Abstract

Introduction

Ultra-processed foods, as defined by the NOVA classification, are industrial formulations of substances extracted or derived from foods, that contain little or no whole food in their composition and typically it is added flavorings, dyes, emulsifiers and other additives that modify the sensory attributes of the final product. The ingredients and procedures used in the manufacture of ultra-processed foods aim to create low-cost, hyper-palatable and convenient products, with the potential to replace fresh or minimally processed foods ¹1. Monteiro CA, Cannon G, Levy RB, Moubarac JC, Louzada ML, Rauber F, et al. Ultra-processed foods: what they are and how to identify them. Public Health Nutr 2019; 22:936-41..

Food sales statistics indicate higher consumption of ultra-processed foods in high-income countries, but rapid and exponential growth in middle-income countries. Between 1998 and 2012, snacks and soft drinks sales increased by 50% in the upper-middle income countries and by more than 100% in the lower-middle income countries ²2. Monteiro CA, Moubarac JC, Cannon G, Ng SW, Popkin B. Ultra-processed products are becoming dominant in the global food system. Obes Rev 2013; 14:21-8.. National surveys show that ultra-processed foods are already half or more of the total energy consumed in some high-income countries, such as the United States, Canada and the United Kingdom ³3. Martínez Steele E, Baraldi LG, Louzada ML, Moubarac JC, Mozaffarian D, Monteiro CA. Ultra-processed foods and added sugars in the US diet: evidence from a nationally representative cross-sectional study. BMJ Open 2016; 6:e009892.^,44. Moubarac JC, Batal M, Louzada ML, Martinez Steele E, Monteiro CA. Consumption of ultra-processed foods predicts diet quality in Canada. Appetite 2017; 108:512-20.^,55. Rauber F, Louzada MLD, Steele EM, Millett C, Monteiro CA, Levy RB. Ultra-processed food consumption and chronic non-communicable diseases-related dietary nutrient profile in the UK (2008-2014). Nutrients 2018; 10:587.^,66. Machado PP, Steele EM, Levy RB, Sui ZX, Rangan A, Woods J, et al. Ultra-processed foods and recommended intake levels of nutrients linked to non-communicable diseases in Australia: evidence from a nationally representative cross-sectional study. BMJ Open 2019; 9:e029544., and between one-fifth and one-third of the energy consumed in middle-income countries, such as Chile and Mexico ⁷7. Cediel G, Reyes M, Louzada MLC, Steele EM, Monteiro CA, Corvalán C, et al. Ultra-processed foods and added sugars in the Chilean diet (2010). Public Health Nutr 2018; 21:125-33.^,88. Marron-Ponce JA, Flores M, Cediel G, Monteiro CA, Batis C. Associations between consumption of ultra-processed foods and intake of nutrients related to chronic non-communicable diseases in Mexico. PLoS One 2019; 119:1852-65.. In Brazil, surveys on the acquisition of foodstuffs for household consumption, carried out in the metropolitan areas between 1987-1988 and 2008-2009 ⁹9. Martins APB, Levy RB, Claro RM, Moubarac JC, Monteiro CA. Increased contribution of ultra-processed food products in the Brazilian diet (1987-2009). Rev Saúde Pública 2013; 47:656-65. and in the country as a whole between 2002-2003 and 2017-2018 ¹⁰10. Instituto Brasileiro de Geografia e Estatística. Pesquisa de Orçamentos Familiares 2017-2018: avaliação nutricional da disponibilidade domiciliar de alimentos no Brasil. Rio de Janeiro: Instituto Brasileiro de Geografia e Estatística; 2020., indicate systematic increases in the participation of ultra-processed foods and a reduction in concomitant of fresh or minimally processed foods and culinary ingredients.

Previous studies show that ultra-processed foods, together, have a higher energy density, more free sugar and unhealthy fats and less fiber, protein and micronutrients than non-ultra-processed foods, and that their acquisition or consumption is systematically associated with the deterioration of the nutritional food quality ³3. Martínez Steele E, Baraldi LG, Louzada ML, Moubarac JC, Mozaffarian D, Monteiro CA. Ultra-processed foods and added sugars in the US diet: evidence from a nationally representative cross-sectional study. BMJ Open 2016; 6:e009892.^,44. Moubarac JC, Batal M, Louzada ML, Martinez Steele E, Monteiro CA. Consumption of ultra-processed foods predicts diet quality in Canada. Appetite 2017; 108:512-20.^,55. Rauber F, Louzada MLD, Steele EM, Millett C, Monteiro CA, Levy RB. Ultra-processed food consumption and chronic non-communicable diseases-related dietary nutrient profile in the UK (2008-2014). Nutrients 2018; 10:587.^,66. Machado PP, Steele EM, Levy RB, Sui ZX, Rangan A, Woods J, et al. Ultra-processed foods and recommended intake levels of nutrients linked to non-communicable diseases in Australia: evidence from a nationally representative cross-sectional study. BMJ Open 2019; 9:e029544.^,77. Cediel G, Reyes M, Louzada MLC, Steele EM, Monteiro CA, Corvalán C, et al. Ultra-processed foods and added sugars in the Chilean diet (2010). Public Health Nutr 2018; 21:125-33.^,88. Marron-Ponce JA, Flores M, Cediel G, Monteiro CA, Batis C. Associations between consumption of ultra-processed foods and intake of nutrients related to chronic non-communicable diseases in Mexico. PLoS One 2019; 119:1852-65.^,1111. Louzada MLC, Ricardo CZ, Steele EM, Levy RB, Cannon G, Monteiro CA. The share of ultra-processed foods determines the overall nutritional quality of diets in Brazil. Public Health Nutr 2018; 21:94-102.^,1212. Martínez Steele E, Monteiro CA. Association between dietary share of ultra-processed foods and urinary concentrations of phytoestrogens in the US. Nutrients 2017; 9:209.. Experimental studies also show that when compared to non-ultra-processed foods, ultra-processed foods have a low satiety power and induce high glycemic responses ¹³13. Fardet A. Minimally processed foods are more satiating and less hyperglycemic than ultra-processed foods: a preliminary study with 98 ready-to-eat foods. Food Funct 2016; 7:2338-46., that are associated with a higher speed of energy intake ¹⁴14. Forde CG, Mars M, de Graaf K. Ultra-processing or oral processing? A role for energy density and eating rate in moderating energy intake from processed foods. Curr Dev Nutr 2020; 4:nzaa019. and the presence of contaminants, including toxic compounds newly formed during processing or released synthetic packaging ¹⁵15. Buckley JP, Kim H, Wong E, Rebholz CM. Ultra-processed food consumption and exposure to phthalates and bisphenols in the US National Health and Nutrition Examination Survey, 2013-2014. Am J Clin Nutr 2019; 131:105057.^,1616. Kim H, Rebholz CM, Wong E, Buckley JP. Urinary organophosphate ester concentrations in relation to ultra-processed food consumption in the general US population. Environ Res 2020; 182:109070. and create an intestinal environment that favors microbes that promote inflammatory diseases ¹⁷17. Zinöcker M, Lindseth I. The Western diet-microbiome-host interaction and its role in metabolic disease. Nutrients 2018; 10:365.. Therefore, studies with different designs have investigated the association between the consumption of ultra-processed foods and the diseases or risk factors for diseases in different populations. However, there is still no clarity about the totality of information available in this rapidly growing field of publications. Consequently, the present scope review was conducted in order to map the literature about the impact of ultra-processed foods on health.

Methods

Eligibility criteria

The question that guided the review was: “Is the consumption of ultra-processed foods (defined by the NOVA classification) associated with diseases?”. To answer it, the review considered all studies that investigated the association between the consumption of ultra-processed foods (exposure) and health outcomes, including indicators related to obesity (body mass index - BMI, waist circumference and body fat), metabolic risk markers (such as blood pressure, lipid profile and blood glucose), diabetes, cardiovascular diseases, cancer, among others. The studies should have assessed the exposure (the consumption of ultra-processed foods) based on the definition by the NOVA classification ¹1. Monteiro CA, Cannon G, Levy RB, Moubarac JC, Louzada ML, Rauber F, et al. Ultra-processed foods: what they are and how to identify them. Public Health Nutr 2019; 22:936-41.. Case studies, reviews, comments, editorials, conference proceedings or theses/dissertations or restricted to people with specific diseases were excluded.

Search strategy

The search for indexed articles was carried out in three databases: PubMed and Web of Science, of international scope, and LILACS, covering Latin America and the Caribbean. The keywords used for the exhibition of interest were “ultra-processed” combined with “food OR product” for international databases, and “ultraprocessado OR ultraprocesado OR ultra-processed” combined with “alimento OR produto OR food OR product” for the Lilacs database. No topic, language or publication date limits were used. The search included records published as of August 18th, 2020. Additionally, records identified through other sources, such as articles in press/published after the search were incorporated.

Studies selection

All titles and abstracts found in the electronic search were imported for assessment using EndNote version X9 (http://www.endnote.com/) software, with duplicate studies removed from the list. The titles and abstracts of the remaining articles were analyzed by two independent reviewers, considering the inclusion criteria mentioned above. Articles with insufficient information in the abstract were not discarded. After the selection by titles and abstracts, the same reviewers independently read the full texts to select the studies to be included. In the case of discordant selection, the studies were evaluated by a third reviewer.

