Impact of Gluten-free Diet on Anthropometric Indicators in Individuals With and Without Celiac Disease: A Systematic Review and Meta-analysis.

PURPOSE: Previous studies have found that a gluten-free diet (GFD) may have improve obesity-related factors. For this reason, we conducted a systematic review and meta-analysis to investigate the effect of a GFD on anthropometric indicators. METHODS: We performed a systematic search in databases from inception until July 12, 2022. We included all relevant articles that evaluate efficacy of a GFD on anthropometric indicators in patients with and without celiac disease (CD). Random-effects models were applied to combine the data. The main outcomes were then analyzed using weight mean differences (WMDs) and 95% CIs. FINDINGS: A total of 27 articles met the eligible criteria and were included. Pooled results from the random-effects model indicated that the GFD has no significant effect on any of the factors of anthropometry, including weight (WMD, 1.20 kg; 95% CI, -1.16 to 3.55 kg; P = 0.319), body mass index (WMD, 0.70 kg/m2; 95% CI, -0.45 to 1.84 kg/m2; P = 0.233), waist circumference (WMD, 0.92 cm; 95% CI, -1.34 to 3.17 cm; P = 0.497), and body fat (WMD, 1.02%; 95% CI, -0.38% to 2.42%; P = 0.153). The subgroup results indicated that after implementation of a GFD significant increased weight and body fat occurred in patients with compared with without CD. In addition, the effect of this diet on the increase of BMI and body fat in the intervention of more than 48 weeks was significantly higher. IMPLICATIONS: The results of the present study indicate that a GFD can have a significant and beneficial effect on weight and body fat in patients with CD.

Assessment of Nutritional Status by Bioelectrical Impedance in Adult Patients with Celiac Disease: A Prospective Single-Center Study.

The gluten-free diet [GFD] has been linked to an increased risk of weight gain and the development of metabolic disorders. Most of the studies have focused on the effect of GFD on the Body Mass Index [BMI]. We aimed to evaluate the nutritional status using specific nutritional parameters in patients with celiac disease [CeD] at diagnosis and on a GFD compared to healthy controls. We recruited subjects at our outpatient clinic at the University of Padua. We collected demographic and clinical data and values obtained with bioelectrical impedance analysis. A total of 24 CeD patients and 28 healthy controls were enrolled. CeD patients at diagnosis had a lower body cell mass index [BCMI, p = 0.006], fat-free mass index [FFMI, p = 0.02], appendicular skeletal muscle index [ASMI, p = 0.02], and phase angle [PA] [p < 0.001] compared to controls. Their percentage of extracellular water [ECW] was also higher [p < 0.001]. Considering CeD patients after GFD, nutritional status significantly improved after 6 months of GFD. We did not observe differences in BMI among groups [p = ns]. CeD patients at diagnosis were found to have a poorer nutritional status than healthy controls, with a positive effect of the GFD on their nutritional status, underlining the inefficacy of evaluating this aspect through only BMI evaluation.

Risk of obesity during a gluten-free diet in pediatric and adult patients with celiac disease: a systematic review with meta-analysis.

CONTEXT: Obesity is a significant risk factor for many pathological conditions. Whether a gluten-free diet (GFD) is a risk factor for overweight or obesity remains controversial. OBJECTIVE: The primary aim of this study was to assess the prevalence of body mass index (BMI) categories at disease presentation and the variation in BMI category from underweight/normal to overweight/obese and vice versa during a GFD. DATA SOURCES: PubMed, Scopus, and Web of Science databases were searched through February 2021 for retrospective, cross-sectional, and prospective studies reporting BMI categories at disease diagnosis and during a GFD. DATA EXTRACTION: Data were extracted by 2 reviewers independently. Disagreements were resolved by consensus; a third reviewer was consulted, if necessary. Risk of bias was assessed with the Cochrane ROBINS-I tool. DATA ANALYSIS: Subgroup analysis based on age (pediatric/adult patients), study design (prospective, cross-sectional, retrospective), and duration of GFD was performed.. Forty-five studies were selected (7959 patients with celiac disease and 20 524 healthy controls). The mean BMI of celiac patients at presentation was significantly lower than that of controls (P < 0.001). During a GFD, the mean BMI increased significantly (mean difference = 1.14 kg/m2 [95%CI, 0.68-1.60 kg/m2]; I2 = 82.8%; P < 0.001), but only 9% of patients (95%CI, 7%-12%; I2 = 80.0%) changed from the underweight/normal BMI category to the overweight/obese category, while 20% (95%CI, 11%-29%; I2 = 85.8%) moved into a lower BMI category. CONCLUSION: Most celiac patients had a normal BMI at presentation, although the mean BMI was significantly lower than that of controls. A GFD does not increase the risk of becoming overweight/obese, especially in children. The quality of several studies was suboptimal, with moderate or high overall risk of bias and heterogeneity.

