1. family and parenting
2. children

Gastrointestinal Disorders of
Children with Autistic
Spectrum Disorders
Joseph Levy, M.D.
Professor of Clinical Pediatrics
Director, Program in Neurogastroenterology
Columbia University Medical Center
Morgan Stanley Children’s Hospital of NY Presbyterian
Outline and Goals

Review the GI and nutritional issues impacting
on the health of children on the autism spectrum

Prepare parents and professionals to critically
appraise the pertinent information…or how
much can we trust anecdotes?

Propose guidelines for assessing adequacy of
nutritional intake and the need for supplements
Autistic Spectum Disorders
1.
2.
3.
4.
Social interaction
Verbal and nonverbal
communication
Repetitive behaviors or
interests
? GI disorders
GI symptoms reported in ASD

Nonspecific symptoms:
Chronic Diarrhea
 Constipation
 Foul-smelling stools
 Excessive gas
 Abdominal bloating
 Abdominal pain
 Vomiting

GI symptoms in ASD

Do children with ASD really have more
gastrointestinal symptoms than other
children?

Lack of published rigorous data that
show increased GI symptoms in
children with ASD
Prevalence of GI symptoms:
A Little Perspective

Gastrointestinal complaints are very
common in children with normal
development:

Constipation rates 16%-37%

Cow‟s milk protein intolerance 0.3-7.5%
of otherwise normal infants
Loening-Baucke, NEJM 1998
Prevalence of GI symptoms


There is very little reliable information
about whether GI symptoms are part
of ASD.
Bias:
Selection
 Referral
 Recall

Prevalence of GI symptoms

Retrospective survey comparing 412 children
with ASD and 43 siblings:

85.3% ASD had at least one GI symptom compared
to 28.6% siblings.
Horvath & Perman, Current Gast Reports 2002a, Current Op Ped 2002
Prevalence of GI symptoms

Survey of 500 parents:
50% reported daily loose stools or frequent diarrhea
 33% abdominal pain
 20% more than 3 stools a day


No control group, no note of selection criteria
Lightdale, Siegel & Heyman, Clin Perspect Gast, 2001
Prevalence of GI symptoms

Review of medical histories of 285 children with
PDD, 48 non-autistic siblings, and 102 unrelated
controls:
19% of children with PDD had constipation
 19% diarrhea, 7% alternating constipation/diarrhea.
 <10% controls had diarrhea or constipation.

Melmed, Schneider, Fabes, Phillips & Reichelt, J Ped Gastro & Nut, 2000
Prevalence of GI symptoms:
Asking a few questions goes a long way…

How was the survey developed?

How were the patients selected?

Was information obtained from the parents
or from medical records?

What was the working definition of
„diarrhea‟ and „constipation‟ ?
Prevalence of GI symptoms:
A matter of timing

Case-controlled study from UK evaluated the
frequency of GI complaints before ASD was
diagnosed:

Exactly the same percentage (9%) of autistic and
normally developing children had GI symptoms
before the date of diagnosis.
Black, Kaye & Jick, Brit Med J, 2002
Prevalence of GI symptoms in
ASD vs. Controls

Most recent study compared 50 ASD children
with 50 having other developmental delays (DD)
and 50 with normal development:
History of GI symptoms:
 70% ASD
 28% Normal Children
 42% Other DD
Valicenti-McDermott, McVicar, Rapin, et al. J Dev Behav Pediatr, 2006
Prevalence of GI symptoms in
ASD vs. Controls

Abnormal stooling pattern:
 18%
ASD
 4% Normal
 2% DD

Food selectivity:
 60%
ASD
 22% Normal
 36% DD
Prevalence of GI symptoms:
It’s all over!

Most of the data published regarding GI
symptoms is derived from parental recall
or medical records

Places the prevalence of GI symptom
somewhere between…
17%-86%!
(Erickson, Stigler, Corkins, et al, J Autism & Dev Disorders, 2005)
What Triggers GI Symptoms?

Immaturity of the nerves and muscles
responsible for moving food along

Enzyme deficiencies

Malabsorption of nutrients (sugars, fats,
proteins)

Immune-mediated inflammation and damage
Structure of the GI Tract
Structural relations of the ENS
Sources of Intestinal Pain

Overstretching of muscles (gas, spastic
contractions)

Acid-mediated irritation of esophagus (GERD)

Hypersensitive “second brain” (The brain in the
gut or the ENS)

Abnormal blood flow
Consequences of GI Dysfunction

Acute and chronic pain

Interference with consumption of adequate
nutrients
Aversive conditionings
 Food intolerance and protein allergy
 Limited food choices


Abnormal stooling patterns
Diet and Nutrition

Repetitive behaviors and insistence on sameness
in ASD can have negative effect on diet

Limited food choices is frequent complaint of
families with autistic children

A higher incidence of pica has also been noted
by parents of autistic children
Pica (hair ball) in ASD Child
Diet and Nutrition

Nutritional status has been evaluated by
several small controlled and uncontrolled
studies

