Ultra-processed food – a threat to liver health

Summary

Ultra-processed foods (UPF) are often characterized by low nutritional quality, high energy density, and the presence of additives, substances from packaging, and compounds formed during production, processing, and storage. UPF includes industrial formulations, and usually contains many ingredients. UPF includes sugar, oils, fats, salt, antioxidants, stabilizers and preservatives, food additives, and emulsifiers. Beyond the poor nutritional value, food processing promotes the creation of harmful compounds in the food. Food additives within UPF, promote inflammation, liver dysfunction, and metabolic syndrome, which are based on changes in the microbiome. Obesogens are environmental substances that alter the balance between energy intake and energy expenditure. Obesogens are a subset of environmental chemicals that act as endocrine disruptors affecting metabolic endpoints. The consumption of ultra-processed products has increased dramatically worldwide in the last decades. UPF contributed more than 60% of the mean energy intake. The average content of protein, fiber, vitamins, and calcium in the diet decreases significantly. The roducy contribution of UPFs, while carbohydrate, added sugar, and saturated fat contents increase. Ultra-processed foods contribute most of the added sugars in the western diet. Fructose – the most frequent obesogen, is associated with an increased risk of liver fibrosis. In recent years, there has been growing evidence about the harmful effect of UPF. UPF consumption is associated with metabolic alterations, the incidence of chronic diseases, and excess mortality. There is also evidence for an association with NAFLD, NASH, and fibrosis. High UPF consumption is related to harmful metabolic and hepatic parameters in NAFLD population. Furthermore, the combination of smoking and high UPF intake may amplify liver damage. The evidence from studies, a recommendation to reduce ultra-processed food intake to a minimum should be considered in nutritional guidelines and implemented by public health policy measures.

Keywords:

metabolic syndrome – non-alcoholic fatty liver disease (NAFLD) – ultra-processed food (UPF) – obesogens – endocrine disrupting chemicals (EDCs)

Introduction

Food has a profound impact on health. The scientific connection between food and health has been well documented for many decades, with substantial and increasingly robust evidence showing that a healthy lifestyle, including a healthy dietary pattern, can help achieve and maintain good health and reduce the risk of chronic diseases throughout the lifespan. The core elements of a healthy dietary pattern are remarkably consistent across the lifespan and health outcomes. Food as one of the necessities of life can be defined as a repertoire of nutrients and substances essential for the growth, repair, and maintenance of body tissues and for the regulation of vital processes. Nutrients provide the energy that bodies need to function. A revolution in food science and the food industry over the last 60 years has led to explosive growth in the manufacturing and consumption of ultra-processed foods (UPFs). This shift began in high-income countries but has now reached countries at all income levels [1,2]. In the 60^s of the 20^th century, the association of cholesterol (Framingham study) and cardiovascular diseases was discovered, and therefore fats became enemies in nutrition for several decades [3]. UPF can be considered a starting point for covering the needs of the population. Increasing population density in developed countries and the increase of the concentration of population in large cities presents a logistical problem with the distribution and availability of fresh food. The rapid development of the food industry with an increase in the production of UPF can be considered a natural phenomenon associated with the development of civilization. UPF is a substantial factor affecting worldwide increases in the prevalence and incidence of obesity and other non-communicable diseases [4,5]. UPFs’ poor nutritional profiles, hyperpalatability (and, arguably, addictive nature), and content of biologically harmful compounds harm health status. The recommendation to prefer unprocessed/minimally processed foods and freshly made meals instead of ultra-processed foods are being increasingly adopted in the new official dietary guidelines issued by national governments and international health associations. This recommendation is supported by systematic reviews and meta-analyses of nationally representative dietary surveys and long-term cohort studies [6]. These data show that increased intake of UPF is associated with increased morbidity and mortality from several chronic diseases. Nevertheless, our modern eating patterns don’t reflect this recommendation. A recent survey revealed that 75% of people don’t eat enough vegetables, fruits and dairy [6]. Sixty-three percent exceed the limit for added sugars, and 77% exceed the limit for saturated fats. Not only the quantity but also the quality of the food contributes to heart disease, high blood pressure, type 2 diabetes, certain types of cancer or nonalcoholic steatohepatitis, and liver cirrhosis.

