1. “Senza il pane tutto diventa
orfano”
Gluten Sensitivity,
(Without bread everyone’s an
orphan)
Coeliac Disease and
Chronic Brain Syndromes
Along with dairy products,
wheat
has become the most
James Braly, MD
commonly eaten food in the
USA and UK….
2. Gluten is an elastic, malleable,
storage protein found in all gluten
grains.
Gluten is composed of two smaller
proteins called peptides or prolamines.
Glutenin is one peptide and the other
peptide, gliadin, is responsible for
Coeliac Disease.
3. Gluten grains
Wheat
Rye
Barley
Oats (contains gluten but not gliadin)
Spelt
Kamut
Triticale
5. Key historical events in the early
domestication of gluten grains
Ancestors & Events Time Period Location
Cereal-less homo sapiens 500,000 – 8,000 BC Worldwide
First Wheat Farmers 8,000 BC Near East
3,500 BC England
Domestication of Wheat & Barley 8,000 BC Near East
Domestication of Rye 3,000 BC SW Asia
Domestication of Oats 1,000 BC Europe
6. Wheat & Dairy Products
Dominant U.S. Diet Today
Top nine American foods
rated by calories eaten annually
Whole cow’s milk
7. Refined sugars (accounts
2% cow’s milk for 10% to 20% of all calories)
Processed American 8. Soda, fruit juice (more soda
cheese consumed each year in the U.S.
& England than water - 20% of
all calories now consumed as
White wheat bread liquids)
White wheat flour 9. Ground beef (grain-fed)
Wheat rolls U.S. Department of Agriculture
7. “From great hunters & meat eaters
to canaries in only 10,000 years.”
Harlan JR: Crops and Man (1992)
American Society of Agronomy
8.
9. Gluten, Coeliac Disease
& Cancer
“Malignancy may be the first
manifestation of subclinical
[silent] coeliac disease.”
Cronin & Shanahan
Lancet, April 12, 1997;
349: 1096-1097.
10. “Overall mortality in adult coeliacs is
approximately twice that of the general
population, mostly due to cancer
deaths…Deaths are greatest within
the first year of diagnosis.”
Logan RF et al. Mortality in coeliac disease.
Gastroenterology, 1989 Aug; 97(2):265-271.
11. Coeliac disease affects ~2.5 million in USA
(more than twice as common as ulcerative colitis,
Crohn’s disease, Down’s syndrome, multiple
sclerosis, & cystic fibrosis combined)
Ulcerative colitis 500,000
Crohn's disease 500,000
Down’s syndrome 350,000
Multiple sclerosis 333,000
Cystic fibrosis 30,000
Total = 1,713,000
Source: National Institute of Health
13. Coeliac disease is the most common
autoimmune genetic disorder in
Europe, United Kingdom, and
the United States.
14. “Untreated coeliac disease
increases the risk of over 185
different medical conditions,
including many chronic brain
disorders in children & adults.”
Braly & Hoggan. Dangerous Grains
Penguin Putnam, 2003.
15. Gluten Sensitivity, Coeliac disease
and the Brain
Weepy, irritable children
Irritable bowel syndrome
Autism
Depression
ADHD
Epilepsy
Down’s syndrome
Schizophrenia
Low IQ children &
maternal thyroid disease
16. What is Coeliac Disease?
(“The great modern-day imposter”)
A genetic, autoimmune disorder caused
by sensitivity to gluten, a protein found
in wheat, barley, rye, (oats), spelt, kamut
and triticale.
Gluten-caused inflammation results in
damage to mucosal lining of the small
intestine, bringing about both
autoimmune diseases and malabsorption
of essential nutrients.
22. A good set of stomach and
bowels is more important to
human health and happiness
than a large amount of brains…
23. Coeliac Disease,
a worldwide problem
Studies have expanded to other regional areas,
including Middle East, North Africa, India, Asia,
Oceania, and South America where coeliac
disease is now recognized as a frequent
condition affecting approximately 0.5 to 1
percent of the general population, almost the
same as that in Western countries
Catassi C et al. The Global Village of Celiac Disease. Basel, Switzerland: Karger Press; 2005.