Data-mapping process

Relevant data were extracted from each selected article, with the aid of a standardized spreadsheet, including the author and year of publication, study design, participants, operational definition of exposure and outcome, control variables and results. The studies were organized into three large groups according to the outcomes found and presented, within each outcome group, for adults, pregnant women, children/adolescents (in that order) and, within each population subgroup, by type of study design - randomized clinical trial, cohort, case-control, cross-sectional with national representativeness and local cross-sectional (in that order).

Methodological quality assessment

The selected articles were analyzed by the same reviewers, independently, in terms of methodological quality using the tool from the National Institutes of Health (NIH) ¹⁸18. National Institutes of Health. Study quality assessment tools. https://www.nhlbi.nih.gov/health-topics/study-quality-assessment-tools (acessado em Abr/2020).
https://www.nhlbi.nih.gov/health-topics/... . This tool provides 14 questions (specific to each study design) to be answered by the reviewers in order to assist in the internal validity assessment (or risk of bias) of each study (Supplementary Material: http://cadernos.ensp.fiocruz.br/static//arquivo/suppl-e00323020-ingles_2541.pdf). The questions are focused on key concepts related to the study design, the research question, eligibility, sample selection and recruitment, the validity of the exposure and outcome measures, losses to follow-up and statistical analysis. Reviewers can select “yes”, “no” or “cannot be determined/not reported/not applicable” in response to each question. The instrument does not provide an objective rating scale, but, for each item in which “no” was selected, reviewers are instructed to consider the risk of bias that could be introduced by this failure. For each question, there is a detailed instruction for its assessment, which has also been developed by the NIH. It was considered important for the methodological study quality, for example, the purpose clarity, the definition and appropriate description of the exposure and the outcomes, the loss of follow-up below 20% (in the case of the cohort studies) and the statistical control for at least age, sex and socioeconomic characteristics. From the questions, the reviewers attributed to each article a high, mean or low assessment of its methodological quality. Disagreements were resolved by consensus or by the third reviewer.

Results

The selection process was described in Figure 1. The search originated 1,614 articles. After removing duplicates and sorting by title and abstract, 141 articles were selected for review of the full text by reviewer 1 and 109 by reviewer 2. With the complete reading, 48 articles were selected by both reviewers and 48 conflicting articles were evaluated by the third reviewer, including 9 more articles. It was added 6 articles in press/published after the search, totaling 63 articles included and evaluated qualitatively.

The studies evaluated the association between the consumption of ultra-processed foods and weight gain (n = 3), BMI (n = 17), overweight/obesity (n = 25), waist circumference (n = 9), body fat (n = 4), hypertension/blood pressure levels (n = 4), serum lipid levels (n = 4), blood glucose (n = 1), serum levels of C-reactive protein (n = 1), subclinical atherosclerosis (n = 1), short telomeres (n = 1), urinary levels of 8-hydroxy-2’-deoxyguanosine (8-OHdG) (n = 1), metabolic syndrome (n = 4), gestational diabetes (n = 1), cardiovascular disease (n = 1), type 2 diabetes (n = 2), breast cancer (n = 2), prostate cancer (n = 2), colorectal cancer (n = 1), wheezing/asthma (n = 3), mortality from cardiovascular diseases (n = 2), all-cause mortality (n = 4), depression (n = 3), frailty syndrome (n = 1) and gastrointestinal diseases (n = 2). The studies were carried out in Brazil (n = 24), France (n = 9), Spain (n = 9), United States (n = 6), United Kingdom (n = 4), Canada (n = 4), Australia (n = 1), Norway (n = 1), Lebanon (n = 1) and Iran (n = 1). Three ecological studies evaluated data from 19 European countries, 13 Latin American countries and 80 countries from different regions, respectively. Author and year of publication, design, participants (covering sample size), operational definition of exposure and outcome, control variables and main results of these studies are described in separate tables according to the type of health outcome.

Obesity and obesity-related indicators and metabolic risk markers

Adults

Box 1 describes the studies’ main characteristics that assessed the association of the consumption of ultra-processed foods with the indicators related to obesity and metabolic risk markers in adults.

a) Obesity and obesity-related indicators

In adults, the association between the consumption of ultra-processed foods and obesity or obesity-related indicators were examined in an randomized clinical trial (high methodological quality) ¹⁹19. Hall KD, Ayuketah A, Brychta R, Cai H, Cassimatis T, Chen KY, et al. Ultra-processed diets cause excess calorie intake and weight gain: an inpatient randomized controlled trial of ad libitum food intake. Cell Metab 2019; 30:67-77.e3., four cohort studies (high quality) ²⁰20. Canhada SL, Luft VC, Giatti L, Duncan BB, Chor D, Fonseca MJM, et al. Ultra-processed foods, incident overweight and obesity, and longitudinal changes in weight and waist circumference: the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Public Health Nutr 2020; 23:1076-86.^,2121. Mendonça RD, Pimenta AM, Gea A, de la Fuente-Arrillaga C, Martínez-González MA, Lopes AC, et al. Ultraprocessed food consumption and risk of overweight and obesity: the University of Navarra Follow-Up (SUN) cohort study. Am J Clin Nutr 2016; 104:1433-40.^,2222. Rauber F, Chang K, Vamos EP, Louzada MLC, Monteiro CA, Millett CJ, et al. Ultra-processed food consumption and risk of adiposity: a prospective cohort study of UK Biobank. Eur J Nutr 2021; 60:2169-80.^,2323. Beslay M, Srour B, Méjean C, Allès B, Fiolet T, Debras C, et al. Ultra-processed food intake in association with BMI change and risk of overweight and obesity; a prospective analysis of the French NutriNet-Santé cohort. PLoS Med 2020; 17:e1003256., seven cross-sectional studies with national representativeness (five with mean ²⁴24. Adams J, White M. Characterisation of UK diets according to degree of food processing and associations with socio-demographics and obesity: cross-sectional analysis of UK National Diet and Nutrition Survey (2008-12). Int J Behav Nutr Phys Act 2015; 12:160.^,2525. Louzada ML, Baraldi LG, Steele EM, Martins AP, Canella DS, Moubarac JC, et al. Consumption of ultra-processed foods and obesity in Brazilian adolescents and adults. Prev Med 2015; 81:9-15.^,2626. Juul F, Martínez-Steele E, Parekh N, Monteiro CA, Chang VW. Ultra-processed food consumption and excess weight among US adults. Br J Nutr 2018; 120:90-100.^,2727. Machado PP, Martínez-Steele E, Levy RB, Louzada MLC, Rangan A, Woods J, et al. Ultra-processed food consumption and obesity in the Australian adult population. Nutr Diabetes 2020; 10:39.^,2828. Rauber F, Martínez-Steele E, Louzada MLC, Millett C, Monteiro CA, Levy RB. Ultra-processed food consumption and indicators of obesity in the United Kingdom population (2008-2016). PLoS One 2020; 15:e0232676. and two with low quality ²⁹29. Nardocci M, Leclerc BS, Louzada ML, Monteiro CA, Batal M, Moubarac JC. Consumption of ultra-processed foods and obesity in Canada. Can J Public Health 2019; 110:4-14.^,3030. Seale E, Greene-Finestone LS, de Groh M. Examining the diversity of ultra-processed food consumption and associated factors in Canadian adults. Appl Physiol Nutr Metab 2020; 45:857-64.), three local cross-sectional studies (two with mean ³¹31. Julia C, Martinez L, Allès B, Touvier M, Hercberg S, Méjean C, et al. Contribution of ultra-processed foods in the diet of adults from the French NutriNet-Santé study. Public Health Nutr 2018; 21:27-37.^,3232. Silva FM, Giatti L, Figueiredo RC, Molina MDB, Cardoso LD, Duncan BB, et al. Consumption of ultra-processed food and obesity: cross sectional results from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) cohort (2008-2010). Public Health Nutr 2018; 21:2271-9. and one with low quality ³³33. Djupegot IL, Nenseth CB, Bere E, Bjørnarå HBT, Helland SH, Øverby NC, et al. The association between time scarcity, sociodemographic correlates and consumption of ultra-processed foods among parents in Norway: a cross-sectional study. BMC Public Health 2017; 17:447.) and three ecological studies (two with mean ³⁴34. Pan American Health Organization. Ultra-processed food and drink products in Latin America: trends, impact on obesity, policy implications. Washington DC: Pan American Health Organization; 2015.^,3535. Vandevijvere S, Jaacks LM, Monteiro CA, Moubarac JC, Girling-Butcher M, Lee AC, et al. Global trends in ultraprocessed food and drink product sales and their association with adult body mass index trajectories. Obes Rev 2019; 20 Suppl 2:10-9. and one with low quality ³⁶36. Monteiro CA, Moubarac J-C, Levy RB, Canella DS, Louzada MLC, Cannon G. Household availability of ultra-processed foods and obesity in nineteen European countries. Public Health Nutr 2018; 21:18-26.).

