Open Journal of Psychiatry, 2013, 3, 56-60 OJPsych
doi:10.4236/ojpsych.2013.32A009 Published Online April 2013 (http://www.scirp.org/journal/ojpsych/)
The varied rate of response to dietary intervention in
Jørgen Klaveness1, Jay Bigam2, Karl L. Reichelt3*
3Department of Pediatric Research, University of Oslo Hospital, Oslo, Norway
Received 4 December 2012; revised 10 January 2013; accepted 19 January 2013
Copyright © 2013 Jørgen Klaveness et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Exorphins from casein and gluten have been found by
HPLC and mass spectroscopy with fragmentation
pattern in quickly frozen urine. Removing the pro-
teins that contain these peptides, by dietary interven-
tion has been tried with behavioral effects. We wanted
to know how fast such changes take place. Method:
Parents and caregivers filled out ATEC scores (Au-
tism treatment evaluation checklist) over time so that
changes in scores could be registered. Results: In this
group of children who all responded to diet the time
required for a positive effect was months rather than
weeks. Conclusion: Short term interventions are pro-
bably a waste of time and money, and at least 3 - 6
months trials seem to be necessary.
Keywords: ATEC-Score; Autism; Casein; Diet; Gluten
Exorphins from casein, glutenin and gliadin have been
reported in urine from autistic children [1,2] using HPLC
and spiking with standards. This has now been firmly es-
tablished by the use of mass spectroscopy and fragmen-
tation mass spectroscopy (MS/MS) , when precautions
are taken to prevent peptidase activity in the urine by
rapid freezing or adding 1% by volume concentrated ace-
tic acid (In prep). Also antibodies especially of the IgA
type have been found in autism against these same pro-
teins [4-7], as well as expected physiological effects in
animal models [8,9] It is therefore reasonable to remove
the source of these peptides using gluten and casein free
There are several open and positive reports on gluten
and casein free diet [2,8-14]. Controlled single blind ei-
ther paired or grouped randomly assigned studies [15,16]
have been published. One study was followed up for 4
years , to counter placebo effects, which are not very
likely after such a long time. However, trials that turned
out negative so far have employed GF/CF diet for only a
few weeks [18,19]. Due to experiments on semi-chronic
schizophrenic patients, where it took 28 weeks to nor-
malize their peptiduria , we suspect that sufficient
time is a major factor when intervening with a GF/CF
diet. This report therefore tries to document the rate of
improvement in a group of children on GF/CF diet. We
did not obtain any negative cases, and the parents would
probably not participate in such cases.
2. PATIENTS AND METHODS
Parents and caregivers who had taken an interest in the
GF/CF diet by joining the GFCFKIDS discussion group
at www.yahoo.com, were encouraged to fill out an online
survey before starting dietary intervention, and at regular
intervals thereafter. The survey was based on the ATEC
(Autism Treatment Evaluation Checklist), developed by
ARI (the Autism Research Institute in San Diego, USA)
and freely available at www.autism.com/atec/index.html.
The ATEC score sheet is considered to have high general
reliability (http:/www.autism.com/arec/report1.html). Pa-
rents or caregivers have used it for several years to report
on the effectiveness of treatment alternatives .
The checklist was filled in by the parents and/or care-
givers themselves. Responses to the survey were gath-
ered in a secure database on line (set up by Bigam) and
analyzed by Klaveness. A reasonably high number re-
ported in first time at the start of dieting, before any ef-
fects were known. These conformed to the general pat-
tern and strengthen the data. All the children had an offi-
cial diagnosis within the autism spectrum (DSMIV and
Published Online April 2013 in SciRes. http://www.scirp.org/journal/ojpsych
J. Klaveness et al. / Open Journal of Psychiatry 3 (2013) 56-60 57
Complience is a problem because gluten and gliadin is
widely used a thickener, to add body to fluids, soups etc.