Definition of ultra-processed food

Ultra-processed consists of ready-to-consume formulations of industrially extracted ingredients and additives, typically created by series of industrial techniques and chemical processes. The consumption of ultra-processed food is linked to many diseases and is associated with several health negatives. Diets relying on highly processed foods comprise not only food-derived substances, along with additives, furthermore, are associated with exposure to industrialized preservatives and pesticides.

Processed food is defined by 7 food engineering criteria:

1. it is mass-produced,

2. is consistent batch to batch,

3. is consistent from country to country,

4. uses specialized ingredients from specialized companies,

5. consists of pre-frozen macronutrients,

6. stays emulsified, and

7. has long shelf life or freezer life [7].

Food processing generally refers to any action that alters food from its natural states, such as drying, freezing, milling, canning and adding salt, sugar, fat or other additives for flavor or preservation [8].

Furthermore, as professor Robert Lustig underscores in his work, there are additional nutritional properties that distinguish processed food [7]:

• Too little fiber. Fiber (soluble and insoluble) forms a gelatinous barrier along the intestinal wall. This delays the intestine’s ability to absorb nutrients, instead of feeding the gut microbiome. Physiological attenuation of the glucose rise results in beneficial insulin level reduction. Attenuation of fructose absorption reduces liver fat accumulation.
• Too few ω-3 and too many ω-6 fatty acids. ω-3s are precursors to docosahexaenoic and eicosapentaenoic acids (anti-inflammatory). Conversely, ω-6s are precursors of arachidonic acid (pro-inflammatory). The ratio of ω-6 to ω-3 fatty acids should be approximately 1: 1. Currently, this ratio is about 25: 1, favoring a pro-inflammatory state, which can drive oxidative stress and cell damage.
• Too few micronutrients. Antioxidants, such as vitamins C and E, quench oxygen radicals in peroxisomes to prevent cellular damage, while others, such as carotenoids and a-lipoic acid, prevent lipid peroxidation.
• Too many trans-fats. These fats cannot be oxidized by mitochondria owing to the trans-double bond, so they can damage arteries and the liver with the generation of reactive oxygen radicals.
• Too many branched-chain amino acids. Valine, leucine, and isoleucine are essential amino acids required for muscle biosynthesis. But when consumed in excess, they are deaminated in the liver and diverted to de novo lipogenesis, which increases liver fat.
• Too many emulsifiers. Emulsifiers prevent fat and water from separating. However, emulsifiers are detergents and may strip away the mucin layer that protects intestinal epithelial cells, predisposing individuals to leaky gut, intestinal disease, or food [9].
• Too many nitrates. Nitrates (cured meat) can be metabolized into nitrosoureas, which can predispose individuals to colon cancer.
• Too much salt. Approximately 15% of the population is salt sensitive and can manifest with hypertension and cardiac disease. Dietary salt may increase intestinal permeability and induce intestinal inflammation.
• Too much ethanol. Ethanol is converted into liver fat and drives oxidative stress.

Too much fructose. Fructose is metabolized by de novo lipogenesis in the liver. 74% of all the items in the grocery store contain added sugar; this makes sugar the basic marker for processed food [10].

The need to assess the quality of food was the basis for the creation of many existing classification systems. Researchers developed the NOVA classification system to categorize foods and beverages into one of four groups according to the extent and purpose of processing [11]:

• Group 1 (Unprocessed/minimally processed): Foods unaltered or altered by processes such as removing inedible parts, drying, grinding, cooking, pasteurization, freezing, or non-alcoholic fermentation. No substances are added. Processing aims to increase food stability and enable easier or more diverse preparation.

Unprocessed or minimally processed foods are whole foods in which the vitamins and nutrients are still intact. The food is in its natural (or nearly natural) state. These foods may be minimally altered by removal of inedible parts, drying, crushing, roasting, boiling, freezing, or pasteurization, to make them suitable to store and safe to consume. Unprocessed or minimally processed foods would include fruits and vegetables, and raw, unsalted nuts.