After adjusting for confounders, positive associations between the consumption of ultra-processed foods and overweight/obesity or the BMI in adults were demonstrated in the four cohort studies (NutriNet Santé, ELSA-Brasil, The Sun and UK Biobank) ²⁰20. Canhada SL, Luft VC, Giatti L, Duncan BB, Chor D, Fonseca MJM, et al. Ultra-processed foods, incident overweight and obesity, and longitudinal changes in weight and waist circumference: the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Public Health Nutr 2020; 23:1076-86.^,2121. Mendonça RD, Pimenta AM, Gea A, de la Fuente-Arrillaga C, Martínez-González MA, Lopes AC, et al. Ultraprocessed food consumption and risk of overweight and obesity: the University of Navarra Follow-Up (SUN) cohort study. Am J Clin Nutr 2016; 104:1433-40.^,2222. Rauber F, Chang K, Vamos EP, Louzada MLC, Monteiro CA, Millett CJ, et al. Ultra-processed food consumption and risk of adiposity: a prospective cohort study of UK Biobank. Eur J Nutr 2021; 60:2169-80.^,2323. Beslay M, Srour B, Méjean C, Allès B, Fiolet T, Debras C, et al. Ultra-processed food intake in association with BMI change and risk of overweight and obesity; a prospective analysis of the French NutriNet-Santé cohort. PLoS Med 2020; 17:e1003256., in nine out of the ten cross-sectional studies ²⁵25. Louzada ML, Baraldi LG, Steele EM, Martins AP, Canella DS, Moubarac JC, et al. Consumption of ultra-processed foods and obesity in Brazilian adolescents and adults. Prev Med 2015; 81:9-15.^,2626. Juul F, Martínez-Steele E, Parekh N, Monteiro CA, Chang VW. Ultra-processed food consumption and excess weight among US adults. Br J Nutr 2018; 120:90-100.^,2727. Machado PP, Martínez-Steele E, Levy RB, Louzada MLC, Rangan A, Woods J, et al. Ultra-processed food consumption and obesity in the Australian adult population. Nutr Diabetes 2020; 10:39.^,2828. Rauber F, Martínez-Steele E, Louzada MLC, Millett C, Monteiro CA, Levy RB. Ultra-processed food consumption and indicators of obesity in the United Kingdom population (2008-2016). PLoS One 2020; 15:e0232676.^,2929. Nardocci M, Leclerc BS, Louzada ML, Monteiro CA, Batal M, Moubarac JC. Consumption of ultra-processed foods and obesity in Canada. Can J Public Health 2019; 110:4-14.^,3030. Seale E, Greene-Finestone LS, de Groh M. Examining the diversity of ultra-processed food consumption and associated factors in Canadian adults. Appl Physiol Nutr Metab 2020; 45:857-64.^,3131. Julia C, Martinez L, Allès B, Touvier M, Hercberg S, Méjean C, et al. Contribution of ultra-processed foods in the diet of adults from the French NutriNet-Santé study. Public Health Nutr 2018; 21:27-37.^,3232. Silva FM, Giatti L, Figueiredo RC, Molina MDB, Cardoso LD, Duncan BB, et al. Consumption of ultra-processed food and obesity: cross sectional results from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) cohort (2008-2010). Public Health Nutr 2018; 21:2271-9.^,3333. Djupegot IL, Nenseth CB, Bere E, Bjørnarå HBT, Helland SH, Øverby NC, et al. The association between time scarcity, sociodemographic correlates and consumption of ultra-processed foods among parents in Norway: a cross-sectional study. BMC Public Health 2017; 17:447. (five of which were representative samples from Brazil, Canada, United States, Australia and the United Kingdom ²⁵25. Louzada ML, Baraldi LG, Steele EM, Martins AP, Canella DS, Moubarac JC, et al. Consumption of ultra-processed foods and obesity in Brazilian adolescents and adults. Prev Med 2015; 81:9-15.^,2626. Juul F, Martínez-Steele E, Parekh N, Monteiro CA, Chang VW. Ultra-processed food consumption and excess weight among US adults. Br J Nutr 2018; 120:90-100.^,2727. Machado PP, Martínez-Steele E, Levy RB, Louzada MLC, Rangan A, Woods J, et al. Ultra-processed food consumption and obesity in the Australian adult population. Nutr Diabetes 2020; 10:39.^,2828. Rauber F, Martínez-Steele E, Louzada MLC, Millett C, Monteiro CA, Levy RB. Ultra-processed food consumption and indicators of obesity in the United Kingdom population (2008-2016). PLoS One 2020; 15:e0232676.^,2929. Nardocci M, Leclerc BS, Louzada ML, Monteiro CA, Batal M, Moubarac JC. Consumption of ultra-processed foods and obesity in Canada. Can J Public Health 2019; 110:4-14.) and in the three ecological studies (which assessed exposure to the consumption of ultra-processed foods based on purchases or sales of these foods in different countries) ³⁴34. Pan American Health Organization. Ultra-processed food and drink products in Latin America: trends, impact on obesity, policy implications. Washington DC: Pan American Health Organization; 2015.^,3535. Vandevijvere S, Jaacks LM, Monteiro CA, Moubarac JC, Girling-Butcher M, Lee AC, et al. Global trends in ultraprocessed food and drink product sales and their association with adult body mass index trajectories. Obes Rev 2019; 20 Suppl 2:10-9.^,3636. Monteiro CA, Moubarac J-C, Levy RB, Canella DS, Louzada MLC, Cannon G. Household availability of ultra-processed foods and obesity in nineteen European countries. Public Health Nutr 2018; 21:18-26.. The UK Biobank cohort study demonstrated a direct association between the consumption of ultra-processed foods and the percentage of body fat assessed by bioimpedance ²²22. Rauber F, Chang K, Vamos EP, Louzada MLC, Monteiro CA, Millett CJ, et al. Ultra-processed food consumption and risk of adiposity: a prospective cohort study of UK Biobank. Eur J Nutr 2021; 60:2169-80..

Crossover-type randomized clinical trial in adults conducted by the NIH showed an association between the exposure to a diet based on ultra-processed foods and obesity indicators. Its results showed that, when exposed to ad libitum diets with more than 80% of calories from ultra-processed foods, participants consumed, on average, 508Kcal/day more than when exposed to diets without ultra-processed foods and that, at the end of two weeks, participants increased 0.9kg in weight and 0.4kg in body fat by consuming the ultra-processed diet and decreased 0.9kg in weight and 0.3kg in body fat by consuming the non-ultra-processed diet. The ultra-processed and non-ultra-processed diets offered to the participants were matched in terms of the amount of energy, macronutrients, sugar, sodium and fiber ¹⁹19. Hall KD, Ayuketah A, Brychta R, Cai H, Cassimatis T, Chen KY, et al. Ultra-processed diets cause excess calorie intake and weight gain: an inpatient randomized controlled trial of ad libitum food intake. Cell Metab 2019; 30:67-77.e3..

After adjusting for confounders, there was a positive association between the consumption of ultra-processed foods in adults and the waist circumference in all studies in which this outcome was assessed, including two cohort studies (ELSA-Brasil and UK Biobank) ²⁰20. Canhada SL, Luft VC, Giatti L, Duncan BB, Chor D, Fonseca MJM, et al. Ultra-processed foods, incident overweight and obesity, and longitudinal changes in weight and waist circumference: the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Public Health Nutr 2020; 23:1076-86.^,2222. Rauber F, Chang K, Vamos EP, Louzada MLC, Monteiro CA, Millett CJ, et al. Ultra-processed food consumption and risk of adiposity: a prospective cohort study of UK Biobank. Eur J Nutr 2021; 60:2169-80. and three cross-sectional studies with national representativeness (United States , United Kingdom and Australia) ²⁶26. Juul F, Martínez-Steele E, Parekh N, Monteiro CA, Chang VW. Ultra-processed food consumption and excess weight among US adults. Br J Nutr 2018; 120:90-100.^,2727. Machado PP, Martínez-Steele E, Levy RB, Louzada MLC, Rangan A, Woods J, et al. Ultra-processed food consumption and obesity in the Australian adult population. Nutr Diabetes 2020; 10:39.^,2828. Rauber F, Martínez-Steele E, Louzada MLC, Millett C, Monteiro CA, Levy RB. Ultra-processed food consumption and indicators of obesity in the United Kingdom population (2008-2016). PLoS One 2020; 15:e0232676. and a local cross-sectional ³²32. Silva FM, Giatti L, Figueiredo RC, Molina MDB, Cardoso LD, Duncan BB, et al. Consumption of ultra-processed food and obesity: cross sectional results from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) cohort (2008-2010). Public Health Nutr 2018; 21:2271-9..

b) Metabolic risk markers

In adults, the association between the consumption of ultra-processed foods and hypertension was examined in a cohort study (high methodological quality) ³⁷37. Mendonça RD, Lopes ACS, Pimenta AM, Gea A, Martínez-González MA, Bes-Rastrollo M. Ultra-processed food consumption and the incidence of hypertension in a Mediterranean cohort: The Seguimiento Universidad de Navarra Project. Am J Hypertens 2017; 30:358-66., metabolic syndrome in three cross-sectional studies (one with mean ³⁸38. Martínez Steele E, Juul F, Neri D, Rauber F, Monteiro CA. Dietary share of ultra-processed foods and metabolic syndrome in the US adult population. Prev Med 2019; 125:40-8. and two with low ³⁹39. Lavigne-Robichaud M, Moubarac J-C, Lantagne-Lopez S, Johnson-Down L, Batal M, Sidi EAL, et al. Diet quality indices in relation to metabolic syndrome in an Indigenous Cree (Eeyouch) population in northern Quebec, Canada. Public Health Nutr 2018; 21:172-80.^,4040. Nasreddine L, Tamim H, Itani L, Nasrallah MP, Isma'eel H, Nakhoul NF, et al. A minimally processed dietary pattern is associated with lower odds of metabolic syndrome among Lebanese adults. Public Health Nutr 2018; 21:160-71.), serum levels of C-reactive protein under cross-sectional study (mean quality) ⁴¹41. Lopes A, Araújo LF. Association between consumption of ultra-processed foods and serum C-reactive protein levels: cross-sectional results from the ELSA-Brasil study. São Paulo Med J 2019; 137:169-76., subclinical atherosclerosis in a cross-sectional study (mean quality) ⁴²42. Montero-Salazar H, Donat-Vargas C, Moreno-Franco B, Sandoval-Insausti H, Civeira F, Laclaustra M, et al. High consumption of ultra-processed food may double the risk of subclinical coronary atherosclerosis: the Aragon Workers' Health Study (AWHS). BMC Med 2020; 18:235. and telomere length in a cross-sectional study (mean quality) ⁴³43. Alonso-Pedrero L, Ojeda-Rodríguez A, Martínez-González MA, Zalba G, Bes-Rastrollo M, Marti A. Ultra-processed food consumption and the risk of short telomeres in an elderly population of the Seguimiento Universidad de Navarra (SUN) Project. Am J Clin Nutr 2020; 111:1259-66..

