Special Issue "Advance in Gluten-Free Diet"

A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Phytochemicals and Human Health".

Deadline for manuscript submissions: closed (31 August 2020).

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Special Issue Editor

Dr. Usai-Satta Paolo
E-Mail Website1 Website2
Guest Editor
Department of Gastroenterology, Azienda Ospedaliera Brotzu, Piazzale Alessandro Ricchi, 1, 09134 Cagliari CA, Italy
Interests: celiac disease and alimentary intolerances; irritable bowel syndrome, chronic constipation, gut motor disorders, gastric emptying and functional dyspepsia
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Special Issue Information

Dear Colleagues,

The only effective and safe treatment of celiac disease (CD) and gluten-related disorders is a lifelong, strict exclusion of gluten—the so-called gluten-free diet (GFD). Although this treatment is highly successful, following a strict GFD causes difficulties to patients in social and working contexts. As a consequence, a strict adherence to the GFD is not so easy to achieve in some patients. These findings have led to an interest in drug development, either as an addition to the GFD or as a substitute. On the other hand, many subjects are following a GFD without a specific diagnosis, but, to date, no controlled studies support or exclude a positive health effect of a GFD. In addition, the increasing interest in the interaction between a GFD and microbiota can develop our understanding in the knowledge and management of gluten-related disorders. New insights into the GFD are an exciting scientific challenge for researchers.

Dr. Paolo Usai-Satta
Guest Editor

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Keywords

  • Gluten free diet
  • Celiac disease
  • Gluten related disorders
  • Diet adherence
  • Non celiac gluten/wheat sensitivity
  • Novel therapies
  • Gut microbiota

Published Papers (9 papers)

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Editorial

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Editorial
New Perspectives on Gluten-Free Diet
Nutrients 2020, 12(11), 3540; https://doi.org/10.3390/nu12113540 - 18 Nov 2020
Cited by 1 | Viewed by 939
Abstract
Celiac disease (CD) is a permanent, chronic, gluten-sensitive disorder characterized by small intestinal inflammation and malabsorption in genetically predisposed individuals [...] Full article
(This article belongs to the Special Issue Advance in Gluten-Free Diet)