Also starch sold as gluten free may contain up to 1% by
weight of wheat, which many celiacs tolerate. In short,
we do not know how strict the diets really were. Re-
ported complience is generally very unreliable. Even in a
metabolic ward, strict diet does at times pose problems.
When dietary infringements did take place, the time be-
fore symptoms reappeared, was registered.
Of the original group of 137 children, seven were eli-
minated from the calculations since their age was 1 year
old at the start, and the diagnosis of autism at that age is
uncertain and difficult. The participants all had official
diagnoses of autism covered by ICD-10 registrations
F84.0 and F 84.1.
The age range will be seen from Table 1. Average ±
SD = 4.75 ± 2.49 (n = 130).
Statistics: Instat program was used throughout. When
the collected data did not show normal distribution, non
parametric statistics were used (Mann Whitney U test). If
the distribution was normal, t test was used, but when the
standard deviations differed significantly the Welch cor-
rection for the t-test was employed...
Ethics: The data were volunteered from parents and
collected by the parents. (Parent driven effort) .We also
have ethical committee clearance for the study of psy-
chiatric and neurological disorders (S-06270a) for south
Overall results of collected data can be seen in Table 1.
The difference in ATEC score before and after is highly
significant (unpaired t-test with a p value < 0.001 with
Welch correction for unequal SD, and normal distribu-
tion of data.
The initial score compared to the last score obtained is
statistically very different with a highly significant p
value of 0.001 (n = 130) two tailed. The average de-
crease pr month = 2.9 points. Given the average rate and
comparing this to the average initial score it is obvious
that many months must be necessary for significant im-
provements (Table 1).
In Table 2 we looked at children with ATEC score
less than 50 points before and after intervention, the p
value is <0. 001 and n = 28. For those with ATEC scores
higher than 100 points non-parametric statistics had to be
used. n = 28 and Mann Whitney U = 3.00 and U’ = 781.00
Table 1. Overall changes found.
Item Age at 1st
in ATEC score
mean 4.75 76.1 41.26 10.01 −35.25 41.85
SD 2.49 30.91 21.26 13.38 30.21 26.45
Number 130 130 130 130 130 130
95% Conf Interval lower 4.32 70.79 37.61 7.69 −39.06 37.30
95% Conf Interval upper 15 81.43 44.91 12.33 −40.45 46.39
Passed normality test No Yes Yes No No Yes
Minimum 2.00 8.00 6.00 0.25 +12 −36.00
Maximum 15.00 154.00 103.00 120.00 −147.00 96.00
Table 2. Comparing children with ATEC scores > 100 with scores < 50 (The last four columns).
Item Age at start ATEC at start Months on diet ATEC after diet Age at start ATEC at start Months on diet ATEC after diet
Mean 4.84 121.89 17.61 46.37 5.36 37.89 7.56 25.32
SD 3.16 14.64 24.62 25.92 2.68 10.50 5.80 11.66
N = 28 28 28 28 28 28 28 28
95% CI upper 6.96 127.57 27.15 13.0 6.4 41.97 9.81 29.84
95% CI Lower 3.61 116.21 8.06 4..0 4.32 33.82 5.31 20.8
Minimum 2.00 100.00 1.00 7.00 2.00 8.00 0.5 6.0
Maximum 13.00 154.00 120.00 163.00 15.00 50.00 24.0 47.0
Normality No Yes No No No Yes No Yes
Copyright © 2013 SciRes. OJPsych
J. Klaveness et al. / Open Journal of Psychiatry 3 (2013) 56-60
and p < 0.0001 (two tailed).
The 28 highest scores on ATEC compared to the 28
lowest scores (Table 2).
Comparing the group scoring higher than 100 with the
group scoring at the start less than 50, the rate of de-
crease was again different. The high scoring group had a
monthly decrease of 4.4 units per month, while the low
scoring group had a monthly decrease of 1.6 points per
month. It is therefore obvious that long observation pe-
riod especially in the high functioning children is a ne-
Rate of change per month for the whole group can be
seen in Table 1. The relationship of age to decrease in
rating scale had to be calculated nonparameterically and
the Spearman coefficient r = −0.2482 (corrected for ties)
was very significant and different from zero with a p
value = 0.0059.