After adjusting for confounders, The Sun cohort study found, in Spanish middle-aged adults, a positive association between the consumption of ultra-processed foods and the risk of developing hypertension ³⁷37. Mendonça RD, Lopes ACS, Pimenta AM, Gea A, Martínez-González MA, Bes-Rastrollo M. Ultra-processed food consumption and the incidence of hypertension in a Mediterranean cohort: The Seguimiento Universidad de Navarra Project. Am J Hypertens 2017; 30:358-66..

After adjusting for confounders, a positive association between the consumption of ultra-processed foods and metabolic syndrome in adults was found in two out of three studies that assessed this outcome, those were the cross-sectional study with a sample from the National Health and Nutrition Examination Survey (NHANES) ³⁸38. Martínez Steele E, Juul F, Neri D, Rauber F, Monteiro CA. Dietary share of ultra-processed foods and metabolic syndrome in the US adult population. Prev Med 2019; 125:40-8. and one local study with Canadian indigenous people ³⁹39. Lavigne-Robichaud M, Moubarac J-C, Lantagne-Lopez S, Johnson-Down L, Batal M, Sidi EAL, et al. Diet quality indices in relation to metabolic syndrome in an Indigenous Cree (Eeyouch) population in northern Quebec, Canada. Public Health Nutr 2018; 21:172-80..

A cross-sectional study with middle-aged Brazilian adults showed that, among women, after adjusting for sociodemographic characteristics, smoking status and physical activity, the consumption of ultra-processed foods was associated with higher levels of C-reactive protein; however, this association lost statistical significance with the inclusion of BMI in the model. Among men, there was no association between ingestion of ultra-processed foods and C-reactive protein ⁴¹41. Lopes A, Araújo LF. Association between consumption of ultra-processed foods and serum C-reactive protein levels: cross-sectional results from the ELSA-Brasil study. São Paulo Med J 2019; 137:169-76.. A cross-sectional study with Spanish adult men demonstrated, after adjusting for confounders, an association between the consumption of ultra-processed foods and the coronary calcium score, which assesses subclinical atherosclerosis ⁴²42. Montero-Salazar H, Donat-Vargas C, Moreno-Franco B, Sandoval-Insausti H, Civeira F, Laclaustra M, et al. High consumption of ultra-processed food may double the risk of subclinical coronary atherosclerosis: the Aragon Workers' Health Study (AWHS). BMC Med 2020; 18:235.. A cross-sectional study with Spanish adults demonstrated, after adjusting for confounders, an association between the consumption of ultra-processed foods and short telomeres, an aging biomarker ⁴³43. Alonso-Pedrero L, Ojeda-Rodríguez A, Martínez-González MA, Zalba G, Bes-Rastrollo M, Marti A. Ultra-processed food consumption and the risk of short telomeres in an elderly population of the Seguimiento Universidad de Navarra (SUN) Project. Am J Clin Nutr 2020; 111:1259-66..

Pregnant woman

Box 2 describes the studies’ main characteristics that assessed the association between the consumption of ultra-processed foods and the indicators related to obesity and metabolic risk markers in pregnant women.

a) Obesity and obesity-related indicators

In pregnant women, the association between the consumption of ultra-processed food and the obesity-related indicators was examined in two cohort studies (one with high methodological quality ⁴⁴44. Rohatgi KW, Tinius RA, Cade WT, Steele EM, Cahill AG, Parra DC. Relationships between consumption of ultra-processed foods, gestational weight gain and neonatal outcomes in a sample of US pregnant women. PeerJ 2017; 5:e4091-e. and the other with mean ⁴⁵45. Gomes CB, Malta MB, Benício MHD'A, Carvalhaes MABL. Consumption of ultra-processed foods in the third gestational trimester and increased weight gain: a Brazilian cohort study. Public Health Nutr 2021; 24:3304-12.) and two cross-sectional studies (both with low quality ⁴⁶46. Crivellenti LC, Zuccolotto DCC, Sartorelli DS. Association between the Diet Quality Index Adapted for Pregnant Women (IQDAG) and excess maternal body weight. Rev Bras Saúde Mater Infant 2019; 19:275-83.^,4747. Sartorelli DS, Crivellenti LC, Zuccolotto DCC, Franco LJ. Relationship between minimally and ultra-processed food intake during pregnancy with obesity and gestational diabetes mellitus. Cad Saúde Pública 2019; 35:e00049318.). After adjusting for confounders, the cohort study demonstrated, in pregnant women from the United States, that the participation of ultra-processed foods in the diet was associated with an increase in gestational weight gain (and higher values of thigh and subscapular folds and percentage of body adiposity of the newborn) ⁴⁴44. Rohatgi KW, Tinius RA, Cade WT, Steele EM, Cahill AG, Parra DC. Relationships between consumption of ultra-processed foods, gestational weight gain and neonatal outcomes in a sample of US pregnant women. PeerJ 2017; 5:e4091-e.. A cohort study with Brazilian pregnant women demonstrated, after adjusting for confounders, that the consumption of ultra-processed foods in the 2nd and 3rd trimesters of pregnancy was positively associated with the average weight gain in the same period ⁴⁵45. Gomes CB, Malta MB, Benício MHD'A, Carvalhaes MABL. Consumption of ultra-processed foods in the third gestational trimester and increased weight gain: a Brazilian cohort study. Public Health Nutr 2021; 24:3304-12.. The two cross-sectional studies, both conducted in a medium-sized Brazilian city, demonstrate, after adjusting for confounders, a positive association of the consumption of ultra-processed foods with overweight/obesity in pregnant women ⁴⁶46. Crivellenti LC, Zuccolotto DCC, Sartorelli DS. Association between the Diet Quality Index Adapted for Pregnant Women (IQDAG) and excess maternal body weight. Rev Bras Saúde Mater Infant 2019; 19:275-83.^,4747. Sartorelli DS, Crivellenti LC, Zuccolotto DCC, Franco LJ. Relationship between minimally and ultra-processed food intake during pregnancy with obesity and gestational diabetes mellitus. Cad Saúde Pública 2019; 35:e00049318..

b) Metabolic risk markers

In pregnant women, a small cross-sectional study (low quality) carried out in a medium-sized city in Brazil assessed the association between the consumption of ultra-processed foods and gestational diabetes and found no significant results ⁴⁷47. Sartorelli DS, Crivellenti LC, Zuccolotto DCC, Franco LJ. Relationship between minimally and ultra-processed food intake during pregnancy with obesity and gestational diabetes mellitus. Cad Saúde Pública 2019; 35:e00049318..

Children and adolescents

Box 3 describes the studies’ main characteristics that assessed the association of the consumption of ultra-processed foods with the indicators related to obesity and metabolic risk markers in children and adolescents.

