We Are What We Eat: The Association Between Ultra-Processed Food Consumption, Colon Cancer Risk and All-Cause Mortality

Wang L, Du M, Wang K, et al. Association of ultra-processed food consumption with colorectal cancer risk among men and women: results from three prospective US cohort studies. BMJ 2022;378:e068921. Bonaccio M, di Castelnuovo A, Ruggiero E, et al. Joint association of food nutritional profile by Nutri-Score front-of-pack label and ultra-processed food intake with mortality: Moli-sani prospective cohort study. BMJ 2022;378:e070688. Ultra-processed foods (UPFs) are made by deconstructing whole foods into chemical constituents, altering them, and recombining them with additives into products which are ready to consume, affordable owing to the use of low-cost ingredients, and highly palatable. They represent the group 4 of the NOVA classification, which stratifies all foods into 4 groups according to the extent and purpose of their processing. Typical examples include soft drinks, packaged snacks, and biscuits, commercial cake and bread, commercial breakfast, sweetened cereals, sugared milk-based and fruit drinks, margarine, and pre-processed “ready-to-eat or -heat” products such as burgers and pizzas. Most UPFs are high in fat, sugar, refined starch, and salt and low in micronutrients and fiber, leading to an overall poor nutritional profile. High consumption of UPFs has been shown in cohort studies to be associated with an increased risk of obesity, type 2 diabetes, hypertension, depression, and cardiovascular and cerebrovascular diseases. Two recent prospective trials shed further light on this matter, by correlating UPF intake with colorectal cancer (CRC) risk and all-cause mortality. First, a U.S. investigation by Wang et al included 46,341 men and 159,907 women with validated and repeated dietary intake assessments, followed for 24 to 28 years, and documented 3216 cases of CRC. Compared with those in the lowest fifth of UPF consumption (based on the NOVA classification), men in the highest fifth of consumption had a 29% increased risk of developing CRC (hazard ratio [HR] 1.29, 95% confidence interval [CI] 1.08–1.53). This positive association was limited to the distal colon and remained significant after further adjustment for body mass index or indicators of nutritional quality of the diet. In contrast, there was no significant association between overall UPF consumption and CRC among women. The findings suggest that the negative impact of UPFs on important health outcomes such as CRC may go beyond excess weight or a diet of poor nutritional quality. The second study by Bonaccio et al involved 22,895 participants from Italy followed up for 14 years to define associations between dietary exposures and mortality risk. Food intake evaluation was stratified by a) the NOVA classification for UPF consumption, and b) the Food Standards Agency Nutrient Profiling System (FSAm-NPS) to compute the Nutri-Score front-of-pack label, which is a 5-color coded scheme visible on the product packaging, ranging from dark green (high nutritional quality) to dark orange (low nutritional quality), associated with letters A to E. A total of 2205 deaths occurred during 272,960 person-years of follow-up. Individuals in the highest fourth of the FSAm-NPS index, compared with the lowest fourth, had increased rates of all-cause mortality (HR 1.19, 95% C.I 1.04–1.35), and cardiovascular mortality (HR 1.32, 95% C.I 1.06–1.64). Similar results were found when comparing the 2 extreme categories of NOVA classification for all-cause mortality (HR 1.19, 95% C.I 1.05–1.36) and cardiovascular mortality (HR 1.27, 95 C.I 1.02–1.58). When these 2 indices were analyzed jointly, the degree of the association of a low-quality Nutri-Score with all-cause and cardiovascular mortality was attenuated by 22.3% and 15.4%, respectively, whereas mortality risks associated with high UPF intake were not modified. This suggests that part of the excess mortality risk associated with a nutrient-poor diet, as reflected by increased values of the Nutri-Score, was significantly explained by a higher degree of food processing. In contrast, UPF intake remained associated with mortality even after the poor nutritional quality of the diet was considered. Similarly, a previous Spanish study including 20,503 participants showed that the association between a higher Nutri-Score and all-cause mortality was stronger among participants with a high intake of UPFs. Additional factors may explain these findings. UPFs, by their composition, may alter gut microbiota composition unfavorably, therefore leading to an increased cancer risk. Furthermore, diets high in UPFs are low in nutrients and bioactive compounds that are protective against CRC (eg, fiber, calcium, and vitamin D). Another concern is the presence of food additives such as emulsifiers and artificial sweeteners, which have been shown to increase the pro-inflammatory potential of the gut microbiome. Likewise, potential carcinogens may be formed during the processing of meats containing sodium nitrates (eg, nitrosamines) or by heat treatment (eg, acrylamide). Finally, the packaging of UPFs is a major source of synthetic chemicals, such as phthalates and bisphenols, which are among the so-called endocrine-disrupting chemicals and considered “substances of very high concern” by the European Chemicals Agency. Both studies have undeniable strengths, including prospective design, large number of participants, and long follow-up. Nevertheless, as in all observational studies, the potential role of residual confounding by unmeasured factors cannot be excluded. Additional bias includes recall bias due to self-reporting and limitation of generalizing results to other populations. The increased consumption of UPFs has raised concerns about the magnitude of the impact on public health. Indeed, UPFs represent 57% of total daily calories consumed by American adults, have an addictive potential, and are currently replacing minimally processed foods and freshly prepared meals. Usually, they are subjected to aggressive marketing and branding, therefore increasing consumption. Furthermore, numerous UPFs are promoted as healthy products, such as breakfast cereals or cereal bars. The environmental impact of industrial agriculture related to mass production of UPFs is clearly an additional threat. Although the risks related to UPF consumption have been clearly identified, tackling the problem is a major challenge. The reasonable solution is adopting official public policies, including guidelines advising avoidance, and implementing actions designed to reduce production and consumption of UPFs by restricting their promotion. Incorporation of a front-of-pack warning label for UPFs similar to the Nutri-Score may act as an additional measure to guide people toward improving their diets. Nevertheless, significant efforts are needed to make minimally processed or fresh foods easily accessible, inexpensive, and attractive, while increasing public awareness on healthy eating.