The attached figure (Figure 1) compiled by J. Klave-
ness and Bigam show this graphically. The Y axis score
is Rimlands ATEC score and the X axis is the time in-
tervals in months. The parents reported the scores over
the internet. A conference report has been published in
proceedings of that meeting .
The best reacts one third of the autistic children (Fig-
Infringements are extremely difficult to detail. How-
ever, the time elapsed after accidentally or intentionally
breaking the diet, and the appearance of symptoms, can
be seen in Table 3. Hyperactivity, aggression and emo-
tional aloofness seemed to be the cardinal symptoms.
Of the total participants 16 did not answer questions
about dietary breaks etc. Those that answered made up
86.7% of the total. We do not know why there are such
large differences (Table 3).
The respondents are not a random sample of parents or
caregivers. Persons, who think they see changes in their
autistic children, are probably more likely to respond to
the survey and fill out the ATEC score sheet. The figure
cannot tell us anything about those who did not respond
at all, and where the parents may be suspected of not re-
porting in their autistic children’s data. The survey can
therefore not be used to determine the percentage of chil-
dren that will improve on a GF/CF diet, or how much the
average child will improve. It can, however, be used to
make two other predictions, that should be taken into
consideration when future studies are designed.
The first is that if the positive effect of the GF/CF diet
that is reported in this survey is real, it does not seem to
be a very rare phenomenon. It is fully possible that en-
thusiastic parents have over-estimated the effects. The
Table 3. Time elapsed after dietary infringement to noticed
Less than 30 min 14 13%
30 min to 3 hours 34 33%
3 - 12 hours 31 30%
More than 12 hours 25 24%
Total that answered 104 100%
0 5 10 15 20 25
Months on diet
Figure 1. The ATEC score is plotted along the ordinate against months on diet along the abscissa.
Copyright © 2013 SciRes. OJPsych
J. Klaveness et al. / Open Journal of Psychiatry 3 (2013) 56-60 59
effect is so strong however, that it would still be highly
significant if divided by a factor of 10. If the diet is help-
ful for some children, the effect ought therefore to be
common enough to be observable in relatively small
The second is that future studies must allow for the
possibility that the helpful effect of the diet is slow to
materialize, and that it could be seen at very different
rates in different children. This is demonstrated by this
report (Figure 1). These data conform to studies on semi-
chronic schizophrenic patients where it took 28 weeks to
completely normalize the urine pattern and levels 
though behavioral changes were registered earlier. This
prediction would be equally reasonable since a change in
physiology still demands relearning of social skills. Mor-
phological changes in the brain, for example, need con-
siderable time to be ameliorated. Antibodies against food
proteins have very different rates of decrease, and anti-
bodies to gliadin also have effects on cerebellar Purkinje
A dietary effect is a physiological and biochemical
possibility and probability has been documented [23,24].
We do not know why the variation in improvement is so
great. However there may be problems of compliance es-
pecially in the most severely ill group. Furthermore stud-
ies of those with IgA and or IgG antibody increases [4-7]
indicate that a subgroup show increased protein uptake
from the gut, and we suspect that breaks in the diet takes
more time to recover (preliminary observations). Since
there is a correlation of severity of autism and peptide
levels , we may suspect that it takes more time to
correct or ameliorate damaged CNS function. Casomor-
phins cause FOS antigen activation in the CNS 
blocked by naloxone, and opioids interfere with brain
maturation . Thus it seems from the collected data
that the higher the initial score the slower the improve-
ment. This is also what is found by Pennessi .
For the members of the internet survey, who reported in
using the ATEC scores, as seen in Figure 1 and Table 1,
it is clear that some show very slow improvement. 14
days interventions are a waste of time, as it takes time to
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