Estimated Levels of Gluten Incidentally Present in a Canadian Gluten-Free Diet

Avoiding exposure to gluten is currently the only effective treatment for celiac disease. However, the evidence suggests that for most affected individuals, exposure to less than 10 mg/day is unlikely to cause histological changes to the intestinal mucosa. The daily diet of people with celiac disease does not rely solely on gluten-free pre-packaged foods, but also on naturally gluten-free grains (e.g., rice, buckwheat, ...) and foods with grain-derived ingredients (i.e., flour and starches) used for cooking and baking at home. The objective of this study was to estimate the level of incidental gluten potentially present in gluten-free diets from a Canadian perspective. We have conducted gluten exposure estimations from grain-containing foods and foods with grain-derived ingredients, taking into consideration the various rates of food consumption by different sex and age groups. These estimates have concluded that if gluten was present at levels not exceeding 20 ppm, exposure to gluten would remain below 10 mg per day for all age groups studied. However, in reality the level of gluten found in naturally gluten-free ingredients is not static and there may be some concerns related to the flours made from naturally gluten-free cereal grains. It was found that those containing a higher level of fiber and that are frequently used to prepare daily foods by individuals with celiac disease could be a concern. For this category of products, only the flours and starches labelled “gluten-free” should be used for home-made preparations.     

Food Safety and Cross-Contamination of Gluten-Free Products: A Narrative Review

A gluten-free diet (GFD) is currently the only effective treatment for celiac disease (CD); an individual’s daily intake of gluten should not exceed 10 mg. However, it is difficult to maintain a strict oral diet for life and at least one-third of patients with CD are exposed to gluten, despite their best efforts at dietary modifications. It has been demonstrated that both natural and certified gluten-free foods can be heavily contaminated with gluten well above the commonly accepted threshold of 20 mg/kg. Moreover, meals from food services such as restaurants, workplaces, and schools remain a significant risk for inadvertent gluten exposure. Other possible sources of gluten are non-certified oat products, numerous composite foods, medications, and cosmetics that unexpectedly contain “hidden” vital gluten, a proteinaceous by-product of wheat starch production. A number of immunochemical assays are commercially available worldwide to detect gluten. Each method has specific features, such as format, sample extraction buffers, extraction time and temperature, characteristics of the antibodies, recognition epitope, and the reference material used for calibration. Due to these differences and a lack of official reference material, the results of gluten quantitation may deviate systematically. In conclusion, incorrect gluten quantitation, improper product labeling, and poor consumer awareness, which results in the inadvertent intake of relatively high amounts of gluten, can be factors that compromise the health of patients with CD.     

Dynamics and Considerations in the Determination of the Excretion of Gluten Immunogenic Peptides in Urine: Individual Variability at Low Gluten Intake

Background: A lifelong strict gluten-free diet is the only available treatment for celiac disease, but total exclusion of gluten is difficult to achieve. The aim of this study was to determine the range of time and the amount of gluten immunogenic peptides (GIP) excreted in urine after specific gluten ingestions. Methods: 20 healthy participants followed the same diet for 12 days in which 50 mg and 2 g of gluten were ingested and all the urinations were collected. GIP were analyzed by lateral flow immunoassay (LFIA) tests and quantified using an LFIA reader. Results: GIP were detected in 15% and 95% of participants after 50 mg and 2 g gluten intakes, respectively. The higher frequency and concentration of GIP was found between 6 and 9 h after both gluten ingestions. The ranges of detection were 3–12 h (50 mg) and 0–15 h (2 g). Conclusions: An increase in the frequency of urine tests may be a suitable approach to avoid false negative results. The use of the LFIA test in three urine samples collected at different times may show a sensitivity of 19.6% for a gluten ingestion like 50 mg, increasing to 93% after 2 g consumption.     