• Group 2 (Processed culinary ingredients): Substances obtained directly from Group 1 foods or from nature, created by industrial processes such as pressing, centrifuging, refining, extracting or mining. Processing aims to create products to be used in the preparation, seasoning, and cooking of Group 1 foods.
• Group 3 (Processed foods): Products made by adding edible substances from Group 2 to Group 1 foods using preservation methods such as non-alcoholic fermentation, canning or bottling. Processing aims to increase the stability and durability of Group 1 foods and to make them more enjoyable.

Group 4 (Ultra-processed foods): Formulations of low-cost substances derived from Group 1 foods with little to no whole foods; always contain edible substances not used in home kitchens (e. g. protein isolates) and/or cosmetic additives (e. g. flavors, colors, emulsifiers). Processing involves multiple steps and industries and aims to create products liable to replace all other NOVA groups [12].

When foods are highly processed or ultra-processed, they have many added ingredients (such as sugar, salt, fat, and artificial colors, or preservatives). Ultra-processed foods are made from substances extracted from foods, such as fats, starches, added sugars, and hydrogenated fats. They may also contain additives like artificial colors and flavors or stabilizers. Examples of these foods are frozen meals, soft drinks, hot dogs and cold cuts, fast food, packaged cookies, cakes and salty snacks.

UPFs are not simply foods that have been modified by processing, but rather edible products formulated from food-derived substances, along with additives that heighten their appeal and durability. UPFs are designed and manufactured for maximum profit: they contain low-cost ingredients, have long shelf lives, are hyper-palatable, and are highly branded and marketed to consumers. They are typically calorie-dense and high in free sugars, refined starches, unhealthy fats, and sodium. Today, UPFs are well recognized for their addictive qualities [13,14].

Changes in UPF consumption

UPFs have rapidly displaced unprocessed or minimally processed foods, freshly prepared meals, and traditional cooking in the diet in most countries, causing significant nutritional, social, economic, and environmental disruption and damage worldwide. UPFs – which did not exist before the mid-20^th century now account for roughly half or more of the total calories consumed in the United States [15], and United Kingdom [16], with sales growing rapidly every year [1]. This worldwide shift towards greater consumption of UPFs coincided with global increases in obesity prevalence and other nutrition-related chronic diseases [17]. The detrimental health effects of UPFs tend to combine. UPF consumption worsens nutritional intake. UPFs are energy-dense and disproportionately contribute added sugars, sodium, unhealthy saturated and trans-fats, and highly refined carbohydrates to the diet while displacing consumption of less-processed and freshly prepared foods and their many beneficial nutrients [18,19]. UPFs inherently encourage overconsumption. For this issue of UPFs plays a role in convenience (i.e. products are typically ready-to-eat or ready-to-heat) [20,21]; hyper-palatability (formulations engineered to maximally please all the senses) [22]; disrupted satiety signaling [23,24]; and marketing that is highly pervasive and persuasive and often targeting children, as well as effective branding [25,26].

UPFs often contain harmful chemical substances. [27]. They include contaminants formed during high-temperature cooking [28].

Industrial additives linked to inflammation and gut dysbiosis (imbalances in the diversity and composition of gut microbiota) [29], and hormone-disrupting chemical compounds leached from plastics in food manufacturing and packaging materials [30–32].

Agrifood corporations are driving industrialization along the entire global food chain, from farm to plate. The driving force is profit. A key sector in agriculture is fertilizers and pesticide production and utilization. An analogous example is antibiotics use in large-scale meat production. Corporate-driven food systems have failed to deliver food security. That is because food systems severely harm both nature and the people on whom they depend.

UPF and obesogens

Obesogens are environmental chemicals that disrupt the action of receptors to promote adiposity or alter metabolism. Today, many thousands of chemicals are used in commerce. Chemical toxins have several modes of action. They can disrupt hormone levels or action. Their characteristics include the ability to interact with or activate hormone receptors, antagonize hormone receptors, alter hormone receptor expression, alter signal transduction in hormone-responsive cells, induce epigenetic modifications in hormone-producing or hormone-responsive cells, alter hormone synthesis, alter hormone transport across cell membranes, alter hormone distribution or circulating hormone levels.

