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.
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.
Prevalence
• 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
Colon cancer
Liver enzymes, elevated (ALT,
ALK, ALP)
Occult blood in stool
Liver disease
Pancreatitis
Primary biliary cirrhosis
Primary sclerosing cholangitis
Lactose intolerance
Fructose intolerance
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
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
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 smallbowel 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 NonCeliac 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.
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):1648. 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 NonCeliac 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
• 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!
Summary
• 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.
Due Out
Fall 2008
The End!