Non-Celiac Gluten Sensitivity in the Context of Functional Gastrointestinal Disorders

Gluten-free diets are increasingly chosen in the Western world, even in the absence of a diagnosis of celiac disease. Around 10% of people worldwide self-report gluten-related complaints, including intestinal and extra-intestinal symptoms. In most cases, these subjects would be labeled as patients suffering from irritable bowel syndrome (IBS) who place themselves on a gluten-free diet even in the absence of celiac disease. In some instances, patients report a clear benefit by avoiding gluten from their diet and/or symptom worsening upon gluten reintroduction. This clinical entity has been termed non-celiac gluten sensitivity (NCGS). The symptoms referred by these patients are both intestinal and extra-intestinal, suggesting that similarly to functional gastrointestinal disorders, NCGS is a disorder of gut–brain interaction. It remains unclear if gluten is the only wheat component involved in NCGS. The mechanisms underlying symptom generation in NCGS remain to be fully clarified, although in the past few years, the research has significantly moved forward with new data linking NCGS to changes in gut motility, permeability and innate immunity. The diagnosis is largely based on the self-reported reaction to gluten by the patient, as there are no available biomarkers, and confirmatory double-blind challenge protocols are unfeasible in daily clinical practice. Some studies suggest that a small proportion of patients with IBS have an intolerance to gluten. However, the benefits of gluten-free or low-gluten diets in non-celiac disease-related conditions are limited, and the long-term consequences of this practice may include nutritional and gut microbiota unbalance. Here, we summarize the role of gluten in the clinical features, pathophysiology, and management of NCGS and disorders of gut–brain interaction.     

Self-Reported Prevalence of Symptomatic Adverse Reactions to Gluten and Adherence to Gluten-Free Diet in an Adult Mexican Population

The prevalence of symptomatic adverse reactions to gluten and adherence to gluten-free diet in Latin American countries is unknown. These measurements are strongly linked to gluten-related disorders. This work aimed to estimate the prevalence of adverse reactions to oral gluten and the adherence to gluten-free diet in the adult Mexican population. To reach this aim, a self-administered questionnaire was designed and tested for clarity/comprehension and reproducibility. Then, a self-administered questionnaire-based cross-sectional study was conducted in the Mexican population. The estimated prevalence rates were (95% CI): 11.9% (9.9–13.5) and 7.8 (6.4–9.4) for adverse and recurrent adverse reactions to gluten respectively; adherence to gluten-free diet 3.7% (2.7–4.8), wheat allergy 0.72% (0.38–1.37); celiac disease 0.08% (0.01–0.45), and NCGS 0.97% (0.55–1.68). Estimated pooled prevalence of self-reported physician-diagnosis of gluten-related disorders was 0.88% (0.49–1.5), and 93.3% respondents reported adherence to gluten-free diet without a physician-diagnosis of gluten-related disorders. Symptom comparisons between those who reported recurrent adverse reactions to gluten and other foods showed statistically significant differences for bloating, constipation, and tiredness (p < 0.05). Gluten-related disorders may be underdiagnosed in the Mexican population and most people adhering to a gluten-free diet are doing it without proper diagnostic work-up of these disorders, and probably without medical/dietician advice.     

Non-Celiac Gluten Sensitivity Has Narrowed the Spectrum of Irritable Bowel Syndrome: A Double-Blind Randomized Placebo-Controlled Trial

Several studies have shown that a large number of patients who are fulfilling the criteria for irritable bowel syndrome (IBS) are sensitive to gluten. The aim of this study was to evaluate the effect of a gluten-free diet on gastrointestinal symptoms in patients with IBS. In this double-blind randomized, placebo-controlled trial, 148 IBS patients fulfilling the Rome III criteria were enrolled between 2011 and 2013. However, only 72 out of the 148 commenced on a gluten-free diet for up to six weeks and completed the study; clinical symptoms were recorded biweekly using a standard visual analogue scale (VAS). In the second stage after six weeks, patients whose symptoms improved to an acceptable level were randomly divided into two groups; patients either received packages containing powdered gluten (35 cases) or patients received placebo (gluten free powder) (37 cases). Overall, the symptomatic improvement was statistically different in the gluten-containing group compared with placebo group in 9 (25.7%), and 31 (83.8%) patients respectively (p < 0.001). A large number of patients labelled as irritable bowel syndrome are sensitive to gluten. Using the term of IBS can therefore be misleading and may deviate and postpone the application of an effective and well-targeted treatment strategy in gluten sensitive patients.     

