Food Allergies–Finding Help on the Internet

ABSTRACT

Food allergies present real challenges to those who must deal with them on a daily basis. When food provokes an immune response, perhaps inducing a severe condition such as anaphylactic shock, it becomes the enemy and an obstacle to be overcome. For some this is a problem of infancy soon outgrown, but for many others it is a life-long problem requiring special diets, emergency medication kits, and a perpetual vigilance regarding all food consumed. The Internet enables those afflicted with food hypersensitivities to learn about their condition as well as methods for dealing with it in their daily lives. This paper describes Web sites that provide information and support for those with food allergies.     

Gluten and Autism Spectrum Disorder

An expanding body of literature is examining connections between Autism Spectrum Disorder (ASD) and dietary interventions. While a number of specialist diets have been suggested as beneficial in ASD, gluten has received particularly close attention as a potentially exacerbating factor. Reports exist suggesting a beneficial effect of the gluten-free diet (GFD) in ameliorating behavioural and intellectual problems associated with ASD, while epidemiological research has also shown a comorbidity between ASD and coeliac disease. However, both caregivers and clinicians have expressed an uncertainty of the value of people with ASD going gluten-free, and as the GFD otherwise receives considerable public attention a discussion which focuses specifically on the interaction between ASD and gluten is warranted. In this review we discuss the historical context of ASD and gluten-related studies, and expand this to include an overview of epidemiological links, hypotheses of shared pathological mechanisms, and ultimately the evidence around the use and adoption of the GFD in people with ASD.     

Do we need to worry about eating wheat?

Wheat is a staple food throughout the temperate world and an important source of nutrients for many millions of people. However, the last few years have seen increasing concerns about adverse effects of wheat on health, particularly in North America and Europe, with the increasing adoption of wheat‐free or gluten‐free diets. This relates to two concerns: that wheat products are disproportionally responsible for increases in obesity and type 2 diabetes and that wheat gluten proteins cause a range of adverse reactions, including allergies, coeliac disease and ‘non‐coeliac gluten sensitivity’. The first concern has been refuted in previous publications, and we therefore focus on the second here. Current evidence indicates that allergy to ingested wheat and coeliac disease (and related intolerances) each occur in up to 1% of the population. The extent to which their prevalence has increased is difficult to quantify due to improved diagnosis and increased awareness. However, neither appears to be increasing disproportionally when compared with other immunologically mediated adverse reactions to food. Other adverse reactions to wheat are more difficult to define as their mechanisms are not understood and they are therefore difficult to diagnose. In particular, ‘non‐coeliac wheat sensitivity’ has been reported to occur in 6% or more of the population in the US. However, the application of more rigorous diagnostic criteria is likely to give substantially lower estimates of prevalence. It is therefore unlikely that the health of more than a small proportion of the population will be improved by eliminating wheat or gluten from the diet. In fact, the opposite may occur as wheat is an important source of protein, B vitamins, minerals and bioactive components.     

Non-Responsive and Refractory Coeliac Disease: Experience from the NHS England National Centre

We characterised the aetiology of non-responsive coeliac disease (NRCD) and provided contemporary mortality data in refractory coeliac disease (RCD) from our centre. We also measured urine gluten immunogenic peptides (GIPs) in patients with established RCD1 to evaluate gluten exposure in these individuals. Methods: This was a longitudinal cohort study conducted in Sheffield, UK. Between 1998 and 2019, we evaluated 285 adult (≥16 years) patients with NRCD or RCD. Patients with established RCD1 and persisting mucosal inflammation and/or ongoing symptoms provided three urine samples for GIP analysis. Results: The most common cause of NRCD across the cohort was gluten exposure (72/285; 25.3%). RCD accounted for 65/285 patients (22.8%), 54/65 patients (83.1%) had RCD1 and 11/65 patients (16.9%) had RCD2. The estimated 5-year survival was 90% for RCD1 and 58% for RCD2 (p = 0.016). A total of 36/54 (66.7%) patients with RCD1 underwent urinary GIP testing and 17/36 (47.2%) had at least one positive urinary GIP test. Conclusion: The contemporary mortality data in RCD2 remains poor; patients with suspected RCD2 should be referred to a recognised national centre for consideration of novel therapies. The high frequency of urinary GIP positivity suggests that gluten exposure may be common in RCD1; further studies with matched controls are warranted to assess this further.     

