Cereal Foods World, Vol. 64, No. 5
Print To PDF
Wheat and Gluten: Impacts of a Food Trend that Ripples Around the World1
Bruna Mattioni,2 Michael Tilley,3,4 Katharina A. Scherf,5 and Patricia M. Scheuer6
This article is in the public domain and not copyrightable. It may be freely reprinted with customary crediting of the source. AACC International, Inc., 2019.
Celiac disease affects approximately 1% of the global population, and there are considerable differences among countries due to a combination of cultural and genetic factors. The only treatment for celiac disease is adherence to a gluten-free diet and avoidance of foods made from or containing ingredients derived from wheat, rye, and barley. According to the Codex Alimentarius, foods that contain <20 mg of gluten/kg should be labeled as gluten-free; those containing >20 and up to 100 mg of gluten/kg should be labeled as reduced gluten content; and those containing >100 mg of gluten/kg should be labeled as containing gluten. Most countries have accepted the limits specified in the Codex Alimentarius; however, labeling requirements for food products vary considerably. For countries in the European Union, it is mandatory to label all food products regarding the presence of gluten, whereas labeling is voluntary in the United States. Regulations in South and Central America range from strict labeling laws to no rules. Legislation and current issues in the European Union, United States, and Central and South America are reviewed in this article.
Hypersensitivities toward Cereal Proteins
Adverse reactions to foods can be divided into metabolic dysfunctions, such as inherited enzyme deficiencies; toxic reactions to contaminated foods; non–immune-mediated reactions, such as lactose or fructose malabsorption; and immune-mediated reactions, such as allergies, non-celiac gluten sensitivity (NCGS), and celiac disease. Hypersensitivities toward cereal proteins can be subdivided further based on the pathomechanism into immunoglobulin E (IgE)-mediated allergies: a predominantly innate immune response (NCGS) and a mostly autoimmunogenic response (celiac disease) (Fig. 1) (24,34,42). Another emerging field is that of non–IgE-mediated allergies.
Celiac disease is a chronic immune-mediated enteropathy of the small intestine caused by dietary gluten from wheat, rye, and barley in genetically predisposed individuals (24). The prevalence of celiac disease worldwide is between 0.7% (biopsy-confirmed) and 1.4% (seroprevalence), and there are considerable differences in prevalence among countries (38). A combination of environmental and genetic factors is known to cause celiac disease. The most important environmental factor is the consumption of gluten in the diet. The genetic factor is associated with human leukocyte antigens (HLA)-DQ2 and HLA-DQ8. These antigen receptors are expressed on the surface of antigen-presenting cells and have a high affinity toward gluten peptides, especially deamidated peptides. Presentation of bound gluten peptides to gluten-specific CD4+ T cells triggers the release of cytokines, which activates a localized cytotoxic immune response that results in villous atrophy (32).
There is a significant association between the prevalence of celiac disease, the frequency of HLA-DQ2 and -DQ8, and the level of wheat consumption, but there are several exceptions in regions such as northwestern India, northern Africa, Mexico, Finland, and Russia. For example, the prevalence of celiac disease in Tunisia is very low (0.3%), whereas the prevalence in neighboring Algeria is one of the highest in the world (5.6%), even though the genetic predisposition and levels of wheat and barley consumption are similar (1). This discrepancy can only be explained by a third factor that causes the immune system to recognize gluten as an antigen. The most likely factors are viral infections, changes in intestinal microbiota, increased small intestinal permeability, and the so-called “hygiene hypothesis” (3).
The characteristic clinical picture of celiac disease is inflammatory damage to the upper small intestine, with infiltration of intraepithelial lymphocytes (IEL), crypt hyperplasia, and partial to total villous atrophy. This loss of surface area causes malabsorption of nutrients and subsequent signs of nutrient deficiencies. Celiac disease has frequently been described as a chameleon, because it presents in symptomatic, asymptomatic, potential, and refractory manifestations. The common features of all symptom manifestations are genetic predisposition (HLA-DQ2 and -DQ8 positive) and the presence of celiac disease-specific IgA and IgG antibodies in the blood.
Symptomatic celiac disease patients have intestinal and/or extraintestinal symptoms, including diarrhea, steatorrhea, and abdominal pain, as well as anemia, thyroid dysfunction, decreased bone mineral density, and night blindness. The essential treatment for celiac disease is adherence to a strict gluten-free diet, which causes disease symptoms to disappear in most patients. However, some patients suffer from persistent villous atrophy despite following a strict gluten-free diet. This condition, called refractory celiac disease, is divided into two types, and whereas type I (normal IEL phenotype) can usually be treated with corticosteroids, type II (aberrant IEL phenotype) poses a serious risk of enteropathy-associated T-cell lymphoma and ulcerative jejunitis (33).
Asymptomatic celiac disease patients may have some small intestinal damage but do not have symptoms associated with gluten ingestion. These patients are often diagnosed by screening at-risk populations, such as first-degree relatives of celiac disease patients and patients suffering from other autoimmune diseases or genetic disorders that are commonly associated with celiac disease.
Potential celiac disease patients have neither symptoms nor evidence of small intestinal damage, but they do have celiac disease-specific antibodies in their blood. Therefore, they have an increased risk of developing celiac disease, and regular follow-up on a normal diet is recommended.
