SCIENTIFIC REFERENCES
Listed below are
links to four key scientific papers regarding effects of food additives and
then relevant scientific papers organised by additive group. The listing is not exhaustive and is not
intended to be repetitive, therefore it does not contain, for instance, the
references already given in the major CSPI review.
If you take the time
to examine the scientific literature, we think you will agree that there has
been enough science to justify changing the basis on which additives are
approved and to ensure monitoring by review after release.
References for the
DVD “Fed Up with Children’s Behaviour”:
KEY
PAPERS
CSPI Review 1999 (PDF)
Swain et al 1985 (PDF)
Clarke et al 1996 (2MB PDF)
McCann et al 2007 (PDF)
EFSA Response from Professor Jim Stevenson (PDF)
REFERENCES
Effects of food additives on
behaviour, health and learning
Abstracts
for most of the articles listed below are available on www.pubmed.com
In the US in 1999, a quarter century review of 23
controlled studies
regarding diet and behaviour concluded that ’17 of the studies found evidence
that some children's behaviour significantly worsens after they consume
artificial colours or certain foods such as wheat or milk’ (Jacobson MF and
Schardt MS 1999) and ‘research with electroencephalography
(EEG) indicates that certain foods trigger physiological changes in sensitive
individuals’ (Uhlig, Merkenschlager et al. 1997). This review can be easily
downloaded from www.cspinet.org/reports/
A review
commissioned by the US National Institutes of Mental Health concluded that
success of dietary management depends on the type of diet used (Arnold 1999).
The
Feingold diet introduced in the US in 1970s is a low chemical elimination diet
excluding food additives and certain foods containing salicylates (Feingold
1968; Feingold 1977; Feingold 1979).
In
Australia, major clinical research concerning the effects of food additives and
salicylates led to the development of low chemical elimination diets excluding
more additives and more salicylates than the Feingold diet as well as biogenic
amines in chocolate and other foods, and natural glutamates. This research was
carried out with 20,000 patients over 20 years by the Royal Prince Alfred
Hospital Allergy Unit and identified nearly 50 problem-causing food additives
(artificial colours, annatto natural colour, sorbates, benzoates, sulphites,
nitrates, propionates, gallates, TBHQ, BHA, BHT and MSG). Unfortunately,
comparatively little has been published in peer reviewed journals although a
wide range of food intolerance symptoms from children’s behaviour to asthma,
eczema, urticaria, irritable bowel symptoms, migraine and depression have been
found to improve on diet. (Loblay RH and Swain AR; Allen DH, Van Nunen S et al.
1984; Swain, Soutter et al. 1985; Clarke L, McQueen J et al. 1996; Hodge, Yan
et al. 1996; Parker and Watkins 2002).
In a trial
of the LALS diet (low additive, low salicylate), nearly 80% of 516 children
improved significantly(Breakey, Hill et al. 1991) and in an open trial of the
Failsafe diet (free of additives, low in salicylates, amines and flavour
enhancers), 100% of 27 children who completed 2-3 weeks of their elimination
diet improved significantly (Dengate and Ruben 2002).
Other diets
that have been used successfully to reveal the effects of food additives and
other foods include the Few Foods or oligoantigenic diet, and the ketogenic
diet. The Few Foods diet, developed in the UK, involves wholefood exclusion and
has been used for children’s behaviour, migraine, epilepsy, enuresis and a wide
range of other food intolerance symptoms although it is considered by many to
be difficult to follow (Bennett CPW, McEwen LM et al. 1998) (Egger, Carter et
al. 1983; Carter, Egger et al. 1985; Egger, Carter et al. 1985; Egger, Carter
et al. 1989; Egger, Carter et al. 1992; Carter, Urbanowicz et al. 1993;
Schulte-Korne, Deimel et al. 1996; Schmidt, Mocks et al. 1997; Pelsser and
Buitelaar 2002).
The
ketogenic (low carbohydrate) diet has been used for eight decades to treat
children’s epilepsy. More recently, behaviour, autism and depression have been
found to improve on this diet (Pulsifer, Gordon et al. 2001; Evangeliou,
Vlachonikolis et al. 2003; Murphy, Likhodii et al. 2004; Murphy, Likhodii et
al. 2005). Since the ketogenic diet excludes many processed foods as well as
many fruits and vegetables, in practice it is a low additive, low salicylate
diet.
Adverse effects by additive
- Colours
Since Speer reported six cases of childhood asthma
related to food dyes in 1958(Speer 1958), artificial colours have been
implicated in a wide range of adverse reactions (Lockey 1959; Chafee and
Settipane 1967; Settipane, Chafee et al. 1976; Freedman 1977; Swanson and
Kinsbourne 1980; Weiss, Williams et al. 1980; Rowe 1988; Boris and Mandel 1994;
Rowe and Rowe 1994; Jacobson MF and Schardt MS 1999; Bateman, Warner et al.
2004). Latest study by McCann et al (2007) in The Lancet.
- Natural colour annatto
E160b
Annatto is the only natural colour to affect consumers
at least as badly as artificial colours (Mikkelsen, Larsen et al. 1978; Clarke
L, McQueen J et al. 1996).
- Sorbates
Sorbates are one of the preservatives identified by
RPAH as implicated in a wide range of food intolerance reactions (Rietschel
1978; Swain AR, Soutter VL et al. 2002). More references at the end of this
file.
