ABSTRACT: Context-Certain
compounds found by gas chromatography-mass Spectrometry in urine samples
of children with autism might
be produced by yeast in the gastrointestinal tract. Therefore, treatment
with antifungal drugs might reduce clinical symptoms of autism.
Objective-To determine if symptoms of autism and chemical compounds in
urine samples of children with autism decreased after antifungal treatment.
Design-A number of urinary organic acids first characterized as elevated
in 2 brothers with autism were tested in urine samples of 23 children
with autism (21 boys and 2 girls) before and after treatment with the
antifungal drug nystatin.
Patients-Twenty-one boys and 2 girls with a mean age of 7.1 years with
diagnosis of autism. Twenty boys and 17 girls with a mean age of 7.7 years,
who were normal children of hospital employees, served as controls for
urine testing.
Interventions-Children with abnormal baseline organic acid results received
oral nystatin suspension at a dose of 100000 units 4 times a day for 10
days. If abnormalities were still present after 10 days, an additional
60 days of antifungal treatment were offered. An additional urine organic
acid test was then performed.
Results-The mean childhood autism rating scale, an indicator of the severity
of autism, improved significantly after antifungal treatment based on
the paired t test (P=.037). Seven of the urine markers were significantly
higher in autistic males than in the control males. The concentration
of several of the urine markers of autistic children decreased after antifungal
treatment.
Conclusions-Antifungal drug therapy may be a promising therapeutic method
for the treatment of autism. Organic acid testing appears to be a useful
diagnostic test to indicate an overgrowth of yeast and bacteria in the
gastrointestinal tract of children with autism and to predict the response
of antifungal drug therapy, and may indicate relapse following the cessation
of antifungal drug therapy. (Clinical Practice of Alternative Medicine
1(1): 15-26, 2000)
stimulated by the referral of 2 brothers with autism, on
whom numerous urinary organic acid profiles were per-
formed over a 2-year period.' These tests revealed a con-
sistent excretion of a number of compounds of possible
microbial origin identified as the carbohydrate arabinose,
analogs of normal Krebs cycle intermediates including 3-
oxoglutaric acid, tartaric (3-hydroxymalic) acid, citra-
malic (methylmalic) acid, and a new tentatively identi-
fied analog of citric acid (carboxycitric acid) not previ-
ously reported in the medical literature.' High concentra-
tions of a compound identified as a phenylcarboxylic acid
were also found; the mass spectrum of this compound did
not correspond to the mass spectrum of any known com-
pound in gas chromatography/mass spectrometry (GC/MS)
libraries.' Hydroxymethylfurancarboxylic acid, furandi-
carboxylic acid, furancarbonylglycine, and 3-(3-hydrox-
yphenyl)-3-hydroxypropionic acid were also found in
urine samples of the 2 autistic brothers. Elevations of the
latter 4 compounds were not previously reported by Shaw
et al'; each of these compounds was positively identified by
comparison to mass spectra in GC/MS libraries, published
oratories. The structures of the above compounds and
closely related compounds are shown in Figure 1.
These findings of chemicals of possible microbial ori-
gin are of particular interest because of a report that autis-
tic children have a greater incidence of ear infections than
peers of the same age; that lower functioning autistic
children had an earlier onset of ear infections than their
higher functioning autistic peers; and that the ears of chil-
dren with autism were anatomically positioned different-
ly than those of normal children, perhaps leading to
greater ear infection susceptibility.2 The use of oral antibi-
otics is the most prevalent therapy for ear infections in the
US and many other nations. Furthermore, yeast and path-
ogenic bacterial overgrowth of the gastrointestinal (GI)
tract commonly follows the use of oral antibiotics.3 '5
Therefore, compounds produced by antibiotic-resistant
bacteria, yeast, or fungi in the GI tract and then absorbed
into the bloodstream might be involved in the etiology of
autism just as abnormal elevations of phenylalanine and
its metabolites cause the disease phenylketonuria (PKU).
The production of microbial compounds due to microbial