Research

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Article
Gluten-Free Diet in Prisons in Poland: Nutrient Contents and Implementation of Dietary Reference Intake Standards
Nutrients 2020, 12(9), 2829; https://doi.org/10.3390/nu12092829 - 16 Sep 2020
Cited by 1 | Viewed by 947
Abstract
The gluten-free diet (GFD) requires special attention from nutritionists due to the potential risk of nutrient deficiencies in its users. This risk may be greater when this type of nutrition is implemented in prisons due to the limited possibilities of external control, a [...] Read more.
The gluten-free diet (GFD) requires special attention from nutritionists due to the potential risk of nutrient deficiencies in its users. This risk may be greater when this type of nutrition is implemented in prisons due to the limited possibilities of external control, a low catering budget for meals, and insufficiently defined recommendations regulating nutrition for prisoners. The aim of the present study was to assess the nutritional value of GFD and regular diet meals served in some Polish prisons and to compare the values to the dietary reference intake (DRI) standards. Using a specialized computer program, 7-day menus of both types of diet provided in 10 prisons were analyzed. The percentage coverage of the DRI was calculated based on the recommendations of the Polish National Food and Nutrition Institute. GFD was characterized by lower average contents of energy and 11 out of 14 essential nutrients, i.e., protein, carbohydrates, dietary fiber, starch, ash, sodium, calcium, iron, zinc, folate, and vitamin B12. The average content of phosphorus, niacin, and riboflavin in the gluten-free diet was higher than that in the regular diet. It was shown that the meals in GFD and the regular diet did not provide the recommended amounts of calcium (38 and 44% DRI, respectively), vitamin D (29 and 30% DRI), vitamin C (86 and 76% DRI), and folate (51 and 56% DRI). In turn, the supply of sodium, phosphorus, copper, and vitamins A and B6 substantially exceeded the recommended levels. The results indicate a need for greater quality control of GFD meals served in catering facilities. It is also necessary to develop legal provisions that will regulate more specifically the nutrition for prisoners in terms of an adequate supply of minerals and vitamins. Full article
(This article belongs to the Special Issue Advance in Gluten-Free Diet)
Article
Updated Food Composition Database for Cereal-Based Gluten Free Products in Spain: Is Reformulation Moving on?
Nutrients 2020, 12(8), 2369; https://doi.org/10.3390/nu12082369 - 07 Aug 2020
Cited by 8 | Viewed by 1592
Abstract
We developed a comprehensive composition database of 629 cereal-based gluten free (GF) products available in Spain. Information on ingredients and nutritional composition was retrieved from food package labels. GF products were primarily composed of rice and/or corn flour, and 90% of them included [...] Read more.
We developed a comprehensive composition database of 629 cereal-based gluten free (GF) products available in Spain. Information on ingredients and nutritional composition was retrieved from food package labels. GF products were primarily composed of rice and/or corn flour, and 90% of them included added rice starch. The most common added fat was sunflower oil (present in one third of the products), followed by palm fat, olive oil, and cocoa. Only 24.5% of the products had the nutrition claim “no added sugar”. Fifty-six percent of the GF products had sucrose in their formulation. Xanthan gum was the most frequently employed fiber, appearing in 34.2% of the GF products, followed by other commonly used such as hydroxypropyl methylcellulose (23.1%), guar gum (19.7%), and vegetable gums (19.6%). Macronutrient analysis revealed that 25.4% of the products could be labeled as a source of fiber. Many of the considered GF food products showed very high contents of energy (33.5%), fats (28.5%), saturated fatty acids (30.0%), sugars (21.6%), and salt (28.3%). There is a timid reformulation in fat composition and salt reduction, but a lesser usage of alternative flours and pseudocereals. Full article
(This article belongs to the Special Issue Advance in Gluten-Free Diet)
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Article
Beneficial Effects of a Low-Nickel Diet on Relapsing IBS-Like and Extraintestinal Symptoms of Celiac Patients during a Proper Gluten-Free Diet: Nickel Allergic Contact Mucositis in Suspected Non-Responsive Celiac Disease
Nutrients 2020, 12(8), 2277; https://doi.org/10.3390/nu12082277 - 29 Jul 2020
Cited by 3 | Viewed by 1853
Abstract
Background and Aim: Nickel (Ni)-rich foods can induce allergic contact mucositis (ACM) with irritable bowel syndrome (IBS)-like symptoms in predisposed subjects. Ni ACM has a high prevalence (>30%) in the general population and can be diagnosed by a Ni oral mucosa patch test [...] Read more.
Background and Aim: Nickel (Ni)-rich foods can induce allergic contact mucositis (ACM) with irritable bowel syndrome (IBS)-like symptoms in predisposed subjects. Ni ACM has a high prevalence (>30%) in the general population and can be diagnosed by a Ni oral mucosa patch test (omPT). Many celiac disease (CD) patients on a gluten-free diet (GFD) often show a recrudescence of gastrointestinal and extraintestinal symptoms, although serological and histological remission has been achieved. Since a GFD often results in higher loads of ingested alimentary Ni (e.g., corn), we hypothesized that it would lead to a consequent intestinal sensitization to Ni in predisposed subjects. We wanted to (1) study Ni ACM prevalence in still symptomatic CD patients on a GFD and (2) study the effects of a low-Ni diet (LNiD) on their recurrent symptoms. Material and Methods: We recruited 102 consecutive CD patients (74 female, 28 male; age range 18–65 years, mean age 42.3 ± 7.4) on a GFD since at least 12 months, in current serological and histological remission (Marsh–Oberhuber type 0–I) who complained of relapsing gastrointestinal and/or extraintestinal symptoms. Inclusion criteria: presence of at least three gastrointestinal symptoms