- Benzoates
Benzoate preservatives have been implicated in a range
of adverse reactions from children’s behaviour to urticaria to asthma and most
recently with preschoolers’ behaviour (Freedman 1977; Petrus, Bonaz et al.
1996; Bateman, Warner et al. 2004).
- Sulphites
Sulphite preservatives in both foods and medications
have been associated with asthma exacerbation in many countries over many years
(Kochen J 1973; Freedman 1977; Baker, Collett et al. 1981; Towns and Mellis
1984; Steinman and Weinberg 1986; Friedman ME and Easton JG 1987; Timberlake,
Toun et al. 1992; Steinman, Le Roux et al. 1993; Gastaminza, Quirce et al.
1995; Hodge, Yan et al. 1996; American Academy of Pediatrics Committee on Drugs
1997).
However, the effects of food additives on children may
have been underestimated. With the realisation that children eat and drink
significantly more than adults proportional to their body weight and
consequently take in more food additives, the World Health Organisation (WHO)
revised upward their estimate of prevalence of sulphite sensitivity from 4% of
the asthmatic population to 20-30% of asthmatic children (Fifty-first meeting
of the Joint FAO/WHO Expert Committee on Food Additives). The main sulphite
vectors for children are drinks (Steinman and Weinberg 1986; Food Standards
Agency (UK) 2004), sulphited meats such as sausages and illegally sulphited
mince (Scottish Food Co-ordination Committee; Armentia-Alvarez,
Fernandez-Casero et al. 1993), and potato products including hot chips
(Ministry of Agriculture Fisheries and Food 1993), due to the level of
sulphites used in these foods and the frequency of consumption. For those who eat them, dried fruit can be
the greatest sulphite vector especially for young children, with Australian
2-year-olds consuming 70 times more dried fruit than 12-year-olds (on average
21.5 compared to 0.3 grams/per day)(Australia New Zealand Food Authority 1996).
The Food Intolerance Network recently received a report of a two-year-old who
had regularly consumed 20 times the Acceptable Daily Intake for sulphites
through a very high intake of dried apricots and similar tree fruits (Rigg
1997). The anti-nutritional properties of sulphites may be a concern, since
sulphites can destroy thiamine (Vitamin B1) and folates in the body, even when
sourced from supplements (Studdert and Labuc 1991; Quattrucci and Masci 1992;
Steel 1997). Sulphites have been shown to be neurotoxic in the laboratory
(Baud, Laudenbach et al. 2001).
- Nitrates
Nitrates are associated with a wide range of food
intolerance reactions including headaches, irritable bowel symptoms (Loblay RH
and Swain AR) and children’s behaviour (Swain, Soutter et al. 1985).
- Propionates
There is little information in the medical literature
about the effects of low doses of propionates on humans (Joint FAO/WHO Expert
Committee on Food Additives; Swain, Soutter et al. 1985; Dengate and Ruben
2002). However, the association between the very high levels of propionic acid
seen in some metabolic diseases and severe neurological problems is well
recognised in paediatric medicine. In addition, a number of studies on rats
suggest that early administration of propionic acid alters normal development
and induces long-lasting behavioural deficits and that administration of
ascorbic acid can prevent the behaviour alterations provoked by propionic acid
(Brusque, Terracciano et al. 1998; Wyse, Brusque et al. 1998; Brusque, Mello et
al. 1999; Fontella, Pulrolnik et al. 2000; Trindade, Brusque et al. 2002).
While the propionic acid doses used were around four times higher than might be
expected from bread alone in the average diet for a child in Australia, the
effects were marked. It is extraordinary that this widely used substance has
not been tested more extensively in humans, especially as neurological
presentation is not always associated with metabolic crises (Nyhan, Bay et al.
1999).
- Antioxidants: gallates,
TBHQ, BHA, BHT
According to Additive Code Breaker (Hanssen 2002),
additives in this class are known to cause gastric or skin irritation in some
consumers; TBHQ has been associated with ‘nausea, vomiting, ringing in the
ears, suffocating feelings and collapse’; BHA is known to promote forestomach cancers
in rats and BHT is associated with pulmonary inflammation and various tumours.
None are permitted in foods intended specifically for infants and young
children, yet are widely eaten because they are frequently used in commercially
prepared and frozen hot chips. Under the 5% labelling loophole, these additives
are not always listed on the label, for example, in frozen hot chips. Gallates
(310-312), TBHQ (319) and particularly BHA and BHT (320-321) have been
associated with a wide range of food intolerance reactions including asthma and
children’s learning and behaviour problems (Loblay RH and Swain AR; Fisherman
EW and Cohen G 1973; Schoenthaler, Doraz et al. 1986) .
- Flavour enhancers
When reviewing double blind placebo controlled MSG
studies, it is important to ascertain whether the study was industry funded
(Samuels 1999). MSG has been associated with children’s behaviour (Swain,
Soutter et al. 1985), asthma (Allen, Delohery et al. 1987; Moneret-Vautrin
1987; Hodge, Yan et al. 1996) and a range of other food intolerance symptoms
including migraines (Loblay RH and Swain AR).
Food Intolerance Network researchers have been unable
to find any evidence that flavour enhancers 627 (disodium guanylate), 631
(disodium inosinate) and 635 (ribonucleotides – a mixture of 627 and 631) have
ever been tested for adverse effects on either humans or animals before
approval. FSANZ was unable to provide
any scientific evidence. Although we have received numerous reports of itchy skin
rashes, swelling of lips and tongue (angio-edema), and behaviour problems in
children and adults associated with these additives, we have been unable to
report these adverse effects to any authority because there is no post-approval
monitoring in Australia or New Zealand.