Celiac disease is diagnosed based on symptoms and patient history, detection of celiac disease-specific antibodies (IgA/IgG anti-tissue transglutaminase, IgA anti-endomysium antibodies, IgG anti-deamidated gliadin peptides) in the blood, histologic assessment of at least five small intestinal biopsies, and follow-up after starting a gluten-free diet. HLA-DQ genotyping may be performed in ambiguous cases, because of its high negative predictive value. It is important to note that diagnosis can only be made while gluten is still ingested in the diet. Therefore, patients with suspected, but undiagnosed, celiac disease who are already following a gluten-free diet need to undergo gluten challenge (23).
A gluten-free diet, as the only safe treatment for celiac disease, relies on excluding products made with wheat (e.g., common and durum wheat, spelt, emmer, einkorn, triticale, and Khorasan wheat [kamut]), rye, and barley from the diet. Only trace levels (20 mg of gluten daily) may be tolerated without recurrent small intestinal damage (5). Oats generally are regarded as safe for most celiac disease patients if they are specially grown and processed to avoid cross-contamination with wheat, rye, and barley.
Compared with celiac disease and wheat allergies, NCGS is the least understood condition, because diagnostic biomarkers are missing and the triggers have not been elucidated in detail. Due to the significant overlap between NCGS and irritable bowel syndrome, it is difficult to make a precise assessment of its prevalence, and numbers range from 0.6 to 6% of the population in Europe and North America. NCGS symptoms include both intestinal and extraintestinal manifestations and occur several hours to a few days after wheat consumption but disappear when a gluten-free or gluten-reduced diet is followed. NCGS patients have a normal small intestinal mucosa but show evidence of activated innate immunity. The diagnosis of NCGS is based on patient history and the exclusion of celiac disease, wheat allergy, and other food intolerances. To confirm the diagnosis, a double-blind placebo-controlled challenge with crossover is recommended (4). alpha-Amylase/trypsin inhibitors (ATIs) have been shown to trigger the innate immune response and act as adjuvants of preexisting inflammatory adaptive immune responses (45). These ATI-induced effects are dose-dependent, suggesting that a reduction in nutritional ATI intake may be sufficient to prevent inflammation. It is also possible that NCGS could be a non–IgE-mediated allergy. Until the pathomechanism of NCGS is elucidated in more detail, NCGS patients are advised to follow a gluten-free diet.
Wheat allergies can affect either the skin or respiratory tract or can be triggered by ingestion of wheat products. The prevalence of wheat allergies is estimated to be between 0.1 and 3.6% of the population (31). The diagnosis of wheat allergy is made by assessing patient history, skin prick tests, detection of specific IgE antibodies, basophil activation tests, or oral food challenge. Antihistamines or corticosteroids are suitable to treat acute cases, but the most common treatment is avoidance of exposure.
Baker’s asthma and allergic rhinitis, both caused by the inhalation of flour and dust, are among the most common occupational diseases of bakers, millers, and confectioners and may necessitate vocational retraining. The major allergens are ATIs, lipid transfer proteins, and non-specific lipid transfer proteins; however, more than 100 IgE-binding proteins have been identified (40). Skin allergies to wheat, such as contact urticaria and contact dermatitis, also are prevalent among people who work with flours.
Wheat is the third most common cause of food allergy and is surpassed only by milk and egg. Wheat food allergy occurs within a few hours of wheat ingestion and may present with symptoms on the skin, in the respiratory tract, in the gastrointestinal tract, and even anaphylaxis. The dose of wheat proteins needed to trigger allergic reactions is usually quite high (about 1 g) but may also be lower (10 mg) depending on individual sensitivities. The causative factors are both gluten and non-gluten proteins. Wheat-dependent, exercise-induced anaphylaxis (WDEIA) is a rare, but potentially life-threatening, form of wheat allergy (35). It only occurs in sensitized individuals when wheat ingestion is combined with augmenting cofactors, of which exercise (80%), alcohol (25%), and nonsteroidal anti-inflammatory drugs (9%) (e.g., acetylsalicylic acid) are the most prevalent factors. Treatment of WDEIA is based on the avoidance of combining wheat ingestion and cofactors, but a gluten-free diet provides more safety for affected individuals, especially because some cofactors, such as infections, cannot be avoided.
Legislation and Issues in the European Union
The definitions, threshold (20 mg of gluten/kg), and labeling requirements for gluten-free products in the European Union specified in EU Regulation 1169/2011 (12) are equivalent to those described in Codex Standard 118-1979 (7). Under this regulation, indication of any ingredient or processing aid listed in Annex II that causes allergies or intolerances that is used in the preparation of a food and still present in the finished product, even if in altered form, is mandatory. Among the substances listed in Annex II are cereals containing gluten (i.e., wheat, rye, barley, oats, spelt, kamut, or their hybridized strains and products thereof). Provided that the gluten-free threshold is met and additional certifications for in-house and external gluten analyses, appropriate audits, hazard control, and traceability are provided, an annual license with a code of registration is granted to the manufacturer of a gluten-free product by national celiac societies under the European Licensing System of the Association of European Coeliac Societies (AOECS). This license permits the use of the internationally recognized and well-known crossed grain symbol on the product label.
AOECS currently has 38 European full-member societies and represents the interests of approximately 300,000 celiac disease patients. Association activities include representation at international consultations and events, exchange of information, and support of emerging societies. One important aspect of AOECS is its observer status with the Codex Alimentarius Commission, and through its regular participation, several Codex standards and guidelines have been improved to protect gluten-sensitive individuals.