a) Obesity and obesity-related indicators

In children and adolescents, the association between the consumption of ultra-processed foods and obesity-related indicators was examined in five cohort studies (three with high methodological quality ⁴⁸48. Bawaked RA, Fernández-Barrés S, Navarrete-Muñoz EM, González-Palacios S, Guxens M, Irizar A, et al. Impact of lifestyle behaviors in early childhood on obesity and cardiometabolic risk in children: results from the Spanish INMA birth cohort study. Pediatr Obes 2020; 15:e12590.^,4949. Costa CS, Rauber F, Leffa PS, Sangalli CN, Campagnolo PDB, Vitolo MR. Ultra-processed food consumption and its effects on anthropometric and glucose profile: a longitudinal study during childhood. Nutr Metab Cardiovasc Dis 2019; 29:177-84.^,5050. Costa CS, Assunção MCF, Mola CL, Cardoso JS, Matijasevich A, Barros AJD, et al. Role of ultra-processed food in fat mass index from 6 to 11 years of age: a cohort study. Int J Epidemiol 2021; 50:256-65., one with mean ⁵¹51. Cunha DB, Costa THM, Veiga GV, Pereira RA, Sichieri R. Ultra-processed food consumption and adiposity trajectories in a Brazilian cohort of adolescents: ELANA study. Nutr Diabetes 2018; 8:28. and one with low ⁵²52. Gadelha P, Arruda IKG, Coelho PBP, Queiroz PMA, Maio R, Diniz AD. Consumption of ultraprocessed foods, nutritional status, and dyslipidemia in schoolchildren: a cohort study. Eur J Clin Nutr 2019; 73:1194-9. - the latter making only a cross-sectional analysis at two points of the cohort), in four small local cross-sectional studies ⁵³53. De Melo ISV, Costa C, dos Santos JVL, Santos AF, Florencio T, Bueno NB. Consumption of minimally processed food is inversely associated with excess weight in adolescents living in an underdeveloped city. PLoS One 2017; 12:e0188401.^,5454. Enes CC, Camargo CM, Justino MIC. Ultra-processed food consumption and obesity in adolescents. Rev Nutr (Online) 2019; 32:e180170.^,5555. D'Avila HF, Kirsten VR. Energy intake from ultra-processed foods among adolescents. Rev Paul Pediatr 2017; 35:54-60.^,5656. Lacerda AT, Carmo AS, Sousa TM, Santos LC. Participation of ultra-processed foods in Brazilian school children's diet and associated factors. Rev Paul Pediatr 2020; 38:e2019034. (all with low quality) and in a cross-sectional study with national representativeness of the adolescent population in Brazil (mean quality) ²⁵25. Louzada ML, Baraldi LG, Steele EM, Martins AP, Canella DS, Moubarac JC, et al. Consumption of ultra-processed foods and obesity in Brazilian adolescents and adults. Prev Med 2015; 81:9-15..

After adjusting for confounders, a positive association between the consumption of ultra-processed foods and overweight/obesity or BMI’s magnitude was demonstrated in the study with national representativeness of the adolescent population in Brazil ²⁵25. Louzada ML, Baraldi LG, Steele EM, Martins AP, Canella DS, Moubarac JC, et al. Consumption of ultra-processed foods and obesity in Brazilian adolescents and adults. Prev Med 2015; 81:9-15.. A small cross-sectional study demonstrated, after adjusting for confounders, an association between the consumption of ultra-processed foods and excess weight in Brazilian schoolchildren ⁵⁶56. Lacerda AT, Carmo AS, Sousa TM, Santos LC. Participation of ultra-processed foods in Brazilian school children's diet and associated factors. Rev Paul Pediatr 2020; 38:e2019034.. A study of the Spanish birth cohort INMA (Infancia y Medio Ambiente) demonstrated that low intake of ultra-processed foods at 4 years old was associated with a lower z-score of BMI at 7 years old in a model adjusted for sociodemographic characteristics, but the association became “borderline” (p-value = 0,07) with the addition of the maternal BMI variable in the model ⁴⁸48. Bawaked RA, Fernández-Barrés S, Navarrete-Muñoz EM, González-Palacios S, Guxens M, Irizar A, et al. Impact of lifestyle behaviors in early childhood on obesity and cardiometabolic risk in children: results from the Spanish INMA birth cohort study. Pediatr Obes 2020; 15:e12590.. A Pelotas (Rio Grande do Sul State, Brazil) birth cohort study in 2004 found an association between the increase in consumption of ultra-processed foods between 6 and 11 years old and the change in body fat content (assessed by air displacement plethysmography) in the same period ⁵⁰50. Costa CS, Assunção MCF, Mola CL, Cardoso JS, Matijasevich A, Barros AJD, et al. Role of ultra-processed food in fat mass index from 6 to 11 years of age: a cohort study. Int J Epidemiol 2021; 50:256-65..

The association between the consumption of ultra-processed foods and waist circumference was demonstrated in one of the two cohorts in which this outcome was assessed. After adjusting for confounders, a 4-year study that followed a cohort of children from 3 to 4 years old of low socioeconomic status demonstrated that the intake of ultra-processed foods at preschool-age was positively associated with an increase in waist circumference values from preschool-age to school-age ⁴⁹49. Costa CS, Rauber F, Leffa PS, Sangalli CN, Campagnolo PDB, Vitolo MR. Ultra-processed food consumption and its effects on anthropometric and glucose profile: a longitudinal study during childhood. Nutr Metab Cardiovasc Dis 2019; 29:177-84..

b) Metabolic risk markers

In children and adolescents, studies assessed the association between the consumption of ultra-processed foods and blood pressure levels in a cohort study (high methodological quality) ⁴⁸48. Bawaked RA, Fernández-Barrés S, Navarrete-Muñoz EM, González-Palacios S, Guxens M, Irizar A, et al. Impact of lifestyle behaviors in early childhood on obesity and cardiometabolic risk in children: results from the Spanish INMA birth cohort study. Pediatr Obes 2020; 15:e12590. and two local cross-sectional studies (both with low quality) ⁵³53. De Melo ISV, Costa C, dos Santos JVL, Santos AF, Florencio T, Bueno NB. Consumption of minimally processed food is inversely associated with excess weight in adolescents living in an underdeveloped city. PLoS One 2017; 12:e0188401.^,5555. D'Avila HF, Kirsten VR. Energy intake from ultra-processed foods among adolescents. Rev Paul Pediatr 2017; 35:54-60., serum lipids in two cohort studies (high quality) ⁵⁷57. Rauber F, Campagnolo PDB, Hoffman DJ, Vitolo MR. Consumption of ultra-processed food products and its effects on children's lipid profiles: a longitudinal study. Nutr Metabol Cardiovasc Dis 2015; 25:116-22.^,5858. Leffa PS, Hoffman DJ, Rauber F, Sangalli CN, Valmórbida JL, Vitolo MR. Longitudinal associations between ultra-processed foods and blood lipids in childhood. Br J Nutr 2020; 124:341-8. and two cross-sectional analysis nested in a cohort study (one with high quality ⁴⁸48. Bawaked RA, Fernández-Barrés S, Navarrete-Muñoz EM, González-Palacios S, Guxens M, Irizar A, et al. Impact of lifestyle behaviors in early childhood on obesity and cardiometabolic risk in children: results from the Spanish INMA birth cohort study. Pediatr Obes 2020; 15:e12590. and one with low ⁵²52. Gadelha P, Arruda IKG, Coelho PBP, Queiroz PMA, Maio R, Diniz AD. Consumption of ultraprocessed foods, nutritional status, and dyslipidemia in schoolchildren: a cohort study. Eur J Clin Nutr 2019; 73:1194-9.), blood glucose in a cohort study (high quality) ⁴⁹49. Costa CS, Rauber F, Leffa PS, Sangalli CN, Campagnolo PDB, Vitolo MR. Ultra-processed food consumption and its effects on anthropometric and glucose profile: a longitudinal study during childhood. Nutr Metab Cardiovasc Dis 2019; 29:177-84., metabolic syndrome in a cross-sectional study (low quality) ⁵⁹59. Tavares LF, Fonseca SC, Rosa MLG, Yokoo EM. Relationship between ultra-processed foods and metabolic syndrome in adolescents from a Brazilian Family Doctor Program. Public Health Nutr 2012; 15:82-7. and urinary levels of 8-OHdG in a cross-sectional study (low quality) ⁶⁰60. Edalati S, Bagherzadeh F, Jafarabadi MA, Ebrahimi-Mamaghani M. Higher ultra-processed food intake is associated with higher DNA damage in healthy adolescents. Br J Nutr 2021; 125:568-76..

A study of the Spanish birth cohort INMA showed that low intake of ultra-processed foods at 4 years old was associated with lower values of diastolic blood pressure at 7 years old. No associations were found for this outcome in cross-sectional studies ⁴⁸48. Bawaked RA, Fernández-Barrés S, Navarrete-Muñoz EM, González-Palacios S, Guxens M, Irizar A, et al. Impact of lifestyle behaviors in early childhood on obesity and cardiometabolic risk in children: results from the Spanish INMA birth cohort study. Pediatr Obes 2020; 15:e12590..

After adjusting for confounders, a 4-year study that followed a cohort of children from 3 to 4 years old of low socioeconomic status demonstrated that the intake of ultra-processed foods at preschool-age was associated with increases in serum cholesterol and LDL-cholesterol in preschool-age to school-age. After adjusting for confounders, a cohort study showed that the intake of ultra-processed foods at 3 years old was positively associated with serum levels of total cholesterol and triglycerides at 6 years old ⁵⁸58. Leffa PS, Hoffman DJ, Rauber F, Sangalli CN, Valmórbida JL, Vitolo MR. Longitudinal associations between ultra-processed foods and blood lipids in childhood. Br J Nutr 2020; 124:341-8.. No associations were found for this outcome in cross-sectional studies ⁵⁷57. Rauber F, Campagnolo PDB, Hoffman DJ, Vitolo MR. Consumption of ultra-processed food products and its effects on children's lipid profiles: a longitudinal study. Nutr Metabol Cardiovasc Dis 2015; 25:116-22.. No association was found between the consumption of ultra-processed foods and blood glucose ⁴⁹49. Costa CS, Rauber F, Leffa PS, Sangalli CN, Campagnolo PDB, Vitolo MR. Ultra-processed food consumption and its effects on anthropometric and glucose profile: a longitudinal study during childhood. Nutr Metab Cardiovasc Dis 2019; 29:177-84..

A study with adolescents between 12 and 19 years old in the city of Rio de Janeiro, Brazil, found a positive cross-sectional association between the consumption of ultra-processed foods and the metabolic syndrome ⁵⁹59. Tavares LF, Fonseca SC, Rosa MLG, Yokoo EM. Relationship between ultra-processed foods and metabolic syndrome in adolescents from a Brazilian Family Doctor Program. Public Health Nutr 2012; 15:82-7..

