Protein Labelling Accuracy for UK Patients with PKU Following a Low Protein Diet.

A phenylalanine (protein)-restricted diet is the primary treatment for phenylketonuria (PKU). Patients are dependent on food protein labelling to successfully manage their condition. We evaluated the accuracy of protein labelling on packaged manufactured foods from supermarket websites for foods that may be eaten as part of a phenylalanine-restricted diet. Protein labelling information was evaluated for 462 food items ("free from", n = 159, regular, n = 303), divided into 16 food groups using supermarket website data. Data collection included protein content per portion/100 g when food was "as sold", "cooked" or "prepared"; cooking methods, and preparation instructions. Labelling errors affecting protein content were observed in every food group, with overall protein labelling unclear in 55% (n = 255/462) of foods. There was misleading, omitted, or erroneous (MOE) information in 43% (n = 68/159) of "free from" foods compared with 62% (n = 187/303) of regular foods, with fewer inaccuracies in "free from" food labelling (p = 0.007). Protein analysis was available for uncooked weight only but not cooked weight for 58% (n = 85/146) of foods; 4% (n = 17/462) had misleading protein content. There was a high rate of incomplete, misleading, or inaccurate data affecting the interpretation of the protein content of food items on supermarket websites. This could adversely affect metabolic control of patients with PKU and warrants serious consideration.

Dietary Gluten and Neurodegeneration: A Case for Preclinical Studies.

Although celiac disease (CD) is an autoimmune disease that primarily involves the intestinal tract, mounting evidence suggests that a sizeable number of patients exhibit neurological deficits. About 40% of the celiac patients with neurological manifestations have circulating antibodies against neural tissue transglutaminase-6 (tTG6). While early diagnosis and strict adherence to a gluten-free diet (GFD) have been recommended to prevent neurological dysfunction, better therapeutic strategies are needed to improve the overall quality of life. Dysregulation of the microbiota-gut-brain axis, presence of anti-tTG6 antibodies, and epigenetic mechanisms have been implicated in the pathogenesis. It is also possible that circulating or gut-derived extracellular structures and including biomolecular condensates and extracellular vesicles contribute to disease pathogenesis. There are several avenues for shaping the dysregulated gut homeostasis in individuals with CD, non-celiac gluten sensitivity (NCGS) and/or neurodegeneration. In addition to GFD and probiotics, nutraceuticals, such as phyto and synthetic cannabinoids, represent a new approach that could shape the host microbiome towards better prognostic outcomes. Finally, we provide a data-driven rationale for potential future pre-clinical research involving non-human primates (NHPs) to investigate the effect of nutraceuticals, such as phyto and synthetic cannabinoids, either alone or in combination with GFD to prevent/mitigate dietary gluten-induced neurodegeneration.

Micronutrients Dietary Supplementation Advices for Celiac Patients on Long-Term Gluten-Free Diet with Good Compliance: A Review.

Background and objective: Often micronutrient deficiencies cannot be detected when patient is already following a long-term gluten-free diet with good compliance (LTGFDWGC). The aim of this narrative review is to evaluate the most recent literature that considers blood micronutrient deficiencies in LTGFDWGC subjects, in order to prepare dietary supplementation advice (DSA). Materials and methods: A research strategy was planned on PubMed by defining the following keywords: celiac disease, vitamin B12, iron, folic acid, and vitamin D. Results: This review included 73 studies. The few studies on micronutrient circulating levels in long-term gluten-free diet (LTGFD) patients over 2 years with good compliance demonstrated that deficiency was detected in up to: 30% of subjects for vitamin B12 (DSA: 1000 mcg/day until level is normal, then 500 mcg), 40% for iron (325 mg/day), 20% for folic acid (1 mg/day for 3 months, followed by 400-800 mcg/day), 25% for vitamin D (1000 UI/day or more-based serum level or 50,000 UI/week if level is <20 ng/mL), 40% for zinc (25-40 mg/day), 3.6% of children for calcium (1000-1500 mg/day), 20% for magnesium (200-300 mg/day); no data is available in adults for magnesium. Conclusions: If integration with diet is not enough, starting with supplements may be the correct way, after evaluating the initial blood level to determine the right dosage of supplementation.