Alencar ML et al. Prevalence of celiac disease among blood donors in Sao Paulo City, Brazil.
Gastroenterology. 2006; vol 130:A-668. [#S1110]
Mendez-Sanchez N et al. Seroprevalence of anti-gliadin and anti-endomysium antibodies in
Mexican adults. Gastroenterology. 2006; vol 130:A-155.
24. Coeliac disease is now thought to
have a prevalence of between 1:100
and 1:200 in the UK population.
Hourigan CS. The molecular basis of coeliac
disease. Clin Exp Med. 2006 June; vol 6(2): pp53-59
25. Prevalence of Coeliac Disease among
American adults & children
1 : 111 of the 2,785 healthy, asymptomatic
adults tested had coeliac disease
1 : 167 of the 1505 healthy, asymptomatic
children tested had coeliac disease
Gerarduzzi T, et al. J Pediatric Gastroenterology and
Nutrition 2000; volume 31 (Suppl.3): S29.
26. Prevalence of coeliac disease
among of high risk groups
Children testing positive for both IgG
and IgA anti-gliadin antibodies….… 90:100
Identical twins………………................ 70:100
HLA-identical siblings……………….. 30:100
First-degree relatives…...................... 22:100
Down’s syndrome…………………….. 16:100
Autoimmune thyroid disease……….. 14:100
Insulin-dependent diabetes…….…… 11:100
27. Other at-risk for coeliac groups
Children testing positive for only IgG
antigliadin antibodies………………. 7.7:100
Osteoporosis………………………….… 4.5:100
Irritable bowel syndrome……………… 3.3:100
Second-degree relatives…………….… 3:100
Iron deficiency anemia………………… 2.8:100
ADHD……………………………………… 2.5:100
Women with recurring pregnancies
of poor outcomes ……………………. 2:100
28. Four Types of Coeliac Disease
Clinical – symptomatic, positive serology
& positive small intestine biopsy for coeliac disease
Silent – asymptomatic even on gluten diet, but
with positive serology & positive intestinal biopsy
Latent – asymptomatic, positive IgG/IgA anti-
gliadin antibodies, but negative intestinal biopsy
Abortive – biopsy-proven coeliac disease
which remits for some unknown reason
29. Clinical, symptomatic
coeliac disease,
the tip of the iceberg
Clinical
CD
(positive serology,
symptoms, flat gut)
Silent CD
(positive serology,
no symptoms, flat gut)
Latent CD
(positive serology, no symptoms
& normal mucosa--later converts)
30. Gluten sensitivity, coeliac disease
and chronic brain syndromes
Weepy, irritable
children
Irritable bowel syndrome
Autism
Depression
ADHD
Epilepsy
Downs syndrome
Schizophrenia
Low IQ children &
maternal thyroid disease
31. WEEPY, IRRITABLE,
UNHAPPY CHILDREN
Coeliac children are
often weepy, often
discontented or surly,
quiet, turned inward,
and apparently lack
all joy in living.
Kaser. J of Pediatrics 1961
32. Coeliac children often have foul
smelling stools, occasionally big
and bulky stools. A small number of
children will develop severe diarrhea.
34. Gluten Allergy – Gluten Addiction
Possible mechanisms of addiction include:
Gluten sensitivity often results in significant
serotonin, norepinephrine, and dopamine
depletion, the same brain neurochemistry often
associated with addictive behavior.
Gluten sensitivity suppresses gut hormone release
(secretin, VIP, & CCK), adversely affecting
cognition, emotions, appetite/satiation, and
behavior.
35. Gluten’s mood & behavior modulating
morphine-like peptides
When gluten is broken down in the
intestines during digestion, opioid-like
peptides are formed; specifically,
certain peptides, called Gluteomorphin
and Gliadorphin, mimic the effects of
morphine on the brain as they enter the
bloodstream.
