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 manual searches of reference lists from 2009 to June 2023. Eligibility criteria for selecting studies Systematic reviews and meta-analyses of cohort, case-control, and/or cross sectional study designs. To evaluate the credibility of evidence, pre-specified evidence classification criteria were applied, graded as convincing (“class I”), highly suggestive (“class II”), suggestive (“class III”), weak (“class IV”), or no evidence (“class V”). The quality of evidence was assessed using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) framework, categorised as “high,” “moderate,” “low,” or “very low” quality. Results The search identified 45 unique pooled analyses, including 13 dose-response associations 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 parameters spanning mortality, cancer, and mental, respiratory, cardiovascular, gastrointestinal, and metabolic health outcomes. Based on the 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 (risk ratio 1.50, 95% confidence interval 1.37 to 1.63; GRADE=very low) and type 2 diabetes (dose-response risk ratio 1.12, 1.11 to 1.13; moderate), as well as higher risks of prevalent anxiety outcomes (odds ratio 1.48, 1.37 to 1.59; low) and combined common mental disorder outcomes (odds ratio 1.53, 1.43 to 1.63; low). Highly suggestive (class II) evidence indicated that greater exposure to ultra-processed foods was directly associated with higher risks of incident all cause mortality (risk ratio 1.21, 1.15 to 1.27; low), heart disease related mortality (hazard ratio 1.66, 1.51 to 1.84; low), type 2 diabetes (odds ratio 1.40, 1.23 to 1.59; very low), and depressive outcomes (hazard ratio 1.22, 1.16 to 1.28; low), together with higher risks of prevalent adverse sleep related outcomes (odds ratio 1.41, 1.24 to 1.61; low), wheezing (risk ratio 1.40, 1.27 to 1.55; low), and obesity (odds ratio 1.55, 1.36 to 1.77; low). 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). Overall, using the GRADE framework, 22 pooled analyses were rated as low quality, with 19 rated as very low quality and four rated as moderate quality. Conclusions Greater exposure to ultra-processed food was associated with a higher risk of adverse health outcomes, especially cardiometabolic, common mental disorder, and mortality outcomes. These findings provide a rationale to develop and evaluate the effectiveness of using population based and public health measures to target and reduce dietary exposure to ultra-processed foods for improved human health. They also inform and provide support for urgent mechanistic research. Systematic review registration PROSPERO CRD42023412732.

Since previous meta-analyses, which were limited only to depression and by a small number of studies available for inclusion at the time of publication, several additional studies have been published assessing the link between ultra-processed food consumption and depression as well as other mental disorders. We aimed to build on previously conducted reviews to synthesise and meta-analyse the contemporary evidence base and clarify the associations between the consumption of ultra-processed food and mental disorders. A total of 17 observational studies were included (n = 385,541); 15 cross-sectional and 2 prospective. Greater ultra-processed food consumption was cross-sectionally associated with increased odds of depressive and anxiety symptoms, both when these outcomes were assessed together (common mental disorder symptoms odds ratio: 1.53, 95%CI 1.43 to 1.63) as well as separately (depressive symptoms odds ratio: 1.44, 95%CI 1.14 to 1.82; and, anxiety symptoms odds ratio: 1.48, 95%CI 1.37 to 1.59). Furthermore, a meta-analysis of prospective studies demonstrated that greater ultra-processed food intake was associated with increased risk of subsequent depression (hazard ratio: 1.22, 95%CI 1.16 to 1.28). While we found evidence for associations between ultra-processed food consumption and adverse mental health, further rigorously designed prospective and experimental studies are needed to better understand causal pathways.

Advanced glycation end products (AGEs) are glycated proteins or lipids formed endogenously in the human body or consumed through diet. Ultra-processed foods and some culinary techniques, such as dry cooking methods, represent the main sources and drivers of dietary AGEs. Tissue accumulation of AGEs has been associated with cellular aging and implicated in various age-related diseases, including type-2 diabetes and cardiovascular disease. The current review summarizes the literature examining the associations between AGEs and neurocognitive and mental health disorders. Studies indicate that elevated circulating AGEs are cross-sectionally associated with poorer cognitive function and longitudinally increase the risk of developing dementia. Additionally, preliminary studies show that higher skin AGE accumulation may be associated with mental disorders, particularly depression and schizophrenia. Potential mechanisms underpinning the effects of AGEs include elevated oxidative stress and neuroinflammation, which are both key pathogenetic mechanisms underlying neurodegeneration and mental disorders. Decreasing dietary intake of AGEs may improve neurological and mental disorder outcomes. However, more sophisticated prospective studies and analytical approaches are required to verify directionality and the extent to which AGEs represent a mediator linking unhealthy dietary patterns with cognitive and mental disorders.

Background: Few studies have examined associations between ultra-processed food intake and biomarkers of inflammation, and inconsistent results have been reported in the small number of studies that do exist. As such, further investigation is required. Methods: Cross-sectional baseline data from the Melbourne Collaborative Cohort Study (MCCS) were analysed (n = 2018). We applied the NOVA food classification system to data from a food frequency questionnaire (FFQ) to determine ultra-processed food intake (g/day). The outcome was high-sensitivity C-reactive protein concentration (hsCRP; mg/L). We fitted unadjusted and adjusted linear regression analyses, with sociodemographic characteristics and lifestyle- and health-related behaviours as covariates. Supplementary analyses further adjusted for body mass index (kg/m²). Sex was assessed as a possible effect modifier. Ultra-processed food intake was modelled as 100 g increments and the magnitude of associations expressed as estimated relative change in hsCRP concentration with accompanying 95% confidence intervals (95%CIs). Results: After adjustment, every 100 g increase in ultra-processed food intake was associated with a 4.0% increase in hsCRP concentration (95%CIs: 2.1–5.9%, p < 0.001). Supplementary analyses showed that part of this association was independent of body mass index (estimated relative change in hsCRP: 2.5%; 95%CIs: 0.8–4.3%, p = 0.004). No interaction was observed between sex and ultra-processed food intake. Conclusion: Higher ultra-processed food intake was cross-sectionally associated with elevated hsCRP, which appeared to occur independent of body mass index. Future prospective and intervention studies are necessary to confirm directionality and whether the observed association is causal.