A study with Iranian adolescents between 13 to 19 years old found, after adjusting for confounders, a cross-sectional association between the consumption of ultra-processed foods and urinary levels of 8-OHdG, an oxidative DNA damage marker ⁶⁰60. Edalati S, Bagherzadeh F, Jafarabadi MA, Ebrahimi-Mamaghani M. Higher ultra-processed food intake is associated with higher DNA damage in healthy adolescents. Br J Nutr 2021; 125:568-76..

Finally, an ecological study conducted with a survey of Brazilian family budgets showed, after adjusting for confounders, that the availability of ultra-processed foods at home was positively associated with the mean BMI value and the prevalence of overweight and obesity among its residents of all ages ⁶¹61. Canella DS, Levy RB, Martins AP, Claro RM, Moubarac JC, Baraldi LG, et al. Ultra-processed food products and obesity in Brazilian households (2008-2009). PLoS One 2014; 9:e92752..

Cardiovascular diseases, type 2 diabetes, cancer, asthma and mortality

Box 4 describes the studies’ main characteristics that assessed the association between the consumption of ultra-processed foods, cardiovascular diseases, type diabetes, cancer and mortality in adults and asthma in children.

Adults

a) Cardiovascular diseases

The association between the consumption of ultra-processed foods and cardiovascular diseases was examined in a NutriNet Santé cohort study of French adults (high methodological quality). After adjusting for confounders, the consumption of ultra-processed foods was associated with a higher incidence of cardiovascular disease in general and for the subgroups of coronary heart disease and cerebrovascular diseases ⁶²62. Srour B, Fezeu LK, Kesse-Guyot E, Alles B, Mejean C, Andrianasolo RM, et al. Ultra-processed food intake and risk of cardiovascular disease: prospective cohort study (NutriNet-Santé). BMJ 2019; 365:l1451..

b) Type 2 diabetes

The association between the consumption of ultra-processed foods and type 2 diabetes in adults was examined in two cohort studies (high methodological quality). Analysis of the NutriNet Santé ⁶³63. Srour B, Fezeu LK, Kesse-Guyot E, Alles B, Debras C, Druesne-Pecollo N, et al. Ultraprocessed food consumption and risk of type 2 diabetes among participants of the NutriNet-Santé prospective cohort. JAMA Intern Med 2020; 180:283-91. and UK Biobank ⁶⁴64. Levy RB, Rauber F, Chang K, Louzada MLC, Monteiro CA, Millett C, et al. Association between ultra-processed food consumption and type 2 diabetes incidence: a prospective cohort study using UK Biobank. Clin Nutr 2021; 40:3608-14. cohorts demonstrated associations (after adjusting for confounders) between the consumption of ultra-processed foods and the incidence of type 2 diabetes.

c) Cancer

The association between the consumption of ultra-processed foods and general, prostate, colorectal and breast cancer in adults was examined in a cohort study (high methodological quality) ⁶⁵65. Fiolet T, Srour B, Sellem L, Kesse-Guyot E, Allès B, Méjean C, et al. Consumption of ultra-processed foods and cancer risk: results from NutriNet-Santé prospective cohort. BMJ 2018; 360:k322. and breast and prostate cancer also in two case-control studies (mean and low quality, respectively) ⁶⁶66. Queiroz SA, Sousa IM, Silva FRD, Lyra CD, Fayh APT. Nutritional and environmental risk factors for breast cancer: a case-control study. Sci Med (Porto Alegre, Online) 2018; 28:ID28723.^,6767. Trudeau K, Rousseau M-C, Parent M-E. Extent of food processing and risk of prostate cancer: The PROtEuS Study in Montreal, Canada. Nutrients 2020; 12:637..

After adjusting for confounders, a study carried out in the NutriNet Santé cohort showed direct associations for general and breast cancer (but not for prostate and colorectal cancer) ⁶⁵65. Fiolet T, Srour B, Sellem L, Kesse-Guyot E, Allès B, Méjean C, et al. Consumption of ultra-processed foods and cancer risk: results from NutriNet-Santé prospective cohort. BMJ 2018; 360:k322.. A hospital-based case-control study conducted in Brazil showed that participants with breast cancer had a higher intake of ultra-processed foods when compared to those in the control group (non-cancer patients from the same hospital) ⁶⁶66. Queiroz SA, Sousa IM, Silva FRD, Lyra CD, Fayh APT. Nutritional and environmental risk factors for breast cancer: a case-control study. Sci Med (Porto Alegre, Online) 2018; 28:ID28723..

d) Mortality

The association between the consumption of ultra-processed foods and all-cause mortality was assessed in four cohort studies (high methodological quality) ⁶⁸68. Kim H, Hu EA, Rebholz CM. Ultra-processed food intake and mortality in the USA: results from the Third National Health and Nutrition Examination Survey (NHANES III, 1988-1994). Public Health Nutr 2019; 22:1777-85.^,6969. Rico-Campà A, Martínez-González MA, Alvarez-Alvarez I, Mendonça RD, de la Fuente-Arrillaga C, Gómez-Donoso C, et al. Association between consumption of ultra-processed foods and all cause mortality: SUN prospective cohort study. BMJ 2019; 365:l1949.^,7070. Schnabel L, Kesse-Guyot E, Alles B, Touvier M, Srour B, Hercberg S, et al. Association between ultraprocessed food consumption and risk of mortality among middle-aged adults in France. JAMA Intern Med 2019; 179:490-8.^,7171. Blanco-Rojo R, Sandoval-Insausti H, Lopez-Garcia E, Graciani A, Ordovas JM, Banegas JR, et al. Consumption of ultra-processed foods and mortality: a national prospective cohort in Spain. Mayo Clin Proc 2019; 94:2178-88. and mortality from cardiovascular diseases was studied in two cohort studies (high methodological quality) ⁶⁸68. Kim H, Hu EA, Rebholz CM. Ultra-processed food intake and mortality in the USA: results from the Third National Health and Nutrition Examination Survey (NHANES III, 1988-1994). Public Health Nutr 2019; 22:1777-85.^,7272. Zhong G-C, Gu H-T, Peng Y, Wang K, Wu Y-Q-L, Hu T-Y, et al. Association of ultra-processed food consumption with cardiovascular mortality in the US population: long-term results from a large prospective multicenter study. Int J Behav Nutr Phys Act 2021; 18:21.. After adjusting for possible confounders, analysis of the NHANES III ⁶⁸68. Kim H, Hu EA, Rebholz CM. Ultra-processed food intake and mortality in the USA: results from the Third National Health and Nutrition Examination Survey (NHANES III, 1988-1994). Public Health Nutr 2019; 22:1777-85. follow-up study, and of The Sun study ⁶⁹69. Rico-Campà A, Martínez-González MA, Alvarez-Alvarez I, Mendonça RD, de la Fuente-Arrillaga C, Gómez-Donoso C, et al. Association between consumption of ultra-processed foods and all cause mortality: SUN prospective cohort study. BMJ 2019; 365:l1949., NutriNet Santé ⁷⁰70. Schnabel L, Kesse-Guyot E, Alles B, Touvier M, Srour B, Hercberg S, et al. Association between ultraprocessed food consumption and risk of mortality among middle-aged adults in France. JAMA Intern Med 2019; 179:490-8. and Study on Nutrition and Cardiovascular Risk in Spain (ENRICA) ⁷¹71. Blanco-Rojo R, Sandoval-Insausti H, Lopez-Garcia E, Graciani A, Ordovas JM, Banegas JR, et al. Consumption of ultra-processed foods and mortality: a national prospective cohort in Spain. Mayo Clin Proc 2019; 94:2178-88. cohorts found dose-response associations between the consumption of ultra-processed foods and the risk of all-cause death. After adjusting for possible confounders, association and dose-response between the consumption of ultra-processed foods and the risk of death from cardiovascular diseases was found in the PLCO Cancer Screening Trial⁷²72. Zhong G-C, Gu H-T, Peng Y, Wang K, Wu Y-Q-L, Hu T-Y, et al. Association of ultra-processed food consumption with cardiovascular mortality in the US population: long-term results from a large prospective multicenter study. Int J Behav Nutr Phys Act 2021; 18:21. study, but not in the NHANES III ⁶⁸68. Kim H, Hu EA, Rebholz CM. Ultra-processed food intake and mortality in the USA: results from the Third National Health and Nutrition Examination Survey (NHANES III, 1988-1994). Public Health Nutr 2019; 22:1777-85. follow-up study.

Children

a) Asthma or wheezing

The association between the consumption of ultra-processed foods and asthma or wheezing was assessed in adolescents in a cohort study (high methodological quality) ⁷³73. Azeredo CM, Cortese M, Costa CD, Bjornevik K, Barros AJD, Barros FC, et al. Ultra-processed food consumption during childhood and asthma in adolescence: data from the 2004 Pelotas birth cohort study. Pediatr Allergy Immunol 2020; 31:27-37. and two cross-sectional studies with national representativeness samples (both with medium quality) ⁷⁴74. Melo B, Rezende L, Machado P, Gouveia N, Levy R. Associations of ultra-processed food and drink products with asthma and wheezing among Brazilian adolescents. Pediatr Allergy Immunol 2018; 29:504-11.^,7575. Elias BC, Silva JB, Mais LA, Warkentin S, Konstantyner T, Solé D. Factors associated with asthma in brazilian adolescents: national adolescent school-based health survey (pense-2012). Rev Paul Pediatr 2019; 37:406-13..