36. Irritable bowel syndrome in children
Irritable bowel syndrome (IBS) is a
digestive disorder that causes abdominal
pain, bloating, gas, diarrhea, and
constipation—or some combination of
these problems.
IBS physically and psychologically affects
people of all ages, including children.
37. Irritable bowel syndrome (IBS),
depression, anxiety & panic attacks
There is an association of panic disorder with
IBS symptoms (1/3 of patients presenting with
panic disorder have IBS symptoms)
Chronically constipated patients with IBS as a
group are more anxious and more depressed
than the general population
38. Link between IBS symptoms
& IgG-mediated food allergy
Recent evidence suggests significant
reduction in IBS symptom severity in
patients on elimination diets, provided
that dietary elimination is based on foods
against which the individual has
generated food-specific IgG antibodies.
Isolauri E et al. Gut. 2004 Oct;53(10):1391-1393
39. Up to one-third of all coeliac
disease patients have been
previously diagnosed with
IBS &/or lactose intolerant.
40. IBS children at higher
risk of coeliac disease
The prevalence of undiagnosed coeliac
disease in irritable bowel syndrome
was 3.3% (4 out of 123 tested).
Sanders DS et al. Eur J Gastroenterol
Hepatol. 2003;15:407-413.
42. Over two-thirds of depressed
people are not responsive to any
prescription anti-depressants
now available.
43. In December 2004 Britain's drug regulatory
agency issued a report that warned that all
SSRIs "may be associated with withdrawal"
and noted that Paxil and Effexor "seem to
be associated with a greater frequency of
withdrawal reactions."
44. Depression & Coeliac Disease
In all 3 biopsy-proven coeliac teenagers, depressive
symptoms improved quickly on a gluten-free diet.
“Coeliac disease should be considered in the
presence of depression, particularly if not
responsive to the usual antidepressant therapy.”
Corvaglia et al. American Journal of Gastroenterol, 1999.
45. Depression-coeliac disease clusters
Both depression and coeliac disease
are found more often in:
Hypothyroidism
Insulin-dependent diabetes
IBS, depression, anxiety and panic attacks
Osteoporosis
Problem pregnancies
Heart attacks
Migraine headaches
46. Omega-3 fatty acids & depression:
A review of the evidence
In controlled studies, concentrations of omega-3
fatty acids were lower in participants with unipolar
and postpartum depression.
Infrequent fish consumption (the major source
of omega-3 fatty acids) is associated with
depression in epidemiological studies.
In four of seven double-blind, randomized controlled
trials, depression was significantly improved with at
least 1 gram a day of EPA fish oil.
Sontrop J et al. Preventive Medicine. 2006 Jan; 42(1): 4-13.
47. Alternative Therapies
for Depression
Staying clean & sober Fish oil (DHA & EPA)
Folic acid, B12, B6
Oily fish 2-3X/week
NADH
Daily sunlight
5-HTP + B6
Daily exercise
L-Tryptophan + B6
L-Tyrosine + B6 Deep, restful sleep
SAMe Reduce refined sugars
St. John’s Wort (std) Zinc
Ginkgo biloba (std) Magnesium
Gluten-free diet for Others…
depressed gluten
sensitive clients
48. As high as 1 in six Down’s
syndrome subjects have
coeliac disease…
49. “It is recommended that children
with Down’s syndrome be screened
for coeliac disease.”
10% of first-degree relatives of
coeliac Down’s children test
positive for coeliac disease.
Book L et al. Am J Med Genetics
2001 Jan; vol 98: pages 70-74.
50. Coeliac-related diseases commonly
found in Down’s syndrome individuals
Epilepsy occurs in 5-10% of all Down’s
syndrome subjects
About 15% suffer from autoimmune thyroid
disease (hypo- and hyperthyroidism)
Suffer higher incidence of Type 1 diabetes
than the general population
Shortness/small stature
Some Down’s individual suffer from autism
Short 5th finger
51. Short 5th Finger
Is often observed in
• Down’s syndrome
• Coeliac disease
• Autoimmune hypo-
& hyperthyroidism
↔
distal joint
ring finger
52. Short Fifth Finger &
Autoimmune Thyroid Disease
Ber. A. Fingers and toes
in Endocrinology,
Endokrynologia Polska
1956; volume 7: page 9.
