Testing for Non-Celiac Gluten Intolerance

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Testing for Non-Celiac Gluten Intolerance

  • Dr. Stephen Wangen
  • Founder, IBS Treatment Center
  • www.IBSTreatmentCenter.com

What Keeps Me Awake At Night

What is wanted is not the will to believe, but the wish to find out, which is the exact opposite.

  • What is wanted is not the will to believe, but the wish to find out, which is the exact opposite.
  • Bertrand Russell (1872-1970)
  • Sceptical Essays, 1928

What Is Gluten?

  • A protein found in wheat, barley, rye, and several other grains.
  • Reactions to gluten are common and can cause many different problems. The most well known is celiac disease.

Gluten Intolerance and Celiac Disease

  • Celiac Disease is a very specific type of damage done to the digestive tract resulting from a gluten intolerance.
  • This damage is the result of an autoimmune reaction that results in villous atrophy.

What Is Villous Atrophy?

  • Villous atrophy is damage to the surface of the small intestine.
  • This damage is a sign of gluten intolerance.

Diagnosing Celiac Disease

  • Celiac disease is diagnosed by measuring the damage in the digestive tract by either a:
    • Biopsy of the small intestine
    • And/or
    • Blood test called tissue transglutaminase antibody.


  • Nearly 3 million people in the United States have celiac disease.
  • But many more are gluten intolerant.

Gluten Intolerance Does Not Have to Mean Celiac Disease.

  • Many people know or suspect that there exist non-celiac forms of gluten intolerance.
  • Patients test negative on blood work and biopsy for celiac disease, yet they know that wheat and gluten trigger their symptoms.

How and Why Does This Happen?

  • First we must understand and define celiac disease in order to put this issue into the proper perspective.

Celiac Disease and Villous Atrophy

  • Celiac disease is defined by villous atrophy.
  • Without villous atrophy, you can’t have celiac disease.
  • But villous atrophy must be put into its proper context

Other Signs and Symptoms Associated With Celiac Disease and Gluten Intolerance

  • What are all of the signs and symptoms associated with celiac disease and gluten intolerance?

Signs and Symptoms Associated with Gluten Intolerance

  • Digestive
  • Diarrhea
  • Constipation
  • Abdominal pain
  • Cramping
  • Dyspepsia
  • Gas
  • Bloating
  • Steatorrhea (fatty stools)
  • Encopresis
  • Enamel defects in teeth
  • Heartburn
  • Gastroparesis
  • GERD
  • Reflux
  • IBS (irritable bowel syndrome)
  • Esophagitis
  • Eosinophilic gastroenteritis
  • Eosinophilic esophagitis
  • Canker sores
  • Apthous ulcers


  • Vomiting
  • Nausea
  • Intestinal bleeding
  • Liver enzymes, elevated (ALT, ALK, ALP)
  • Liver disease
  • Pancreatitis
  • Primary biliary cirrhosis
  • Primary sclerosing cholangitis
  • Colon cancer
  • Lactose intolerance
  • Fructose intolerance
  • Occult blood in stool
  • Hepatitis, autoimmune
  • Hepatic steatosis
  • Hepatic t-cell lymphoma
  • Pancreatic exocrine function may be impaired
  • Villous atrophy (celiac disease)


  • Skin
  • Acne
  • Eczema
  • Dermatitis
  • Dermatitis herpetiformis
  • Dry skin
  • Follicular keratosis
  • Hives
  • Rashes
  • Itchiness
  • Welts
  • Redness
  • Dark circles under eyes
  • Physical well-being
  • Fatigue
  • Weight loss
  • Weight gain
  • Poor endurance
  • Inability to gain weight
  • Chronic fatigue
  • Failure to thrive
  • Short stature
  • Emotional
  • Anxiety
  • Irritability
  • Depression
  • Up and downs


  • Mind/neurological
  • Autism
  • ADHD
  • Difficulty concentrating
  • Cerebellar atrophy
  • Mental fog
  • Brain white-matter lesions
  • Insomnia/difficulty sleeping
  • Schizophrenia
  • Ataxia/difficulty with balance
  • Epilepsy (with or without brain calcifications)
  • Multifocal axonal polyneuropathy
  • Neuropathy, peripheral (numbness or tingling of hands or feet)
  • Musculoskeletal
  • Arthritis
  • Fibromyalgia
  • Rheumatoid arthritis
  • Muscle aches
  • Joint pain
  • Osteoporosis
  • Osteopenia
  • Osteomalacia
  • Polymyositis
  • Dental enamel defects
  • Loss of strength
  • Short stature
  • MS (multiple sclerosis)
  • Myasthenia gravis

