Gluten-Related Disorders and Gluten Free Diet Plan

Introduction:

Gluten-related disorders result from an immune system response to wheat gluten, (an elastic protein in wheat) which may occur as a severe disease with malabsorption or as a mild disease in the form of sensitivity. Both genetic makeup, diet, and environmental factors lead to gluten-related disorders. The widespread use of gluten in a large number of food sources over long term by modern society has contributed to a significantly increased incidence of gluten-related disorders in recent years. A gluten-related disorder may occur in any age group as either gastrointestinal symptoms, as non-gastrointestinal symptoms, or a combination of both. A celiac disease diet will improve gluten intolerance symptoms and gluten sensitivity. Find a list of gluten free foods in the gluten free diet plan listed below. According to the Mayo clinic, the incidence of celiac disease has increased four-fold since 1950 and significantly increases the risk of mortality and gastrointestinal cancer if left untreated (1). Celiac disease (CD) and gluten-related disorder are more common in patients of northern European descent than other ethnic backgrounds.

 

Definitions of gluten-related disorders:

According to The Oslo Definitions for Celiac Disease and Related Terms by Ludvigsson JF et al (2):

• Gluten-related disorder is a term used to include all diseases triggered by gluten consumption.
• Celiac disease (CD) is a chronic autoimmune small bowel disease occurring after gluten consumption in genetically susceptible patients.
• Classical CD is a presentation of signs and symptoms of malabsorption which includes weight loss, diarrhea, steatorrhea, or poor growth.
• Other gluten related disorders include: non-classical CD without malabsorption, subclinical CD without gastrointestinal symptoms, symptomatic CD, refractory CD, potential CD, CD autoimmunity, genetically at-risk CD, non-celiac gluten sensitivity, Gliadin-specific antibodies, gluten ataxia, and dermatitis herpetiformis (blistering rash).

 

Symptoms of gluten related disorder:

Symptoms of gluten related disorder may be difficult to separate from other gastrointestinal illnesses, and include diarrhea, constipation, weight loss, weight gain, abdominal bloating, malodorous stool, and abdominal pain. Gluten related disease may also cause extraintestinal health problems such as bone demineralization, osteoporosis, joint pains, weight gain, weight loss, elevated liver function tests, enamel defects, apthous stomatitis, lower birth weights, poor childhood weight gain, hypocalcemia, fatigue, weakness, dry skin, blistering rash, eczema, iron deficiency anemia, infertility, microscopic colitis, pancreatic exocrine dysfunction, depression, neuropathy or numbness of the extremities, cerebellar ataxia, epilepsy, dementia, and headaches. The tongue is also commonly affected with soreness, burning, redness or atrophy. Infrequent diarrhea plus tongue symptoms have often led to a diagnosis of celiac disease (3).

 

Gluten-related disorder screening:

Screening and testing for celiac disease: According to Rubio-Tapia A et al, the following patients should be evaluated for celiac disease (4):

• Patients with signs, symptoms, or lab testing which show evidence of malabsorption.
• Patients with signs, symptoms, or lab testing concerning for celiac disease who are candidates for treatment once diagnosed.
• Patients with signs, symptoms, or lab testing concerning for celiac disease who have a first degree relative with the condition.
• It may be appropriate to screen patients without any symptoms who have a first degree relative with celiac disease.
• Patients with unknown cause of elevated liver function tests should be evaluated for celiac disease.
• Diabetes mellitus type 1 patients with gastrointestinal signs, symptoms, or lab testing concerning for celiac disease.

 

Diagnosis of celiac disease:

Proper diagnosis may be complicated and is best accomplished by the primary care physician and gastroenterologist. Celiac disease should not be self-diagnosed by patients since the condition has non-specific symptoms which require to be distinguished from other gastrointestinal conditions. If a patient is believed to have symptoms of celiac disease, testing should ideally be done while on a diet containing gluten.