- Artificial flavours
In 1968, Feingold reported adverse respiratory, skin,
gastrointestinal, neurological and arthralgia symptoms associated with
synthetic flavours, more recently reported by others (Feingold 1968; Clarke L,
McQueen J et al. 1996).
The
references
Allen DH, Van Nunen S, et al. (1984). "Adverse
reactions to food." Med J Aust 141
(Suppl): 37-42.
Allen, D. H., J. Delohery, et al. (1987).
"Monosodium L-glutamate-induced asthma." J Allergy Clin Immunol
80(4): 530-7.
Ingested chemicals, including aspirin
and sulfites, are becoming increasingly recognized as provokers of acute severe
asthma. In order to investigate the asthma-provoking potential of the widely
used flavor enhancer, monosodium L-glutamate (MSG), we challenged 32 subjects
with asthma, a number of whom gave histories of severe asthma after Chinese
restaurant meals or similarly spiced meals. The subjects received an
additive-free diet for 5 days before challenge and were challenged in hospital,
after an overnight fast, with 500 mg capsules of MSG. They were challenged in a
single-blind, placebo-controlled fashion with increasing doses of MSG from 0.5
gm to 5.0 gm. Thirteen subjects reacted. Seven subjects (group 1) developed
asthma and symptoms of the Chinese restaurant syndrome 1 to 2 hours after
ingestion of MSG. Six subjects (group 2) did not develop symptoms of Chinese
restaurant syndrome, and their asthma developed 6 to 12 hours after ingestion
of MSG. These challenge studies confirm that MSG can provoke asthma. The
reaction to MSG is dose dependent and may be delayed up to 12 hours, making
recognition difficult for both patient and physician.
Because of an increasing number of
reports of adverse reactions associated with pharmaceutical excipients, in 1985
the Committee on Drugs issued a position statement recommending that the Food
and Drug Administration mandate labeling of over-the-counter and prescription
formulations to include a qualitative list of inactive ingredients. However,
labeling of inactive ingredients remains voluntary. Adverse reactions continue
to be reported, although some are no longer considered clinically significant,
and other new reactions have emerged. The original statement, therefore, has
been updated and its information expanded.
Armentia-Alvarez, A., A. Fernandez-Casero, et al.
(1993). "Residual levels of free and total sulphite in fresh and cooked
burgers." Food Addit Contam 10(2):
157-65.
Forty samples of fresh and fried
burgers were analysed. A habitual use and often abuse of sulphites was
detected. In the case of the uncooked samples, 62.5% contained residual levels
of total SO2 above 450 micrograms/g. The frying process was found to lead to a
mean reduction of 36.8 +/- 11.1% in the case of free sulphite and of 40.9 +/-
12.6% for total sulphite. This reduction was independent of the concentration
of sulphite present and did not seem to be related to the type of meat used.
Most burgers cooked in restaurants were found to contain sulphites, sometimes
at elevated levels. The HPLC analytical method for the determination of
sulphite contents in burgers, previously applied to fresh sausages, was
compared with the optimized Monier-Williams method. The results obtained with
both methods in the determination of total SO2 were found to have the same
precision although there were significant differences in the contents of
additive (p < 0.05).
Arnold, L. E. (1999). "Treatment alternatives for
Attention-deficit/hyperactivity disorder." Journal of Attention
Disorders 3(1):30-48.
Baker, G. J., P. Collett, et al. (1981).
"Bronchospasm induced by metabisulphite-containing foods and drugs." Med
J Aust 2(11): 614-7.
Bateman, B., J. O. Warner, et al. (2004). "The
effects of a double blind, placebo controlled, artificial food colourings and
benzoate preservative challenge on hyperactivity in a general population sample
of preschool children." Arch Dis Child 89(6): 506-11.
AIMS: To determine whether
artificial food colourings and a preservative in the diet of 3 year old
children in the general population influence hyperactive behaviour. METHODS: A
sample of 1873 children were screened in their fourth year for the presence of
hyperactivity at baseline (HA), of whom 1246 had skin prick tests to identify
atopy (AT). Children were selected to form the following groups: HA/AT,
not-HA/AT, HA/not-AT, and not-HA/not-AT (n = 277). After baseline assessment,
children were subjected to a diet eliminating artificial colourings and
benzoate preservatives for one week; in the subsequent three week within
subject double blind crossover study they received, in random order, periods of
dietary challenge with a drink containing artificial colourings (20 mg daily)
and sodium benzoate (45 mg daily) (active period), or a placebo mixture,
supplementary to their diet. Behaviour was assessed by a tester blind to
dietary status and by parents' ratings. RESULTS: There were significant
reductions in hyperactive behaviour during the withdrawal phase. Furthermore,
there were significantly greater increases in hyperactive behaviour during the
active than the placebo period based on parental reports. These effects were
not influenced by the presence or absence of hyperactivity, nor by the presence
or absence of atopy. There were no significant differences detected based on
objective testing in the clinic. CONCLUSIONS: There is a general adverse effect
of artificial food colouring and benzoate preservatives on the behaviour of 3
year old children which is detectable by parents but not by a simple clinic
assessment. Subgroups are not made more vulnerable to this effect by their
prior levels of hyperactivity or by atopy.
Baud, O., V. Laudenbach, et al. (2001).
"Neurotoxic effects of fluorinated glucocorticoid preparations on the
developing mouse brain: role of preservatives." Pediatr Res 50(6): 706-11.