The Gluten-Free Diet for Celiac Disease and Beyond

The gluten-free diet (GFD) has gained popularity beyond its main medical indication as the treatment for gluten-induced immune-mediated disorders such as celiac disease (CD), dermatitis herpetiformis, gluten ataxia, wheat allergy, and non-celiac gluten sensitivity. However, the diet carries some disadvantages such as elevated costs, nutritional deficiencies, and social and psychological barriers. The present work aims to review indications, proven benefits, and adverse events of a gluten-free diet. Close follow-up with patients following the diet is recommended. More data is needed to assess the effectiveness of the diet in managing mental and cognitive disorders and to establish a connection between the brain and gluten.     

Dose-Escalating (50–500 mg) Gluten Administration Leads to Detectable Gluten-Immunogenic-Peptides in Urine of Patients with Coeliac Disease Which Is Unrelated to Symptoms,a Placebo Controlled Trial

Background: To determine the applicability and sensitivity of a urine self-test to detect gluten-immunogenic-peptides (GIP) in daily-life for patients with coeliac disease and correlate the test results with reported symptoms. Methods: We performed a prospective double-blinded placebo-controlled study, including adults with coeliac disease adhering to a strictly gluten-free diet. Patients were administered gluten in test-cycles of ascending doses of 50, 100, 200, and 500 mg alternated with placebo. Urine portions from 2, 5–17 h after the ingestion were collected and analyzed for GIP using the iVYCHECK-GIP-Urine rapid lateral flow test. Patients completed a diary mapping symptoms (nausea, bloating, diarrhea, abdominal pain, and lower level of energy). Results: We enrolled 15 patients and 7 received all 4 cycles with increasing gluten dosing. GIP was detected from urine in 47% of the patients receiving 50 mg gluten and in 86% with 500 mg gluten. We detected GIP in 20–50% of urine samples after placebo. There was no correlation between symptoms, gluten administration and/or GIP in urine. Conclusions: Gluten intake, even with a dose as low as 50 mg, leads to detectable urinary GIP concentrations. There is no correlation of coeliac disease ascribed symptoms with detection of urinary GIP.     

Prevalence of Wheat/Gluten-Related Disorders and Gluten-Free Diet in Paraguay: An Online Survey-Based Study

Gluten-related disorders (GRDs) are increasing around the world, but their magnitude and relevance remain unknown in most Latin American countries. Thus, an online survey was conducted to estimate the prevalence of GRDs as well as adherence to a gluten-free diet (GFD) in Paraguayan adult population. There were 1058 individuals surveyed using a validated questionnaire (response rate of 93.9%). The self-reported prevalence rates were as follows (95% CI): gluten sensitivity (GS), 10.30% (8.53–12.29); non-celiac GS (NCGS), 5.19% (3.94–6.71); physician-diagnosed celiac disease (PD-CD), 3.11% (2.15–4.35); wheat allergy (WA), 2.07% (1.30–3.13); and adherence to GFD, 15.69% (13.55–18.02). Excluding CD, more women than men met the criteria for GRDs, adverse food reactions, and GFD (p < 0.05). Eight respondents reported the coexistence of NCGS with PD-CD and/or WA. Most cases on a GFD indicated medical/dietitian advice for following the diet (68.07%). Non-self-reported GS individuals indicated weight control (46.4%) and the notion that the GFD is healthier (20.2%) as the main motivations for following the diet. GRDs are not uncommon in Paraguayan adult population. It seems that there is awareness about GRDs and the GFD, but training about the diagnosis of GRDs is desirable because of the informed overlapping diagnoses of CD or WA with NCGS. Future studies involving face-to-face interviews are necessary.     

Evaluation of gluten in gluten-free-labeled foods and assessment of exposure level to gluten among celiac patients in Lebanon

The aim of the study was to evaluate gluten contamination in all the gluten-free (GF)-labeled food products sold in Lebanon. Over a 2-year period, a total of 173 food samples collected from 135 brand names were analyzed. Gluten contamination was detected in 33 of 173 (19%) samples, and its content ranged between 2.5 and >80?mg?kg^?1. In 10 of the 173 samples (6%), the quantity of gluten exceeded the upper limit of 20?mg?kg^?1. Out of the 10 contaminated products, eight (80%) were locally manufactured. Among these 10 products, eight (80%) were wheat-starch-based foods. Of the 40 brand names tested twice in 2014 and 2015, 15 (38%) showed significantly (p?相似文献   

Evaluation of the Presence of Gluten in Beans Served at Self-Service Restaurants: A Problem for Celiac Disease Carriers

The aim of this study is to evaluate the gluten contamination in beans served in self-service restaurants. The study was conducted in self-service restaurants in Brasilia, where samples of common beans were collected and later analyzed using the ELISA technique. The results showed that 16% of the samples were contaminated by gluten and almost 45% of the restaurants showed at least one day of gluten contamination. This shows the lack of standardization of the preparation of beans, a fact that exposes celiac disease (CD) patients to great risk. Therefore, public health actions are necessary to ensure safe access to gluten-free food in order to avoid further complications related to celiac disease and improve quality of life for these individuals.     