Metabolic interventions in Autism Spectrum Disorder.

Metabolic interventions including special diets and supplements are commonly used in Autism Spectrum Disorder (ASD). Yet little is known about how these interventions, typically initiated by caregivers, may affect metabolic function or the core symptoms of ASD. This review examines possible direct and indirect roles for metabolism in the core symptoms of ASD as well as evidence for metabolic dysfunction and nutritional deficiencies. We also discuss some of the most popular diets and supplements used in our patient population and suggest strategies for discussing the utility of these interventions with patients, families, and caregivers.

Promotion of Testing for Celiac Disease and the Gluten-Free Diet Among Complementary and Alternative Medicine Practitioners.

INTRODUCTION: We identified the frequency and assessed the validity of marketing claims made by American chiropractors, naturopaths, homeopaths, acupuncturists, and integrative medicine practitioners relating to the diagnosis and treatment of celiac disease and nonceliac gluten sensitivity (NCGS), both of which have increased in prevalence in recent years. METHODS: We performed a cross-sectional study analyzing websites of practitioners from 10 cities in the United States and analyzed the websites for any mention of celiac or NCGS as well as specific claims of ability to diagnose, ability to treat, and treatment efficacy. We classified treatments promoted as true, false, or unproven, as assessed independently by 2 authors. RESULTS: Of 500 clinics identified, 178 (35.6%) made a claim regarding celiac disease, NCGS, or a gluten-free diet. Naturopath clinic websites have the highest rates of advertising at least one of diagnosis, treatment, or efficacy for celiac disease (40%), followed by integrative medicine clinics (36%), homeopaths (20%), acupuncturists (14%), and chiropractors (12%). Integrative medicine clinics have the highest rates of advertising at least one of diagnosis, treatment, or efficacy for NCGS (45%), followed by naturopaths (37%), homeopaths (14%), chiropractors (14%), and acupuncturists (10%). A geographic analysis yielded no significant variation in marketing rates among clinics from different cities. Of 232 marketing claims made by these complementary and alternative medicine (CAM) clinic websites, 138 (59.5%) were either false or unproven. DISCUSSION: A significant number of CAM clinics advertise diagnostic techniques or treatments for celiac disease or NCGS. Many claims are either false or unproven, thus warranting a need for increased regulation of CAM advertising to protect the public.

Beneficial Effect of Oligofructose-Enriched Inulin on Vitamin D and E Status in Children with Celiac Disease on a Long-Term Gluten-Free Diet: A Preliminary Randomized, Placebo-Controlled Nutritional Intervention Study.

Prebiotics have been shown to improve absorption of some nutrients, including vitamins. This pilot study evaluated the effect of the prebiotic oligofructose-enriched inulin (Synergy 1) on fat-soluble vitamins status, parathormone, and calcium-related elements in pediatric celiac disease (CD) patients (n = 34) on a strict gluten-free diet (GFD). Participants were randomized into a group receiving 10 g of Synergy 1 or placebo (maltodextrin) together with a GFD. At baseline and after 3 months of intervention, 25-hydroxyvitamin D [25(OH)D], parathormone, vitamin E and A, calcium, phosphate, magnesium, total protein, and albumin were determined. Concentration of 25(OH)D increased significantly (p < 0.05) by 42% in CD patients receiving Synergy 1 in GFD, whereas no change was observed in placebo. Vitamin D status reached an optimal level in 46% of patients receiving Synergy 1. No significant difference in parathormone, calcium, and phosphate levels was observed. Concentration of vitamin E increased significantly (p < 0.05) by 19% in patients receiving Synergy 1, but not in the placebo. Vitamin A levels were not changed. Supplementation of GFD with Synergy 1 improved vitamin D and vitamin E status in children and adolescents with CD and could be considered a novel complementary method of management of fat-soluble vitamins deficiency in pediatric CD patients.

Use of a Gluten-Free Diet in Schizophrenia: A Systematic Review.