Prenatal betamethasone (Celestene)
therapy reduces the incidence of brain damage, whereas prenatal or neonatal
dexamethasone (Soludecadron) increases the risk of brain lesions or neuromotor
deficits. To determine whether this increase is ascribable to the sulfites used
as preservatives in Soludecadron, we investigated the effects of 12 h of
exposure to pure dexamethasone, Soludecadron, pure betamethasone, Celestene,
and sulfites on in vitro and in vivo death of neurons cultured under basal
conditions or with excitotoxic agents (N-methyl-D-aspartate or
(S)-5-bromowillardiine) or hypoxia. Apoptotic features were quantitated using a
fluorescent chromatin stain (Hoechst 33258). Neuronal viability was unaffected
by pure dexamethasone, pure betamethasone, or Celestene. Soludecadron or
sulfites significantly increased neuronal loss. Pure dexamethasone or pure
betamethasone produced a 40-50% decrease in neuronal death induced by
N-methyl-D-aspartate, (S)-5-bromowillardiine, or hypoxia, whereas Soludecadron had
no effect and sulfites significantly increased the neurotoxicity of excitotoxic
agents. In in vivo experiments involving terminal deoxynucleotidyl
transferase-mediated dUTP nick-end labeling after several i.p. injections of
fluorinated glucocorticoids, Soludecadron, but not pure dexamethasone,
significantly increased the number of terminal deoxynucleotidyl
transferase-mediated dUTP nick-end labeling-stained cells in neocortical layers
and thalamus. These experimental findings suggest that injectable dexamethasone
should be used with caution during the perinatal period.
Bennett CPW, McEwen LM, et al. (1998). "The
Shipley Project: treating food allergy to prevent criminal behaviour in
community settings." J Nutr Envir Med 8: 77-83.
Boris, M. and F. S. Mandel (1994). "Foods and
additives are common causes of the attention deficit hyperactive disorder in
children." Ann Allergy 72(5):
462-8.
The attention deficit hyperactive
disorder (ADHD) is a neurophysiologic problem that is detrimental to children
and their parents. Despite previous studies on the role of foods, preservatives
and artificial colorings in ADHD this issue remains controversial. This
investigation evaluated 26 children who meet the criteria for ADHD. Treatment
with a multiple item elimination diet showed 19 children (73%) responded
favorably, P < .001. On open challenge, all 19 children reacted to many
foods, dyes, and/or preservatives. A double-blind placebo controlled food
challenge (DBPCFC) was completed in 16 children. There was a significant
improvement on placebo days compared with challenge days (P = .003). Atopic
children with ADHD had a significantly higher response rate than the nonatopic
group. This study demonstrates a beneficial effect of eliminating reactive
foods and artificial colors in children with ADHD. Dietary factors may play a
significant role in the etiology of the majority of children with ADHD.
Breakey, J., M. Hill, et al. (1991). "A report on
a trial of the low additive, low salicylate diet in the treatment of behaviour
and learning problems in children." Aust J Nutr Diet 48(3): 89-94.
Brusque, A. M., C. F. Mello, et al. (1999).
"Effect of chemically induced propionic acidemia on neurobehavioral
development of rats." Pharmacol Biochem Behav 64(3): 529-34.
High levels of propionic acid (PPA)
comparable to those of human propionic acidemia were achieved in blood (1-5
mmol/l) and brain (1 micromol/g) of rats by administering saline-buffered
propionate (pH 7.4) subcutaneously twice a day from the 6th to the 28th day of
life. PPA doses ranged from 1.44 to 1.92 micromol/g body weight as a function
of animal age. Control rats were treated with saline in the same volumes.
Growth and development of physical landmarks were assessed by monitoring the
following parameters daily: body weight, upper incisor eruption, eye opening,
and hair coat. Development of some reflexes was also monitored, and a specific
subset of motor skills was evaluated at days 14 and 21 of life by the free-fall
righting test and the spontaneous alternation test. Chronic PPA administration
had no effect on body weight, cerebral cortex weight, or cerebellum weight, but
caused slight but significant delays in the day of appearance of hair coat and
eye opening, indicating an effect of PPA on the development of physical
parameters. Free-fall righting was impaired in PPA-treated animals. On the
other hand, PPA administration had no effect on the performance of the animals
in the spontaneous alternation tests. Long-term effects of early PPA
administration were investigated by assessing animal performance in an aversive
task (two-way shuttle avoidance task) and in a nonaversive (open-field task)
behavioral task at 60 days of age. PPA-treated rats did not habituate to the
open field, and presented a lack of retention of the shuttle-avoidance task.
Our results suggest that early postnatal PPA administration to rats alters
normal development and induces long-term behavioral deficits in aversive and
nonaversive tasks.
Brusque, A. M., S. T. Terracciano, et al. (1998).
"Chronic administration of propionic acid reduces ganglioside
N-acetylneuraminic acid concentration in cerebellum of young rats." J
Neurol Sci 158(2): 121-4.
Elevated levels of propionate
comparable to those of human propionic acidaemia were achieved in the blood of
young rats by injecting subcutaneously buffered propionic acid (PPA) twice a
day at 8-h intervals from the 6th to the 28th day of life. A matched group of
animals (controls) was treated with the same volumes of saline. The animals
were weighed and sacrificed by decapitation at 28, 35 or 60 days of age.