The Clinical Response to Gluten Challenge: A Review of the Literature

The aim of this review was to identify, evaluate and summarize all relevant studies reporting on the clinical response to gluten challenge by adult or pediatric patients with suspected or diagnosed coeliac disease (CD) on a gluten-free diet. We evaluated the effect of gluten challenge on changes in symptoms, intestinal mucosa histology, and serum antibodies. A systematic electronic search was performed for studies published as of 1966 using PubMed and Scopus databases. In the reviewed studies, doses ranged from 0.2 to 30 g/day of wheat gluten or comprised a gluten-containing diet. The onset of symptoms upon gluten intake varied largely from days to months and did not parallel serum antibody or histological changes. Within 3 months of gluten challenge, 70%–100% of pediatric CD patients became positive for AGA-IgA and EMA-IgA antibodies and 50%–70% for AGA-IgG. A limited number of trials suggest that no more than half of adult patients developed positive AGA-IgA, EMA-IgA, tTG-IgA or DGP-IgA/IgG titers. Approximately 50%–100% of pediatric and adult patients experienced mucosal relapse of gluten provocation within 3 months, which was preceded by increased mucosal intra-epithelial lymphocytes within several days of challenge. A 3-month high-dose gluten challenge should be suitable to diagnose the majority of CD patients. In some cases prolonged challenge may be needed to verify diagnosis. Combination testing for antibodies and mucosal histology may fasten the diagnosis.     

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.     

The Role of Gluten in Celiac Disease and Type 1 Diabetes

Celiac disease (CD) and type 1 diabetes (T1D) are autoimmune conditions in which dietary gluten has been proven or suggested to play a pathogenic role. In CD; gluten is established as the instigator of autoimmunity; the autoimmune process is halted by removing gluten from the diet; which allows for resolution of celiac autoimmune enteropathy and subsequent normalization of serological markers of the disease. However; an analogous causative agent has not yet been identified for T1D. Nevertheless; the role of dietary gluten in development of T1D and the potentially beneficial effect of removing gluten from the diet of patients with T1D are still debated. In this review; we discuss the comorbid occurrence of CD and T1D and explore current evidences for the specific role of gluten in both conditions; specifically focusing on current evidence on the effect of gluten on the immune system and the gut microbiota.     

Psyllium as a Substitute for Gluten in Pastas

The aim of the present study was to evaluate the effect of replacing gluten in favor of psyllium in pasta’s characteristics. This study takes an exploratory and quantitative approach and was sub-divided into four steps: selection and development of recipes and chemical and sensorial analysis. Modified samples of the pasta presented 100.0% of acceptance for individuals with celiac disease and up to 94.0% for individuals without celiac disease. The most affected characteristics were odor and texture. In terms of chemical composition, reduction of energy value was 26.5% and of proportional fat was 85.4% before being cooked. Substituting wheat flour for a mixture of gluten-free flours with psyllium did not alter preference or acceptability of modified products in relation to standardized ones and amplified feeding options for celiac disease patients. Thus, there were no damages in sensorial characteristics of these products.     

Effect of Gliadin on Permeability of Intestinal Biopsy Explants from Celiac Disease Patients and Patients with Non-Celiac Gluten Sensitivity

