KEY FIGURE

Highlights

· Food quality may not always align with processing levels.

· Emphasize nutritional content’s role in dietary patterns, not just processing.

· Differentiate processing impacts from overall diet quality.

· Explore the roles of metabolomics and gut microbiome in processing effects.

· Highlight healthful foods and dietary patterns to prevent disease.

INTRODUCTION

In the modern era, diet has undergone significant shifts over the past few decades, with a marked increase in the consumption of ultra-processed foods (UPFs) [1,2]. These foods, characterized by industrial processing and use of additives, have become popular in human diets due to their convenience, affordability, and palatability [3]. However, there is growing concern about the potential health implications associated with UPFs. Research has suggested links between high overall UPF consumption and risks of cardiometabolic diseases, including obesity, type 2 diabetes mellitus (T2DM), and cardiovascular disease (CVD), as well as certain cancers [4], and evidence is accumulating quickly. Despite the highly consistent findings regarding the overall UPF intake in relation to human health, there is also ongoing debate about whether the adverse health effects are directly attributable to food processing per se or if they are driven by the low diet quality of overall UPF intake [5]. This review aims to briefly summarize or elucidate the current UPF consumption levels, how they may influence human health, their complex relationship with diet quality, and the future directions for UPF research and public health interventions.

The Nova classification system for food items

The Nova classification is a system that categorizes foods according to the degree and purpose of their industrial processing [3,6]. Nova classifies food items into four categories: (1) Unprocessed or minimally processed foods: These foods remain in their natural state or undergo slight processing such as grinding, drying, freezing, or pasteurization, without the addition of any substances. Typical Nova category 1 foods include fresh fruits, vegetables, grains, milk, eggs, and unprocessed meat. (2) Processed culinary ingredients: These are derived from unprocessed foods through extraction or refinement and are used in cooking or seasoning, such as salt, sugar, vegetable oils, butter, and starches. (3) Processed foods: These foods are made using simple processing methods, including adding salt, sugar, or fats to enhance flavor or extend shelf life, typically containing two to three ingredients, such as canned vegetables and fruits, cheese, home-made bread, and smoked meats. Essentially, food items in this category are produced when adding Nova category 2 ingredients to Nova category 1 food items. (4) UPFs: UPFs are food products made of industrial formulations with ingredients that are of exclusive industrial use. As such, UPFs often contain industrial additives such as preservatives, flavor enhancers, artificial colors, and emulsifiers. Examples include soft drinks, packaged snacks, processed meat products, and sweetened breakfast cereals that are usually high in sugar, fat, and salt and designed to be convenient, appealing, and long-lasting. Of note, mass production through industrial packaging process is also considered as a defining criterion for UPF categorization.

Current UPF consumption in different populations

The contribution of UPFs to total energy intake may vary across regions, but overall they have become one of the major sources of energy in human diets. According to the National Health and Nutrition Examination Survey (NHANES) using 24-hour dietary recall data, the consumption of UPFs accounted for 58.2% of total energy intake in the United States (US) [1]. And this survey showed that the consumption of UPFs among children and adolescents in the US (aged 2 to 19 years) had risen from 61.4% to 67.0% over the past 20 years [2]. The 2015 Canadian Community Health Surveys showed that UPF intake, assessed using 24-hour recalls, contributed 45.7% of total daily energy among the overall population [7]. A review study of 22 European countries reported UPF energy contributions ranging from 14% to 44%, with Italy and Romania having the lowest levels, and the United Kingdom (UK) and Sweden the highest [8]. A systematic review involving 99 studies highlighted the global variability in UPF consumption, noting that the US and the UK had the highest percentages (generally over 50%), whereas Italy had the lowest [9]. These global variability underscores the diverse dietary patterns and the significant role that UPFs play in energy intake across different regions [8]. The overall prevalence is, in general, higher in developed countries compared to developing countries (Fig. 1). In Brazil, a survey involving 124 cities reported that UPFs comprised 28% of total energy intake among adolescents [10]. Data from Mexico National Health and Nutrition Survey indicated a 29.8% share among adults [11]. The China Health and Nutrition survey showed that the daily energy contribution of UPF increased from 1.4% in 1997 to 4.9% in 2011 [12]. It is important to note that these surveys all employed 24-hour recalls or diet records, which are valid approaches to evaluating the average consumption of UPF intake within the target population. Besides the regional variations, there are no comprehensive studies specifically focusing on particular populations or patient groups that may consume even higher levels of UPFs.