Hepatic Steatosis in Patients with Celiac Disease: The Role of Packaged Gluten-Free Foods.

Background: An increased risk of nonalcoholic fatty liver disease (NAFLD) in patients with celiac disease (CD) adhering to a gluten-free diet (GFD) was recently reported. The nutritional composition of packaged gluten-free foods (PGFF) has been proposed as a possible cause. This hypothesis has not been investigated further, since a systematic structural nutritional interview for all patients would be problematic in clinical practice. Methods: We administered a simple questionnaire based on a Recency, Frequency, and Monetary value (RFM) analysis (a cornerstone of direct marketing segmentation) to consecutive CD patients on a GFD for >6 months and verified its association with NAFLD. Subgroup analyses were performed to understand whether specific patterns of PGFF consumption were significantly associated with NAFLD. Results: Amongst 147 patients (female 82%, median age 42 years), 45 (30.6%) had NAFLD. Total RFM score (adjusted odds ratio = 1.223, 95% CI: 1.059−1.413, p = 0.006), body mass index, and total cholesterol and triglycerides were independently related to NAFLD, and "Bread and bakery" (p = 0.002), "salty convenience" (p = 0.005), and "sweet convenience" (p = 0.049) products were significantly related with NAFLD. Also, questions about the number of purchased PGFF in the last month (monetary value) and different categories of PGFF consumed in the last week (recency) were particularly able to identify NAFLD patients. Conclusions: The specific GFD dietary habits of CD patients were correlated with the degree of risk of NAFLD. Information was obtained through a questionnaire which could be used in clinical practice to favor a patient-tailored approach and in future studies to verify the reproducibility of our results in different geographical areas.

The effect of gluten in adolescents and young adults with gastrointestinal symptoms: a blinded randomised cross-over trial.

BACKGROUND: The popularity of the gluten-free diet and sales of gluten-free products have increased immensely. AIMS: To investigate whether gluten induces gastrointestinal symptoms, measured by self-reported questionnaires, as well as mental health symptoms in adolescents from a population-based cohort. METHODS: The eligible participants (n = 273) were recruited from a population-based cohort of 1266 adolescents and had at least four different gastrointestinal symptoms. Phase one (n = 54) was a run-in phase where the participants lived gluten-free for 2 weeks. If they improved they continued to phase 2 (n = 33), a blinded randomised cross-over trial. Participants were blindly randomised either to start with 7 days of gluten, eating two granola bars containing 10 g of gluten or to 7 days on placebo, eating two granola bars without gluten, followed by the reverse and separated by a 7-day washout period. The effects of the intervention on gastrointestinal symptoms and mental health symptoms were assessed. RESULTS: In total, 54/273 participants entered the run-in phase and 35 were eligible for randomization. A total of 33 were randomised and 32 completed the trial. The median age was 20.3 (IQR 19.2-20.9) and 32/33 participants were females. Compared with a placebo, gluten did not induce gastrointestinal symptoms. The difference in the average VAS was -0.01 (95% confidence interval -2.07 to 2.05). Nor did we find a difference in the outcomes measuring mental health. CONCLUSION: Compared with placebo, adding gluten to the diet did not induce gastrointestinal symptoms or worsened mental health in adolescents recruited from a population-based cohort. The trial registration number is NCT04639921.

Nutritional status, nutrient imbalances, food-related behaviors and dietary supplements use among patients with celiac disease on a gluten free diet in Lebanon: a national cross-sectional study.