The initial test is immunoglobulin A (IgA) anti-tissue transglutaminase (TTG) antibody in patients over 2 years old. If this serology is positive, the patient should proceed to an endoscopic small bowel biopsy of the duodenum. If a patient has a typical symptoms and high probability of celiac disease, the physician may advise to proceed directly to a small bowel biopsy. A positive biopsy will have a pathology showing lymphocytes within the epithelium, hypertrophy of crypts, and diminished villous height. A genetic test is also available which determines susceptibility of the patient to celiac disease.

Additional testing of routine complete blood count may show anemia and nutrient testing might reveal vitamin and mineral deficiencies. Basic metabolic panel may show electrolyte abnormalities related to malabsorption. Liver function tests may be elevated.

Genetic testing for risk of celiac disease may be done once in a persons lifetime using blood or a swab from the inside of the cheek. About 95% of individuals with celiac disease have the HLA DQ2 gene and about 5% of individuals with celiac disease have the HLA DQ8 gene. These 2 genes are present in up to 40% of the population. However, only 3% of these individuals with the genes will develop celiac disease. If the individual does not have these genes, celiac disease is extremely unlikely.

 

Disorders affected by gluten:

Autism and gluten:

Diets free of gluten and casein have some evidence of benefit in autism. Gluten is found in many common foods made from wheat, barley, rye grains or flour from these grains. Casein is a protein found in dairy products. It has been suggested that abnormal levels of peptides by excessive opioid activity caused by the ingestion of gluten and casein may play a role in autism.

The School of Public Health, University of California, Berkeley, USA, has demonstrated that children with autism displayed unusual eating patterns such as a lower appetite, selective eating, and displayed digestive problems which warranted additional investigation (5).

Mulloy A, et al in a systematic review reported that research on gluten-free and/or casein-free (GFCF) diet may help treat autism in as little as 2 weeks after intervention (6). The research reviewed by this author reported improvements in the following while on this diet: social isolation, eye contact, speech, learning skills, hyperactivity, stereotypical activity, panic attacks, self-mutilation, total autistic trait score (measured by the Diagnosis of Psychotic Behavior in Children [DIPAB]), nonverbal communication, stereotypy, social interactions, normalizing of behavior, language skills after 1 year, language skills after 4 years, social interaction, play based creativity, motor abilities, decrease in urine peptide levels (UPL), decrease in urinary metal concentrations, and behavioral improvements (6)

In a study on the efficacy of a gluten-free and dairy-free diet in autism, autistic symptoms and urinary peptide levels were monitored in subjects over 12 weeks. Only subjective improvement was noted by parents only in the symptoms of their children on this diet. (7)

A Cochrane Database Systematic Review evaluated several randomized clinical trials including diets free of gluten and/or casein, and noted that only small trial out of several reviewed reported a reduction of autistic traits, but a benefit in cognitive skills, linguistic ability and motor ability was not seen (8).

 

Food allergies and autism:

A study on the effects of food allergies and infantile autism shows that there is a possible relationship. According to a study in Italy entitled “Food allergy and infantile autism” done at the Department of Paediatrics, University of Rome Las Sapienza found that worsening neurological symptoms has been reported in autistic patients after consuming milk and wheat containing foods. In a study group of 36 autistic patients and 20 healthy controls, antibodies for milk proteins including casein, lactalbumin and beta-lactoglobulin were seen. After the elimination of these foods for an 8 week period, there was improvement in the behaviors of the autistic patients despite the fact that the milk antibodies were found to be higher in the controls. (9)

 

Schizophrenia and gluten:

It is possible that a gluten free diet may be used to help treat schizophrenia in the future. Antibodies are known to be produced by the body in genetically susceptible individuals after exposure to gluten. Cascella, NG et al investigated the association of transglutaminase autoantibodies with schizophrenia, and found that a specific type of this antibody was found in higher levels in schizophrenic patients than in healthy controls. According to the authors, this antibody test may have future application in testing for patients who might respond to a diet free of gluten. (10)

 

Gluten and bone mineral density:

All patients with celiac disease should undergo bone mineral density scans. 40% of adults and as many as three fourths of patients with celiac disease have been reported to have a low bone mineral density (11).