Legislation and Issues in the United States
The U.S. Food and Drug Administration (FDA) is responsible for issues regarding product safety and labeling in accordance with the Food Allergen Labeling and Consumer Protection Act of 2004 (43). In 2011, the FDA posted its request for comments regarding the definition for gluten, and in 2013, the FDA issued a final rule defining “gluten-free” for food labeling. The FDA ruling was in accordance with that of European and Codex Alimentarius specifications, preserving global uniformity. According to the FDA, any product labeled as gluten-free must contain <20 mg of gluten/kg; however, in the United States it is not mandatory to label any food item regarding the presence or absence of gluten (44):
|Besides the limit of gluten to 20 ppm, the rule permits labeling a food ‘gluten-free’, if the food does not contain: an ingredient that is any type of wheat, rye, barley, or crossbreeds of these grains; an ingredient derived from these grains that has not been processed to remove gluten; or, an ingredient derived from these grains that has been processed to remove gluten, but results in the food containing more than 20 ppm of gluten.|
The FDA regulation established a federal definition of the term “gluten-free” for manufacturers of all foods and beverages produced and imported into the United States (including packaged foods, dietary supplements, fruits and vegetables, shell eggs, and fish), except for foods that are regulated by other agencies: the U.S. Department of Agriculture (USDA) (meats and poultry); the Alcohol and Tobacco Tax and Trade Bureau (TTB); the U.S. Department of the Treasury (distilled spirits, wines with 7% or more alcohol by volume, and beverages made with malted barley and hops).
The FDA does not require mandatory labeling or require or recommend testing methods or certification programs for gluten-free labeling. Product labeling is voluntary, and thus, highly variable, ranging from pictograms to simply stating “Gluten Free.” This lack of standardization can result in confusion for the consumer. To aid consumers, several manufacturers apply certification programs to include a gluten-free logo on food labels. This has been a mission of nationwide support groups. There are several nationwide and community information and support groups available to help consumers and patients.
The National Celiac Association (NCA) (https://nationalceliac.org) provides a searchable database of certified gluten-free products and restaurants (https://gf-finder.com). The association endorses the Gluten-Free Food Program certification labeling (Fig. 2A). The NCA has also been active in preparation of the language of H.R. 2074, the Gluten in Medicine Disclosure Act of 2019. If passed, this bill will amend the Federal Food, Drug, and Cosmetic Act to require labeling of prescription medicines containing gluten excipients.
The Gluten Intolerance Group of North America (GIG) (https://gluten.org) has more than 90 GIG branches and Generation GF support groups. The Gluten-Free Certification Organization (GFCO), a GIG program, provides third-party certification, as well as risk assessment, plant audits, equipment testing, and product testing, both in the plant and at point of consumer purchase. GFCO has certified more than 50,000 products in 46 countries with distinctive labeling (Fig. 2B).
The Celiac Disease Foundation (https://celiac.org) collaborates with physicians, dietitians, mental health professionals, and researchers to improve the quality of life for celiac patients, including development of a celiac disease patient registry. The organization is active in the National Institutes of Health Celiac Disease Awareness Program.
Once limited to small, independent companies, often founded by families or friends of celiac patients, the gluten-free product market is now one of the fastest growing markets. It was valued at around US$4.72 billion in 2017 and is expected to reach approximately US$7.60 billion by 2024, growing at a compound annual growth rate of around 7.12% between 2018 and 2024 (47). Recently, several home-delivery meal kits and services have begun providing gluten-free options as well.
There are several medical research groups in the United States with expertise ranging from clinical and scientific research in celiac disease to diagnosis and individual and family nutritional education and counseling:
Colorado: Children’s Hospital Colorado Center for Celiac Disease
California: Stanford Healthcare Celiac Disease Program; University of California Los Angeles Celiac Disease Program; University of California San Diego Health Celiac Disease Clinic
Illinois: University of Chicago Celiac Disease Center; Advocate Children’s Hospital Celiac Center
Massachusetts: Massachusetts General Hospital Center for Celiac Research; Beth Israel Deaconess Medical Center Celiac Center, Harvard Medical School; Boston Children’s Hospital Celiac Disease Program
Minnesota: Mayo Clinic
New Jersey: Saint Barnabas Health Care System, Kogan Celiac Center
New York: Columbia University Celiac Disease Center
Ohio: Nationwide Children’s Hospital Celiac Disease Center
Pennsylvania: Paoli Hospital Celiac Center; Jefferson University Hospital Celiac Center; Children’s Hospital of Philadelphia Center for Celiac Disease; Allegheny Center for Digestive Health Celiac Center
Tennessee: University of Tennessee Medical Center Celiac Center
Wisconsin: Children’s Hospital of Wisconsin, Bonnie Lynn Mechanic Celiac Disease Clinic
A multitude of blogs on gluten-free living exist and can be accessed by the public. However, users should be aware that information provided may not reflect current scientific findings.
Legislation and Issues in Central and South America
In general, it is difficult to find specific legislation concerning gluten-free labeling in Latin America. There is a wide range of regulations, from Argentina and Brazil, which have strict labeling laws that require mandatory labeling of all foods, to Bolivia, the Dominican Republic, Ecuador, Guatemala, Haiti, Honduras, Nicaragua, and Panama, where no legislation or celiac associations were found. In some countries, there are labeling rules only for gluten-free foods, while others include public assistance for celiac patients provided by the public health system and/or mandatory clinical protocols for patients.