Overall, it appears their nutrition is adequate

Selectivity does not result in malnutrition
Raiten &Massaro, J Autism and Dev Disorders, 1986;
Shearer, et al, J Autism and Dev Disorders, 1982;
Ahearn et al, J Autism and Dev Disorders, 2001;
Field & Williams, J Ped Child Health, 2003
Food Intolerance and Allergy

Anecdotal reports from parents of children
with ASD

Most report intolerance for
cow‟s milk (casein protein) or
 wheat (gluten protein)

Food Intolerance and Allergy

In 1971 investigators reported a case of a
child with ASD and celiac disease:

Autistic behaviors worsened when exposed to
gluten after a period with gluten-free diet
(Goodwin, Cowen & Goodwin, J Autism Child Schizophrenia, 1971)
Food Intolerance and Allergy

This case inspired a study which measured
trancephalic direct current (TDC) in children
with ASD and GI symptoms:
ASD children showed inhibition of frontal voltage in
response to 1 g PO dose gliadin
 No inhibition with 1 g sugar
 Siblings and normal controls showed no response to
either gliadin or sugar


“Gluten has a direct effect on the central
nervous system”
Goodwin, Cowen & Goodwin, J Autism Child Schizophrenia, 1971
Another source of bias


All the ASD children in study had previous GI
complaints.
Error:


Generalizing differences found in a subset of
children
Do all children with ASD have changes in
response to a gluten challenge?

We do not know
Food Intolerance and Allergy

Long-term prospective study of gluten and milk-free
diet in children with abnormal urinary peptide levels:

15 children in first report, original 15 + 15 new
participants in second report


Behavioral improvement noted by parents and teachers in
both reports
Urine peptide levels normalized by one year
Reichelt, et al. J App Nutr, 1990
Reichelt, et al. Brain Dysfunction, 1991
Food Intolerance and Allergy

Another study with 15 participants:
Improved behavior and communication after 1 and 4
year periods
 Also limited to ASD children with abnormal urinary
peptides; no control group


None of the studies controlled for concomitant
educational or other behavioral interventions
that could have caused improvement
Food Intolerance and Allergy

Single study with control group and blinded
evaluators:

Found significant improvement in social abilities,
cognition and attention after 1 year
Knivsberg, et al, Scan J Edu & Research, 1995
Knivsberg et al, Nutri Neurosci 2002
Food Intolerance and Allergy

Most studies of gluten and/or casein-free diets
have included only children with abnormal urine
peptide levels
Cannot generalize to all children with ASD
 Little evidence that dietary protein intolerance is
more prevalence in ASD population


Small sample size, lack of control group also
make the studies hard to interpret.
The Leaky Gut Hypothesis

Based on the observations that autistic
behaviors improved on dietary protein-free
diets

Theory is that a „leaky‟ intestinal mucosa
allows foods to enter the bloodstream.
The Leaky Gut Hypothesis

Digestion of gluten and
casein releases short chain
peptides which are similar to
endorphins.

These peptides are called
„exorphins‟


Wheat products
gliadomorphins
Milk protein
caseomorphins
Zioudrou, Streaty, Klee. J Biol Chem. 1979
A Close Look At Membranes
www.biology.arizona.edu/
Abnormal Gut Permeability:
Associated Conditions
Symptoms Associated with
A Leaky Gut
The Leaky Gut Hypothesis

Orally administered gluten fragments have been
detected in rat brains

Opiate receptors in brain bind gluten exorphins

Casein exorphins infused into bloodstream of rats
activates the rat brain.
Dohan, Adv Biochem Psychopharmocol, 1980; Hemmings, Proc Roy Coc London Ser B, 1978)
The Leaky Gut Hypothesis

Hypothesis: Gliadomorphins and casomorphins
from partially digested gluten and casein are:
Absorbed through a leaky gut
 Enter the CNS
 Interfere with normal brain function by mimicking
the opioid hormone beta-endorphin.

Lymphoid Nodular Hyperplasia
(LNH)
LNH:
What does it supposed to mean?...
Enhanced activation of lymphoid tissue in the
intestine
Triggered by food or viral antigens
Causing an inflammatory reaction
Resulting in increased permeability and a leaky gut
ASD and the GI Tract:
Lessons Learned
Future Directions and Challenges
Getting It Right:
Commonsense Principles

No two ASD/PDD children are exactly alike

Generalizing is always tempting and an easier path
to take

Human behavior is controlled by a complex
interplay of factors

“Cookbook” recommendations are not going to
benefit all children

Pushing the envelope of conventional medicine is
commendable…up to a point
Expanding Knowledge

Anecdotal reports are the landmines of
medicine

Sound principles of science should not be
sacrificed in the name of ideologies

Progress will only evolve from well gathered
information and data interpretation

Medical providers and families can be a
powerful team…or they can easily become
antagonistic aliens!
Summary

Providing adequate nutrition to children with
ASD remains a major challenge

Working close with a nutritionist or dietitian is
important to avoid preventable deficiencies (or
excesses)

Understanding the neurobiology of autism will
foster development of well founded interventions
And Finally….
 To
understand the proper role of GI
complaints and nutritional issues
impacting on the behavior of ASD
children requires constant reevaluation
and an open (but always critical) mind