Obesity is recognized as a multifactorial disease with both genetic and environmental components. The prevailing view is that obesity results from an imbalance between energy intake and expenditure caused by overeating and insufficient exercise. There is another important environmental element that can alter the balance between energy intake and energy expenditure: obesogens. Obesogens are a subset of environmental chemicals that act as endocrine disruptors affecting metabolic endpoints. The obesogen hypothesis posits that exposure to endocrine disruptors and other chemicals can alter the development and function of the adipose tissue, liver, pancreas, gastrointestinal tract, and brain, thus changing the set point for control of metabolism. Obesogens can determine how much food is needed to maintain homeostasis and thereby increase the susceptibility to obesity. Obesogens are chemicals that elicit increased white adipose tissue mass [33].

A variety of commonly prescribed drugs have adverse effects that result in weight gain (thiazolidinediones, tricyclic antidepressants, selective 5hydroxytryptamine uptake inhibitors and atypical antipsychotic drugs). Other chemical substances indicate that EDCs such as tributyltin, estrogenic chemicals such as bisphenol A, and chemicals acting via other mechanisms such as perfluorooctanoic acid, phthalates, polychlorinated biphenyls, some pesticides, dichlorodiphenyltrichloroethane (DDT). Polycyclic aromatic hydrocarbons (PAHs) are a family of environmental chemicals that are produced as byproducts of fuel burning. Benzopyrene as an example is a PAH that has been shown to inhibit lipolysis and cause increased fat accumulation [30].

Fructose cause changes in liver metabolism and energy signaling, creating a feedback loop in which insulin resistance and overeating occur. Fructose serves as a substrate for de novo lipogenesis and promotes hepatic insulin resistance, dyslipidemia and hepatic steatosis. Fructosylation of proteins with superoxide formation can result in hepatic inflammation-steatohepatitis. Fructose with its addictive properties and metabolic alterations in both hepatic metabolism and central nervous system energy signaling leads to excessive consumption and is consistent with metabolic syndrome development and its complications.

Health outcomes related to UPF consumption

A large and growing body of evidence has found strong associations between high UPF intake and health risks, including obesity, type 2 diabetes, depression, cardiovascular and cerebrovascular disease, mortality, cancer, chronic liver disease – especially NAFLD, and all-cause mortality [34–41].

Many systematic and narrative reviews have assessed the body of evidence for UPFs’ role in these and other health outcomes and they are consistent in their interpretation of the literature: high consumption of UPF is significantly associated with one or more adverse health outcomes in nearly every study to date [42].

Studies directly show that UPFs cause greater calorie intake and subsequent weight gain. High UPF intake was significantly associated with 23–51% greater odds of obesity and 39–49% greater odds of riskier abdominal obesity across three meta-analyses of observational studies comparing groups with highest vs. lowest UPF consumption. Added intake of UPF foods increases weight gain and the risk of overweight/obesity [4,5,35].

In studies comparing participants with the highest vs. lowest UPF consumption, the highest intake was significantly associated with a pooled:

• 29% greater relative risk of cardiovascular disease and/or mortality, and
• 34% greater relative risk of cerebrovascular disease and/or mortality [4].

High UPF intake was associated with a 22% greater risk of developing hypertension compared to low intake in a prospective study of 8,000 adults in Brazil [43]. Among children and adolescents, studies have found significant associations between high UPF intake and increases in total and LDL cholesterol from preschool to school age as well as increased cardiovascular disease risk into early adulthood [39,44].

Large prospective studies in the United Kingdom, France, and Spain have found 44–65% greater risk of developing type 2 diabetes among people in the highest vs. lowest groups of UPF consumption as well as a significant dose-response relationship, wherein every 10% increase in absolute UPF intake was associated with 12–15% greater risk of developing type 2 diabetes [36,37,45].

Studies examining UPF and depression found that participants in the highest quartile of UPF consumption had a 33% greater risk of developing depression relative to consumers in the lowest quartile and that for every 10% increase in UPF consumption, participants faced a 21% greater relative risk of depressive symptoms [38,46].