Legislation may be related to food habits, culture, and/or political interests. In countries where celiac associations are more organized and exert greater pressure on the government, the laws concerning gluten-free labeling are better. These celiac associations also influence the food industry to produce safe products. The aim of most celiac associations in Latin America is to provide information and an introduction for celiac individuals, family members, and friends and to provide access to qualified professionals in the area, short courses on good manufacturing practices, and nutritional support, including gluten-free recipes. Around the world gluten-free food products are considerably more expensive than their gluten-containing counterparts. Latin America is not different with respect to this price disparity, and not all individuals with celiac disease can afford gluten-free products.
In the following section, we highlight gluten-free labeling legislation and related laws for individual countries in Latin America. The most curious findings were related to the Roman Catholic Church, which does not recognize gluten-free communion hosts (wafers) as valid. According to the Vatican, the body of Christ must be an unleavened bread composed entirely of wheat. In response, a group of German nuns in Chile began to make low-gluten wafers based on wheat starch. Laboratory analysis of the wafers measured gluten at 16 mg/kg, which meant the wafers were doubly accepted for both the Rite of Eucharistic consecration and for the celiac community who can tolerate a small amount of gluten. Many dioceses will provide low-gluten communion wafers for individuals with celiac disease who present a medical certificate (6).
Argentina. In 2009, Argentina enacted Law No. 26588, the Celiac Disease Act, which states that it is in the nation’s interest to carry out clinical and epidemiological research, professional training, diagnosis, and treatment of celiac disease. This broad law requires several governmental agencies to disseminate knowledge and provide for improvement of the overall quality of life by including labeling standards that must be approved by the Ministry of Health; policies to improve the diagnosis of celiac disease; incentives for study of the disease; and determination of punishment for those who do not comply with the law (28). Through this law, medical care; clinical and epidemiological research; and professional training in early detection, diagnosis, and treatment of celiac disease are declared to be of national interest and are included in the Obligatory Medical Plan (Plan Medico Obligatorio). Resolution No. 102, enacted February 2, 2011, made it mandatory for health insurance to cover IgA anti-tranglutaminase and duodenum histology in suspected cases of celiac disease (25).
Joint Resolutions Nos. 131 and 414, enacted July 8, 2011, regulate the labeling of foods for the presence or absence of gluten using the R5 Méndez analytical method (ELISA). A national logo was created for labeling of gluten-free products “without TACC” (wheat, oats, barley, or rye) (Fig. 3) (29). In 2012, the Argentinian Ministry of Health determined that all responsible public institutions must provide gluten-free flours and premixes for each person with celiac disease, in the amount around US$20.00 (36). In addition to national legislation, there is also legislation in Argentinian provinces and municipalities to disseminate knowledge and provide supervision and support for celiac patients (2). A resolution modified Article No. 1383 of the Argentinian Food Code, lowering the threshold of gluten-free foods from 20 mg/kg to <10 mg/kg.
Brazil. The Brazilian National Codex Alimentarius Committee, (CCAB) was established in 1980 by Resolution CONMETRO 01/80, with the aim to represent the national interests of Brazil. CCAB uses Codex standards as references for legislation for foods commercialized in Brazil (21). The first Brazilian gluten label regulation is Law No. 8.543, enacted December 23, 1992 (13), which requires all commercial food products that contain wheat, barley, rye, and oats to be labeled as “contains gluten,” whereas all other foods made without these ingredients can be labeled as “does not contain gluten.”
In 2003, with the enactment of Law No. 10.674 (14), it became mandatory that all food products commercialized in Brazil be labeled as “contains gluten” or “does not contain gluten.” This was followed by resolution RDC No. 137 (15), which requires all drugs that contain gluten as an excipient to contain a warning label, “patients with celiac disease or celiac syndrome attention: contains gluten” or “attention: this medication contains gluten, and therefore is not indicated for patients with celiac disease or celiac syndrome.” In 2012, the Brazilian government created the Technical Committee of Full Attention to Celiac People, through resolution RDC No. 460 (16), with the aim to create, plan, monitor, and evaluate the Cross-Section Policy of Full Attention to Celiac People. In response to this legislation and pressure from the Celiac Association, Brazilian states and municipalities are required to create their own laws, such as “compulsory safe meals for students with food intolerances in public schools”; “incorporation of celiac products into the market chain”; “separation of gluten-free foods in the supermarket including separate shelves from other products”; “training of public health professionals in municipalities” (www.fenacelbra.com.br/fenacelbra/leis-para-celiaco). The Celiac Association continues to pressure the government to assign the permissible level of gluten in products at “zero.” This demand is quantitatively impossible, especially given that current regulations do not specify a detection method.
Chile. In 1997, Chile established guidelines for food to be characterized as “gluten-free” through the Food Sanitary Regulation, Title XXVIII, Paragraph VI, Articles 516, 517, and 518 (26). The threshold was set at 5 mg of gluten/kg of finished product (27). In 2015, these documents were updated by Decree 134, which states that the term “gluten-free” and the symbol of a cut wheat spike can only be used when the results of laboratory testing of a food product does not exceed 3 mg of gluten/kg of food. According to COACEL (Corporación de Apoyo al Celíaco), these regulations for gluten-free foods have a cutoff point of 3 mg of gluten/kg, which makes them suitable for consumption by celiac patients. At the same time, COACEL guides celiac patients by supporting clinical referrals and offering access to relevant information (10).