We performed a systematic review of the literature to determine whether adherence to a gluten-free diet (GFD) leads to improved outcomes for patients with schizophrenia. We searched the AMED (Allied and Complementary Medicine; 1985-June 2016), MEDLINE (1946-June 2016), and Embase (1980-2016 week 24) databases using the terms "wheat" or "glutenin" or "gliadin" or "gluten" AND "schizophrenia." A total of 9 studies met the inclusion criteria for this review: 1 randomized controlled trial, 7 crossover studies, and 1 open-label pilot study. Six of the included studies demonstrated beneficial effects including improved functioning and decreased symptom severity after the course of a GFD, whereas 3 studies found no benefits. All of the included studies found that a GFD is well tolerated and can be adhered to by patients with schizophrenia. The findings of this systematic review should be interpreted with caution due to limitations inherent to nonrandomized trials, as well as the heterogeneity in the study design and the length of the GFD applied in each study. Publication bias is another potential limitation. Further research is required to examine the biomarkers of gluten sensitivity and inflammation to effectively target those patients with schizophrenia who will benefit most from this dietary intervention.

A Toddler With Treatment-Resistant Iron Deficiency Anemia.

A 19-month-old girl with a history of asthma and atopic dermatitis presented to her pediatrician because of parental concerns of pallor and fatigue. On dietary history, it was discovered that she was a picky eater and consumed 26 oz of homogenous milk daily. Her physical examination was unremarkable aside from pallor, and both her height and weight plotted between the 50th and 75th percentile for age. Therefore, she was investigated for iron deficiency anemia and indeed her blood work was consistent. Despite appropriate iron supplementation and dietary milk restriction, there was no improvement in her hemoglobin or iron studies. Our expert panel examines the case and offers a differential diagnosis for a child presenting with treatment-resistant iron deficiency anemia.

A concise review of Hashimoto thyroiditis (HT) and the importance of iodine, selenium, vitamin D and gluten on the autoimmunity and dietary management of HT patients.Points that need more investigation.

Hashimoto's thyroiditis (HT) is a chronic autoimmune thyroid disease caused by an interaction between genetic factors and environmental conditions, both of which are yet to be fully understood. The management of HT depends on its clinical manifestations, commonly including diffuse or nodular goiter with euthyroidism, subclinical hypothyroidism and permanent hypothyroidism. However, in most cases of patients with HT, lifelong levothyroxine substitution is required. The additional role of diet for the management of HT is usually overlooked. A literature search regarding the importance and the influence of iodine, selenium, vitamin D and gluten on HT was conducted. In HT careful supplementation of possible deficiencies is recommended for the dietary management of these patients. The use of a diet low in gluten among HT patients with or without celiac disease (CD) is discussed.

Celiac patients' attitudes regarding novel therapies.

BACKGROUND: The only current treatment for celiac disease (CD) is a gluten-free diet (GFD). Novel therapies are in development to supplement or replace a GFD. Knowledge of patients' attitudes toward these therapies is limited. The aim of this study was to determine attitudes about novel therapies in securely diagnosed patients with CD on a GFD and to correlate factors associated with these attitudes. METHODS: A survey was created with two scenarios: a novel therapy that protects against cross contamination while on a GFD and one that allows intentional gluten consumption. The survey also included the Celiac Dietary Adherence Test and the CD Quality of Life (QOL) surveys. RESULTS: A total of 182/284 (64%) CD patients completed the survey. Significantly more respondents would take a novel therapy to protect against cross contamination compared with one that allows intentional gluten consumption (87% vs. 65%; P<0.001). This difference was significant among women but not men. In both scenarios, protection against bowel inflammation was significantly more important than symptom control, and side effects were more important than cost. For a novel therapy that would allow intentional gluten consumption, a one-time injection was preferred over a daily pill, and patients willing to take this therapy had significantly lower QOL scores. CONCLUSIONS: CD patients on a GFD are interested in novel therapies. There were notable differences in attitudes by gender and QOL. Considering patient preferences, drugs with daily or less frequent dosing that protect against bowel inflammation from gluten cross contamination would be best accepted.

Gastrointestinal effects of eating quinoa (Chenopodium quinoa Willd.) in celiac patients.