UPF CONSUMPTION AND HEALTH

UPF consumption and health impact

Research across various studies indicates that higher consumption of overall UPFs is highly consistently associated with multiple adverse health outcomes. A study involving approximately 300,000 participants from seven European countries found that increased UPF intake was linked to a higher risk of multimorbidity, including cardiometabolic diseases and cancer [13]. Similarly, a meta-analysis of 22 prospective studies revealed that individuals with the highest intake of UPFs, compared to those with the lowest, had a 17% increased risk of CVD, a 23% increased risk of coronary heart disease (CHD), and a 9% higher risk of stroke [14]. A 10% rise in the consumption of UPFs may result in a 15% increased risk of developing T2DM among adults [15]. The associations between UPFs and cardiometabolic diseases reported in selected meta-analyses were summarized in Table 1. Furthermore, a long-term populationbased cohort study in the US demonstrated that participants with the highest UPF intake had a 4% higher all-cause mortality risk and a 9% higher mortality risk from non-cancer and non-cardiovascular causes compared to those with the lowest intake level [16]. Additional evidence from the Nurses’ Health Study and the Health Professionals Follow-up Study revealed that high UPF consumption was associated with increased risks of frailty [17], gallstone disease [18], Crohn’s disease [19], systemic lupus erythematosus [20], colorectal cancer precursors [21], and mortality among colorectal cancer patients [22]. A comprehensive meta-analysis of 54 studies found a significant association between UPF intake and increased risks of common pregnancy adverse outcomes, including gestational diabetes mellitus (GDM) and preeclampsia, with a 100 g increment in UPF intake related to a 27% increase in GDM risk [23]. A randomized controlled trial investigated the effects of UPFs on energy intake and body weight by comparing 2-week periods of consuming either ultra-processed or less processed diets, indicating that the ultra-processed diet led to significantly higher energy intake and weight gain [24].

Umbrella reviews further supported these findings, showing that greater UPF consumption was linked to elevated risks of CVD, T2DM, mental disorders, and overall mortality [4]. Moreover, an updated umbrella review identified 25 health outcomes associated with UPF intake, highlighting evidence of adverse effects on renal function and wheezing in children, diabetes, obesity, and mental health disorders [25]. Compared to whole foods, the intake of UPFs is linked to greater energy intake and a higher risk of weight gain in both adults and children, as well as an elevated risk of obesity-related health issues in adults [26]. Another recent umbrella review revealed a 23% higher incidence of hypertension associated with high UPF consumption compared to low UPF consumption [27]. Furthermore, diets high in overall UPFs are implicated in various gut diseases, such as inflammatory bowel disease, colorectal cancer, and irritable bowel syndrome, with food additives potentially exacerbating issues related to gut microbiome, intestinal permeability, and inflammation [28].

UPF categorization and diet quality

The Nova classification of a food as UPF refers primarily to the extent and purpose of its processing rather than nutritional content. Indeed, UPFs can vary significantly in nutritional content and quality (Fig. 2). For example, a fiber-fortified breakfast cereal and a sugar-loaded soft drink are both UPFs, yet the quality of these two food items apparently differs significantly. Some UPF foods, such as whole-grain breads, cold breakfast cereals, yogurt, etc., may contain many beneficial nutrients and non-nutrient constituents, including fiber, vitamins, minerals, and phytochemicals. In contrast, food items, such as unprocessed red meats, butter, home-made desserts, etc., despite being non-UPF, may contain excess amounts of sugar, saturated fats, or other unhealthful ingredients [29]. Foods that are modified to provide health benefits, such as folate-fortified breakfast cereals, plant-based milk with added calcium and vitamins, or food item enriched with omega-3 fatty acids are other examples of UPFs with potentially high quality [29].