Colombia. In Colombia, Law No. 100, Article 245, enacted December 23, 1993, mandates that the Institute for Drug and Food Surveillance implement policies related to sanitary surveillance and quality control of medicines and food, medical, and cosmetic products that may have an impact on individual and collective health. The registries and licenses are regulated by the national government (18). Resolution No. 5.109, enacted December 29, 2005, establishes a technical regulation regarding the requirements for labeling of foodstuffs for human consumption (30):
|Cereals containing gluten (wheat, rye, oats, barley, spelt or their strains, hybrids and products thereof), in compliance with the standard for declaration of allergens. In the case of allergens, one of the following must be included in the labeling: ‘contain traces of cereals’; ‘contains gluten’; ‘may contain traces of gluten’; ‘the product is manufactured where other products are made with wheat flour or wheat flour is added in the ingredients.’|
The Institute for the Surveillance of Medicines and Foods in Colombia has an internal Review Committee that is tasked with meeting all legal requests. These concepts were published in the ACTA No. 05/2012, on July 26, 2012, and concur with the Codex Alimentarius in both defining “gluten free” as 20 mg of gluten/kg and specifying R5 Méndez ELISA as the method of analysis (22).
Costa Rica. In Costa Rica, according to the National Standard for the Care of Persons with Celiac Disease, a food can be labeled as “gluten free” if it contains <20 mg of gluten/kg of food, as specified in the Codex standards. Foods with a reduced gluten content should contain between 20 and 100 mg of gluten/kg of product (39).
Cuba. In Cuba, clinical protocols for the diagnosis of celiac disease have been in place since the 1970s (20), as well as the provision of free gluten-free foods for celiac patients up to 18 years of age. The emphasis for diagnosis and treatment of celiac disease is on children. Another relevant aspect of Cuban regulations is that the political context blocks the importation of “gluten-free” products.
El Salvador. The Association of Celiac and Sensitive to Gluten in El Salvador (https://celiac.org/eat-gluten-free/gf-services/association-of-celiac-and-sensitive-to-gluten-from-el-salvador) requested that the government establish legislation defining gluten-free food as “zero gluten” (using rapid gluten detection tests), which is not possible. It is notable that, despite Agreement No. 480, enacted July 10, 2000, which follows the Codex threshold of 20 mg of gluten/kg, it also stipulates that “gluten-free” food should not exceed 0.05 g of nitrogen in 100 g of cereal (wheat, triticale, rye, barley, or oats), which is a deviation from the Codex standard (11).
Mexico. In Mexico, in accordance with the NORMA Oficial Mexicana NOM No. 247, enacted in 2008, all products made with cereals that contain gluten (wheat, barley, rye, and oats) must be labeled as “contains gluten” or an equivalent statement (37). The Civil Organization of Celiacs of Mexico sent the government a manifesto with a proposed law initiative requesting gluten-free products be analyzed, lists of suitable foods be published, clinical protocols for disease identification be developed, and mandatory availability of gluten-free menu items for celiac patients in public agency food establishments.
Paraguay. In Paraguay, Law No. 3,109, enacted on December 15, 2006, adopts the international symbol of “gluten-free” food products directed toward celiac patients and arbitrates measures of use and control thereof, such as the “gluten free” statement shall be clearly and legibly printed on the packaging of foods not containing wheat, oats, barley, or rye in the formulation; the presence of gluten in products called “gluten free” will result in civil and criminal penalties in accordance with the law; the executive branch will develop a joint action plan for the Ministry of Public Health and Social Welfare with the Ministry of Industry and Commerce to apply the effects of the law and its supervision; and foods and beverages should provide information on the gluten content in their formulation (8).
In addition, the Ministry of Public Health and Social Welfare should provide a list of foodstuffs suitable for consumption by celiac patients; establish adequate analytical methodology for the certification of food products suitable for the consumption by celiac patients; prepare a national register of foodstuffs suitable for consumption by celiac patients, which must be published annually with semiannual updates; create a national statistical survey; promote the training of health professionals; promote basic and clinical research on the diagnosis of celiac disease following updated methodologies for product certification; and socially disseminate information about celiac disease and coordinate prevention and education activities regarding the problem with competent authorities.
It is the responsibility of the Ministry of Industry and Commerce to supervise foods and beverages marketed as “gluten free,” and for the executive branch to regulate the joint action plan and other necessary measures in compliance with the law. Law No. 6,072, enacted on June 4, 2018, establishes control measures for gluten-free products. In this law, the standards established for “gluten-free” products follow the Codex Alimentarius. Labeling, norms for treatment of celiac patients in the public health system, and guidelines for celiac patients are provided for in this law (9).
Peru. According to the Association of Celiacs of Peru, there are no laws or statistics or studies on celiac disease in Peru because it is not considered a priority by the government (https://celiacosperu.org/index.html). This association, which is the body responsible for certifying companies that sell food products for celiac patients, has written a letter to the Peruvian Health Agency requesting regulation following Codex standards for the labeling of gluten-free products.