Cerebellum and cerebrum were weighed and their protein and ganglioside
N-acetylneuraminic acid (G-NeuAc) contents determined. Body, cerebral and
cerebellar weights were similar in both groups, suggesting that PPA per se
neither alters the appetite of the rats nor causes malnutrition. Brain protein
concentration was also not affected by chronic administration of PPA, in
contrast to G-NeuAc concentration which was significantly reduced in the cerebellum.
Since ganglioside concentration is closely related to the dendritic surface and
indirectly reflects synaptogenesis, our results of an important ganglioside
deficit in the brain of PPA-treated animals may be related to the neurologic
dysfunction characteristic of propionic acidaemic patients.
Carter, C. M., J. Egger, et al. (1985). "A
dietary management of severe childhood migraine." Hum Nutr Appl Nutr
39(4): 294-303.
We describe in detail a dietary
treatment which has been shown to be effective in most children with severe
migraine. Potential adverse nutritional and allergic effects are outlined;
because of the diet should be undertaken only in those ill enough to justify
it. In the first stage very few foods are given, and if the child responds to
this oligoantigenic diet, foods are reintroduced one by one at weekly
intervals. In this way foods causing symptoms are identified and eliminated.
Research is urgently needed to establish simpler empirical diets and diagnostic
tests.
Carter, C. M., M. Urbanowicz, et al. (1993).
"Effects of a few food diet in attention deficit disorder." Arch
Dis Child 69(5): 564-8.
Seventy-eight children, referred to
a diet clinic because of hyperactive behaviour, were placed on a 'few foods'
elimination diet. Fifty nine improved in behaviour during this open trial. For
19 of these children it was possible to disguise foods or additives, or both,
that reliably provoked behavioural problems by mixing them with other tolerated
foods and to test their effect in a placebo controlled double blind challenge
protocol. The results of a crossover trial on these 19 children showed a
significant effect for the provoking foods to worsen ratings of behaviour and
to impair psychological test performance. This study shows that observations of
change in behaviour associated with diet made by parents and other people with
a role in the child's care can be reproduced using double blind methodology and
objective assessments. Clinicians should give weight to the accounts of parents
and consider this treatment in selected children with a suggestive medical
history.
Chafee, F. H. and G. A. Settipane (1967). "Asthma
caused by FD&C approved dyes." J Allergy 40(2): 65-72.
Clarke L, McQueen J, et al. (1996). "The dietary
management of food allergy and food intolerance in children and adults." Australian
Journal of Nutrition and Dietetics 53(3):
89-94.
Dengate, S. and A. Ruben (2002). "Controlled
trial of cumulative behavioural effects of a common bread preservative." J
Paediatr Child Health 38(4):
373-6.
OBJECTIVE: Many anecdotes and one
scientific report describe cumulative behavioural effects of bread preservative
on children. METHODOLOGY: Twenty-seven children, whose behaviour improved
significantly on the Royal Prince Alfred Hospital diet, which excludes food
additives, natural salicylates, amines and glutamates, were challenged with
calcium propionate (preservative code 282) or placebo through daily bread in a
double-blind placebo-controlled crossover trial. RESULTS: Due to four placebo responders,
there was no significant difference by ANOVA of weighted placebo and challenge
Rowe Behaviour Rating Inventory means, but a statistically significant
difference existed in the proportion of children whose behaviours 'worsened'
with challenge (52%), compared to the proportion whose behaviour 'improved'
with challenge (19%), relative to placebo (95% confidence intervals 14-60%).
CONCLUSIONS: Irritability, restlessness, inattention and sleep disturbance in
some children may be caused by a preservative in healthy foods consumed daily.
Minimizing the concentrations added to processed foods would reduce adverse
reactions. Testing for behavioural toxicity should be included in food additive
safety evaluation. Download this paper (6Mb pdf)
Egger, J., C. H. Carter, et al. (1992). "Effect
of diet treatment on enuresis in children with migraine or hyperkinetic
behavior." Clin Pediatr (Phila) 31(5): 302-7.
Twenty-one children with migraine
and/or hyperkinetic behavior disorder which was successfully treated with an
oligoantigenic (few-foods) diet also suffered from nocturnal and/or diurnal
enuresis. On diet, the enuresis stopped in 12 of these children and improved in
an additional four. Identification of provoking foods was by sequential
reintroduction of the foods that were avoided on the oligoantigenic diet. In
eight of the 12 children who recovered on the oligoantigenic diet and in the
four who improved, reintroduction of one or more foods provoked a reproducible
relapse of the enuresis. Nine children were subjected to a placebo-controlled,
double-blind reintroduction of provoking foods. Six children relapsed during
testing with incriminated foods; none reacted to placebo. Enuresis in
food-induced migraine and/or behavior disorder seems to respond, in some
patients, to avoidance of provoking foods.
Egger, J., C. M. Carter, et al. (1985).
"Controlled trial of oligoantigenic treatment in the hyperkinetic
syndrome." Lancet 1(8428):
540-5.
76 selected overactive children were
treated with an oligoantigenic diet, 62 improved, and a normal range of
behaviour was achieved in 21 of these. Other symptoms, such as headaches,
abdominal pain, and fits, also often improved. 28 of the children who improved
completed a double-blind, crossover, placebo-controlled trial in which foods
thought to provoke symptoms were reintroduced. Symptoms returned or were
exacerbated much more often when patients were on active material than on
placebo. 48 foods were incriminated. Artificial colorants and preservatives
were the commonest provoking substances, but no child was sensitive to these
alone.