Background: Intestinal exposure to gliadin leads to zonulin upregulation and consequent disassembly of intercellular tight junctions and increased intestinal permeability. We aimed to study response to gliadin exposure, in terms of barrier function and cytokine secretion, using intestinal biopsies obtained from four groups: celiac patients with active disease (ACD), celiac patients in remission (RCD), non-celiac patients with gluten sensitivity (GS) and non-celiac controls (NC). Methods: Ex-vivo human duodenal biopsies were mounted in microsnapwells and luminally incubated with either gliadin or media alone. Changes in transepithelial electrical resistance were monitored over 120 min. Media was subsequently collected and cytokines quantified. Results: Intestinal explants from all groups (ACD (n = 6), RCD (n = 6), GS (n = 6), and NC (n = 5)) demonstrated a greater increase in permeability when exposed to gliadin vs. media alone. The increase in permeability in the ACD group was greater than in the RCD and NC groups. There was a greater increase in permeability in the GS group compared to the RCD group. There was no difference in permeability between the ACD and GS groups, between the RCD and NC groups, or between the NC and GS groups. IL-10 was significantly greater in the media of the NC group compared to the RCD and GS groups. Conclusions: Increased intestinal permeability after gliadin exposure occurs in all individuals. Following gliadin exposure, both patients with gluten sensitivity and those with active celiac disease demonstrate a greater increase in intestinal permeability than celiacs in disease remission. A higher concentration of IL-10 was measured in the media exposed to control explants compared to celiac disease in remission or gluten sensitivity.     

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.     

An investigation into the nutritional composition and cost of gluten‐free versus regular food products in the UK

Background

The gluten‐free (GF) food market has expanded considerably, although there is limited comparative evidence for the nutritional quality and cost of GF food products. The present study aims to compare the nutrient composition and cost of GF and gluten‐containing (regular) foods across 10 food categories in the UK.

Methods

Nutritional information and the cost of GF foods available in the UK (n = 679) and comparable regular foods (n = 1045) were systematically collected from manufacturer and supermarket websites. Foods were classified using UK front‐of‐pack labelling for content of fat, saturated fat, sugar and salt and nutrient content, and cost per 100 g were identified and compared between GF and regular foods.

Results

Overall, more GF foods were classified as containing high and medium fat, saturated fat, sugar and salt than regular foods, although this was not universally consistent. More GF bread and flour products contained high fat and sugar, whereas fewer GF crackers contained high fat and sugar compared to regular foods. High salt content was found more frequently in GF than regular products. On average, GF products were 159% more expensive than regular (£0.44/100 g versus £1.14/100 g). GF items were also more likely to be lower in fibre and protein content than regular foods.

Conclusions

Differences exist in the nutritional composition of GF and regular food. GF food is unlikely to offer healthier alternatives to regular foods, except for those who require a GF diet for medically diagnosed conditions, and it is associated with higher costs.     

Clinical Value of Tissue Transglutaminase Antibodies in Celiac Patients over a Long Term Follow-Up

Introduction & Aim: Anti-tissue transglutaminase antibody (tTGA) titer is used during the follow-up of celiac patients to evaluate gluten-free diet (GFD) responsiveness. However, no clear data are available on this issue. The aim of this study was to evaluate tTGA significance during celiac disease (CD) monitoring. Methods: From January 2017 to January 2020, consecutive CD patients on a GFD with persistent positive tTGA were enrolled. Antibody titres were evaluated on a yearly basis from CD diagnosis to the last follow-up. Urinary gluten detection tests, duodenal histology and capsule enteroscopy (CE) were performed. A tTGA-positive cohort was compared with a control group composed of 212 treated CD patients with negative tTGA. Results: 65 patients (12% males, median age at enrollment and CD diagnosis, 37 (14–86) and 31 (1–76), respectively, median follow up 4 (1–26) years) presented with positive tTGA during follow-up. Overall, the tTGA titres were 3 (1–79) fold increased (ULN). Three different tTGA trends were recognized: (I) 36 (55%) patients with a progressive titres decrease; (II) 16 (25%) patients with a fluctuating behavior; (III) 13 (20%) patients with a steady state or increased titres. tTGA+ patients did not present with different clinical and demographic parameters. Duodenal atrophy was present in 10% vs. 36% of the tTGA positive vs. negative group (p < 0.005), respectively. Gluten detection results were positive in 3 (8%) cases, all in the III group. In tTGA+ patients, CE did not identify any CD-related complications. Conclusions: tTGA positivity during CD follow up did not present a relevant clinical significance without association with autoimmune comorbidities and mucosal damage.     