Respiratory system

  • Respiratory system
  • Wheezing
  • Sinusitis, chronic
  • Shortness of breath
  • Asthma
  • Women’s health
  • Irregular cycle
  • Infertility (also male infertility)
  • Delayed menarche
  • Premature menopause
  • Spontaneous abortion/miscarriage
  • Head
  • Headaches
  • Migraines
  • Alopecia (hair loss)
  • Chromosomal defects
  • Down syndrome
  • Miscellaneous
  • Fatigue
  • Anemia
  • Iron deficiency
  • Vitamin B12 deficiency (pernicious anemia)
  • Vitamin K deficiency
  • Folate deficiency
  • Impotency
  • Raynaud’s
  • Eosinophils elevated (in blood test)
  • Cystic fibrosis
  • Pulmonary hemosiderosis
  • Vasculitis

Autoimmune disorders

  • Autoimmune disorders
  • Addison’s disease
  • Autoimmune chronic hepatitis
  • Alopecia areata
  • Diabetes, type 1
  • Graves disease
  • Hyperparathyroidism, secondary
  • Hypoparathyroidism, idiopathic autoimmune
  • Lupus (SLE)
  • Myasthenia gravis
  • Sarcoidosis
  • Scleroderma
  • Sjogrens syndrome
  • Hypothyroidism
  • Villous atrophy
  • Thyroiditis
  • ITP (idiopathic thrombocytopenic purpurea)
  • Malignancies
  • Small bowel adenocarcinoma
  • Esophageal and oro-pharyngeal carcinoma
  • Melanoma
  • Non-Hodgkin’s lymphoma

Over 130 Problems!

  • We know that many signs and symptoms can be found associated with gluten intolerance and celiac disease.

Villous Atrophy Is Only One of These.

  • Villous atrophy is only one possible end product of gluten intolerance.
  • Celiac disease = villous atrophy.

What If You Don’t Have Villous Atrophy?

  • Most of these are also signs and symptoms that can be associated with gluten intolerance even when villous atrophy is not present.
  • Celiac disease (villous atrophy) is a gluten intolerance, but
  • Gluten intolerance is not always celiac disease (villous atrophy).
  • Gluten Intolerance
  • Celiac Disease
  • Celiac Disease
  • Gluten Intolerance

How Do We Know This?

  • People tell us
  • Clinical results tell us
  • Blood tests tell us
  • Medical Studies tell us

The Free Market Tells Us

  • The University of Chicago Celiac Disease Center states that 97% of celiacs have not been diagnosed. (Only about 70,000 dx.)
  • The market for gluten free products is now known to be over $1 billion per year (USDA estimates $1.7 bill by 2010).
  • That’s $14,200 per person, per year.

What do the lab results look like for non-celiac gluten intolerance?

Negative Celiac, Positive Gluten Intolerance

  • Tissue Transglutaminase antibody negative and
  • Biopsy negative
  • Gliadin antibody positive (IgA or IgG)
  • Total IgA normal

Some Studies on Non-Celiac Gluten Intolerance

Small-bowel mucosal inflammation in reticulin or gliadin antibody-positive patients without villous atrophy. Scandinavian Journal of Gastroenterology, 33, 944–949. Kaukinen, K., et al. (1998).

  • “CONCLUSIONS: IgA-class … antigliadin antibody-positive patients with normal small-bowel mucosal morphology … implies that they may be gluten-sensitive.”

Intolerance to cereals is not specific for coeliac disease. Scand J Gastroenterol. 2000 Sep;35(9):942-6. Kaukinen K, et al.

  • “Allergy to cereals [other than celiac disease] should be considered even in adults.”

Celiac disease without villous atrophy: Revision of criteria called for. Digestive Diseases and Sciences, 46, 879–887. Kaukinen, K., et al. (2001).

  • “10 adults suspected to have celiac disease, but evincing only minor mucosal inflammation … showed a clinical, histological, and serological recovery on (a gluten free) diet.”