Diagnosis of Non-Celiac Gluten Sensitivity (NCGS): The Salerno Experts’ Criteria

Non-Celiac Gluten Sensitivity (NCGS) is a syndrome characterized by intestinal and extra-intestinal symptoms related to the ingestion of gluten-containing food, in subjects that are not affected by either celiac disease or wheat allergy. Given the lack of a NCGS biomarker, there is the need for standardizing the procedure leading to the diagnosis confirmation. In this paper we report experts’ recommendations on how the diagnostic protocol should be performed for the confirmation of NCGS. A full diagnostic procedure should assess the clinical response to the gluten-free diet (GFD) and measure the effect of a gluten challenge after a period of treatment with the GFD. The clinical evaluation is performed using a self-administered instrument incorporating a modified version of the Gastrointestinal Symptom Rating Scale. The patient identifies one to three main symptoms that are quantitatively assessed using a Numerical Rating Scale with a score ranging from 1 to 10. The double-blind placebo-controlled gluten challenge (8 g/day) includes a one-week challenge followed by a one-week washout of strict GFD and by the crossover to the second one-week challenge. The vehicle should contain cooked, homogeneously distributed gluten. At least a variation of 30% of one to three main symptoms between the gluten and the placebo challenge should be detected to discriminate a positive from a negative result. The guidelines provided in this paper will help the clinician to reach a firm and positive diagnosis of NCGS and facilitate the comparisons of different studies, if adopted internationally.     

Evidence for the Presence of Non-Celiac Gluten Sensitivity in Patients with Functional Gastrointestinal Symptoms: Results from a Multicenter Randomized Double-Blind Placebo-Controlled Gluten Challenge

Non-celiac gluten sensitivity (NCGS) is characterized by the onset of symptoms after eating gluten-containing food. We aimed to single out NCGS subjects among subjects with functional gastrointestinal symptoms. Patients were enrolled in a multicenter double-blind placebo-controlled trial with crossover. Symptoms and quality of life were evaluated by means of 10-cm VAS and SF36. Iron parameters, transaminases and C reactive protein (CRP) were evaluated. After a three-week-long gluten-free diet (GFD), responsive patients were randomly assigned to gluten intake (5.6 g/day) or placebo for seven days, followed by crossover. The primary endpoint was the worsening of symptoms (VAS increase ≥3 cm) during gluten ingestion compared to placebo. One hundred and forty patients were enrolled and 134 (17 males, mean age 39.1 ± 11.7 years, BMI 22.4 ± 3.8) completed the first period. A total of 101 subjects (10 males, mean age 39.3 ± 11.0 years, BMI 22.3 ± 4.0) reported a symptomatic improvement (VAS score 2.3 ± 1.2 vs. 6.5 ± 2.2 before and after GFD, p = 0.001). 98 patients underwent the gluten challenge and 28 (all females, mean age 38.9 ± 12.7 years, BMI 22.0 ± 2.9) reported a symptomatic relapse and deterioration of quality of life. No parameters were found to be statistically associated with positivity to the challenge. However, 14 patients responded to the placebo ingestion. Taking into account this finding, about 14% of patients responding to gluten withdrawal showed a symptomatic relapse during the gluten challenge. This group is suspected to have NCGS.     

Selenium levels in erythrocytes of children with celiac disease

Selenium is the component of the glutationperoxidase one of the most important enzymes in the antioxidant protection of the organism. In preliminary studies the authors found in celiac children increased sensitivity to oxidative stress and biochemical changes referring to decreased activity of glutationperoxidase enzyme. Therefore the selenium content of washed erythrocytes has been determined with fluorimetry in 24 celiac children kept on gluten containing diet and 25 on gluten-free diet. In gluten loading the selenium level was significantly lower than in the healthy control group. The selenium value rose at a small degree in the erythrocytes of celiac children kept on gluten-free diet but did not reach the lower limit of the physiological value. On the basis of these results the malabsorption of selenium was found to play also an important role in the decreased protecting capacity against oxidative stress effects in celiac diseases of childhood. The necessity of supplementing the trace element is raised.     