Osteoporosis appears to occur early in the course of celiac disease. Mazure R, et al found that patients without symptoms of celiac disease at the time of diagnosis had a low bone mineral density (over 1 standard deviation below normal), stressing the importance of early diagnosis and treatment (12).

 

Gluten and tooth enamel defects:

Dentists have an important role in identifying patients with celiac disease. Enamel defects may be the only sign of celiac disease and are found in about 85% of patients with celiac disease at the time of diagnosis (13). Children without signs or symptoms of celiac disease should be screened for celiac disease if hypocalcemia and poor weight gain is present (14).

 

Gluten and recurrent apthous stomatitis:

A high rate of patients with recurrent apthous stomatitis and celiac disease respond well to treatment with a gluten-free diet. Patients with recurrent apthous stomatitis were found to have a higher rate of gluten sensitive bowel disease than the general population which supports screening these patients for celiac disease (15).

 

Gluten and depression:

Patients who self-reported non-celiac gluten sensitivity were given a short term challenge with 16 grams of gluten, 16 grams of whey protein, or placebo daily for 3 days. The subjects were tested for signs of depression with the Spielberger State Trait Personality Inventory (STPI) and found that gluten induced more feelings of depression compared to whey or placebo. (16)

Celiac disease patients with a better adherence to a gluten-free diet over the long term had a lower risk of developing symptoms of depression. About a third of patients developed symptoms of depression over their lifetime despite adherence to a gluten-free diet. (17)

 

Gluten free diet for gluten-related disorders:

Once diagnosed with a gluten-related disorder, treatment is focused on elimination of all sources of gluten from the diet. Even small amounts of residual gluten in the diet are known to contribute to the celiac disease process. Dietary counseling is based on support of the patient in the major lifestyle change of a gluten-free diet for life. This is best accomplished by a qualified dietitian. Adherence may be difficult due to the large variety of processed foods in the U.S. which contain gluten. Patients will require education to avoid all foods containing wheat, rye, barley (including all types of beer), and oats. Distilled alcohol beverages and wine are generally free of gluten. Patients should be counseled to avoid occult sources of gluten in foods. Gluten containing foods should be substituted for corn, soy, buckwheat, beans, vegetables, fruits, nuts, tapioca flour, rice, potatoes, and lean meats. Oat consumption is controversial, with research showing that oats may provoke gluten related disorder, while other research has supported oats as generally safe to consume.

 

 

Assessment and Plan: Gluten and Gluten-related disorder

• The incidence of gluten-related disorders including celiac disease is on the rise and should be included as a possible cause of a chronic gastrointestinal condition or extraintestinal condition. Proper diagnosis may be complicated and is best accomplished by the primary care physician and gastroenterologist.

 

• Gluten-related disorder signs and symptoms:
  • In those with a gluten related disorder, gluten causes inflammation and antibody production in the bowels which results in diarrhea and poor absorption of nutrients. Gluten disorder symptoms can be severe with diarrhea and weight loss, or mild with nausea, abdominal pain and bloating.
  • Gastrointestinal signs and symptoms: diarrhea, constipation, abdominal bloating, malodorous stool, abdominal pain, tongue soreness, burning, redness or atrophy, elevated liver function tests, microscopic colitis, pancreatic exocrine dysfunction
  • Extraintestinal signs and symptoms: bone demineralization, osteoporosis, joint pains, weight gain, weight loss, enamel defects, apthous stomatitis, lower birth weights, poor childhood weight gain, hypocalcemia, fatigue, weakness, dry skin, blistering rash, eczema, iron deficiency anemia, infertility, depression, neuropathy or numbness of the extremities, cerebellar ataxia, epilepsy, dementia, and headaches.