OBJECTIVES: Celiac disease is an enteropathy triggered by dietary gluten found in wheat, rye, and barley. Treatment involves a strict gluten-free diet (GFD). Quinoa is a highly nutritive plant from the Andes that has been recommended as part of a GFD. However, in-vitro data suggested that quinoa prolamins can stimulate innate and adaptive immune responses in celiac patients. Therefore, we aimed to evaluate the in-vivo effects of eating quinoa in adult celiac patients. METHODS: Nineteen treated celiac patients consumed 50 g of quinoa every day for 6 weeks as part of their usual GFD. We evaluated diet, serology, and gastrointestinal parameters. Furthermore, we carried out detail histological assessment of 10 patients before and after eating quinoa. RESULTS: Gastrointestinal parameters were normal. The ratio of villus height to crypt depth improved from slightly below normal values (2.8:1) to normal levels (3:1), surface-enterocyte cell height improved from 28.76 to 29.77 µm and the number of intra-epithelial lymphocytes per 100 enterocytes decreased from 30.3 to 29.7. Median values for all the blood tests remained within normal ranges, although total cholesterol (n=19) decreased from 4.6 to 4.3 mmol/l, low-density lipoprotein decreased from 2.46 to 2.45 mmol/l, high-density lipoprotein decreased from 1.8 to 1.68 mmol/l and triglycerides decreased from 0.80 to 0.79 mmol/l. CONCLUSIONS: Addition of quinoa to the GFD of celiac patients was well tolerated and did not exacerbate the condition. There was a positive trend toward improved histological and serological parameters, particularly a mild hypocholesterolemic effect. Overall, this is the first clinical data suggesting that daily 50 g of quinoa for 6 weeks can be safely tolerated by celiac patients. However, further studies are needed to determine the long-term effects of quinoa consumption.

Latest in vitro and in vivo models of celiac disease.

INTRODUCTION: Currently, the only treatment for celiac disease is a gluten-free diet, and there is an increased desire for alternative therapies. In vitro and in vivo models of celiac disease have been generated in order to better understand the pathogenesis of celiac disease, and this review will discuss these models as well as the testing of alternative therapies using these models. AREAS COVERED: The research discussed describes the different in vitro and in vivo models of celiac disease that currently exist and how they have contributed to our understanding of how gluten can stimulate both innate and adaptive immune responses in celiac patients. We also provide a summary on the alternative therapies that have been tested with these models and discuss whether subsequent clinical trials were done based on these tests done with these models of celiac disease. EXPERT OPINION: Only a few of the alternative therapies that have been tested with animal models have gone on to clinical trials; however, those that did go on to clinical trial have provided promising results from a safety standpoint. Further trials are required to determine if some of these therapies may serve as an effective adjunct to a gluten-free diet to alleviate the adverse affects associated with accidental gluten exposure. A "magic-bullet" approach may not be the answer to celiac disease, but possibly a future cocktail of these different therapeutics may allow celiac patients to consume an unrestricted diet.

Nutrition assessment in celiac disease.

The gluten-free diet is currently the only treatment for celiac disease, and patients should be monitored closely by a dietitian who is knowledgeable regarding this diet. Evaluation by a dietitian includes a comprehensive assessment of dietary history, with an emphasis on caloric and micronutrient intake. Patient knowledge of the gluten-free diet is assessed and interpretation of food labels is taught. Identification of micronutrient deficiencies or comorbid gastrointestinal conditions may occur during a comprehensive dietary assessment. In patients with evidence of gluten exposure, a thorough evaluation for cross-contamination is performed.

Low bone mineral density in adult patients with coeliac disease.

INTRODUCTION: Calcium and vitamin D malabsorption in coeliac disease (CD) predispose to skeletal demineralisation. The aim of this study was to evaluate the prevalence of bone mineral density (BMD) and calcium deficiencies in adult patients with CD and assess whether a gluten-free diet is sufficiently effective for BMD restoration. MATERIAL AND METHODS: BMD and biochemical parameters of bone and mineral metabolism were measured in 35 adult CD patients receiving (19) or not receiving (16) a gluten-free diet (GFD) and in 36 controls. Then the CD patients were treated with a GFD and calcium (1.0 g/day) plus alfacalcidol (0.25-1 µg/day) for one year. RESULTS: Reduced BMD was diagnosed in 57-77% of the patients. Mean calcaemia, calciuria, and 25(OH) vitamin D were lower, but serum PTH and bone-turnover markers (ALP, osteocalcin, ICTP) were significantly higher in the CD patients than in the controls. In the patients on the diet (GFD(+)), BMD was higher than in the GFD(-) patients, but lower than in the controls. The biochemical parameters were normal in the GFD(+) patients except for diminished calciuria. Mean BMD after one year of treatment significantly increased (p < 0.05), mostly in the lumbar spine (mean: 7.3%), but decreased in five patients who did not strictly adhere to the GFD. CONCLUSIONS: Deficiencies in calcium, vitamin D, and BMD are very common in adult CD patients. Gluten avoidance increased BMD, although the values remained markedly lower in several patients. Because of chronic calcium deficiency despite GFD, calcium and vitamin D supplementation in most adult CD patients is proposed.