Background: Celiac disease (CD) is an autoimmune disorder triggered by gluten, that occurs in susceptible individuals and is associated with dietary restriction and subsequent nutritional deficiencies. This study investigated the diet quality, nutrition imbalances and nutrition status among young children, adolescents and adults with CD who were referred to several hospitals in Lebanon. Methods: A cross-sectional study in 50 individuals (31.74 ± 15.64 years) with CD was conducted, using biochemical parameters, anthropometric measurements, dietary and physical activity assessments. Results: Of the 50 participants, 38% and 16% were presenting low serum levels of iron and vitamin B12, respectively. The majority of participants were physically inactive and around 40% of them had low muscle mass. A weight loss of 10% to 30% indicating mild to moderate malnutrition was shown in 14% of individuals. The assessment of food-related behaviors shows that 80% of participants were reading nutrition labels and 96% of them were following gluten-free diets (GFD). Some barriers including family ignorance (6%), language of the nutrition labels (20%) and expensive GF products (78%) were limiting the adherence to GFD. The inadequacy of the daily energy intake along with insufficient intakes of calcium and vitamin D were remarked among individuals with CD. However, protein and iron intake were exceeding the recommendations among all age groups, except in males aged 4-8 years and 19-30 years. Half the study participants were using dietary supplements where 38%, 10%, 46%, 18%, 16% and 4% used vitamin D, vitamin B12, iron, calcium, folate and probiotics, respectively. Conclusion: GFD is the key treatment for CD. However, it is not without inadequacies and may cause certain deficiencies such as calcium and vitamin D leading to reduced bone density. This underlines the critical role of dietitians in education and maintenance of healthy GFD among individuals with CD.

Nutritional Deficiencies in Celiac Disease: Current Perspectives.

Gluten-induced T-cell-mediated immune response damages the villous structure that significantly affects the functioning of the small intestinal mucosa [...].

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.

Nutritional Imbalances in Adult Celiac Patients Following a Gluten-Free Diet.

Celiac disease (CD) is a chronic autoimmune disorder of the small intestine, whose only effective treatment is a gluten-free diet (GFD). It is characterized by the atrophy of the intestinal villi that leads to altered nutrient absorption. This study describes the nutritional imbalances which may be found in adults with CD following a GFD. During the first year of treatment, deficiencies will overcome as the intestinal mucosa recovers. Thus, biochemical data will show this progression, together with the decrease in symptoms. In contrast, in the long term, when a strict GFD is followed and mucosal recovery is achieved, analyzing nutrient intake makes more sense. Macronutrient consumption is characterized by its low complex carbohydrate and fiber intakes, and high fat (especially SFA) and sugar intakes. This profile has been related to the consumption of GFP and their nutritional composition, in addition to unbalanced dietary habits. The most notable deficiencies in micronutrients are usually those of iron, calcium and magnesium and vitamin D, E and some of group B. It is necessary to follow up patients with CD and to promote nutritional education among them, since it could help not only to achieve a gluten free but also a balanced diet.

Knowledge of Medical Students and Medical Professionals Regarding Nutritional Deficiencies in Patients with Celiac Disease.

A gluten-free diet provides relief from symptoms for patients with celiac disease, although there is still a risk of nutritional deficiencies. These patients can potentially consume an excessive amount of fat and insufficient amounts of fiber, iron, vitamin D, and calcium. This study aimed to assess the knowledge of medical students and healthcare professionals in Poland regarding nutritional deficiencies and the prevention of such deficiencies in patients with celiac disease who are on a gluten-free diet. Of the 430 survey participants, 46% did not realize the risk of nutritional deficiencies in patients with celiac disease. The knowledge of the participants was lowest regarding the risk of being overweight or obese. Among the healthcare professionals, an acceptable level of correct answers was provided by only 37% of individuals and was highest for the dietitians' group. Our results demonstrate the need to improve the education of healthcare professionals concerning nutrition in patients with celiac disease.

Immunological Impact of a Gluten-Free Dairy-Free Diet in Children With Kidney Disease: A Feasibility Study.

