Prospective cohort studies show that higher intakes of ultra-processed food (UPF) increase the risk of obesity and obesity-related outcomes, including cardiovascular disease, cancer and type 2 diabetes. Whether ultra-processing itself is detrimental, or whether UPFs just have a lower nutritional quality, is debated. Higher UPF intakes are inversely associated with fruit, vegetables, legumes and seafood consumption. Therefore, the association between UPFs and poor health could simply be from excess nutrient intake or from a less healthful dietary pattern. If so, adjustment for dietary quality or pattern should explain or greatly reduce the size of the significant associations between UPFs and health-related outcomes. Here, we provide an overview of the literature and by using a novel approach, review the relative impact of adjusting for diet quality/patterns on the reported associations between UPF intake and health-related outcomes in prospective cohort studies. We find that the majority of the associations between UPFs, obesity and health-related outcomes remain significant and unchanged in magnitude after adjustment for diet quality or pattern. Our findings suggest that the adverse consequences of UPFs are independent of dietary quality or pattern, questioning the utility of reformulation to mitigate against the obesity pandemic and wider negative health outcomes of UPFs.

Purpose of Review: Obesity is a growing global healthcare concern. A proposed driver is the recent increase in ultra-processed food (UPF) intake. However, disagreement surrounds the concept of UPF, the strength of evidence, and suggested mechanisms. Therefore, this review aimed to critically appraise the evidence on UPF and obesity. Recent Findings: Observational studies demonstrate positive associations between UPF intake, weight gain, and overweight/obesity, more clearly in adults than children/adolescents. This is supported by high-quality clinical data. Several mechanisms are proposed, but current understanding is inconclusive. Summary: Greater UPF consumption has been a key driver of obesity. There is a need to change the obesogenic environment to support individuals to reduce their UPF intake. The UPF concept is a novel approach that is not explained with existing nutrient- and food-based frameworks. Critical analysis of methodologies provides confidence, but future observational and experimental research outputs with greater methodological rigor will strengthen findings, which are outlined.

Ultra-processed food (UPF) intake is associated with increased non-communicable disease risks. However, systematic reports on sociodemographic predictors of UPF intake are lacking. This review aimed to understand UPF consumption based on sociodemographic factors, using nationally representative cohorts. The systematic review was pre-registered (PROSPERO:CRD42022360199), following PRISMA guidelines. PubMed/MEDLINE searches (‘ultra-processed/ultraprocessed’ and ‘ultra-processing/ultraprocessing’) until 7 September 2022 retrieved 1131 results. Inclusion criteria included: observational, nationally representative adult samples, in English, in peer-reviewed journals, assessing the association between sociodemographics and individual-level UPF intake defined by the NOVA classification. Exclusion criteria included: not nationally representative, no assessment of sociodemographics and individual-level UPF intake defined by NOVA. Risk of bias was assessed using the Newcastle–Ottawa Scale (NOS). Fifty-five papers were included, spanning thirty-two countries. All thirteen sociodemographic variables identified were significantly associated with UPF intake in one or more studies. Significant differences in UPF intake were seen across age, race/ethnicity, rural/urbanisation, food insecurity, income and region, with up to 10–20% differences in UPF intake (% total energy). Higher UPF intakes were associated with younger age, urbanisation and being unmarried, single, separated or divorced. Education, income and socioeconomic status showed varying associations, depending on country. Multivariate analyses indicated that associations were independent of other sociodemographics. Household status and gender were generally not associated with UPF intake. NOS averaged 5·7/10. Several characteristics are independently associated with high UPF intake, indicating large sociodemographic variation in non-communicable disease risk. These findings highlight significant public health inequalities associated with UPF intake, and the urgent need for policy action to minimise social injustice-related health inequalities.