A milligram of gluten a day keeps the mucosal recovery away: a case report

In recent years it has been suggested that patients with celiac disease can be adequately followed up on the basis of merely clinical and serological response to a gluten-free diet. Thus, a duodenal biopsy some months after commencement of a gluten-free diet would no longer be necessary. We report here the case of a celiac patient in whom the ingestion of a milligram of gluten every day for 2 years prevented histological recovery in spite of satisfactory clinical and serological response. The literature regarding the minimal amount of gluten that could be harmless to celiac patients is reviewed.     

Gluten Contamination of Grains, Seeds, and Flours in the United States: A Pilot Study

Under the Food Allergen and Consumer Protection Act, the Food and Drug Administration (FDA) must issue a rule for the voluntary labeling of food as gluten-free. In the proposed rule, many single-ingredient foods, such as millet, are considered inherently free of gluten. Inherently gluten-free grains will be considered misbranded if they carry a gluten-free label and do not also state that all foods of the same type are gluten-free (eg, “all millet is gluten free”). Twenty-two inherently gluten-free grains, seeds, and flours not labeled gluten-free were purchased in June 2009 and sent unopened to a company who specializes in gluten analysis. All samples were homogenized and tested in duplicate using the Ridascreen Gliadin sandwich R5 enzyme-linked immunosorbent assay with cocktail extraction. Thirteen of 22 (59%) samples contained less than the limit of quantification of 5 parts per million (ppm) for gluten. Nine of 22 (41%) samples contained more than the limit of quantification, with mean gluten levels ranging from 8.5 to 2,925.0 ppm. Seven of 22 samples (32%) contained mean gluten levels ≥20 ppm and would not be considered gluten-free under the proposed FDA rule for gluten-free labeling. Gluten contamination of inherently gluten-free grains, seeds, and flours not labeled gluten-free is a legitimate concern. The FDA may want to modify their proposed rule for labeling of food as gluten-free, removing the requirement that gluten-free manufacturers of inherently gluten-free grains, seeds, and flours must state on product labels that all foods of that type are gluten-free.     

Advances in celiac disease and gluten-free diet

Celiac disease is becoming an increasingly recognized autoimmune enteropathy caused by a permanent intolerance to gluten. Once thought to be a rare disease of childhood characterized by diarrhea, celiac disease is actually a multisystemic disorder that occurs as a result of an immune response to ingested gluten in genetically predisposed individuals. Screening studies have revealed that celiac disease is most common in asymptomatic adults in the United States. Although considerable scientific progress has been made in understanding celiac disease and in preventing or curing its manifestations, a strict gluten-free diet is the only treatment for celiac disease to date. Early diagnosis and treatment, together with regular follow-up visits with a dietitian, are necessary to ensure nutritional adequacy and to prevent malnutrition while adhering to the gluten-free diet for life. The purpose of this review is to provide clinicians with current updated information about celiac disease, its diverse clinical presentation and increased prevalence, the complex pathophysiology and strong genetic predisposition to celiac disease, and its diagnosis. This review focuses in detail on the gluten-free diet and the importance of intense expert dietary counseling for all patients with celiac disease. Recent advances in the gluten-free diet include food allergen labeling as well as the US Food and Drug Administration's proposed definition of the food-labeling term gluten-free. The gluten-free diet is complex and patients need comprehensive nutrition education from a skilled dietitian.     