O’Donovan DK,
O’Sullivan J.
Hyperthyroidism with
fifth finger
abnormalities. Irish J
Med Sci, 6th series
1996; volume 491: p 540.
53. “It is advisable to screen all
autoimmune thyroid disease
patients for coeliac disease…”
Sategna-Guidetti C et al. Eur J Gastroenterol Hepatol, 1998.
Coeliac disease occurs up to 14 times
more frequently in patients with autoimmune
thyroid disease (14:100) than in normal patients.
Not T et al. Dig Dis Sci 2000; volume 45: pages 403-406.
54. Low IQ children & mothers
with autoimmune thyroid disease
Approximately one out of every
50 women in the UK & U.S. is
thyroid deficient during pregnancy.
55. Hypothyroidism during pregnancy,
risk of miscarriage & low IQ children
Women with untreated thyroid deficiency during
pregnancy are four times more likely to have
children with lower I.Q. scores.
Nineteen percent of the children whose mothers
had undiagnosed hypothyroidism during pregnancy
averaged 85 or less on their I.Q. tests.
Children who have an I.Q. less than 85 are more
likely to have difficulties in school, and may be
less successful in their careers and interpersonal
relationships.
Allan W et al. Journal of Medical Screening, Nov 2002
(specialty publication of the British Medical Journal )
Allan W et al. New England Journal of Medicine, August 18, 1999.
56. Egger’s Epilepsy with Migraine
&/or Hyperactivity Study
The Subjects of the Study:
63 of epileptic children were included in the study.
18 of the 63 children had seizures every day; 11 had seizures
several times a week; and 5 had weekly seizures.
46 children entered the study on anti-convulsive medication,
36 of whom were “poor responders” to the drugs.
45 of the 63 children had epilepsy with migraine headaches
and/or hyperactivity; 18 of the 63 children had epilepsy
without headaches or hyperactivity.
57. Epilepsy with Migraine
&/or Hyperactivity Study, continued…
25 of 45 children with epilepsy, migraines and/or
hyperactivity (55.5%) completely stopped having
seizures; 11 of the same 45 (24.4%) had significantly
fewer seizures (80% were responders).
19 of 46 children who entered the study on anti-seizure
medication were able to completely stop medication.
None of the 18 epileptic children without a history of
migraines and/or hyperactivity responded with fewer
seizures.
Egger et al. Journal of Pediatrics 1989; 114(1): 51-58
58. Four Most Frequent
Seizure-Provoking Foods
Foods # of children % with seizures
tested to foods eaten
Cow milk 35..…...…........37%
Cow cheese 11..........………36
Citrus fruits 24......…………29
Wheat 35....…..........29%
59. Autism much more
common than once thought
Autism and similar disorders may affect up
to one in 100 children, UK researchers now
suggest.
"Prevalence of autism and related autism
spectrum disorders (ASDs) is substantially
higher than previously recognized.”
Professor Gillian Baird et al.
Guy's and St Thomas' Hospital, London
The Lancet. July 2006
60. Change in symptoms in 70 autistic children following a
gluten/casein-free diet are shown below. Mean scores
were recorded for 8 common autistic symptoms.
