M. acknowledge the PRIN 2022 program of the Italian Ministry of University and Research (MUR), funded by the European Union-NextGenerationEU (Grant n: 2022HW2S5T).

The authors thank Melissa M. Lane for her valuable comments and insights during the revision of the manuscript.

The authors declare no conflicts of interest.

During the preparation of this manuscript, the authors used ChatGPT-5 to assist in editing the text and improving its readability. The authors have reviewed and edited the output and take full responsibility for the content of this publication.

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