Sensitive detection of cereal fractions that are toxic to celiac disease patients by using monoclonal antibodies to a main immunogenic wheat peptide

BACKGROUND: Celiac disease is an immune-mediated enteropathy caused by the ingestion of gluten, a protein fraction found in certain cereals. Immunotoxic gluten peptides that are recalcitrant to degradation of digestive enzymes appear to trigger celiac syndromes. A 33-mer peptide from alpha-2 gliadin has been identified as a principal contributor to gluten immunotoxicity. A gluten-free diet is the usual first therapy for celiac disease patients; therefore, the characterization and quantification of the toxic portion of the gluten in foodstuffs is crucial to avoid celiac damage. OBJECTIVE: We aimed to develop immunologic assays as a novel food analysis tool for measuring cereal fractions that are immunotoxic to celiac disease patients. DESIGN: The design focused on the production of monoclonal antibodies against the gliadin 33-mer peptide and the development of enzyme-linked immunosorbent assays (ELISAs) and Western blot analysis with the use of novel antibodies. RESULTS: A sandwich ELISA method showed a detection limit for wheat, barley, and rye of <1 ppm prolamine. However, the method required a sample that was > or =1 order of magnitude greater for the detection of low-toxic oats, and there was no signal with the safe cereals maize and rice. A competitive ELISA method was also developed for detection of the toxic peptide in hydrolyzed food, which had a detection limit of <0.5 ppm gliadin. CONCLUSIONS: Both ELISAs designed for use with the toxic gliadin 33-mer peptide suggested a high correlation between the presence of the peptide and the amount of cereal that was toxic to celiac disease patients. The sensitivity was significantly higher than that of equivalent methods recognizing other gluten epitopes.     

Health-Related Quality of Life in Children with Celiac Disease: A Study Based on the Critical Incident Technique

Celiac Disease (CD) is a chronic autoimmune disease triggered by dietary gluten. Gluten avoidance, which is the only available treatment for CD, could impact on quality of life of children with CD. We present the results of a qualitative study on the emotional impact of gluten free diet (GFD) on the everyday life of children affected with CD. We investigated 76 celiac patients aged 2–18 years (average age: 9.5 years). By using the Critical Incident Technique (CIT), we defined emotions related to difficulties and awkward situations experienced by the patients. Written answers to open-ended questions from either children (older than 8 years) and parents (children younger than 8 years) were analyzed qualitatively. We found 80 dilemmas experienced in three different arenas (food situations at school, meals at home, meals outside) and characterized lived experiences of children with CD in everyday life (specific emotions, difficulties in relationships and in management of daily life). Children with CD experience strong emotions related to the GFD, permeating several aspects of everyday life. These dilemmas may be missed by a conventional, questionnaire-based approach to the psycho-social consequences of CD treatment.     

Suitability and Allocation of Protein-Containing Foods According to Protein Tolerance in PKU: A 2022 UK National Consensus

Introduction: There is little practical guidance about suitable food choices for higher natural protein tolerances in patients with phenylketonuria (PKU). This is particularly important to consider with the introduction of adjunct pharmaceutical treatments that may improve protein tolerance. Aim: To develop a set of guidelines for the introduction of higher protein foods into the diets of patients with PKU who tolerate >10 g/day of protein. Methods: In January 2022, a 26-item food group questionnaire, listing a range of foods containing protein from 5 to >20 g/100 g, was sent to all British Inherited Metabolic Disease Group (BIMDG) dietitians (n = 80; 26 Inherited Metabolic Disease [IMD] centres). They were asked to consider within their IMD dietetic team when they would recommend introducing each of the 26 protein-containing food groups into a patient’s diet who tolerated >10 g to 60 g/day of protein. The patient protein tolerance for each food group that received the majority vote from IMD dietetic teams was chosen as its tolerance threshold for introduction. A virtual meeting was held using Delphi methodology in March 2022 to discuss and agree final consensus. Results: Responses were received from dietitians from 22/26 IMD centres (85%) (11 paediatric, 11 adult). For patients tolerating protein ≥15 g/day, the following foods were agreed for inclusion: gluten-free pastas, gluten-free flours, regular bread, cheese spreads, soft cheese, and lentils in brine; for protein tolerance ≥20 g/day: nuts, hard cheeses, regular flours, meat/fish, and plant-based alternative products (containing 5–10 g/100 g protein), regular pasta, seeds, eggs, dried legumes, and yeast extract spreads were added; for protein tolerance ≥30 g/day: meat/fish and plant-based alternative products (containing >10–20 g/100 g protein) were added; and for protein tolerance ≥40 g/day: meat/fish and plant-based alternatives (containing >20 g/100 g protein) were added. Conclusion: This UK consensus by IMD dietitians from 22 UK centres describes for the first time the suitability and allocation of higher protein foods according to individual patient protein tolerance. It provides valuable guidance for health professionals to enable them to standardize practice and give rational advice to patients.