Egger, J., C. M. Carter, et al. (1989).
"Oligoantigenic diet treatment of children with epilepsy and
migraine." J Pediatr 114(1):
51-8.
We studied the role of
oligoantigenic diets in 63 children with epilepsy; 45 children had epilepsy
with migraine, hyperkinetic behavior, or both, and 18 had epilepsy alone. Of
the 45 children who had epilepsy with recurrent headaches, abdominal symptoms,
or hyperkinetic behavior, 25 ceased to have seizures and 11 had fewer seizures
during diet therapy. Headaches, abdominal pains, and hyperkinetic behavior
ceased in all those whose seizures ceased, and in some of those whose seizures
did not cease. Foods provoking symptoms were identified by systematic
reintroduction of foods, one by one; symptoms recurred with 42 foods, and
seizures recurred with 31; most children reacted to several foods. Of 24
children with generalized epilepsy, 18 recovered or improved (including 4 of 7
with myoclonic seizures and all with petit mal), as did 18 of 21 children with
partial epilepsy. In double-blind, placebo-controlled provocation studies,
symptoms recurred in 15 of 16 children, including seizures in eight; none
recurred when placebo was given. Eighteen other children, who had epilepsy
alone, were similarly treated with an oligoantigenic diet; none improved.
Egger, J., C. M. Carter, et al. (1983). "Is
migraine food allergy? A double-blind controlled trial of oligoantigenic diet
treatment." Lancet 2(8355):
865-9.
93% of 88 children with severe frequent
migraine recovered on oligoantigenic diets; the causative foods were identified
by sequential reintroduction, and the role of the foods provoking migraine was
established by a double-blind controlled trial in 40 of the children. Most
patients responded to several foods. Many foods were involved, suggesting an
allergic rather than an idiosyncratic (metabolic) pathogenesis. Associated
symptoms which improved in addition to headache included abdominal pain,
behaviour disorder, fits, asthma, and eczema. In most of the patients in whom
migraine was provoked by non-specific factors, such as blows to the head,
exercise, and flashing lights, this provocation no longer occurred while they
were on the diet.
Evangeliou, A., I. Vlachonikolis, et al. (2003).
"Application of a ketogenic diet in children with autistic behavior: pilot
study." J Child Neurol 18(2):
113-8.
A pilot prospective follow-up study
of the role of the ketogenic diet was carried out on 30 children, aged between
4 and 10 years, with autistic behavior. The diet was applied for 6 months, with
continuous administration for 4 weeks, interrupted by 2-week diet-free
intervals. Seven patients could not tolerate the diet, whereas five other
patients adhered to the diet for 1 to 2 months and then discontinued it. Of the
remaining group who adhered to the diet, 18 of 30 children (60%), improvement
was recorded in several parameters and in accordance with the Childhood Autism
Rating Scale. Significant improvement (> 12 units of the Childhood Autism Rating
Scale) was recorded in two patients (pre-Scale: 35.00 +/- 1.41[mean +/- SD]),
average improvement (> 8-12 units) in eight patients (pre-Scale: 41.88 +/-
3.14[mean +/- SD]), and minor improvement (2-8 units) in eight patients
(pre-Scale: 45.25 +/- 2.76 [mean +/- SD]). Although these data are very
preliminary, there is some evidence that the ketogenic diet may be used in
autistic behavior as an additional or alternative therapy.
Feingold, B. F. (1968). "Recognition of food
additives as a cause of symptoms of allergy." Ann Allerg 26(309-13).
Feingold, B. F. (1977). "Behavioral disturbances
linked to the ingestion of food additives." Del Med J 49(2): 89-94.
Feingold, B. F. (1979). "Dietary management of
nystagmus." J Neural Transm 45:
107-115.
Fifty-first meeting of the Joint FAO/WHO Expert
Committee on Food Additives "Safety Evaluation of Certain Food Additives:
sulfur dioxide and sulfites; evaluation of national assessments of intake of
benzoates; evaluation of national assessments of intake of butylated
hydroxyanisole (BHA); evaluation of national assessments of intake of butylated
hydroxytoluene. Geneva: World Health Organisation, 1999."
Fisherman EW and Cohen G (1973). "Chemical
intolerance to butylated-hydroxyanisole (BHA) and butylated-hydroxytoluene
(BHT) and vascular response as an indicator and monitor of drug
intolerance." Ann Allerg 31:
126-33.
Fontella, F. U., V. Pulrolnik, et al. (2000).
"Propionic and L-methylmalonic acids induce oxidative stress in brain of
young rats." Neuroreport 11(3):
541-4.
The in vitro effects of propionic
and L-methylmalonic acids on some parameters of oxidative stress were
investigated in the cerebral cortex of 21-day-old rats. Chemiluminescence,
thiobarbituric acid-reactive substances (TBA-RS) and total radical-trapping
antioxidant capacity (TRAP) were measured in brain tissue homogenates in the
presence of propionic or L-methylmalonic acids at concentrations ranging from 1
to 10mM. Both acids significantly increased chemiluminescence and TBA-RS and
decreased TRAP, indicating a simulation of lipid peroxidation and a reduction
of tissue antioxidant potential. Other organic acids tested which accumulate in
some organic acidemias (suberic, sebacic, adipic, 3-methylglutaric and
4-hydroxybutyric acids) did not affect these parameters. This study provides
evidence that free radical generation may participate in the neurological
dysfunction of propionic and methylmalonic acidemias.