 

• Gluten-related disorder screening and diagnosis:
  • According to Rubio-Tapia A et al, the following patients should be evaluated for celiac disease (4):
    • Signs, symptoms, or lab testing showing evidence of malabsorption.
    • Signs, symptoms, or lab testing concerning for celiac disease who are candidates for treatment once diagnosed.
    • Signs, symptoms, or lab testing concerning for celiac disease who have a first degree relative with the condition.
    • It may be appropriate to screen patients without any symptoms who have a first degree relative with celiac disease.
    • Unknown cause of elevated liver function tests should be evaluated for celiac disease.
    • Diabetes mellitus type 1 patients with gastrointestinal signs, symptoms, or lab testing concerning for celiac disease.
  • Diagnosis of celiac disease:
    • Celiac disease may have non-specific symptoms, which requires a diagnostic approach to distinguish it from other gastrointestinal conditions. This is best accomplished by a primary care physician and gastroenterologist. Testing should ideally be done while on a diet containing gluten.
    • The initial test is immunoglobulin A (IgA) anti-tissue transglutaminase (TTG) antibody in patients over 2 years old. If this serology is positive, the patient should proceed to an endoscopic small bowel biopsy of the duodenum. Genetic testing is also available which determines susceptibility of the patient to celiac disease.
    • Additional testing of routine complete blood count may show anemia and nutrient testing might reveal vitamin and mineral deficiencies. Basic metabolic panel may show electrolyte abnormalities related to malabsorption. Liver function tests may be elevated.
  • Genetic test for celiac disease:
    • Genetic testing for risk of celiac disease may be done once in a persons lifetime using blood or a swab from the inside of the cheek. About 95% of individuals with celiac disease have the HLA DQ2 gene and about 5% of individuals with celiac disease have the HLA DQ8 gene. These 2 genes are present in up to 40% of the population. However, only 3% of these individuals with the genes will develop celiac disease. If the individual does not have these genes, celiac disease is extremely unlikely.

 

• Disorders affected by gluten:
  • Autism and a gluten-free diet:
    • Diets free of gluten and casein have some evidence of benefit in autism. Research suggests that abnormal levels of peptides by excessive opioid activity caused by the ingestion of gluten and casein may play a role in autism.
    • In as little as 2 weeks, autistic children changed to a gluten-free diet have shown improvements in social isolation, eye contact, speech, learning skills, hyperactivity, stereotypical activity, panic attacks, self-mutilation, total autistic trait score (measured by the Diagnosis of Psychotic Behavior in Children [DIPAB]), nonverbal communication, stereotypy, social interactions, normalizing of behavior, language skills after 1 year, language skills after 4 years, social interaction, play based creativity, motor abilities, decrease in urine peptide levels (UPL), decrease in urinary metal concentrations, and behavioral improvements (6).
    • A Cochrane Database Systematic Review described research showing a reduction of autistic traits, but a benefit in cognitive skills, linguistic ability and motor ability was not seen (8). Additional research showed that only parents saw some improvement of symptoms by their children on this diet. (7)
  • Schizophrenia and gluten: Some schizophrenia patients have improvement of symptoms on a gluten-free diet. Cascella, NG et al found that testing for a specific type of transglutaminase autoantibody may be useful to identify patients who might respond (10).
  • Gluten and bone mineral density:
    • All patients with celiac disease should undergo bone mineral density scans.
    • Osteoporosis appears to occur early in the course of celiac disease, and patients without symptoms at the time of diagnosis had a bone mineral density of over 1 standard deviation below normal (12).
  • Gluten and tooth enamel defects: Dentists have an important role in identifying patients with celiac disease.
    • Enamel defects may be the only sign of celiac disease and are found in about 85% of patients with celiac disease at the time of diagnosis (13).
    • Children with enamel defects should be screened for celiac disease, especially if hypocalcemia and poor weight gain is present (14).
  • Gluten and recurrent apthous stomatitis: A high rate of patients with recurrent apthous stomatitis and celiac disease respond well to treatment with a gluten-free diet. These patients with recurrent apthous stomatitis should be screened for celiac disease (15).
  • Gluten and depression:
    • Patients who self-reported non-celiac gluten sensitivity given a short term challenge with 16 grams of gluten, 16 grams of whey protein, or placebo daily for 3 days found that gluten induced feelings of depression compared to whey or placebo (16).
    • Celiac disease patients with a better adherence to a gluten-free diet over the long term had a lower risk of developing symptoms of depression (17).