A Pelotas birth cohort study in 2004 found no association between the consumption of ultra-processed foods at 6 years old and the occurrence of wheezing or asthma at 11 years old ⁷³73. Azeredo CM, Cortese M, Costa CD, Bjornevik K, Barros AJD, Barros FC, et al. Ultra-processed food consumption during childhood and asthma in adolescence: data from the 2004 Pelotas birth cohort study. Pediatr Allergy Immunol 2020; 31:27-37.. The two cross-sectional studies were carried out with a representative sample of Brazilian adolescents from the 9th grade. After adjusting for possible confounders, they found dose-response associations between an ultra-processed food consumption score and the occurrence of asthma and wheezing ⁷⁴74. Melo B, Rezende L, Machado P, Gouveia N, Levy R. Associations of ultra-processed food and drink products with asthma and wheezing among Brazilian adolescents. Pediatr Allergy Immunol 2018; 29:504-11.^,7575. Elias BC, Silva JB, Mais LA, Warkentin S, Konstantyner T, Solé D. Factors associated with asthma in brazilian adolescents: national adolescent school-based health survey (pense-2012). Rev Paul Pediatr 2019; 37:406-13..

Frailty, gastrointestinal diseases and depression

Box 5 describes the studies’ main characteristics that assessed the association between the consumption of ultra-processed foods and frailty and gastrointestinal diseases in adults and depression in adults and pregnant women.

Adults

a) Frailty

The association between the consumption of ultra-processed foods and frailty was examined in a cohort study of Spaniards with 60 years old (high methodological quality). After adjusting for confounders, the consumption of ultra-processed foods was associated with a higher incidence of frailty ⁷⁶76. Sandoval-Insausti H, Blanco-Rojo R, Graciani A, López-García E, Moreno-Franco B, Laclaustra M, et al. Ultra-processed food consumption and incident frailty: a prospective cohort study of older adults. J Gerontol A Biol Sci Med Sci 2020; 75:1126-33..

b) Gastrointestinal diseases

The association between the consumption of ultra-processed foods and gastrointestinal disorders in adults was examined in a cohort study (high methodological quality) ⁷⁷77. Vasseur P, Dugelay E, Benamouzig R, Savoye G, Lan A, Srour B, et al. Dietary patterns, ultra-processed food, and the risk of inflammatory bowel diseases in the NutriNet-Santé cohort. Inflamm Bowel Dis 2021; 27:65-73. and a cross-sectional study (mean quality) ⁷⁸78. Schnabel L, Buscail C, Sabate J-M, Bouchoucha M, Kesse-Guyot E, Allès B, et al. Association between ultra-processed food consumption and functional gastrointestinal disorders: results from the French NutriNet-Santé cohort. Am J Gastroenterol 2018; 113:1217-28..

A study carried out with the French cohort NutriNet Santé showed no association between the consumption of ultra-processed foods and the incidence of inflammatory bowel diseases after adjusting for confounders (only in the gross analysis) ⁷⁷77. Vasseur P, Dugelay E, Benamouzig R, Savoye G, Lan A, Srour B, et al. Dietary patterns, ultra-processed food, and the risk of inflammatory bowel diseases in the NutriNet-Santé cohort. Inflamm Bowel Dis 2021; 27:65-73.. A cross-sectional study demonstrated, after adjusting for confounders, the association with the occurrence of irritable bowel syndrome and functional dyspepsia ⁷⁸78. Schnabel L, Buscail C, Sabate J-M, Bouchoucha M, Kesse-Guyot E, Allès B, et al. Association between ultra-processed food consumption and functional gastrointestinal disorders: results from the French NutriNet-Santé cohort. Am J Gastroenterol 2018; 113:1217-28..

c) Depression

The association between the consumption of ultra-processed foods and depression/depressive symptoms in adults was examined in two cohort studies (high methodological quality). Results of studies carried out in the NutriNet Santé ⁷⁹79. Adjibade M, Julia C, Allès B, Touvier M, Lemogne C, Srour B, et al. Prospective association between ultra-processed food consumption and incident depressive symptoms in the French NutriNet-Santé cohort. BMC Med 2019; 17:78. and The Sun ⁸⁰80. Gómez-Donoso C, Sánchez-Villegas A, Martínez-González MA, Gea A, Mendonça RD, Lahortiga-Ramos F, et al. Ultra-processed food consumption and the incidence of depression in a Mediterranean cohort: The Sun. Eur J Nutr 2020; 59:1093-103. cohort showed associations (after adjusting for confounders) between the consumption of ultra-processed foods and the incidence of depression.

The overall evidence quality was assessed as high for the association between the consumption of ultra-processed foods and obesity and mortality indicators, moderate for type 2 diabetes and depression and low for the other outcomes.

Pregnant woman

a) Depression

In pregnant women, a cross-sectional study (low methodological quality) carried out in a medium-sized city in Brazil showed, after adjusting for confounders, a positive association between the consumption of ultra-processed foods and symptoms of depression ⁸¹81. Badanai NL, Zuccolotto DCC, Crivellenti LC, Sartorelli DS. Association of dietary patterns and degree of food processing with feelings of depression in pregnancy. Rev Bras Saúde Mater Infant 2019; 19:581-90..

Discussion

This review described the results of several studies that showed the association between the consumption of ultra-processed foods and some non-communicable diseases and their risk factors. The evidence seems particularly consistent with regard to obesity in adults, whose association with the consumption of ultra-processed foods has been demonstrated, with dose-response effect, in cross-sectional studies with representative samples from five countries (United States, United Kingdom, Australia, Canada and Brazil), in four large cohort studies and in a randomized clinical trial. Large cohort studies have also shown an association between the consumption of ultra-processed foods and the risk of cardiovascular diseases, type 2 diabetes and breast cancer - even after adjusting for obesity. Two cohort studies also demonstrated an association between the consumption of ultra-processed foods and the incidence of depression. Additionally, four large cohort studies have described the association between the consumption of ultra-processed foods and all-cause mortality, the most important indicator of disease burden. Most of these studies were carried out in high-income countries and in adults. In children, studies are limited in number and methodological quality, although the available evidence suggests associations in the same direction. No studies that evaluated outcomes of non-chronic diseases were found.

Although several mechanisms are not completely elucidated, numerous characteristics of ultra-processed foods, determined by the highly processed nature of these foods, contribute to their role in disease risk.

Ultra-processed foods are convenient, practical and portable. They are generally developed to be consumed anywhere. Most of the time, they are sold as snacks, drinks or dishes ready or semi-ready for consumption and promoted by aggressive marketing strategies. Therefore, they are easily associated with ways of eating that induce excessive and “unnoticed” consumption of calories, in addition to replacing freshly made meals, based on fresh or minimally processed foods. Forde et al. ¹⁴14. Forde CG, Mars M, de Graaf K. Ultra-processing or oral processing? A role for energy density and eating rate in moderating energy intake from processed foods. Curr Dev Nutr 2020; 4:nzaa019. showed that people exposed to ultra-processed foods ate meals 50% faster than those exposed to non-ultra-processed foods and suggested that this would be an important mechanism to explain differences in energy consumption. Large portion sizes, a frequent feature in many ultra-processed foods, have also been associated with weight gain ⁸²82. Steenhuis IH, Vermeer WM. Portion size: review and framework for interventions. Int J Behav Nutr Phys Act 2009; 6:58.^,8383. Albar SA, Alwan NA, Evans CE, Cade JE. Is there an association between food portion size and BMI among British adolescents? Br J Nutr 2014; 112:841-51..