Food Standards Agency (UK) (2004). "Survey of
sulphur dioxide in soft drinks." Food Survey Information Sheet May
2004.
Freedman, B. J. (1977). "Asthma induced by
sulphur dioxide, benzoate and tartrazine contained in orange drinks." Clin
Allergy 7(5): 407-15.
Of 272 patients with asthma, thirty
(11%) gave a history of exacerbations occurring after ingestion, solutions of
orange orange drinks. Fourteen of these were given provocation tests by
drinking, on separate occasions of sulphur dioxide, sodium benzoate and
tartrazine, which are present in all orange drinks. Eight reacted to sulphur
dioxide with a fall in FEV1, four to sodium benzoate and one to tartrazine, and
four did not react to any of these agents. Three of the benzoate patients were
also sensitive to sulphur dioxide. The sulphur dioxide sensitive patients were
predominantly young, with extrinsic asthma. The benzoate sensitive patients
were predominantly middle-aged and the proportion with intrinsic asthma was
higher. Prior inhalation of sodium cromoglycate by four patients inhibited the
reaction to these substances. Sulphur dioxide has not previously been reported
to cause exacerbations of asthma when ingested as a food preservative. It is
used as a preservative in a wide range of acidic beverages and foods, and
should be considered as possibly causal in patients suffering from apparently
cryptogenic asthma, and asthma seemingly due to food allergy.
Friedman ME and
Gastaminza, G.,
BACKGROUND: Asthma elicited by
sulfite ingestion has been mainly described in steroid-dependent and in
non-atopic asthmatics. We have studied a group of 18 young extrinsic asthmatics
who presented with asthma attacks immediately after eating pickled onions.
OBJECTIVE: The aim of this study is to ascertain if these asthma attacks are
elicited by sulfites contained in pickled onions and the influence of the dose
and pH of onions. METHODS: The bronchial hyperreactivity of the patients was
assessed by a methacholine challenge test. Oral challenge tests were performed
with sodium metabisulfite (MSB) diluted in lemon juice at pH 4.2 and at pH 3.3
(only in patients who did not react with pH 4.2). Two types of pickled onions,
Spanish and Dutch pickled onions, were used for oral challenge in seven of the
patients. The Monier-Williams method was used to measure the SO2 concentration
in pickled onions. RESULTS: The oral provocation test with MBS, pH 4.2,
elicited a positive response in six patients (33.3%) and the test at pH 3.3 was
positive in three out of 12. No significant difference in PD20 values was found
between these groups. Three of the seven patients challenged with Spanish
pickled onions had a positive reaction but had no reaction with Dutch pickled
onions. The SO2 concentration in Spanish pickled onions varied between 765 and
1182 ppm while in Dutch pickled onions were 200 ppm; this exceeded the permitted
level (100 ppm). SO2 release in Spanish pickled onion samples was nearly 2.5
times higher when the pH of the sample decreased from 4.2 to 3.3. CONCLUSION:
High levels of SO2 in Spanish pickled onions, and their low pH (3.3) would be
the responsible factors of the asthmatic outbreaks after ingestion of Spanish
pickled onions by these patients.
Hanssen, M. (2002). Additive Code Breaker.
Melbourne, Lothian.
Hodge, L., K. Y. Yan, et al. (1996). "Assessment
of food chemical intolerance in adult asthmatic subjects." Thorax 51(8): 805-9.
BACKGROUND: Identification of food
chemical intolerance in asthmatic subjects can be reliably assessed by changes
in the forced expiratory volume in one second (FEV1) in response to double
blind, placebo controlled challenges on a strict elimination diet. However,
this method is cumbersome and time consuming. A study was undertaken to
determine whether changes in bronchial responsiveness to histamine following
food chemical challenge without an elimination diet might be a faster, more
convenient method. METHODS: Eleven adult asthmatic subjects were challenged
twice with metabisulphite, aspirin, monosodium glutamate, artificial food
colours, sodium nitrite/ nitrate, 0.5% citric acid solution (placebo), and sucrose
(placebo) on separate days. During the first set of challenges subjects
consumed a normal diet. Bronchial responsiveness to histamine was assessed 90
minutes after each challenge. A greater than twofold increase in bronchial
responsiveness was considered positive. For one month prior to and during the
second set of challenges subjects followed a strict elimination diet and FEV1
was monitored during and for two hours after each challenge. A fall in FEV1 of
20% or more was considered positive. RESULTS: Of the 77 food chemical
challenges performed on an unmodified diet, 20 were positive (six placebo
responses). In two subjects it was not possible to perform a histamine test
after one of the chemical challenges because of poor spirometric function. Of
the 77 food chemical challenges performed on an elimination diet, 11 were
positive (no placebo responses). Excluding the two challenges in which there
were no corresponding histamine tests, only on two occasions did the positive
responses in both methods coincide, giving the unmodified diet method a
sensitivity of 22%. CONCLUSIONS: Strict dietary elimination and measurement of
FEV1 after double blind food chemical challenge remains the most reliable
method for the detection of food chemical intolerance in asthmatic subjects.
Jacobson MF and Schardt MS (1999). Diet, ADHD and
behaviour: a quarter-century review.
Joint FAO/WHO Expert Committee on Food Additives
"Propionic acid and its calcium, potassium and sodium salts. World Health
Organization,
Kochen J (1973). "Sulfur dioxide, a respiratory
tract irritant, even if ingested." Pediatrics 52(1): 145-6.