with a score ≥5 on the modified Gastrointestinal Symptom Rating Scale (GSRS) questionnaire. Exclusion criteria: IgE-mediated food allergy; history of past or current cancer; inflammatory bowel diseases; infectious diseases including Helicobacter pylori; lactose intolerance. All patients enrolled underwent Ni omPT and followed a LNiD for 3 months. A 24 symptoms questionnaire (GSRS modified according to the Salerno Experts’ Criteria, with 15 gastrointestinal and 9 extraintestinal symptoms) was administered at T0 (free diet), T1 (GFD, CD remission), T2 (recurrence of symptoms despite GFD), and T3 (GFD + LNiD) for comparisons. Comparisons were performed using Wilcoxon signed-rank test. RESULTS: Twenty patients (all female, age range 23–65 years, mean age 39.1 ± 2.9) out of 102 (19.6%) were finally included. All 20 patients enrolled (100%) showed positive Ni omPT, confirming an Ni ACM diagnosis. A correct GFD (T0 vs. T1) induced the improvement of 19 out of the total 24 (79.2%) symptoms, and 14 out of 24 (58.3%) were statistically significant (p-value < 0.0083 according to Bonferroni correction). Prolonged GFD (T1 vs. T2) revealed the worsening of 20 out of the total 24 (83.3%) symptoms, and 10 out of 24 (41.7%) were statistically significant. LNiD (T2 vs. T3) determined an improvement of 20 out of the total 24 (83.4%) symptoms, and in 10 out of 24 (41.7%) symptoms the improvement was statistically significant. Conclusions: Our data suggest that the recrudescence of gastrointestinal and extraintestinal symptoms observed in CD subjects during GFD may be due to the increase in alimentary Ni intake, once gluten contamination and persisting villous atrophy are excluded. Ni overload can induce Ni ACM, which can be diagnosed by a specific Ni omPT. Improvement of symptoms occurs after a proper LNiD. These encouraging data should be confirmed with larger studies. Full article
(This article belongs to the Special Issue Advance in Gluten-Free Diet)
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Article
Efficacy of a High-Iron Dietary Intervention in Women with Celiac Disease and Iron Deficiency without Anemia: A Clinical Trial
Nutrients 2020, 12(7), 2122; https://doi.org/10.3390/nu12072122 - 17 Jul 2020
Cited by 1 | Viewed by 1424
Abstract
Background and Aim. Iron deficiency without anemia (IDWA) is a common finding in celiac disease (CD) and can also persist in case of good compliance and clinical response to a strict gluten-free diet (GFD). This scenario usually presents in CD women of child-bearing [...] Read more.
Background and Aim. Iron deficiency without anemia (IDWA) is a common finding in celiac disease (CD) and can also persist in case of good compliance and clinical response to a strict gluten-free diet (GFD). This scenario usually presents in CD women of child-bearing age in whom the imbalance between menstrual iron loss and inadequate iron intake from their diet plays the major role. A recommended approach to this condition is yet to be established. This study aimed to compare, in this subset of patients, the efficacy of a dietary approach consisting of an iron-rich diet against the traditional pharmacological oral-replacement therapy. Material and Methods. Between February and December 2016, consecutive CD female patients of child-bearing age as referred to our outpatient center with evidence of IDWA (ferritin <15 ng/mL or 15–20 ng/L with transferrin saturation <15%) were enrolled. After the completion of a 7-day weighed food intake recording to assess the usual iron dietary intake, the patients were randomized in two arms to receive a 12-week iron-rich diet (iron intake >20 mg/die) versus oral iron supplementation with ferrous sulfate (FS) (105 mg/day). Blood tests and dietary assessments were repeated at the end of treatment. The degree of compliance and tolerability to the treatments were assessed every month by means of specific questionnaires and symptoms evaluation. Results. A total of 22 women were enrolled and divided in the diet group (n = 10, age 37 ± 8 years) and in the FS group (n = 12, age 38 ± 10 years). The food intake records demonstrated an inadequate daily intake of iron in all the enrolled subjects. At the end of the treatments, ferritin levels were higher in the FS group (8.5 (5) versus 34 (30.8), p = 0.002). Compliance and tolerability were similar in both treatment groups (89% versus 87%, p = ns). Conclusions. These findings did not support any equivalent efficacy of an iron-rich diet compared to a FS supplementation in non-anemic iron-deficient women affected by CD. However, the diet appeared a well-tolerated approach, and adequate dietary instructions could effectively increase the daily iron consumption, suggesting a role in the long-term management of IDWA, especially in patients who do not tolerate pharmacological supplementation. Full article
(This article belongs to the Special Issue Advance in Gluten-Free Diet)
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Article
Wheat Sensitivity and Functional Dyspepsia: A Pilot, Double-Blind, Randomized, Placebo-Controlled Dietary Crossover Trial with Novel Challenge Protocol
Nutrients 2020, 12(7), 1947; https://doi.org/10.3390/nu12071947 - 30 Jun 2020
Cited by 5 | Viewed by 1508
Abstract
Introduction: Functional dyspepsia (FD), characterised by symptoms of epigastric pain or early satiety and post prandial distress, has been associated with duodenal eosinophilia, raising the possibility that it is driven by an environmental allergen. Non-coeliac gluten or wheat sensitivity (NCG/WS) has also been [...] Read more.