Uruguay. Law No. 16,096, entitled “Celiac Disease,” was published in Uruguay in 1989. The law established that manufacturers, retailers, and those who fractionate, pack, and distribute foods can make claims to the Public Health Department for confirmation that their products contain gluten (19). In addition, foods labeled as “gluten free” may be inspected by the government, and in all public establishments celiac patients must receive adequate permanent food supplies for consumption. The Asociacion Celiaca del Uruguay (ACELU) plays an important role in the celiac community, disseminating news and recipes, answering questions, and listing foods and drugs suitable for consumption (www.acelu.org).
Venezuela. After considerable pressure from the Celiac Foundation of Venezuela (Fundação Celíaca da Venezuela) (45), the Celiac Law was approved on July 7, 2016. The law requires mandatory labeling of all food products and drugs commercialized in Venezuela as “contains gluten” or gluten-free.” According to this law, only products made from wheat, barley, rye, or oats must be labeled as “contains gluten.” The law does not identify the threshold for gluten content or identify analytical method(s) for determination of gluten levels (41). In this law, other procedures are established, such as rules for labeling; a list of gluten-free products; a government program of tax incentives to companies that produce and offer gluten-free foods at a reasonable price (if they follow quality control rules); and mandatory health system support for celiac patients. In addition, the Celiac Foundation of Venezuela has been accredited to certify the Course of Food Handling at the national level, with the inclusion of gluten in the fundamental procedures for the management of special dietary regimes. Another important contribution was the approval of the proposed resolution made by the foundation to the Ministerio del Poder Popular de la Salud, which through the Servicio Autónomo de Contraloría Sanitaria published Resolution 416, containing “regulations to regulate and control foodstuffs in order to protect celiac patients and those with gluten sensitivity” in 2016 (17).
ConclusionsGreat strides have been made, particularly in diagnosis and regulations, regarding labeling for celiac disease patients. Yet, issues remain, such as the ongoing discussions concerning gluten-free oats, regarding products that have been treated to remove gluten, and surrounding how to deal with consumer home testing devices, such as the Nima sensor (46).
- Abadie, V., Sollid, L. M., Barreiro, L. B., and Jabri, B. Integration of genetic and immunological insights into a model of celiac disease pathogenesis. Annu. Rev. Immunol. 29:493, 2011.
- Asociacion Celiaca Argentina. Leyes nacional. Published online at www.celiaco.org.ar/index.php/legislacion. Asociacion Celiaca Argentina, Buenos Aires, Argentina, 2019.
- Bach, J.-F. The hygiene hypothesis in autoimmunity: The role of pathogens and commensals. Nat. Rev. Immunol. 18:105, 2018.
- Catassi, C., Alaedini, A., Bojarski, C., Bonaz, B., Bouma, G., et al. The overlapping area of non-celiac gluten sensitivity (NCGS) and wheat-sensitive irritable bowel syndrome (IBS): An update. Nutrients 9:1268, 2017.
- Catassi, C., Fabiani, E., Iacono, G., D’Agate, C., Francavilla, R., et al. A prospective, double-blind, placebo-controlled trial to establish a safe gluten threshold for patients with celiac disease. Am. J. Clin. Nutr. 85:160, 2007.
- Centro de Difusión de la Celiaquía. Comunion de los celiacos. Published online at www.cedice.com.ar/legislacion/iglesia/pact89-78.pdf. Centro de Difusión de la Celiaquía, Buenos Aires, Argentina, 1995.
- Codex Alimentarius Commission. Standard for foods for special dietary use for persons intolerant to gluten. Codex Standard 118-1979. In: Codex Alimentarius International Food Standards. FAO/WHO, Rome, Italy, 2015.
- Congreso de la Nacion Paraguaya. Lei No. 3.109, de 15 de dezembro de 2006. Adota o símbolo internacional de produtos alimentícios “sem glúten” direcionado para doentes celíacos e arbitra medidas de uso e controle do mesmo. Published online at www.cedice.com.ar/jweb/index.php/legislacion/38-internacional/paraguay. Government of Paraguay, Asunción, 2006.
- Congreso de la Nacion Paraguaya. Ley No. 6072. Establece Medidas de Control de Productos sin Gluten. Published online at www.bacn.gov.py/leyes-paraguayas/8495/ley-n-6072-establece-medidas-de-control-de-productos-sin-gluten. Government of Paraguay, Asunción, 2018.
- Corporación de Apoyo al Celíaco. Normativa Chilena para alimentos exentos de gluten. Published online at www.coacel.cl/normativa-chilena-para-alimentos-exentos-de-gluten. COACEL, Santiago, Chile, 2019.
- El Organo Ejecutivo en el Ramo de Economia. Acuerdo No. 480, 10 de julio de 2000. Published online at http://extwprlegs1.fao.org/docs/pdf/els27204.pdf. Government of El Salvador, San Salvador, 2000.
- European Commission. Regulation (EU) No 1169/2011 of the European Parliament and of the Council of 25 October 2011 on the provision of food information to consumers. Off. J. Eur. Union 304:18, 2011.
- Federal Government of Brazil. Lei No. 8.543, de 23 de dezembro de 1992. Determina a impressão de advertência em rótulos e embalagens de alimentos industrializados que contenham glúten, a fim de evitar a doença celíaca ou síndrome celíaca. Diário Oficial da União – Seção 1 – 24/12/1992, Página 18011 (publicação original)—Página 3242 in: Coleção de Leis do Brasil – 1992, vol. 12 (publicação original). Federal Government of Brazil, Brasilia, 1992.