Indeed, despite the highly consistent and convincing evidence underscoring the unfavorable associations between high overall UPF consumption and numerous chronic conditions, emerging evidence shows significant heterogeneity among in-dividual UPF groups in terms of their associations with chronic disease risk. A prior study by Chen et al. [30] showed that while UPFs such as refined grains, animal-based products, and sugar-sweetened beverages were linked to higher T2DM risk, other UPFs such as cereals, dark and whole-grain breads, yogurt, and dairy-based desserts were associated with a lower risk. Similarly, the consumption of ultra-processed savory snacks, cold cereals, yogurt/dairy-based desserts, and ultraprocessed bread was inversely associated with the risk of CVD and CHD [14]. The European Prospective Investigation into Cancer and Nutrition (EPIC) cohort study further supported that high consumption of ultra-processed bread and cereals demonstrated a slightly protective effect on multimorbidity [13]. Evidence from NutriNet Santé study showed that the intakes of UPF fruits and vegetables were not significantly associated with disease outcomes, such as overweight, obesity [31], CVD [32], T2DM [33], or depressive symptoms [34]. In addition, there is abundant evidence suggesting that unprocessed red meats, butter, cream, full-fat milk, salt, and added sugar, despite being Nova category 1 to 3 foods, lead to an increased risk of developing chronic diseases [35-38]. As such, the quality and health consequences of individual food items/groups could well misalign with the processing levels.

Novel UPFs

In addition, some novel UPFs may offer a wide range of benefits such as dietary diversity, convenience, and suitability for specific dietary restrictions, such as plant-based meats, dairyfree yogurts (made from almond, oat, or coconut milk), protein bars, Ready-to-Eat Meals, and fortified breakfast cereals. The improved processing techniques can enrich nutrients in these foods. For example, fortified breakfast cereals may contain added vitamins A, B, E and minerals [39]; fortified plantbased dairy alternatives can provide essential nutrients such as calcium, iodine, and vitamins B2 and B12 in quantities comparable to dairy milk [40]. A modeling study highlighted that replacing traditional American breakfast foods, such as breads and rolls, egg mixed dishes, doughnuts, pancakes, and citrus juice with Ready-to-Eat cereals might lead to higher diet quality, as it increased the consumption of dietary fiber, vitamin D, potassium, calcium, and folic acid intake that are beneficial to health [41,42]. The Study With Appetizing Plant food-Meat Eating Alternative Trial (SWAP-MEAT) demonstrated that replacing red meats with ultra-processed plant-based alternatives led to lower intake of sodium, higher intake of fiber, significant weight loss, lower concentrations of low-density lipoprotein cholesterol, and favorable changes in the gut microbial composition [43].

FUTURE DIRECTIONS

Food processing and diet quality

While many studies have highlighted the potential negative impacts on health associated with overall UPF consumption, there remains a debate on whether these associations are entirely driven by overall low diet quality associated with excess intake of overall UPFs. If this is the case, then the diet quality, rather than the processing levels, shall remain the best metrics that guide individuals for choosing healthful food items for health promotion or maintenance. Some studies suggested that the associations between UPFs and disease outcomes were attenuated after accounting for diet quality [16,44], while other studies supported the notion that the inherent qualities of UPFs, including their high content of refined sugars, unhealthy fats, additives, and low nutritional value, might independently contribute to adverse health effects, regardless of the overall diet quality [5,17,45-47]. Therefore, it is essential to disentangle the health effects of UPF and diet quality. Weighting UPFs based on quality, or creating a scoring system that rates UPFs based on their nutrient profiles may differentiate the specific effects of food processing from overall diet quality.

Metabolomics, gut microbiome, and environmental sustainability

In addition, metabolomics and gut microbiome research can be powerful tools to unravel the complex biological effects of UPFs on human health. Mapping altered metabolites and metabolic pathways may help elucidate the biological processes affected by UPFs, such as lipid metabolism, oxidative stress, and inflammation. Evidence showed that overall UPFs may contribute to chronic inflammation by disrupting the production of beneficial metabolites like short-chain fatty acids [48,49]. UPFs can also alter the metabolomic capacities of intestinal microbiota, elevating the expression of virulence genes in typically mutualistic gut bacteria like Escherichia coli and Bacteroides thetaiotaomicron [50,51]. However, the interactions between metabolites and gut bacteria in response to diets high in UPFs are still not fully understood. In addition, no studies have been conducted to understand whether different UPF groups may have differential impact on human metabolome and the gut microbiome. Additional studies incorporating measurements of food processing level, metabolomics, gut microbiome, and clinical data are needed to elucidate the effects of UPFs versus diet quality on human health. Data regarding industrial additives that render the UPF categorization, such as coloring agents, artificial flavors, sweeteners, etc. are still sparse and mixed. More evidence is needed to fully understand their health impacts. Again, human metabolome and the gut microbiome may be instrumental for scientists to understand biological pathways that are influenced by the intake of these additives. Furthermore, food processing, production, and packaging can have significant environmental impacts, including greenhouse gas emissions, land, water and energy use, biodiversity loss, and food wastage [52]. With the global consumption of UPFs on the rise, it is critical to integrate environmental sustainability considerations into UPF research. By addressing the challenges posed by UPFs and suboptimal diet quality, we advocate for nutritional strategies that support individual and population health while contributing to a more sustainable food system.