0-Normal, 1-Good, 2-Fair, 3-Poor, & 4-Very Poor
- - - On Diet - - - Control 1 month 3 mo 6 mo 12 months
Social Isolation: 3.5 2.9 1.9 1.4 1.4
Eye Contact: 3.2 2.4 2.7 1.2 1.2
Mutism: 2.8 2.1 1.5 0.9 0.8
Learning Skills: 3.3 2.8 2.1 1.6 1.2
Hyperactivity: 3.1 2.1 1.7 1.6 1.5
Stereotypic activity: 3.3 2.8 2.1 1.5 1.1
Self-Mutilation: 0.63 0.57 0.37 0.47 0.30
Panic Attacks: 1.5 1.3 0.80 0.83 0.45
J. Robert Cade, M.D. Professor of Medicine and Physiology,
U. of Florida - http://paleodiet.com/autism/cadelet.txt
61. ADHD and food allergy
“An elimination diet is effective in most cases [of
ADHD]…behavior often reverts to normal to the
great relief of all concerned…In view of the
potential toxicity of medications in [ADHD]
children, all families with hyperactive children
should be offered help in detecting offending
foods. It is more appropriate to reserve
medication in those who fail.”
Anthony HM et al.
Archives of Disease in Childhood 1999; 81: 189.
62. ADHD and food allergy
62 of 76 (81%) severely hyperactive
children improved on an oligoantigenic
(few, hypoallergenic foods); other
symptoms such as migraines, epilepsy,
abdominal pain, conduct disorders,
growing pain, etc. also improved.
Egger J et al. The Lancet, March 9, 1985
64. Gluten sensitivity and ADHD
Foods # of ADHD kids tested # and % of kids
Tested to food items that reacted
Food dyes/additives 34 27 (79%)
Soya 15 11 (73%)
Cow’s milk 55 35 (64%)
Chocolate 34 20 (59%)
Grapes 18 9 (50%)
Wheat 53 28 (49%)
Rye 29 15 (52%)
65. Coeliac Disease & Schizophrenia
Coeliac disease victims are three times
more likely to develop schizophrenia
than those without the disease,
according to Danish and Johns Hopkins
School of Public Health researchers.
British Medical Journal.
February 21, 2004
66. Gluten sensitivity & schizophrenics
A double-blind control trial of gluten-free versus a
gluten-containing diet was carried out in a ward of
maximum security hospital: 24 patients were
studied for 14 weeks. Most suffered from psychotic
disorders, particularly schizophrenia.
Two patients (8%) improved during the gluten-free
period and relapsed when the gluten diet was
reintroduced.
Vlissides DN et al. A double-blind gluten-free/
gluten-load controlled trial in a secure ward
population. Br J Psychiatry 1986 April;48:447-452.
67. Casein & gliadin polypeptides in the urine
of schizophrenics & autistic children
95% of patients with schizophrenia or
childhood autism have a significant
hyperpolypeptiduria.
All of these patients have a greatly
increased amount of peptides derived
from either casein or gliadin.
68. Wheat polypeptides in urine of
schizophrenics & autistic children, continued…
The degree of the polypeptiduria can
be decreased by either dialysis, diet
or the two in combination.
As the polypeptiduria decreases, the
symptoms of schizophrenia or autism
decreases. If the polypeptiduria can
be reduced to normal range, most
patients either improve dramatically
or become completely normal.
69. Gliadorphin and IgG anti-casein
& anti-gluten antibodies
Gliadorphin was found in very large
amounts in 48% of schizophrenics and 54%
of autistic patients, while it was found in
32% of normals in very small amounts.
Among autistic children, 87% had high titer
IgG antibodies to gluten and 90% to casein,
while among schizophrenic patients, 86%
had high titer IgG antibodies to gluten and
93% to casein.
J. Robert Cade, M.D. Professor of Medicine and Physiology,
U. of Florida - http://paleodiet.com/autism/cadelet.txt
70. 80 out of every
100 coeliacs remain
undiagnosed in England.
97 out of every
100 coeliacs remain
undiagnosed in America
71. “The rate of diagnosis of coeliac
disease is proportional to suspicion."
Joseph Murray, MD
Associate Professor of Medicine
University of Iowa Hospitals and Clinics
72. Testing for coeliac disease
In the past 2 decades, a number of
accurate blood tests have been
developed that now have a definitive
role in the coeliac disease diagnostic
process.