- Federal Government of Brazil. Lei No. 10.674, de 16 de maio de 2003. Obriga a que os produtos alimentícios comercializados informem sobre a presença de glúten, como medida preventiva e de controle da doenca celıaca. Diario Oficial da Uniao, Brasılia. Federal Government of Brazil, Brasilia, 2003.
- Federal Government of Brazil. RDC No. 137, de 29 de maio de 2003. O registro/renovação de registro de medicamentos pertencentes às classes/princípios ativos relacionadas em ANEXO, só serão autorizados se as bulas e embalagens contiverem a advertência pertinente, conforme relação anexa. Diario Oficial da Uniao, Brasılia. Federal Government of Brazil, Brasilia, 2003.
- Federal Government of Brazil. Resolução Federal No. 460 de 08 de novembro de 2012. Ministério da Saúde: Que cria o Comitê Técnico Intersetorial de Atenção Integral às Pessoas Celíacas, que tem como objetivo elaborar, planejar, monitorar e avaliar a “Política Intersetorial de Atenção Integral para Pessoas Celíacas.” Published online at http://bvsms.saude.gov.br/bvs/saudelegis/cns/2012/res0460_08_11_2012.html. Federal Government of Brazil, Brasilia, 2012.
- Fundacao Celiaca da Venezuela. Leyes y Normas Sobre Límites y Etiquetado de Productos Aptos para Celíacos. Available online at www.celiacosvenezuela.org.ve/inicio/fcv/leyes-y-etiquetado. Fundacao Celiaca da Venezuela, Caracas, Venezuela, 2017.
- Government of Colombia. Lei No. 100, de 23 de dezembro de 1993. Published online at https://docs.supersalud.gov.co/PortalWeb/Juridica/Leyes/L0100_93.pdf. Government of Colombia, Bogotá, 1993.
- Government of Uruguay. Lei No. 16.096, de 26 de outubro de 1989. Enfermidade Celíaca. Published online at https://legislativo.parlamento.gub.uy/temporales/leytemp6644379.htm. Government of Uruguay, Montevideo, 1989.
- Guillot, C. C. Enfermedad celíaca en Cuba y sus cuarenta anos de experiências y realidades para su dianóstico. Rev. Cubana Pediatr. 88:4, 2016.
- Instituto Nacional de Metrologia, Qualidade e Tecnologia. History of the Codex Alimentarius Committee of Brazil – CCAB. Published online at www.inmetro.gov.br/qualidade/comites/codex_ccab.asp. Federal Government of Brazil, Brasilia, 2012.
- Instituto Nacional de Vigilancia de Medicamentos y Alimentos. ACTA No. 05/2012 de 26 de julho de 2012. Comisión Revisora – Sala Especializada de Alimentos y Bebidas Alcohólicas – SEABA. Available online at www.invima.gov.co/images/pdf/salas-especializadas/bebidas-alimentos/2012/ACTA%2005%2012.pdf. Invima, Bogotá, Columbia, 2012.
- Korponay-Szabó, I. R., Troncone, R., and Discepolo, V. Adaptive diagnosis of coeliac disease. Best Pract. Res. Clin. Gastroenterol. 29:381, 2015.
- Ludvigsson, J. F., Leffler, D. A., Bai, J. A., Biagi, F., Fasano, A., et al. The Oslo definitions for coeliac disease and related terms. Gut 62:43, 2013.
- Ministério da Saúde. Argentina Resolução Federal No. 102 de 02 de fevereiro de 2011. Ministério da Saúde: Investigação através do marcador sérico IgA para a detecção de doença celíaca foi aprovada e incorporada ao programa médico compulsório. Published online at www.msal.gob.ar/celiacos/pdf/resolucion_102-2011.pdf. Ministério da Saúde, Buenos Aires, Argentina, 2011.
- Ministerio de Salud. DTO No. 977/96, de 13 de maio de 1997. Reglamento Sanitario de Los Alimentos. Published online at https://dipol.minsal.cl/wp-content/uploads/2019/04/DECRETO_977_96_2019.pdf. Ministerio de Salud, Santiago, Chile, 1997.
- Ministerio de Salud. DTO No. 134/14, de 14 de janeiro de 2015. Modifica Decreto No. 977, de 1996. Reglamento Sanitario de Los Alimentos. Published online at www.leychile.cl/Navegar?idNorma=1073472&idVersion=2015-07-13. Ministerio de Salud, Santiago, Chile, 2015.
- Ministerio de Salud y Desarrollo Social. Salud Publica. Lei No. 26.588, de 29 de dezembro de 2009. Declara ser de interesse nacional os cuidados médicos, a pesquisa clínica e epidemiológica, o treinamento profissional em detecção precoce, o diagnóstico e o tratamento da doença celíaca. Published online at www.msal.gob.ar/celiacos/pdf/ley-26588.pdf. Government of Argentina, Buenos Aires, 2009.
- Ministerio de Salud y Desarrollo Social. Resolución Conjunta No. 131 y 414, de 8 de julho de 2011. Modifica a lei 26.588 e o artigo 1383 do Código Alimentario Argentino. Published online at www.msal.gob.ar/celiacos/pdf/resolucion-conjunta_131y414-2011.pdf. Government of Argentina, Buenos Aires, 2011.