Kidney disease affects 10% of the world population and is associated with increased mortality. Steroid-resistant nephrotic syndrome (SRNS) is a leading cause of end-stage kidney disease in children, often failing standard immunosuppression. Here, we report the results of a prospective study to investigate the immunological impact and safety of a gluten-free and dairy-free (GF/DF) diet in children with SRNS. The study was organized as a four-week summer camp implementing a strict GF/DF diet with prospective collection of blood, urine and stool in addition to whole exome sequencing WES of DNA of participants. Using flow cytometry, proteomic assays and microbiome metagenomics, we show that GF/DF diet had a major anti-inflammatory effect in all participants both at the protein and cellular level with 4-fold increase in T regulatory/T helper 17 cells ratio and the promotion of a favorable regulatory gut microbiota. Overall, GF/DF can have a significant anti-inflammatory effect in children with SRNS and further trials are warranted to investigate this potential dietary intervention in children with SRNS.

Nutritional Status in Spanish Adults with Celiac Disease Following a Long-Term Gluten-Free Diet Is Similar to Non-Celiac.

The only available treatment for celiac disease is life-long gluten exclusion. We conducted a cross-sectional age- and gender-matched study in 64 celiac adults on a long-term (>1 year) gluten-free diet and 74 non-celiac volunteers from Spain, using dietary, anthropometric, and biochemical parameters, as well as assessing bone mineral density and physical activity. Celiac adults had deficient intake (below 2/3 of the recommended intake) for folates, vitamin E, and iodine and low intake of calcium (below 80% of the recommended intake). Iron intake was also below 2/3 of the recommended intake in celiac women. Vitamin D intake was extremely low, and 34% of celiac patients had moderately deficient plasma levels. According to bone mineral density, celiac women may be more prone to osteopenia and osteoporosis. However, we found a perfectly analogous nutritional status scenario in celiac as compared to healthy volunteers, with the dietary deviations found being similar to those of the Spanish population, i.e., both groups followed a high-lipid, high-protein, and low-carbohydrate diet. Values for biochemical parameters were found within the reference ranges. Celiac disease had no influence on body weight, but body fat in celiac patients tended to be higher. According to our results, vitamin D, calcium, folates, vitamin E, iodine, and iron nutritional status should be specifically assessed and monitored in the celiac population.

The low FODMAP diet for IBS; A multicentre UK study assessing long term follow up.

BACKGROUND: The low FODMAP diet (LFD) is effective in managing irritable bowel syndrome (IBS) in the short term. This study assessed the long-term effect of the LFD on symptoms, nutritional composition and socialising. METHODS: Patients with IBS who received dietetic-led LFD advice were approached at long term follow up (>6 months post LFD advice) from six centres across the United Kingdom. Participants completed questionnaires assessing gastrointestinal symptoms, adherence, nutritional intake, dietary acceptability and food related quality of life (QOL). RESULTS: 205 participants completed the study, with a mean follow up of 44 months (3.7 years). Adequate symptom relief was noted in 60% of individuals at long term follow up, with 76% being on the personalisation phase of the LFD (pLFD). Mean nutritional intake did not differ between individuals on the pLFD versus habitual diet, with no difference in fructan intake (2.9 g/d vs 2.9 g/d, p = 0.96). The majority (80%) of individuals on the pLFD consumed specific 'free-from' products at the long term, with the purchase of gluten or wheat free products being the commonest (68%). CONCLUSION: The majority of patients follow the pLFD in the long term, with a large proportion purchasing gluten or wheat free products to manage their symptoms.

Mycotoxin Occurrence and Risk Assessment in Gluten-Free Pasta through UHPLC-Q-Exactive Orbitrap MS.