Common Blood Tests for Non-Celiac Gluten Intolerance

  • Gliadin antibodies
  • Gliadin IgA
  • Gliadin IgG

Discovery is to see what everyone else has seen and to think what no one else has thought.

  • Discovery is to see what everyone else has seen and to think what no one else has thought.
  • Albert Szent Gyorgyi
  • 1937 Nobel Prize in Medicine

Gliadin Antibodies

  • Not predictive of celiac disease.
  • A great assessment of an immune reaction to gluten.
  • Therefore a great assessment of gluten intolerance.

Commonly Used as a Screening Test for Celiac Disease

  • Numerous studies have used gliadin antibodies to begin screening people for celiac disease, including most studies on the prevalence of celiac disease.
  • Many studies on signs and symptoms associated with gluten intolerance are based on gliadin antibodies and not celiac disease.

Non-Celiac Gluten Intolerance is Not Less Severe Than Celiac Disease

  • Nor is there any evidence that celiac disease is the end stage of gluten intolerance.

Emerging new clinical patterns in the presentation of celiac disease. Arch Pediatr Adolesc Med. 2008 Feb;162(2):164-8. Telega G, Bennet TR, Werlin S

  • Emerging new clinical patterns in the presentation of celiac disease. Arch Pediatr Adolesc Med. 2008 Feb;162(2):164-8. Telega G, Bennet TR, Werlin S
  • [A review of] the medical records of all patients diagnosed with celiac disease at the Children's Hospital of Wisconsin between 1986 and 2003…[demonstrated that patients] with celiac disease usually do not present with classic symptoms; they are more likely to be asymptomatic…”

Some Studies on Signs and Symptoms Associated with Non-Celiac Gluten Intolerance

Dietary treatment of gluten neuropathy. Muscle Nerve. 2006 Dec;34(6):762-6. Hadjivassiliou M, et al.

  • “We studied the effect of a gluten-free diet in patients with idiopathic sensorimotor axonal neuropathy and circulating antigliadin antibodies. A total of 35 patients participated in the study, with 25 patients going on the diet and 10 not doing so. There was a significant difference … with evidence of improvement in the [treatment] group and deterioration in the control group.”

Myopathy associated with gluten sensitivity. Muscle Nerve. 2007 Apr;35(4):443-50. Hadjivassiliou M, et al.  

  • “Among seven patients not on immunosuppressive treatment, four showed clinical improvement of the myopathy with a gluten-free diet. The myopathy progressed in one patient who refused the gluten-free diet. Myopathy may be another manifestation of gluten sensitivity and is likely to have an immune-mediated pathogenesis.”

Gluten sensitivity masquerading as systemic lupus erythematosus. Ann Rheum Dis. 2004 Nov;63(11):1501-3. Hadjivassiliou M, Sanders DS, Grünewald RA, Akil M.

  • “Three patients are described whose original presentation and immunological profile led to the erroneous diagnosis of systemic lupus erythematosus. The correct diagnosis of gluten sensitivity was made after years of treatment…The presence of an enteropathy is no longer a prerequisite for the diagnosis of gluten sensitivity, which can solely present with extraintestinal symptoms and signs. Knowledge of the diverse manifestations of gluten sensitivity is essential in avoiding such misdiagnosis.”

Dietary treatment of gluten ataxia. J Neurol Neurosurg Psychiatry. 2003 Sep;74(9):1221-4. Hadjivassiliou M, Davies-Jones GA, Sanders DS, Grünewald RA.

  • “Gluten ataxia is an immune mediated disease, part of the spectrum of gluten sensitivity, and accounts for up to 40% of cases of idiopathic sporadic ataxia. Twenty six patients (treatment group) adhered to the gluten-free diet and had evidence of elimination of antigliadin antibodies by one year. CONCLUSIONS: Gluten ataxia responds to a strict gluten-free diet even in the absence of an enteropathy.”

Antibodies Against Foods Other Than Gluten

  • In the same way, you can also test for antibodies to wheat, barley, rye, spelt, etc.
  • Typically IgG antibodies.
  • If gliadin antibodies are elevated, these will also be elevated.
  • (Visit www.IBSTreatmentCenter.com for more info).

A Few Studies on IgG Food Antibodies (other than gluten)

The clinical significance of food specific IgE/IgG4 in food specific atopic dermatitis. Pediatric Allergy and Immunology, 18(1), 63–70. Noh, G., et al. (2007).