A 10% increase in the proportion of UPF in the diet was associated with an 11% increase in the risk of breast cancer and a 12% increase in the risk of overall cancer in a large prospective study [47].

In a study that followed roughly 1,300 Spanish older adults over 6 years, those in the highest third of UPF consumption had 74% greater odds of experiencing declining kidney function than those in the bottom third, independent of other chronic diseases or demographic, dietary, and lifestyle factors [48].

High UPF intake was associated with a tripled risk of frailty in older adults in a study comparing the highest and lowest quartiles intake among nearly 2,000 older adults in Spain over 3.5 years [49].

Pooled risk of all-cause mortality was 25–28% greater for the highest consumers of UPF relative to the lowest consumers across five prospective studies [40,50].

The risk of death was 50% higher from cardiovascular disease and 68% higher from heart disease for people in the highest vs. lowest quartiles of UPF intake in a large prospective cohort of over 90,000 participants. These mortality risks were higher for women than men [51].

UPF and IBD

Non-genetic external factors are important contributors to the pathogenesis of inflammatory bowel disease. There are several possible mechanisms through which UPF consumption may influence the development of IBD. UPF consumption may be associated with replacement of fiber. UPF contains additive substances that disrupt mucus-bacterial interaction in the gut. Emulsifying agents are chemically defined as detergent-like molecules. They are ubiquitous components of UPF and predispose to the development of inflammation. These components of UPF correlate with altered species composition and pro-inflammatory potential through mucus layer degradation and increased bacterial translocation [9]. Dietary salt and artificial sweeteners may increase intestinal permeability and induce intestinal inflammation through a reduction in fecal short-chain fatty acid production [52]. UPF intake was in studies associated with a higher risk of IBD. No significant heterogeneity was observed when the results for Crohn’s disease were compared with the results for ulcerative colitis. UPF is a proven environmental factor that increases the risk of IBD [53].

UPF and non-alcoholic fatty liver disease (NAFLD) or metabolic dysfunction-associated fatty liver disease (MAFLD)

Several studies have shown an association between UPFs and the risk of chronic diseases including; obesity, type 2 diabetes, cardiovascular disease, cancer, gastrointestinal disorders, frailty and mortality. Fructose consumption was demonstrated to be independently associated with NASH in children and adolescents, and fructose-containing beverages were also demonstrated to be associated with more severe fibrosis in NAFLD patients [54,55].

A recent study shows the association between the consumption of UPFs and NAFLD and related liver damage. Subjects with high UPF consumption had a higher prevalence of low HDL, hypertriglyceridemia, high TG/HDL ratio, hypertension, metabolic syndrome, higher serum ferritin levels, and a higher FibroTest score. They tended to consume more calories, with a higher proportion of calories from saturated fatty acids (SFA) and carbohydrates and a lower proportion from protein. Also, subjects with high UPF consumption tended to eat less fiber. Association of UPF consumption with NAFLD, presumed NASH and fibrosis. The prevalence of NASH, significant fibrosis, and elevated ferritin were associated with high consumption of UPFs [56]. The ideal diet for NAFLD should reduce fat mass and inflammation in the adipose tissue and liver parenchyma, restore insulin sensitivity and provide low amounts of substrates for de novo lipogenesis. Together with evidence from previous studies, a recommendation to reduce ultra-processed food intake to a minimum should be considered in nutritional guidelines and implemented by public health policy measures.

Conclusions

Consumption of UPFs has been undoubtedly linked with most non-communicable diseases. One of the links is with NAFLD/MAFLD. Combatting the tsunami of NAFLD which has afflicted all the regions of the world including Central Europe, is difficult to conceive without tackling the issue of UPS as one of the main therapeutic targets.

 

Submitted/Doručené: 6. 3. 2023

Accepted/Prijaté: 13. 3. 2023

Marek Rác, MD

Department of Internal Medicine

Teaching Hospital Nitra

Špitálska 6

949 01 Nitra

marek.rac@me.com

Gastroent Hepatol 2023; 77(2): 123– 129