Ultra-processed foods have a higher energy density, more free sugar and saturated and trans fats, and less dietary fiber, protein, micronutrients and bioactive compounds, than non-ultra-processed foods, and its consumption is systematically associated with the deterioration of the nutritional quality of food ³3. Martínez Steele E, Baraldi LG, Louzada ML, Moubarac JC, Mozaffarian D, Monteiro CA. Ultra-processed foods and added sugars in the US diet: evidence from a nationally representative cross-sectional study. BMJ Open 2016; 6:e009892.^,44. Moubarac JC, Batal M, Louzada ML, Martinez Steele E, Monteiro CA. Consumption of ultra-processed foods predicts diet quality in Canada. Appetite 2017; 108:512-20.^,55. Rauber F, Louzada MLD, Steele EM, Millett C, Monteiro CA, Levy RB. Ultra-processed food consumption and chronic non-communicable diseases-related dietary nutrient profile in the UK (2008-2014). Nutrients 2018; 10:587.^,66. Machado PP, Steele EM, Levy RB, Sui ZX, Rangan A, Woods J, et al. Ultra-processed foods and recommended intake levels of nutrients linked to non-communicable diseases in Australia: evidence from a nationally representative cross-sectional study. BMJ Open 2019; 9:e029544.^,77. Cediel G, Reyes M, Louzada MLC, Steele EM, Monteiro CA, Corvalán C, et al. Ultra-processed foods and added sugars in the Chilean diet (2010). Public Health Nutr 2018; 21:125-33.^,88. Marron-Ponce JA, Flores M, Cediel G, Monteiro CA, Batis C. Associations between consumption of ultra-processed foods and intake of nutrients related to chronic non-communicable diseases in Mexico. PLoS One 2019; 119:1852-65.^,1111. Louzada MLC, Ricardo CZ, Steele EM, Levy RB, Cannon G, Monteiro CA. The share of ultra-processed foods determines the overall nutritional quality of diets in Brazil. Public Health Nutr 2018; 21:94-102.^,1212. Martínez Steele E, Monteiro CA. Association between dietary share of ultra-processed foods and urinary concentrations of phytoestrogens in the US. Nutrients 2017; 9:209.. It also induces high glycemic responses and have low satiety potential ¹³13. Fardet A. Minimally processed foods are more satiating and less hyperglycemic than ultra-processed foods: a preliminary study with 98 ready-to-eat foods. Food Funct 2016; 7:2338-46.. Its ingredients, which are mainly characterized by sugars and fats, added to cosmetic additives and processing techniques that use the destruction of the food matrix and the withdrawal of water, prevent its nutritional content from being transmitted accurately to the brain, affecting satiety control systems. Many of these additives, in particular thickeners and dyes, in addition to artificial sweeteners, have also been associated with metabolic changes ⁸⁴84. Chassaing B, Koren O, Goodrich JK, Poole AC, Srinivasan S, Ley RE, et al. Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome. Nature 2015; 519:92-6.^,8585. Bhattacharyya S, Feferman L, Tobacman JK. Carrageenan inhibits insulin signaling through GRB10-mediated decrease in Tyr (P)-IRS1 and through inflammation-induced increase in Ser (P) 307-IRS1. J Biol Chem 2015; 290:10764-74.^,8686. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Carbon black, titanium dioxide, and talc. Lyon: International Agency for Research on Cancer; 2010. (IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, 93).^,8787. Lerner A, Matthias T. Changes in intestinal tight junction permeability associated with industrial food additives explain the rising incidence of autoimmune disease. Autoimmun Rev 2015; 14:479-89.. Increasing evidence indicates that a large part of this mechanism may be associated with disturbances in intestinal microbiota homeostasis caused by the consumption of ultra-processed foods ¹⁷17. Zinöcker M, Lindseth I. The Western diet-microbiome-host interaction and its role in metabolic disease. Nutrients 2018; 10:365.^,8888. Miclotte L, Van de Wiele T. Food processing, gut microbiota and the globesity problem. Crit Rev Food Sci Nutr 2020; 60:1769-82..

Finally, chemical compounds formed during manufacturing processes or released from the packaging materials of ultra-processed foods are also other mechanisms that explain the association between the consumption of ultra-processed foods and the occurrence of diseases. Acrylamide, acrolein and nitrosamine, contaminants present in thermal-treated processed foods, have been associated with an increased risk of cardiovascular diseases ⁸⁹89. Zhang Y, Huang M, Zhuang P, Jiao J, Chen X, Wang J, et al. Exposure to acrylamide and the risk of cardiovascular diseases in the National Health and Nutrition Examination Survey 2003-2006. Environ Int 2018; 117:154-63.^,9090. DeJarnett N, Conklin DJ, Riggs DW, Myers JA, O'Toole TE, Hamzeh I, et al. Acrolein exposure is associated with increased cardiovascular disease risk. J Am Heart Assoc 2014; 3:e000934., neoplasia ⁹¹91. Virk-Baker MK, Nagy TR, Barnes S, Groopman J. Dietary acrylamide and human cancer: a systematic review of literature. Nutr Cancer 2014; 66:774-90. and insulin resistance ⁹²92. Lin C-Y, Lin Y-C, Kuo H-K, Hwang J-J, Lin J-L, Chen P-C, et al. Association among acrylamide, blood insulin, and insulin resistance in adults. Diabetes Care 2009; 32:2206-11.^,9393. Feroe AG, Attanasio R, Scinicariello F. Acrolein metabolites, diabetes and insulin resistance. Environ Res 2016;148:1-6.. Bisphenol A - an industrial chemical used in some plastic packaging for ultra-processed foods - interferes with cellular pathways related to weight and glucose homeostasis and its intake has already been associated with an increased risk of obesity ⁹⁴94. Heindel JJ, Newbold R, Schug TT. Endocrine disruptors and obesity. Nat Rev Endocrinol 2015; 11:653-61. and a number of chronic diseases ⁹⁵95. Muncke J. Endocrine disrupting chemicals and other substances of concern in food contact materials: an updated review of exposure, effect and risk assessment. J Steroid Biochem Molec Biol 2011; 127:118-27.. Recent studies conducted with data from the population in the United States assessed at NHANES have shown that the consumption of ultra-processed foods was associated with a higher urinary concentration of bisphenols, phthalates and organophosphates, all endocrine disruptors used in industrial plastic packaging ¹⁵15. Buckley JP, Kim H, Wong E, Rebholz CM. Ultra-processed food consumption and exposure to phthalates and bisphenols in the US National Health and Nutrition Examination Survey, 2013-2014. Am J Clin Nutr 2019; 131:105057.^,1616. Kim H, Rebholz CM, Wong E, Buckley JP. Urinary organophosphate ester concentrations in relation to ultra-processed food consumption in the general US population. Environ Res 2020; 182:109070..

The findings of this study are even more relevant when we consider that, in the last decades, the consumption of ultra-processed foods has increased significantly and accelerated in several countries driven by recent changes in the food system ²2. Monteiro CA, Moubarac JC, Cannon G, Ng SW, Popkin B. Ultra-processed products are becoming dominant in the global food system. Obes Rev 2013; 14:21-8.. Since the 1980s, economic policies enacted by global organizations supported by the most powerful governments have favored the phenomenal rise of ultra-processed food transnationals. These policies deregulated the industry, promoted the flow of capital, opened countries to foreign investment, allowed transnational companies to take over national companies and restricted national governments from introducing statutory policies to limit their consumption. Meanwhile, economic growth and the increase in the average income of some populations have made ultra-processed foods accessible to more people ⁹⁶96. Monteiro CA, Cannon GJ. The role of the transnational ultra-processed food industry in the pandemic of obesity and its associated diseases: problems and solutions. World Nutr 2019; 10:89-99..

This study has limitations. It was observed that some original studies were more susceptible to bias, such as those that used food consumption data collection instruments subject to memory bias, or self-reported weight and height. The use of the quality assessment tool, however, was important to take into account these possible biases in the presentation of the results. Our study limited the search to articles available in the literature (without accessing “gray literature”, conference proceedings or studies in progress). Thus, for many outcomes, for populations in low- and middle-income countries and for children and adolescents, we find few studies and of low methodological quality. Therefore, some results must be interpreted as not conclusive. On the other hand, this study used a comprehensive and rigorous research and selection strategy that identified studies from different designs carried out in different population subgroups. Although cross-sectional studies contribute less weight in the evaluation of the evidence totality, they are important in a scenario of few studies or in the absence of other available evidence. Thus, we believe that our results summarize the best current data on the association between the consumption of ultra-processed foods and health, also highlighting the gaps in knowledge that need further investigation.

The relevance of the NOVA classification is increasingly recognized, and, in recent years, it has been addressed in the recommendations of several international entities, such as the Food and Agriculture Organization of the United Nations (FAO) ⁹⁷97. Monteiro CA, Cannon G, Lawrence M, Louzada MLC, Machado PP. Ultra-processed foods, diet quality, and health using the NOVA classification system. Rome: Food and Agriculture Organization of the United Nations; 2019., the Pan American Health Organization (PAHO) ⁹⁸98. Pan American Health Organization. Ultra-processed food and drink products in Latin America: sales, sources, nutrient profiles, and policy implications. Washington DC: Pan American Health Organization; 2019. and the Lancet Commission on Obesity ⁹⁹99. Swinburn BA, Kraak VI, Allender S, Atkins VJ, Baker PI, Bogard JR, et al. The global syndemic of obesity, undernutrition, and climate change: the Lancet Commission report. Lancet 2019; 393:791-846., in addition to national food guides ¹⁰⁰100. Food and Agriculture Organization. Food-based dietary guidelines. http://www.fao.org/nutrition/education/food-dietary-guidelines (acessado em Set/2020).
http://www.fao.org/nutrition/education/f... . The Dietary Guidelines for the Brazilian Population, published in 2014, was a pioneer in using this classification as the basis for its recommendations and brings as a golden rule that “it is preferred fresh or minimally processed foods and their culinary preparations to ultra-processed foods” ¹⁰⁰100. Food and Agriculture Organization. Food-based dietary guidelines. http://www.fao.org/nutrition/education/food-dietary-guidelines (acessado em Set/2020).
http://www.fao.org/nutrition/education/f... .

In conclusion, our study described the results of several studies that demonstrated the impact of the consumption of ultra-processed foods on health, with particularly consistent evidence for obesity and other chronic non-communicable diseases and all-cause mortality in adults. Additionally, the review made it possible to identify gaps in the literature, namely studies with outcomes of non-chronic diseases (such as nutritional deficiencies), with children and adolescents and in populations from low- and middle-income countries. Despite this, these results have important implications, considering that the reduction in the consumption of ultra-processed foods by the populations can be reverted in important benefits.

Acknowledgments

To São Paulo State Research Foundation (FAPESP; Project 2015/14900-9 and Project 2019/06852-5) and Brazilian National Research Council (CNPq; Project n. 408462/2017-5).

References

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