Subclinical nutritional deficiency in treated coeliac disease and nutritional content of the gluten free diet

Patients with coeliac disease are started on a gluten free diet at the time of diagnosis, but after a varying period of follow-up are often discharged from outpatient and dietary follow-up. We have studied the nutritional status and dietary intake of 54 patients with treated coeliac disease diagnosed in adult life.
Each patient was paired with a healthy age and sex matched control. There was no difference in height in patients compared to controls, but a greater proportion of patients (15%) than controls (4%) had weight below the UK population lower 5th percentile ( x ² test P <0.05). Triceps skinfold thickness was 102% of age and sex matched mean reference values, but mid-arm circumference and arm muscle circumference were below reference mean values (93.1% and 91.5% of reference values, respectively). Haemoglobin, mean corpuscular volume, red cell folate and 25 hydroxyvitamin D were all in the normal range.
A strict gluten free diet was followed by 78% of patients; 22% had occasional gluten intake. Seventy-four per cent considered that they had reduced their intake of bread since commencing a gluten free diet. In 48% of patients, average daily intake of energy was less than the estimated average requirement, and in more than one-third of patients the intake of iron, copper, magnesium, retinol and folic acid was less than the relevant reference nutrient intake (RNI). In more than 10% of patients, average daily intake of calcium, zinc or vitamin B6 was less than the RNI. Vitamin D intake was lower than the RNI in four of five patients older than 65 years.     

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.     

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.     

Gluten Induces Subtle Histological Changes in Duodenal Mucosa of Patients with Non-Coeliac Gluten Sensitivity: A Multicentre Study

Background: Histological changes induced by gluten in the duodenal mucosa of patients with non-coeliac gluten sensitivity (NCGS) are poorly defined. Objectives: To evaluate the structural and inflammatory features of NCGS compared to controls and coeliac disease (CeD) with milder enteropathy (Marsh I-II). Methods: Well-oriented biopsies of 262 control cases with normal gastroscopy and histologic findings, 261 CeD, and 175 NCGS biopsies from 9 contributing countries were examined. Villus height (VH, in μm), crypt depth (CrD, in μm), villus-to-crypt ratios (VCR), IELs (intraepithelial lymphocytes/100 enterocytes), and other relevant histological, serologic, and demographic parameters were quantified. Results: The median VH in NCGS was significantly shorter (600, IQR: 400–705) than controls (900, IQR: 667–1112) (p < 0.001). NCGS patients with Marsh I-II had similar VH and VCR to CeD [465 µm (IQR: 390–620) vs. 427 µm (IQR: 348–569, p = 0·176)]. The VCR in NCGS with Marsh 0 was lower than controls (p < 0.001). The median IEL in NCGS with Marsh 0 was higher than controls (23.0 vs. 13.7, p < 0.001). To distinguish Marsh 0 NCGS from controls, an IEL cut-off of 14 showed 79% sensitivity and 55% specificity. IEL densities in Marsh I-II NCGS and CeD groups were similar. Conclusion: NCGS duodenal mucosa exhibits distinctive changes consistent with an intestinal response to luminal antigens, even at the Marsh 0 stage of villus architecture.     

Amaranth Pasta in Mexico: A Celiac Overview

Amaranth is one of the most representative crops in Mexico and could represent an alternative for consumers with celiac disease. Since it possesses no gluten, it can be included in the production of non-conventional starchy foods. This work was focused on the evaluation of process conditions and adequacy of a gluten-free lasagna. Four amaranth formulations containing corn and tapioca starches at different concentrations were analyzed. Ready-to-cook samples were obtained after drying (80°C for 45 min). Pasta containing 8% corn starch reported the highest stability during blending (1.5 min) and a firmness value of 16.060 kg. This formulation was subjected to sensory analysis by 10 celiac consumers. Overall acceptability received an average score of 4.7 on a 9-point hedonic scale with a possible intention of buying.     

Mortality in patients with celiac disease

Celiac disease is an autoimmune disorder triggered by ingestion of gluten-containing foods. Epidemiologic studies dating from the 1950s established its association with gastrointestinal malignancies, particularly small bowel lymphoma. Corrao et al. recently demonstrated that patients with celiac disease are at increased risk of mortality. Further, this risk is directly related to compliance with a gluten-free diet. Continued research is needed regarding the development of malignant complications related to celiac disease.