Celiac disease (CD) is a unique disease in its own way, being at the same time a food intolerance and an autoimmune pathology triggered by gluten ingestion. It is a form of enteropathy, which affects the small intestine of genetically predisposed people. It develops as a result of the combination of environmental factors (gluten) and autoantigens (tissue enzyme transglutaminase-tTG). As a result, the inflammatory processes of the small intestine are followed by the flattening of the intestinal villi and, subsequently, the reduction of the intestinal surface area of absorption and malnutrition [5]. The first mentions of celiac disease dated back to about 10,000 years ago, when barley and wheat began to play an important role in human nutrition [3], but the link with gluten was defined only in the last century and the spread of the disease was due to industrial production of wheat and its increase in industrial consumption. In 1970, the European Society of Pediatric Gastroenterology and Nutrition (ESPGAN) defined celiac disease as a permanent intolerance to gluten [6] [7]. In the past it was considered a rare disease, prevalent in childhood and with classic manifestations of malabsorption syndrome. Epidemiological studies based on new antibody tests have shown that

adults are more and more frequently diagnosed, with an average age of about 45 years and about 20% of those diagnosed over 60 years [5] [8] [9]. The disease is more prevalent in women, with a male/female ratio of 1:2.5. Celiac disease can affect any organ or system, with a wide range of clinical manifestations of varying severity [10].

Representing a major cause of malabsorption syndrome, and one not negligible in our geographical area, celiac disease has polarized the attention of researchers. Although the term celiac disease is currently the most widespread, many synonyms remain in circulation: gluten enteropathy, Gee-Thaysen’s disease, idiopathic steatorrhea, netropical sprue or celiac syndrome. The incidence of celiac disease in the world is 6,334,993 people and about 1% of Europe’s population suffers from celiac disease [11] (Figure 2). The difficulty of diagnosis makes it almost impossible to create a real statistical database on this disease [12].

The prevalence of celiac disease is highest in the Saharawi (a town in Africa), followed by Turkey (1:77). Some bibliographic sources indicate the prevalence of celiac disease of 2.22% in Romania, with equal distribution between sexes and the predominance of patients in urban areas aged between 30 - 60 years. The prevalence of celiac disease in the world and in Europe is shown in Table 1 [5] [11] [13].

The pathogenesis of celiac disease involves genetic, environmental and immunological factors. Celiac disease is caused by the improper reaction of T-helper lymphocytes to the gluten contained in the food consumed. The primary symptoms of celiac disease are manifested by histological disorders in the mucosa of the duodenal tract and by an immunological reaction of the laminae. Initially, the damage is cellular, and the cells involved are T-helper lymphocytes [14] [15] [16]. Multiple studies targeting the immune response to gluten have shown that gliadin, the alcohol-soluble glycoprotein fraction of gluten, is responsible for the adverse reaction to gluten. Gliadin peptides were classified into:

● Toxic, capable of causing tissue damage to the intestinal mucosa, independent of the activation of T-helper lymphocytes which explains their activity by activating the innate immune response.

● Immunogenic, able to specifically stimulate the cell lines of HLA-DQ2/DQ8 T lymphocytes and B lymphocytes and, respectively, to activate the acquired immune response [17].

Gliadins are difficult to digest due to their chemical complexity. From the partial digestion of glutamine and proline, fragments capable of revoking an inflammatory response with the destruction of intestinal epithelial cells are obtained [5]. 4 fractions of prolamins were identified: α-, β-, γ- and ω according to their electrophoretic mobility in acidic environment [18].

The α form, with a portion of 266 amino acids, called α-gliadin, is considered to contain the most active epitopes for the immune system and appears to be primarily responsible for toxicity. Fragment 31 - 43 of A-gliadin is transported through the mucosa of celiac patients in twice as large quantities compared to the same process in healthy individuals and has no immunological activity against T-helper lymphocytes [19] (Figure 3).

Under normal conditions, gliadin is degraded in intestinal endothelial cells into small non-immunogenic peptide fragments. But when particular complications occur that intervene with some mechanisms responsible for the passage into the intestinal lumen, gliadin can easily bypass endothelial cells-zonulin (a newly discovered peptide), the secretion of which can be stimulated by numerous pathological events and which is able to trigger, through a receptor binding, an increase in intestinal permeability caused by changes in the cytoskeleton of enterocytes. In the submucosa of a large number of allergens and gliadin [16] [20] [21].

Wheat food allergy is a reaction usually mediated by allergic IgE-antibodies (immunoglobulin E) produced in large quantities by the immune system each time allergenic foods are consumed, and as a result, after a series of processes, causes the production histamine that causes inflammation. It differs from celiac disease in that in the latter we have an immune response to gluten consumption related not to antibodies, but to cells [4] [22]. The patient’s first contact with gluten does not lead to a negative reaction, but the immune system selects it as a “bad” substance, recording it and memorizing it in a process called sensitization. Over time, the immune system becomes increasingly sensitive and initiates the production of large amounts of IgE, which binds to mast cells, inducing the release of histamines [23]. Allergy has different symptoms depending on the subject. Symptoms of gluten allergy can occur immediately after eating gluten-free foods. Affected patients have similar manifestations to other food allergies, with skin symptoms (dermatitis, eczema, hives), respiratory (asthma or allergic rhinitis) and gastrointestinal tract (inflammation of the lips and tongue). It is important to note that the damage caused by gluten on the gastrointestinal tract in cases of allergy is not permanent and passes with the overcoming of the acute phase [3].