Introduction: Functional dyspepsia (FD), characterised by symptoms of epigastric pain or early satiety and post prandial distress, has been associated with duodenal eosinophilia, raising the possibility that it is driven by an environmental allergen. Non-coeliac gluten or wheat sensitivity (NCG/WS) has also been associated with both dyspeptic symptoms and duodenal eosinophilia, suggesting an overlap between these two conditions. The aim of this study was to evaluate the role of wheat (specifically gluten and fructans) in symptom reduction in participants with FD in a pilot randomized double-blind, placebo controlled, dietary crossover trial. Methods: Patients with Rome III criteria FD were recruited from a single tertiary centre in Newcastle, Australia. All were individually counselled on a diet low in both gluten and fermentable oligo-, di-, mono-saccharides, and polyols (FODMAPs) by a clinical dietitian, which was followed for four weeks (elimination diet phase). Those who had a ≥30% response to the run-in diet, as measured by the Nepean Dyspepsia Index, were then re-challenged with ‘muesli’ bars containing either gluten, fructan, or placebo in randomised order. Those with symptoms which significantly reduced during the elimination diet, but reliably reappeared (a mean change in overall dyspeptic symptoms of ≥30%) with gluten or fructan re-challenge were deemed to have wheat induced FD. Results: Eleven participants were enrolled in the study (75% female, mean age 43 years). Of the initial cohort, nine participants completed the elimination diet phase of whom four qualified for the rechallenge phase. The gluten-free, low FODMAP diet led to an overall (albeit non-significant) improvement in symptoms of functional dyspepsia in the diet elimination phase (mean NDI symptom score 71.2 vs. 47.1, p = 0.087). A specific food trigger could not be reliably demonstrated. Conclusions: Although a gluten-free, low-FODMAP diet led to a modest overall reduction in symptoms in this cohort of FD patients, a specific trigger could not be identified. The modified Salerno criteria for NCG/WS identification trialled in this dietary rechallenge protocol was fit-for-purpose. However, larger trials are required to determine whether particular components of wheat induce symptoms in functional dyspepsia. Full article
(This article belongs to the Special Issue Advance in Gluten-Free Diet)
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Article
Wheat Consumption Leads to Immune Activation and Symptom Worsening in Patients with Familial Mediterranean Fever: A Pilot Randomized Trial
Nutrients 2020, 12(4), 1127; https://doi.org/10.3390/nu12041127 - 17 Apr 2020
Cited by 7 | Viewed by 1522
Abstract
We have identified a clinical association between self-reported non-celiac wheat sensitivity (NCWS) and Familial Mediterranean Fever (FMF). Objectives: A) To determine whether a 2-week double-blind placebo-controlled (DBPC) cross-over wheat vs. rice challenge exacerbates the clinical manifestations of FMF; B) to evaluate innate immune [...] Read more.
We have identified a clinical association between self-reported non-celiac wheat sensitivity (NCWS) and Familial Mediterranean Fever (FMF). Objectives: A) To determine whether a 2-week double-blind placebo-controlled (DBPC) cross-over wheat vs. rice challenge exacerbates the clinical manifestations of FMF; B) to evaluate innate immune responses in NCWS/FMF patients challenged with wheat vs. rice. The study was conducted at the Department of Internal Medicine of the University Hospital of Palermo and the Hospital of Sciacca, Italy. Six female volunteers with FMF/NCWS (mean age 36 ± 6 years) were enrolled, 12 age-matched non-FMF, NCWS females, and 8 sex- and age-matched healthy subjects served as controls. We evaluated: 1. clinical symptoms by the FMF-specific AIDAI (Auto-Inflammatory Diseases Activity Index) score; 2. serum soluble CD14 (sCD14), C-reactive protein (CRP), and serum amyloid A (SSA); 3. circulating CD14+ monocytes expressing interleukin (IL)-1β and tumor necrosis factor (TNF)-α. The AIDAI score significantly increased in FMF patients during DBPC with wheat, but not with rice (19 ± 6.3 vs. 7 ± 1.6; p = 0.028). sCD14 values did not differ in FMF patients before and after the challenge, but were higher in FMF patients than in healthy controls (median values 11357 vs. 8710 pg/ml; p = 0.002). The percentage of circulating CD14+/IL-1β+ and of CD14+/TNF-α+ monocytes increased significantly after DBPC with wheat vs. baseline or rice challenge. Self-reported NCWS can hide an FMF diagnosis. Wheat ingestion exacerbated clinical and immunological features of FMF. Future studies performed on consecutive FMF patients recruited in centers for auto-inflammatory diseases will determine the real frequency and relevance of this association. Full article
(This article belongs to the Special Issue Advance in Gluten-Free Diet)
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Communication
Irritable Bowel Syndrome and Gluten-Related Disorders
Nutrients 2020, 12(4), 1117; https://doi.org/10.3390/nu12041117 - 17 Apr 2020
Cited by 6 | Viewed by 1574
Abstract
Background: Irritable bowel syndrome (IBS) is frequently associated with celiac disease (CD) and nonceliac gluten/wheat sensitivity (NCGS/NCWS), but epidemiological and pathophysiological aspects are still unclear. Furthermore, a gluten-free diet (GFD) can positively influence IBS symptoms. Methods: A comprehensive online search for [...] Read more.
Background: Irritable bowel syndrome (IBS) is frequently associated with celiac disease (CD) and nonceliac gluten/wheat sensitivity (NCGS/NCWS), but epidemiological and pathophysiological aspects are still unclear. Furthermore, a gluten-free diet (GFD) can positively influence IBS symptoms. Methods: A comprehensive online search for IBS related to CD, NCGS and GFD was made using the Pubmed, Medline and Cochrane databases. Results: Although a systematic screening for CD in IBS is not recommended, CD prevalence can be increased in diarrhea-predominant IBS patients. On the other hand, IBS symptoms can be persistent in treated CD patients, and their prevalence tends to decrease on a GFD. IBS symptoms may overlap and be similar to those associated to nonceliac gluten and/or wheat sensitivity. Increased gut permeability could explain the gluten/wheat effects in IBS patients. Finally, a GFD could improve symptoms in a subgroup of IBS patients. Conclusions: The possible interplay between IBS and gluten-related disorders represents a scientifically and clinically challenging issue. Further studies are needed to confirm these data and better clarify the involved pathophysiological mechanisms. Full article
(This article belongs to the Special Issue Advance in Gluten-Free Diet)