 

• The dillemma of diagnosing gluten related disorders
  • Gluten antibody testing, this will help diagnose gluten related disorder if symptoms are related to gluten. If gluten disorder is present, the symptoms will get better with eliminating all sources of gluten. One can consider eliminating gluten to see if symptoms get better. However, if this testing is done after eliminating gluten, the antibody levels will decrease and the test will not be accurate.

• Eating a gluten-free diet plan for gluten-related disorders:
  • Even small amounts over 1-2 grams of residual gluten in the diet are known to contribute to the celiac disease processv(inflammation due to gluten). Gluten sensitive individuals are able to tolerate up to 5 grams of gluten without symptoms of sensitivity. The general guideline is that anything containing wheat contains gluten.
  • Dietary counseling is based on support of the patient in the major lifestyle change of a gluten-free diet for life best accomplished by a qualified dietitian.
  • Education is necessary to avoid all foods containing wheat, rye, barley (including all types of beer), and oats. Avoid these gluten containing foods.
  • Distilled alcohol beverages and wine are generally free of gluten.
  • Gluten containing foods should be substituted with the following gluten free foods (Yes, these foods are OK to eat):
    • Grains including rice, corn, quinoa, soy, and buckwheat
    • Acceptable flours include tapioca, rice, potato, corn, and coconut
    • Meats without coatings or additives which include beef, bacon, pork, chicken, and turkey.
    • Fish and shellfish without coatings or additives.
    • Fresh or frozen fruit without additives.
    • Nuts and seeds
    • Vegetables, beans, herbs, spices, and coconut.
    • Gluten free pasta is available containing rice, quinoa, and corn
  • Pay special attention to labels for retail and processed foods and avoid those with labels which include gluten, wheat protein, and vital wheat protein as ingredients.
  • Oat consumption is controversial, with research showing that oats may provoke gluten related disorder, while other research has supported oats as generally safe to consume

 

 

References:

1.Celiac disease: On the rise. Discovery’s Edge. Mayo Clinic’s Online Research Magazine. July 2010. Accessed 5/17/2014. http://www.mayo.edu/research/discoverys-edge/celiac-disease-rise

 

2.Ludvigsson JF, Leffler DA, Bai JC, Biagi F, Fasano A, Green PH, Hadjivassiliou M, Kaukinen K, Kelly CP, Leonard JN, Lundin KE, Murray JA, Sanders DS, Walker MM, Zingone F, Ciacci C.The Oslo definitions for coeliac disease and related terms. Gut. 2013 Jan;62(1):43-52. http://www.ncbi.nlm.nih.gov/pubmed/22345659

 

3.Pastore L, Lo Muzio L, Serpico R. Atrophic glossitis leading to the diagnosis of celiac disease. N Engl J Med. 2007 Jun 14;356(24):2547. http://www.ncbi.nlm.nih.gov/pubmed/17568041

 

4.Rubio-Tapia A, Hill ID, Kelly CP, Calderwood AH, Murray JA; American College of Gastroenterology. ACG clinical guidelines: diagnosis and management of celiac disease. Am J Gastroenterol. 2013 May;108(5):656-76; quiz 677. http://www.ncbi.nlm.nih.gov/pubmed/23609613