Celiac disease: advances in treatment via gluten modification.

Celiac disease (CD) is an autoimmune enteropathy that occurs in genetically susceptible individuals carrying the prerequisite genetic markers HLA DQ2 or DQ8. These genetic markers are present in approximately 30% of the population, and the worldwide prevalence of CD is estimated to be approximately 1%-2%. Currently a gluten-free diet is the only treatment for CD, but novel therapies aimed at gluten modification are underway. This review will discuss gluten-based therapies including wheat alternatives and wheat selection, enzymatic alteration of wheat, oral enzyme supplements, and polymeric binders as exciting new therapies for treatment of CD.

Review article: coeliac disease, new approaches to therapy.

BACKGROUND: Coeliac disease is managed by life-long gluten withdrawal from the diet. However, strict adherence to a gluten-free diet is difficult and is not always effective. Novel therapeutic approaches are needed to supplement or even replace the dietary treatment. AIM: To review recent advances in new therapeutic options for coeliac disease. METHODS: A literature search was performed on MEDLINE, EMBASE, Web of Science, Scopus, DDW.org and ClinicalTrials.gov for English articles and abstracts. The search terms used included, but not limited to, 'Celiac disease', 'new', 'novel', 'Advances', 'alternatives' and 'Drug therapy'. The cited articles were selected based on the relevancy to the review objective. RESULTS: Several new therapeutic approaches for coeliac disease are currently under development by targeting its underlying pathogenesis. Alternative therapies range from reproduction of harmless wheat strains to immunomodulatory approaches. Some of these therapies such as enzymatic cleavage of gluten and permeability inhibitors have shown promise in clinical studies. CONCLUSIONS: Gluten-free diet is still the only practical treatment for patients with coeliac disease. Novel strategies provide promise of alternative adjunctive approaches to diet restriction alone for patients with this disorder.

Refeeding syndrome in children in developing countries who have celiac disease.

OBJECTIVES: The clinical presentations of celiac crisis and refeeding syndrome in celiac disease are almost similar, but information about refeeding syndrome is scarce. We are reporting for the first time 5 cases of refeeding syndrome in children with celiac disease that could have otherwise been labeled as celiac crisis. METHODS: From January to December 2010, a chart review of hospital records of all celiac disease cases was performed, and refeeding syndrome was ascribed in those celiac patients who deteriorated clinically after initiation of a gluten-free diet and had biochemical parameters suggestive of refeeding syndrome such as hypophosphatemia, hypokalemia, hypocalcemia, and hypoalbuminemia. RESULTS: Of the total 35 celiac disease patients, 5 (median age 6.5 [range 2.2-10] years, 3 boys) were identified as having refeeding syndrome. All 5 children were severely malnourished (body mass index <14 kg/m) and all of them had anemia, hypophosphatemia, hypokalemia, hypoalbuminemia, and hypocalcemia, meaning that they had the perfect setting for developing refeeding syndrome. At the same time, their clinical features fulfilled the criteria for celiac crisis except that their symptoms have worsened after the introduction of a gluten-free diet. Nevertheless, instead of using steroids, they were managed as refeeding syndrome in terms of correction of electrolytes and gradual feeding, and that led to a successful outcome in all of them. CONCLUSIONS: Severely malnourished patients with celiac disease are at risk of developing potentially life-threatening refeeding syndrome, which may mimic celiac crisis, especially in developing countries. Early recognition and appropriate treatment are the keys to a successful outcome.