Review

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Review
Low Fermentable Oligo- Di- and Mono-Saccharides and Polyols (FODMAPs) or Gluten Free Diet: What Is Best for Irritable Bowel Syndrome?
Nutrients 2020, 12(11), 3368; https://doi.org/10.3390/nu12113368 - 01 Nov 2020
Cited by 6 | Viewed by 2023
Abstract
Irritable Bowel Syndrome (IBS) is a very common functional gastrointestinal disease. Its pathogenesis is multifactorial and not yet clearly defined, and hence, its therapy mainly relies on symptomatic treatments. Changes in lifestyle and dietary behavior are usually the first step, but unfortunately, there [...] Read more.
Irritable Bowel Syndrome (IBS) is a very common functional gastrointestinal disease. Its pathogenesis is multifactorial and not yet clearly defined, and hence, its therapy mainly relies on symptomatic treatments. Changes in lifestyle and dietary behavior are usually the first step, but unfortunately, there is little high-quality scientific evidence regarding a dietary approach. This is due to the difficulty in setting up randomized double-blind controlled trials which objectively evaluate efficacy without the risk of a placebo effect. However, a Low Fermentable Oligo-, Di- and Mono-saccharides And Polyols (FODMAP) Diet (LFD) and Gluten Free Diet (GFD) are among the most frequently suggested diets. This paper aims to evaluate their possible role in IBS management. A GFD is less restrictive and easier to implement in everyday life and can be suggested for patients who clearly recognize gluten as a trigger of their symptoms. An LFD, being more restrictive and less easy to learn and to follow, needs the close supervision of a skilled nutritionist and should be reserved for patients who recognize that the trigger of their symptoms is not, or not only, gluten. Even if the evidence is of very low-quality for both diets, the LFD is the most effective among the dietary interventions suggested for treating IBS, and it is included in the most updated guidelines. Full article
(This article belongs to the Special Issue Advance in Gluten-Free Diet)
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