The results of a major international study, conducted by the University of Maryland School of Medicine in Baltimore (USA) in collaboration with the University of Naples (Italy), were recently published in the scientific journal BMC Medicine, identifying the differences between celiac disease and susceptibility to gluten [24]. While celiac disease is activated by an autoimmune mechanism, largely determined by the immune system’s adaptive reaction, gluten sensitivity is triggered by an immune mechanism that does not interfere with the functionality of the intestinal barrier. Gluten sensitivity was defined as gluten intolerance in which, unlike celiac disease and gluten allergy, a normal epithelium was found following an intestinal biopsy. It is characterized by symptoms similar to those of irritated bowel (abdominal pain and bloating, diarrhea) and extraintestinal symptoms with neurological prevalence, which manifests itself immediately after eating gluten. It is more common in adults than in children. About 17 million Americans suffer from gluten sensitivity, with a six-fold higher prevalence of celiac disease [10] [25].

The aim of the study is to analyze the food and nutritional security of people with disorders related to gluten consumption from the perspective of assessing the nutritional deficiencies of people diagnosed with CD or gluten intolerance, but also assessing the nutritional deficiencies of gluten-free products (GFP).

Numerous studies have reported that celiac disease has a major impact on the nutritional status of celiac disease at the time of diagnosis and in the pre-diagnosis period. At the time of diagnosis of celiac disease, a transient lactose intolerance, secondary to celiac enteropathy, can be observed. This can cause a tendency to diarrhea, flatulence and persistent abdominal pain, which is why it may be advisable to reduce or omit (during the initial treatment period) the daily intake of lactose, substituting whole milk with low-lactose milk. It is not mandatory to exclude other products such as yogurt or cheese, which have a low content of these carbohydrates. After 3 - 6 months of GFD, the level of intestinal lactase tends to normalize and there is the possibility of reintroducing lactose-containing products into the diet. At diagnosis, depending on the time elapsed since the onset of celiac disease and/or the length of the affected gastrointestinal tract, and/or various levels of malabsorption, a deteriorated nutritional status occurs [27] [28]. In newly diagnosed, iron deficiency, vitamin B12, folate is frequently found [29] [30].

Lipid malabsorption, carbohydrate and vitamin deficiencies (A, D, E, K) were encountered in cases when the intestinal mucosa was severely affected [31]. In some patients there was an increase in alkaline phosphatase, changes in bone mineral density, osteoporosis, osteopenia, depressive disorders [32] [33] [34]. These nutritional deficiencies largely disappear after the initiation of an agglutinative regime, due to the restoration of the integrity of the intestinal mucosa and the villi responsible for the absorption of nutrients. It has been pointed out that, from an initial malnutrition status (deficiencies), some patients may develop an excess malnutrition status due to the consumption of products high in saturated fats, simple sugars and salt. A paradox is currently occurring: in celiac, a rigorous gluten-free diet can become a risk factor for chronic diseases such as cardiovascular disease, obesity, diabetes and cancer [35] [36] (Table 2).

The international market offers consumers, who follow a GFD, a wide range of products: bread and bakery products, pasta, pancakes, dumplings, pickles, biscuits, wafers, sauces, beer etc. Public catering establishments in Italy, for example, offers people with gluten-related disorders gluten-free meals, and the state provides celiacs with monthly monetary rewards. 3.2. The gluten-free products market. In the Russian Federation, following research, technologies have been developed for obtaining pasta based on mixtures of buckwheat, corn and rice flour, using the methods of mixing and pressing the dough with a humidity of 34% - 38% and the temperature at the end. turbulence of 74˚C - 78˚C.

The global gluten-free market has grown considerably in recent decades not only because of the growing number of celiac patients (due to early and more accurate diagnosis), but also because of the increased demand from non-celiac patients, because it is believed that gluten-free products can help relieve and treat disorders such as autism, chronic fatigue, schizophrenia, attention deficit disorders, multiple sclerosis, migraines and fertility problems. Moreover, thanks to celebrities, who have adopted and promoted a GFD, it has become known, has been taken over and included as a lifestyle by many people. As a result of the growing market, companies are expanding their offer with a large number of snacks and beverages designed to attract consumers on a sensory level. Over the last decade, scientific research has come with more and more information about gluten-free ingredients, which has allowed manufacturers to innovate using alternative cereals and new ingredients.

The GFP market grew at an average annual rate of 28% in 2004, when it was valued at $580 million, then in 2008, at $1.56 billion, and is estimated to reach 2.5 in 2012. billion dollars. In reality, this rate was reached in 2010, and in 2012 it reached 4.2 billion euros (for an annual growth rate of 28%). In 2019, the market for gluten-free products in the US was estimated at USD 21.61 billion, and in 2020 it was estimated at only 5.6 billion (Figure 5).