73. Blood tests for diagnosis
of coeliac disease
Total serum IgA
IgG & IgA anti-gliadin antibodies (AGA)
IgA endomysial antibodies (EMA)
IgA (IgG if IgA deficient) anti-tissue
transglutaminase antibodies (tTG)
74. Two Key Steps Needed
to Diagnose Coeliac Disease
1. Begin with a high degree of suspicion
2. Commit to routinely testing high risk
candidates whether symptomatic or not;
if initial tests are negative, commit to
retesting every few years
(concern here with retesting is with
latent coeliac disease in high risk patients)
75. A 10 minute In-Office or Self-Test
The first self-test for coeliac disease is now
available in Europe and England.
Speeds up diagnosis with a kit that lets people
self-test with a finger pinprick blood sample,
with results in under 10 minutes.
“Results are as accurate as a doctor’s or lab
blood test which needs a GP consultation
and a 7 day wait for results.”
76. Accuracy of new medical
office tests for coeliac disease
These two commercial kits (rapid detection of
IgA anti-human-transglutaminase antibodies (tTG)
in serum and tTG antibodies in one drop of whole
blood) produced sensitivities of 96-100% and
specificities of 95-100%, offering the general
practitioner a means of quickly and easily
looking for coeliac disease his own office
during a standard visit at a low cost.
Nemec G et al. Am J Gastroenterology.
2006 July;101(7):1597-600.
77. THERAPY FOR COELIAC DISEASE
There is no cure for coeliac disease.
The only treatment of coeliac
disease is a strict, life-long, gluten-
free diet.
78. New digestive enzyme therapy
for Coeliacs
An enzyme in barley seeds, EP-B2, normally digests
gluten proteins. A recombinant form of EP-B2 has now
been produced that only activates under acidic
conditions similar to the conditions found in the human
stomach.
EP-B2 efficiently digests gluten protein and is most
specific for those parts of gluten that are known to
trigger coeliac disease.
An even more potent double enzyme therapy for
detoxifying gluten has evolved, one including both EP-
B2 and a 2nd enzyme, PEP.
79. PEP and EP-B2 enzyme combination
completely abolishes gluten immunotoxicity
within ten minutes under simulated stomach
and duodenal conditions.
“Hopefully this two enzyme cocktail will help
coeliacs resume a more normal diet in the
future.”
Siegel et al. "Rational Design of Combination Enzyme Therapy
for Celiac Sprue." Chemistry & Biology, June 2006; 13: 649–658
80. “The rate of diagnosis of coeliac
disease is proportional to suspicion."
Joseph Murray, MD
Associate Professor of Medicine
University of Iowa Hospitals and Clinics
81. Prevalence of coeliac disease
among of high risk groups
Children testing positive for both IgG
and IgA anti-gliadin antibodies….… 90:100
Identical twins………………................ 70:100
HLA-identical siblings……………….. 30:100
First-degree relatives…...................... 22:100
Down’s syndrome…………………….. 16:100
Autoimmune thyroid disease……….. 14:100
Insulin-dependent diabetes…….…… 11:100
82. Other at-risk for coeliac groups
Children testing positive for only IgG
antigliadin antibodies………………. 7.7:100
Osteoporosis………………………….… 4.5:100
Irritable bowel syndrome……………… 3.3:100
Second-degree relatives…………….… 3:100
Iron deficiency anemia………………… 2.8:100
ADHD……………………………………… 2.5:100
Women with recurring pregnancies
of poor outcomes ……………………. 2:100
83. No more gluten-induced
• Infertility
• Recurring miscarriages
• Premature births
• Low birth weight,
low IQ babies
• Spina bifida
• Cleft palate, cleft lip
• Down’s syndrome
84. No more gluten-induced
• Weepy, irritable, & surly
• Low IQ
• Poor school performance
• Epilepsy
• Autism
• ADHD
• IBS, anxiety & depression
• Short stature
• Insulin-dependent diabetes
• Recurring canker sores
• Low impact bone fractures
• Iron deficiency anemia
• Bed wetting