  • “Specific IgE and IgG4 concentration were measured ... Double blinded placebo controlled food challenge test (DBPCFC) was performed. Mean IgE/IgG4 levels in DBPCFC (+) subjects is higher than those in DBPCFC (-) subjects in all food items studied. Allergen-specific IgE/IgG4 may provide one of the clues to understand the mechanism of food allergy in atopic dermatitis.”

Food-specific IgG4 antibody-guided exclusion diet improves symptoms and rectal compliance in irritable bowel syndrome. Scandinavian Journal of Gastroenterology, 40, 800–807. Zars, S., et al. (2005).

  • “IgG4 antibodies to common food antigens are elevated in IBS. The aim of this article was to evaluate the effect of exclusion diet based on IgG4 titres… CONCLUSIONS: Food-specific IgG4 antibody-guided exclusion diet improves symptoms in IBS and is associated with an improvement in rectal compliance.”

Food-specific serum IgG4 and IgE titers to common food antigens in irritable bowel syndrome. American Journal of Gastroenterology, 100, 1550–1557. Zars, S., et al. (2005).

  • “No significant difference in IgE titers was observed between IBS and controls. Serum IgG4 antibodies to common foods like wheat, beef, pork, and lamb are elevated in IBS patients. In keeping with the observation in other atopic conditions, this finding suggests the possibility of a similar pathophysiological role for IgG4 antibodies in IBS.”

Food elimination based on IgG antibodies in irritable bowel syndrome: a randomised controlled trial. Gut. 2004 Oct;53(10):1459-64. Atkinson W, et al.

  • “150 outpatients with IBS were randomised to receive, for three months, either a diet excluding all foods to which they had raised IgG antibodies (enzyme linked immunosorbant assay test) or a sham diet excluding the same number of foods but not those to which they had antibodies.
  • CONCLUSION: Food elimination based on IgG antibodies may be effective in reducing IBS symptoms and is worthy of further biomedical research. (The compliant patients experienced significant benefit).”

The therapeutic effects of eliminating allergic foods according to food-specific IgG antibodies in irritable bowel syndrome. Zhonghua Nei Ke Za Zhi. 2007 Aug;46(8):641-3. Yang CM, Li YQ.

  • “CONCLUSIONS: Abnormal immune reactions mediated by IgG antibodies coexisted in patients with IBS. It is of great significance in treating IBS by eliminating the allergic foods according to the serum level of food-specific IgG antibodies.”

IgG and IgE Antibody Testing

  • IgG = gray bar, IgE = black bar
  • IgG = gray bar, IgE = black bar

You Can’t Find What You Don’t Look For

Non-gluten Wheat Reactions

  • It is also possible to react to wheat and other grains without reacting to gluten. There are many other proteins in these foods.
  • Antibody tests to wheat, barley, rye, spelt, etc can be positive when the gliadin test is negative.

Non-immune Reactions to Wheat

  • The ecosystem of the digestive tract plays an important role in how food is digested.
  • Problems here can and do create significant digestive and skin problems.
  • Bacterial and yeast imbalances can simulate a gluten or wheat intolerance.
  • The “intolerance” resolves once the imbalance has been treated.

Stool Testing

  • Thorough stool testing can measure most of the organisms in the digestive tract.
  • Good bacteria: acidophilus and bifidobacterium
  • Bad bacteria: Klebsiella, Psuedomonas, Citrobacter, Aeromonas, many others.
  • Yeast/Candida
  • Parasites.

Lots more information about the

  • Lots more information about the
  • Ecosystem of the digestive tract and
  • Food allergy testing
  • in “The Irritable Bowel Syndrome Solution”
  • by Dr. Stephen Wangen

Other Gluten and Wheat Reactions

  • It would be a mistake to assume that we know everything. Lab tests are just tools.
  • Therefore there are likely other types of reactions to gluten or wheat that we don’t yet know how to measure.
  • So if the patient says that they can’t eat gluten, but the lab work doesn’t support it, then I still believe the patient!


  • Gliadin antibodies indicate gluten intolerance, even in the absence of celiac disease.
  • Gluten intolerance can potentially cause a large number health problems.
  • Gluten intolerance is likely far more common than celiac disease.
  • The End!
  • Due Out Fall 2008

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