- Ministério de Salud y Proteccíon Social. Resolução Federal No. 5.109 de 29 de dezembro de 2005. Published online at www.invima.gov.co%2Fresoluciones-en-alimentos%2Fresolucion-005109-2005-pdf%2Fdownload.html&usg=AOvVaw2A2JJEYMgKDvJ5Q-GVtPRV. Government of Colombia, Bogotá, 2005.
- Nwaru, B. I., Hickstein, L., Panesar, S. S., Roberts, G., Muraro, A., Sheikh, A., and the EAACI Food Allergy and Anaphylaxis Guidelines Group. Prevalence of common food allergies in Europe: A systematic review and meta-analysis. Allergy 69:992, 2014.
- Plugis, N. M., and Khosla, C. Therapeutic approaches for celiac disease. Best Pract. Res. Clin. Gastroenterol. 29:503, 2015.
- Rishi, A. R., Rubio-Tapia, A., and Murray, J. A. Refractory celiac disease. Exp. Rev. Gastroenterol. Hepatol. 10:537, 2016.
- Scherf, K. A. Immunoreactive cereal proteins in wheat allergy, non-celiac gluten/wheat sensitivity (NCGS) and celiac disease. Curr. Opin. Food Sci. 25:35, 2019.
- Scherf, K. A., Brockow, K., Biedermann, T., Koehler, P., and Wieser, H. Wheat-dependent exercise-induced anaphylaxis. Clin. Exp. Allergy 46:10, 2016.
- Secretaria de Gobierno de Salud. Programa Nacional de Detección y Control de Enfermedad Celíaca – Legislacion Vigente. Published online at www.msal.gob.ar/celiacos/w-legislacion.html. Government of Argentina, Buenos Aires, 2019.
- Secretaría de Salud Estados Unidos Mexicanos. Norma Oficial Mexicana NOM-247-SSA1-2008, Productos y servicios. Cereales y sus productos. Cereales, harinas de cereales, sémolas o semolinas. Alimentos a base de: Cereales, semillas comestibles, de harinas, sémolas o semolinas o sus mezclas. Productos de panificación. Disposiciones y especificaciones sanitarias y nutrimentales. Métodos de prueba. Published online at http://depa.fquim.unam.mx/amyd/archivero/NOMcereales_12434.pdf. Government of Mexico, Mexico City, 2008.
- Singh, P., Arora, A., Strand, T. A., Leffler, D. A., Catassi, C., Green, P. H., Kelly, C. P., Ahuja, V., and Makharia, G. K. Global prevalence of celiac disease: Systematic review and meta-analysis. Clin. Gastroenterol. Hepatol. 16:823, 2018.
- Sistema Costa Riquenho de Informação Jurídica. Oficializa la Norma Nacional de Atención a Personas con Enfermedad Celiaca No. 38514-S. Published online at www.pgrweb.go.cr/scij/Busqueda/Normativa/Normas/nrm_texto_completo.aspx?param1=NRTC&nValor1=1&nValor2=77640&nValor3=97433&strTipM=TC. Government of Costa Rica, San José, 2014.
- Tatham, A. S., and Shewry, P. R. Allergens in wheat and related cereals. Clin. Exp. Allergy 38:1712, 2008.
- Transparencia Venezuela. Ley de protección a celiacos obliga etiquetar productos. Published online at https://transparencia.org.ve/ley-de-proteccion-a-celiacos-obliga-etiquetar-productos. Transparencia Venezuela, Caracas, 2016.
- Turnbull, J. L., Adams, H. N., and Gorard, D. A. Review article: The diagnosis and management of food allergy and food intolerances. Aliment. Pharmacol. Ther. 41:3, 2015.
- U.S. Food and Drug Administration, Center for Food Safety and Applied Nutrition. Food Allergen Labeling and Consumer Protection Act of 2004 (Public Law 108-282, Title II). Available online at www.fda.gov/food/food-allergensgluten-free-guidance-documents-regulatory-information/food-allergen-labeling-and-consumer-protection-act-2004-falcpa. FDA, Silver Springs, MD, 2018.
- U.S. Food and Drug Administration, Department of Health and Human Services. 21 CFR, Part 101. Food labeling; Gluten-free labeling of foods; Final rule. Document 78 FR 47154. Fed. Reg. 78:47154, 2013.
- Zevallos, V. F., Raker, V., Tenzer, S., Jimenez-Calvente, C., Ashfaq-Khan, M., Rüssel, N., Pickert, G., Schild, H., Steinbrink, K., and Schuppan, D. Nutritional wheat amylase-trypsin inhibitors promote intestinal inflammation via activation of myeloid cells. Gastroenterology 152:1100, 2017.
- Zhang, J., Barbosa Portela, S., Horrell, J. B., Leung, A., Weitmann, D. R., et al. An integrated, accurate, rapid, and economical handheld consumer gluten detector. Food Chem. 275:446, 2019.
- Zion Market Research. Gluten-free product market by product (bakery products, pasta & pizza, snacks & RTE meals, baby food, condiments & dressings, and other) and by distribution channel (business to business [hospitality services, hotels & restaurants, and online channel] and business to consumer [supermarket/hypermarket, conventional stores, specialty services, and online channel]): Global industry perspective, comprehensive analysis, and forecast, 2017–2024. Available online at www.zionmarketresearch.com/report/gluten-free-product-market. Zion Market Research, New York, NY, 2018.