Assessment of UPF intake

Another challenge for UPF research is the assessment of UPF intake among free-living individuals in large epidemiological studies. Currently, measuring UPF intake primarily relies on food frequency questionnaires (FFQs) and 24-hour dietary recalls [5]. These methods have limitations in accurately estimating the long-term intake of UPFs at individual levels. For example, FFQs often include a limited number of food items without detailed food processing information and are subject to recall bias. Twenty-four-hour recalls are unlikely to capture long-term human diet and are also subject to recall errors. In addition, FFQs often inquire about the intake frequency of broad food categories which may include both UPF and non-UPF version of foods that fall in the same category, leading to potential misclassification of UPF and non-UPF intakes. It is interesting to observe that UPF intake levels were much lower in observational studies that used FFQs to assess UPF intake than those estimated using 24-hour recalls in populations from the same country/region, probably owing to the fact that some UPF food items were not among the FFQ food list [9,53,54]. The classification of foods in FFQs also differed due to variations in food systems across different countries. For example, in the US and UK, bread is often categorized as UPF, while in France and Spain, it is generally regarded as non-UPF products [9]. Moreover, yogurt is often considered UPF because it contains additives and sweeteners, yet it might be regarded as minimally processed in countries that favor traditional recipes without added ingredients [55]. As such, objective biomarkers that are free of recall bias and other errors are needed to further elucidate UPFs’ impact on health. Feeding trials of UPF intake and observational studies that have diet record data are instrumental for discovering and validating novel biomarkers or biomarker indices consisted of food biomarkers and endogenous response biomarkers that can help better characterize UPF intake in free-living individuals. Such biomarkers are also extremely helpful for corroborating associations between UPF intake and chronic disease risk observed in previous studies that used FFQs to assess UPF consumption.

CONCLUSIONS

In summary, while the detrimental effects of overall UPFs, especially those with poor nutrient profiles and lower quality, on human health should be fully acknowledged, the current evidence does not support a shift of priority from emphasizing diet quality to underscoring food processing levels for health promotions. The focus shall remain on promoting the healthy dietary patterns, including the Mediterranean diet, the Dietary Approaches to Stop Hypertension diet, healthy plant-based diets, and other healthful diets, since these high-quality diets have been consistently linked to a lower risk of chronic diseases. They are rich in nutrients, antioxidants, anti-inflammatory compounds, and other bioactive substances that support immune function, reduce oxidative stress, improve cardiometabolic health, and promote a longer healthy life expectancy [56-59]. Meanwhile, more research is needed to further elucidate the impact of food processing and industrial additives on human health.

NOTES

CONFLICTS OF INTEREST

No potential conflict of interest relevant to this article was reported.

FUNDING

The current study was funded by the National Institutes of Health (grant No. UM1 CA186107, U01 CA176726, U01 CA-167552, P01 CA87969, R01 HL034594, R01 HL035464, R01 HL60712, R01 DK120870, R01 DK126698, R01 DK119268, U2C DK129670, DK119268, R01 ES022981, and R21 AG070375). The funders had no role in the study design; in the collection, analysis, and interpretation of data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. All authors confirm the independence of researchers from funders.

Acknowledgements

None

Fig. 1.

The level of consumption of ultra-processed foods (UPFs). These surveys employed 24-hour recalls or diet records to evaluate the average consumption of UPF intake within the target population. Data were sourced from the studies cited in the text.

Fig. 2.

The relationship between food processing level and diet quality. Food in quadrant A: Low processing levels, high diet quality; Quadrant B: High processing levels, high diet quality; Quadrant C: Low processing levels, low diet quality; Quadrant D: High processing levels, low diet quality.

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Wang X, Sun Q. Ultra-Processed Foods and the Impact on Cardiometabolic Health: The Role of Diet Quality. Diabetes Metab J. 2024;48(6):1047-1055.

Received: Oct 24, 2024; Accepted: Nov 05, 2024

DOI: https://doi.org/10.4093/dmj.2024.0659.

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