Ultraprocessed food (UPF) consumption is associated with noncommunicable disease risk, yet no trial has assessed its health impact within the context of national dietary guidelines. In a 2 × 2 crossover randomized controlled feeding trial, 55 adults in England (body mass index ≥25 to <40 kg m ⁻² , habitual UPF intake ≥50% kcal day ⁻¹ ) were provided with two 8-week ad libitum diets following the UK Eatwell Guide: (1) minimally processed food (MPF) and (2) UPF, in a random order. Twenty-eight people were randomized to MPF then UPF, and 27 to UPF then MPF; 50 participants comprised the intention-to-treat sample. The primary outcome was the within-participant difference in percent weight change (%WC) between diets, from baseline to week 8. Participants were blinded to the primary outcome. MPF (%WC, −2.06 (95% confidence interval (CI), −2.99, −1.13) and UPF (%WC, −1.05 (95% CI, −1.98, −0.13)) resulted in weight loss, with significantly greater %WC on MPF (Δ%WC, −1.01 (95% CI, −1.87, −0.14), P = 0.024; Cohen’s d , −0.48 (95% CI, −0.91, −0.06)). Mild gastrointestinal adverse events were common on both diets. Findings indicate greater weight loss on MPF than UPF diets and needing dietary guidance on food processing in addition to existing recommendations. Clinicaltrials.gov registration: NCT05627570 .

It is unknown whether the association between ultra-processed food (UPF) intake and type 2 diabetes mellitus differs from other degrees of food processing. We examined the association between degree of food processing and incident type 2 diabetes mellitus. This was a prospective cohort analysis of the European Prospective Investigation into Cancer and Nutrition (EPIC). Dietary intake was assessed at baseline using dietary questionnaires and classified according to the Nova classification into unprocessed/minimally processed food (MPF), processed culinary ingredients (PCI), processed food (PF) and UPF. Type 2 diabetes mellitus cases were verified through multiple methods. Cox regression and statistical substitution analysis was used to estimate associations between MPF + PCI, PF and UPF intake and incident type 2 diabetes mellitus. To investigate heterogeneity in the association between UPF and incident type 2 diabetes mellitus, UPF sub-group analysis was conducted. Different reference groups were used in each analysis. Over an average 10.9 years follow-up of 311,892 individuals, 14,236 type 2 diabetes mellitus cases were identified. Each 10% increment of total daily food intake from UPF (%g/day) was associated with 17% (95% confidence interval (95%CI): 1.14–1.19) higher incident type 2 diabetes mellitus. Each 10% increment in MPF + PCI or PF intake was associated with lower incident type 2 diabetes mellitus (MPF + PCI hazard ratio: 0.94 (95%CI: 0.92–0.96); PF hazard ratio: 0.92 (95%CI: 0.89–0.95)). Replacing UPF with MPF + PCI or PF was associated with lower incident type 2 diabetes mellitus. However, heterogeneity was observed across UPF sub-groups, with breads, biscuits and breakfast cereals, sweets and desserts, and plant-based alternatives associated with lower incident type 2 diabetes mellitus. These findings support recommendations to focus on reducing intake of specific UPF for lowering type 2 diabetes mellitus risk. 10.13039/100008700 International Agency for Research on Cancer .

The emergence of SARS‐CoV‐2 variants has exacerbated the COVID‐19 global health crisis. Thus far, all variants carry mutations in the spike glycoprotein, which is a critical determinant of viral transmission being responsible for attachment, receptor engagement and membrane fusion, and an important target of immunity. Variants frequently bear truncations of flexible loops in the N‐terminal domain (NTD) of spike; the functional importance of these modifications has remained poorly characterised. We demonstrate that NTD deletions are important for efficient entry by the Alpha and Omicron variants and that this correlates with spike stability. Phylogenetic analysis reveals extensive NTD loop length polymorphisms across the sarbecoviruses, setting an evolutionary precedent for loop remodelling. Guided by these analyses, we demonstrate that variations in NTD loop length, alone, are sufficient to modulate virus entry. We propose that variations in NTD loop length act to fine‐tune spike; this may provide a mechanism for SARS‐CoV‐2 to navigate a complex selection landscape encompassing optimisation of essential functionality, immune‐driven antigenic variation and ongoing adaptation to a new host.