The COVID-19 pandemic has affected the global market, including gluten-free products. Due to the limited activities of the supply chain, producers are not able to procure raw materials and manufacture goods to meet demand [50]. However, after the pandemic, the market for gluten-free products is expected to show an optimistic upward trend, due to increasing consumer demand, due to a change in lifestyle, towards a healthier diet. It is expected to expand in 2025, by 8.3 billion to a CAGR of 8.1%, which will increase by 2027 to 9.2%. In Europe, an increase of USD 2.7 billion is expected by 2025 at a CAGR of 8.7%. The gluten-free bakery segment (which includes bread, cookies, cakes, biscuits) is expected to witness the fastest CAGR of 10.4% in that period [48] [49].

The gluten-free diet requires the complete elimination of all foods that contain gluten-generating cereals or their derivatives. Therefore, pasta, bread and all

traditional flour products (wheat varieties, camut, faro, spelled, wheat malt) should be avoided, which will be replaced with gluten-free products (Table 3).

Opinions on the membership of oats and oat derivatives in the category of gluten-free cereals are contradictory, so the International Celiac Association (IAC) recommends the use of other cereals, which do not present risks of gluten contamination during cultivation and/or processing. Sorghum, also due to the large number of hybrids, could also present risks of gluten contamination. Rice, corn, potatoes have over the years been the most used raw materials in the diet of people intolerant to gluten, and in recent years new possibilities have focused the attention of nutritionists such as cereals, pseudo-cereals and legumes. There are no restrictions on vegetables, fruits, meat, fish, eggs, milk and dairy products. It should be noted, however, that these gluten-free products may contain gluten in the commercially available finished product due to cross-contamination.

Gluten proteins are not essential for human nutrition, but the percentage distribution of gluten-generating protein fractions directly influences the technological properties of products [15] [52]. Nutritionally, the biological value of gluten is modest, being poor in some essential amino acids. The absence of this compound in the diet does not bring any specific nutritional risk, especially in the first years of life, but guarantees a major palatability of the products.

Otherwise, the guidelines for proper nutrition are valid. It is fundamental to focus not only on the nutritional aspects of each food, but to consider the more general aspects such as: the correct distribution of meals per day, avoiding food excesses or abuses. Fresh and seasonal products are always favored, including their diversification, as far as possible, to the extent that they cover the daily nutritional needs [36] [41] [53].

Although considerable progress has been made in the development of gluten-free products, their limited quality and rapid aging are a problem. As the niche for these products on the market is still small, their rotation is very low, so inevitably there is a need to create gluten-free products with a longer shelf life. This is difficult to achieve, especially for bread and bakery products, due to the inherent characteristics of the products. Therefore, in many cases, the quality of gluten-free products is not acceptable when they reach celiac people. In addition, gluten, free products are more expensive than their wheat counterparts [69] [70]. Most gluten-free products are limited in nutrients and can carry risks if not detected in time and treated properly [2]. Some studies have shown that GF products have a low caloric and protein intake, dietary fiber deficiencies, vitamins (D, riboflavin, niacin, folic acid (B9) B12, K), and some minerals (Fe, Ca, Mg, Zn) [71] [72]. Often these products, probably due to its technological peculiarities, contain excessive amounts of lipids, hydrogenated fatty acids, phosphorus etc. (Table 4).

Some GF products marketed lack detailed information on the nutritional value on the label [43]: mineral content, vitamins. Gluten-contaminated GF-branded products have also been identified [69] (gluten content exceeds 20 ppm), which poses risks to people with gluten-related disorders. Researchers in the field are largely unanimous about the impact of GFD on quality of life, and the recommendations involve: Researchers in the field are largely unanimous about the impact of GFD on quality of life, and the recommendations involve:

● Direct assessment of the nutritional quality of GF products and identification of deficiencies [2] [81];

● Development of educational strategies focused on the relationship between nutrients, food and human health, optimization of services etc [36] [75] [81] [82] [80];

● Diversification of the food ration by including in the menus pseudocereals, legumes, natural products rich in calcium, iron, fiber, folate [32] [41] [78];

● Extension of fortification legislation for GF flour products [77];

● Counseling and psychological support can also improve diet compliance [32].

According to some authors, the adoption of a GFD requires, at the initial stage, an increase in protein intake to 140 - 160 g/day (meat, fish, cheese, legumes, eggs) and a quantitative reduction of carbohydrates to 200 g/day. The recommended amount of lipids (vegetable and animal) should not exceed 100 g/day. The energy value of the gluten-free diet should be 2300 - 3337 kcal [83]. Carbohydrate intake may be increased to 400 g/day with normalization of the intestinal epithelium. Limit products that stimulate the secretion of gastric juice and products that can affect the liver. 10 years ago, there was talk of a gluten-free diet focused mainly on safety, referring to the level of gluten (values below 20 ppm/kg produced) in celiac products. In the following years, the concept of product quality also adhered to the safety concept: organoleptic, technological and nutritional. Today, in particular, it focuses on personalized nutrition and nutritional quality: the composition and ratio of macro- and micronutrients in dietary products.