 

5.M. Potts, B. Bellows, “Autism and Diet”. J Epidemiol Community Health. 2006 May; 60(5): 375. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2563974/

 

6.Mulloy A, Lang R, O’Reilly M, Sigafoos J, Lancioni G, Rispoli M. Gluten-free and casein-free diets in the treatment of autism spectrum disorders: a systematic review. Research in Autism Spectrum Disorders 2010; 4(3): 328-339. http://www.edb.utexas.edu/education/assets/files/ltc/gfcf_review.pdf

 

7.“The gluten-free, casein-free diet in autism: results of a preliminary double blind clinical trial.” College of Nursing, University of Florida, Gainesville, 32610, USA. http://www.ncbi.nlm.nih.gov/pubmed/16555138

 

8.“Gluten- and casein-free diets for autistic spectrum disorder.” Cochrane Database Syst Rev. 2004:92):CD003498. http://www.ncbi.nlm.nih.gov/pubmed/15106205

 

9.“Food allergy and infantile autism” Department of Paediatrics(sic), University of Rome Las Sapienza, Itally. Panminerva Med. 1995 Sep; 37(3): 137-41. http://www.ncbi.nlm.nih.gov/pubmed/8869369

 

10.Cascella NG1, Santora D, Gregory P, Kelly DL, Fasano A, Eaton WW. Increased prevalence of transglutaminase 6 antibodies in sera from schizophrenia patients. Schizophr Bull. 2013 Jul;39(4):867-71. http://www.ncbi.nlm.nih.gov/pubmed/22516148

 

11.Lucendo AJ, García-Manzanares A. Bone mineral density in adult coeliac disease: an updated review.Rev Esp Enferm Dig. 2013 Mar;105(3):154-62. http://www.ncbi.nlm.nih.gov/pubmed/23735022

 

12.Mazure R, Vazquez H, Gonzalez D, Mautalen C, Pedreira S, Boerr L, Bai JC. Bone mineral affection in asymptomatic adult patients with celiac disease. Am J Gastroenterol. 1994 Dec;89(12):2130-4. http://www.ncbi.nlm.nih.gov/pubmed/7977227

 

13.Trotta L, Biagi F, Bianchi PI, Marchese A, Vattiato C, Balduzzi D, Collesano V, Corazza GR.Dental enamel defects in adult coeliac disease: prevalence and correlation with symptoms and age at diagnosis. Eur J Intern Med. 2013 Dec;24(8):832-4. http://www.ncbi.nlm.nih.gov/pubmed/23571066

 

14.El-Hodhod MA, El-Agouza IA, Abdel-Al H, Kabil NS, Bayomi KA. Screening for celiac disease in children with dental enamel defects. ISRN Pediatr. 2012;2012:763783. http://www.ncbi.nlm.nih.gov/pubmed/22720168

 

15.Shakeri R, Zamani F, Sotoudehmanesh R, Amiri A, Mohamadnejad M, Davatchi F, Karakani AM, Malekzadeh R, Shahram F.Gluten sensitivity enteropathy in patients with recurrent aphthous stomatitis. BMC Gastroenterol. 2009 Jun 17;9:44. http://www.ncbi.nlm.nih.gov/pubmed/19534771

 

16.Peters SL, Biesiekierski JR, Yelland GW, Muir JG, Gibson PR. Randomised clinical trial: gluten may cause depression in subjects with non-coeliac gluten sensitivity – an exploratory clinical study. Aliment Pharmacol Ther. 2014 May;39(10):1104-12. http://www.ncbi.nlm.nih.gov/pubmed/24689456

 

17.van Hees NJ, Van der Does W, Giltay EJ. Coeliac disease, diet adherence and depressive symptoms. J Psychosom Res. 2013 Feb;74(2):155-60. http://www.ncbi.nlm.nih.gov/pubmed/23332531