(6) Because valid dietary testing requires that a food substance be absorbed
through the usual pathway at the usual rate, each food must be tested in the
form in which it is normally consumed.
Based on these principles, Egger, Carter and Soothill developed a standard
diagnostic protocol and used it for two trials. In the first they studied childhood
migraine 45, in the second hyperkinetic syndrome/attention deficit disorder46.
All stages of the work were carried out while the children lived at home. The
response of children to the diagnostic diet and reintroduction of foods were
first determined by open experiment. The initial oligoantigenic diet was followed
for four weeks. It consisted of one meat (chicken, lamb or turkey), one starch
(potatoes or rice), one fruit (apples, pears or bananas), one vegetable from
the brassica family, sunflower oil, a multivitamin, calcium and mineral water.
The results were assessed by parents at home and by doctors during visits to
the clinic. At the conclusion of the open phase of the trials, each child was
considered to be food-intolerant if he remained symptom-free on the oligoantigenic
diet and relapsed with addition of specific foods. To be included in the second
phase, each child had to remain symptom-free by avoiding only those foods to
which he was thought to be reactive. In phase two, the results of the open trial
were tested in a double-blind, placebo-controlled cross-over experiment. One
food to which the child had reacted in the open trial was consumed daily for
a week, in a disguised form, indistinguishable from placebo, in quantities which
the child would normally eat. The base in which the foods were hidden consisted
of rice flour, carrot or banana, caramel, onion and salt or cane sugar and citric
acid. Accuracy of blinding was assessed by the investigators. Only 5% of parents
were able to correctly separate placebo and active challenge food by taste or
smell. Most parents were unable to distinguish one substance from another and
12% guessed incorrectly.
The migraine study involved 40 boys and 48 girls, aged 3 to16, with headaches
occurring at least once a week for six months to eleven years (mean 3.73 years),
associated with two of the following symptoms: pallor, photophobia, dizziness,
nausea, abdominal pain, visual disturbances or focal neurologic deficits. Classical
migraine was the diagnosis in 39, common migraine in 49. During the open trial,
78 children (89%) became symptom-free and 4 children greatly improved. Relapse
with refeeding of specific foods occurred in 90% of the responders. The interval
between exposure and provocation varied from one hour to one week but averaged
two to three days. The number of foods which provoked headache ranged from one
to twenty-four. The frequency with which specific foods provoked headache is
shown in Table 1. Forty children were selected for
the double-blind placebo-controlled crossover study, the results of which are
summarized in Table 2. This trial confirmed 65% of the food reactions identified
in the open trial, using the strictest criteria available for clinical studies.
Considering the total group of 88 children with severe and frequent migraine,
52% were shown to be intolerant of specific foods in this experiment. It is
of note that when children were maintained on a dietary regime devoid of provoking
foods, they were also resistant to other, non-specific triggers which had previously
been thought to activate migraines, such as emotional distress, physical activity
and temperature change.
When the trial of children with attention deficit disorder produced similarly
dramatic results, the findings were challenged by Professor P. J. Graham in
the Department of Psychiatry at Great Ormond Street and Dr. Eric Taylor, Head
of Child Psychology at the Maudsley Hospital. A second study involving hyperkinetic
children was instituted at Great Ormond Street, with the sceptical participation
of Graham and Taylor, and the results of the first study were confirmed47.
Table 2. Results of double-blind placebo-controlled
cross-over trial, 40 children, one food each
(Egger et al, Lancet 1983)
Soothill's group also studied 36 children with refractory epilepsy, half of
whom suffered from migraine and half of whom did not. None of the children Nvith
epilepsy alone responded to diet but 89% of the children with both epilepsy
and migraine showed improvement in both sezures and headaches during the oligoantigenic
diet48. The strong association between reactions to cow's milk and
cow's cheese but not sheep cheese was interpreted by the authors as indicating
an allergic mechanism rather than a biochemical mechanism.
Four other studies performed in children have since found a positive effect
of oligoantigenic diets in migraine, although none attempted to confirm their
findings with a double-blind placebo-controlled followup49-52. In
all studies, long term improvement in frequency mid severity of headache was
achieved by those children who complied with the specific food elimination diet.,
but compliance was often difficult. In some cases, re-exposure after prolonged
avoidance (e.g. two years) was no longer associated with provocation of symptoms,
indicating a loss of sensitivity.
HYPOSENSITIZATION FOR FOOD-INDUCED MIGRAINE
In 1992. Egger, McEwen an J. Stolla completed a double-blind placebo-controlled
trial of immunologic hyposensitization for children with food-induced migraine
at Universitatskinderklinik, Munich (unpublished results). Children with frequent
severe migraine were initially selected by the methods used in the study of
diet and pediatric migraine at Great Ormond Street, ie freedom from headache
during the oligoantigenic diet period and provocation of headache upon exposure
to individual foods. Participation in the hyposensitization trial was offered
to children who fulfilled these criteria but for whom a safe diet was unacceptably
restricted. The active treatment consisted
of an intradermal injection of food antigens mixed with the enzyme beta-glucuronidase,
a technique developed by McEwen called Enzyme-Potentiated Desensitization (EPD)53.
A parallel. study of EPD in food-sensitive hyperkinetic children was conducted
at the same time; the protocols were the same in both trials54.
Forty children took part in the double-blind placebo-controlled trial of hyposensitization
for migraine, each receiving an injection of placebo or active material every
eight to ten weeks for a total of three injections. Provoking foods were
Enzyme-potentiated densensitization for childhood migraine, response to
double-blind, placebo-controlled trial