Celiac disease (CD) is a genetic-based autoimmune disorder which is characterized by inflammation in the small intestinal mucosa due to the intolerance to gluten. Celiac people should consume products without gluten, which are elaborated mainly with maize or other cereals. Contamination of cereals with mycotoxins, such as fumonisins (FBs) and aflatoxins (AFs) is frequently reported worldwide. Therefore, food ingestion is the main source of mycotoxin exposure. A new analytical method was developed and validated for simultaneous analysis of 21 mycotoxins in gluten-free pasta, commonly consumed by celiac population as an alternative to conventional pasta. Ultrahigh-performance liquid chromatography coupled to quadrupole Orbitrap high-resolution mass spectrometry (UHPLC-Q-Exactive Orbitrap MS) was used for analyte separation and detection. The mycotoxins included in this work were those widely reported to occur in cereal samples, namely, ochratoxin-A (OTA), aflatoxins (AFB1, AFB2, AFG1 and AFG2), zearalenone (ZON), deoxynivalenol (DON), 3-acetyl-deoxynivalenol and 15-acetyl-deoxynivalenol (3-AcDON and 15-AcDON, respectively), nivalenol (NIV), neosolaniol (NEO), fusarenone-X, (FUS-X), T-2 toxin (T-2) and HT-2 toxin (HT-2), fumonisin B1 and B2 (FB1 and FB2, respectively), enniatins (ENN A, ENN A1, ENN B and ENN B1) and beauvericin (BEA). The validated method was successfully applied to 84 gluten-free pasta samples collected from several local markets of Campania region (Italy) during September to November 2020 to monitor the occurrence of mycotoxins and to assess the exposure to these food contaminants. A significant number of samples (95%) showed mycotoxin contamination, being Fusarium mycotoxins (FB1, ZON and DON) the most commonly detected ones. Regarding the risk assessment, the higher exposures were obtained for NIV, DON and FB1 for children and teenagers age group which can be explained due to their lower body weight.

The Effect of a Combined Gluten- and Casein-Free Diet on Children and Adolescents with Autism Spectrum Disorders: A Systematic Review and Meta-Analysis.

There has been a growing interest in the gastrointestinal system and its significance for autism spectrum disorder (ASD), including the significance of adopting a gluten-free and casein-free (GFCF) diet. The objective was to investigate beneficial and safety of a GFCF diet among children with a diagnosis of ASD. We performed a systematic literature search in Medline, Embase, Cinahl, and the Cochrane Library up to January 2020 for existing systematic reviews and individual randomized controlled trials (RCTs). Studies were included if they investigated a GFCF diet compared to a regular diet in children aged 3 to 17 years diagnosed with ASD, with or without comorbidities. The quality of the identified existing reviews was assessed using A Measurement Tool to Assess Systematic Reviews (AMSTAR). The risk of bias in RCTs was assessed using the Cochrane Risk of Bias Tool, and overall quality of evidence was evaluated using Grades of Recommendation, Assessment, Development, and Evaluation (GRADE). We identified six relevant RCTs, which included 143 participants. The results from a random effect model showed no effect of a GFCF diet on clinician-reported autism core symptoms (standardized mean difference (SMD) -0.31 (95% Cl. -0.89, 0.27)), parent-reported functional level (mean difference (MD) 0.61 (95% Cl -5.92, 7.14)) or behavioral difficulties (MD 0.80 (95% Cl -6.56, 10.16)). On the contrary, a GFCF diet might trigger gastrointestinal adverse effects (relative risk (RR) 2.33 (95% Cl 0.69, 7.90)). The quality of evidence ranged from low to very low due to serious risk of bias, serious risk of inconsistency, and serious risk of imprecision. Clinical implications of the present findings may be careful consideration of introducing a GFCF diet to children with ASD. However, the limitations of the current literature hinder the possibility of drawing any solid conclusion, and more high-quality RCTs are needed. The protocol is registered at the Danish Health Authority website.

Small intestinal bacterial overgrowth among patients with celiac disease unresponsive to a gluten free diet.

BACKGROUND/AIMS: Little is known about the relationship between small intestinal bacterial overgrowth (SIBO) and celiac disease (CeD) in patients who are unresponsive to a gluten-free diet (GFD). This study aimed to determine the SIBO prevalence in patients with CeD who are unresponsive to a GFD. MATERIALS AND METHODS: We conducted a case-control study from July 2012 to September 2014. We included 32 patients with CeD who were unresponsive to a GFD and 52 healthy age- and sex-matched controls. Demographic, clinical, and laboratory data were obtained from patients' medical records. Antitissue transglutaminase antibody determined by enzyme-linked immunosorbent assay was recorded, and lactulose hydrogen breath test (LHBT) was used to detect SIBO in all participants. Microbiological analysis, including jejunal aspirates obtained using upper endoscopy, was performed for only 20 patients with CeD. RESULTS: A total of 10 (31%) of 32 patients with CeD and 4 (7.7%) of 52 controls tested positive for LHBT, with a statistically significant difference (p=0.007). Of 20 cultures, 3 (15%) were positive with no statistically significant correlation between the cultures and LHBT (p=0.05). In a subgroup analysis of children who were 18 years old or younger, 7/24 (29.2%) patients with CeD had a positive LHBT compared with 3/32 (9.4%) controls, but this difference was not statistically significant (p=0.08). CONCLUSION: The prevalence of SIBO was 31% in unresponsive patients with CeD according to LHBT and 15% in the quantitative culture of the jejunal aspirate, which is comparable with the published Western literature.

Gluten-Free Diet and Migraine.

Migraine is common in celiac disease (CD) and usually improves on a gluten-free diet (GFD). The benefit for people impacted by migraine without CD is poorly evidenced. A GFD may have adverse health consequences and is expensive.

Anxiety and depression: a study of psychoaffective, family-related, and daily-life factors in celiac individuals.

OBJECTIVE: To identify the prevalence of anxiety and depression and its association with psychoaffective, family-related, and daily-life variables of celiac individuals. METHODS: Crosssectional study, developed with 83 celiac patients in Fortaleza. An instrument was applied with variables grouped in the categories: psychoaffective, family-related, and daily-life. RESULTS: It was found that 52 celiac patients (62.7%) had anxiety and 29 (34.9%) had depression. The clinical conditions found and the number of symptoms increased the chance of anxiety/depression. The predominant factors in those with anxiety were Lack of control of the celiac disease (98.1%), Perceived clinical condition (75.0%), Daily obstacles for maintaining a gluten-free diet (63.4%), and Daily activities (55.8%). In those with depression, there was a higher prevalence of Lack of control of the celiac disease (100.0%), Perceived clinical condition (82.2%), and Daily obstacles for maintaining a gluten-free diet (69.0%). CONCLUSION: Celiac individuals with anxiety and depression frameworks presented a higher frequency of Perceived clinical condition, Insufficient social support (psychoaffective factors) and Daily obstacles for maintaining a gluten-free diet (daily-life factor).

Alterations in Intestinal Microbiota of Children With Celiac Disease at the Time of Diagnosis and on a Gluten-free Diet.

BACKGROUND AND AIMS: It is not clear whether alterations in the intestinal microbiota of children with celiac disease (CD) cause the disease or are a result of disease and/or its treatment with a gluten-free diet (GFD). METHODS: We obtained 167 fecal samples from 141 children (20 with new-onset CD, 45 treated with a GFD, 57 healthy children, and 19 unaffected siblings of children with CD) in Glasgow, Scotland. Samples were analyzed by 16S ribosomal RNA sequencing, and diet-related metabolites were measured by gas chromatography. We obtained fecal samples from 13 children with new-onset CD after 6 and 12 months on a GFD. Relationships between microbiota with diet composition, gastrointestinal function, and biomarkers of GFD compliance were explored. RESULTS: Microbiota α diversity did not differ among groups. Microbial dysbiosis was not observed in children with new-onset CD. In contrast, 2.8% (Bray-Curtis dissimilarity index, P = .025) and 2.5% (UniFrac distances, P = .027) of the variation in microbiota composition could be explained by the GFD. Between 3% and 5% of all taxa differed among all group comparisons. Eleven distinctive operational taxonomic units composed a microbe signature specific to CD with high diagnostic probability. Most operational taxonomic units that differed between patients on a GFD with new-onset CD vs healthy children were associated with nutrient and food group intake (from 75% to 94%) and with biomarkers of gluten ingestion. Fecal levels of butyrate and ammonia decreased during the GFD. CONCLUSIONS: Although several alterations in the intestinal microbiota of children with established CD appear to be effects of a GFD, specific bacteria were found to be distinct biomarkers of CD. Studies are needed to determine whether these bacteria contribute to pathogenesis of CD.