Loblay RH and
Lockey, S. D. (1959). "Allergic reactions due to
F D and C Yellow No. 5, tartrazine, an aniline dye used as a coloring and
identifying agent in various steroids." Ann Allergy 17: 719-21.
McCann, D., Barrett, A., Cooper, A., Crumpler, D.,
Dalen, L., Grimshaw, K., Kitchin, E., Lok, K., Porteous, L., Prince, E.,
Sonuga-Barke, E., Warner, J., and Stevenson, J. (2007)
“Food additives and hyperactive behaviour in
3-year-old and 8/9-year-old children in the community: a randomised,
double-blinded, placebo-controlled trial” The Lancet
Summary:
Background We undertook a randomised, double-blinded, placebo-controlled,
crossover trial to test whether intake of artifi cial food colour and additives
(AFCA) aff ected childhood behaviour. Methods 153 3-year-old and 144
8/9-year-old children were included in the study. The challenge drink contained
sodium benzoate and one of two AFCA mixes (A or B) or a placebo mix. The main
outcome measure was a global hyperactivity aggregate (GHA), based on aggregated
z-scores of observed behaviours and ratings by teachers and parents, plus, for
8/9-year-old children, a computerised test of attention. This clinical trial is
registered with Current Controlled Trials (registration number ISRCTN74481308).
Analysis was per protocol. Findings 16 3-year-old children and 14 8/9-year-old
children did not complete the study, for reasons unrelated to childhood
behaviour. Mix A had a signifi cantly adverse eff ect compared with placebo in
GHA for all 3-year-old children (eff ect size 0⋅20
[95% CI 0⋅01–0⋅39],
p=0⋅044) but not mix B versus placebo. This result
persisted when analysis was restricted to 3-year-old children who consumed more
than 85% of juice and had no missing data (0⋅32
[0⋅05–0⋅60], p=0⋅02).
8/9-year-old children showed a signifi cantly adverse eff ect when given mix A
(0⋅12 [0⋅02–0⋅23],
p=0⋅023) or mix B (0⋅17
[0⋅07–0⋅28], p=0⋅001)
when analysis was restricted to those children consuming at least 85% of drinks
with no missing data. Interpretation Artifi cial colours or a sodium benzoate
preservative (or both) in the diet result in increased hyperactivity in
3-year-old and 8/9-year-old children in the general population.
Mikkelsen, H., J. Larsen, et al. (1978).
"Hypersensitivity reactions to food colours with special reference to the
natural colour annatto extract (butter colour)." Arch Toxicol Suppl(1):
141-3.
It is well known that synthetic food
colours especially some azo dyes can provoke hypersensitivity reactions such as
urticaria, angioneurotic oedema, and astma (Michaelsson and Juhlin, 1973,
Granholt and Thune, 1975). Natural food colours are scarcely investigated with
respect to potential allergic properties. Annatto extract, a commonly used food
colour in edible fats e.g. butter, has been tested in patients. Among 61
consecutive patients suffereing from chornic urticaria and/or angioneurotic
oedema 56 patients were orally provoked by annatto extract during elimination
diet. Challenge was performed with a dose equivalent to the amount used in 25
grammes of butter. Twentysix per cent of the patients reacted to this colour 4
hours (SD: 2,6) after intake. Similar challenges with synthetic dyes showed the
following results: Tartrazine 11%, Sunset Yellow FCF 17%, Food Red 17 16%,
Amaranth 9%, Ponceau 4 R 15%, Erythrosine 12% and Brillant Blue FCF 14%. The
present study indicates that natural food colours may induce hypersensitivity
reactions as frequent as synthetic dyes.
Ministry of Agriculture Fisheries and Food (1993).
Dietary intake of food additives in the
Moneret-Vautrin, D. A. (1987). "Monosodium
glutamate-induced asthma: study of the potential risk of 30 asthmatics and
review of the literature." Allerg Immunol (
Monosodium glutamate is a physiological
nutrient, and food additive used as a taste enhancer. Several cases of
intolerance to MSG in patients with asthma and with a Chinese Restaurant
Syndrome have been published. A high dose of 2.5 g was tested in 6 healthy
controls and 30 asthmatics (7: allergic asthma; 15: intrinsic asthma with
intolerance to aspirin; 8: intrinsic asthma with aspirin intolerance,
intolerance to alcohol or to food additives). Two patients presented with a
mild bronchospasm, occurring 6 to 10 hours after the ingestion. Different
mechanisms are discussed. A cholinergic mechanism might be incriminated, either
due to stimulation of the synthesis of acetylcholine, or due to a vagal reflex
elicited by a reflux esophagitis. However, a high vagal hyperreactivity seems
to be needed for the occurrence of asthma. It is concluded that a very small
subset of patients with intrinsic asthma might present with an intolerance to
MSG if high doses are consumed.
Murphy, P.,
BACKGROUND: The ketogenic diet is
used to treat epilepsy refractory to anticonvulsant medication. Individuals
with epilepsy often have behavioral problems and deficits in attention and
cognitive functioning. The ketogenic diet has been found to effect improvements
in these domains. It has also been suggested that the ketogenic diet may act as
a mood stabilizer. METHODS: The present research used the Porsolt test, an
animal model of depression, to determine whether the ketogenic diet has
antidepressant properties. Porsolt test scores of rats on the ketogenic diet
were compared with those of rats on a control diet. RESULTS: The rats on the
ketogenic diet spent less time immobile, suggesting that rats on the ketogenic
diet, like rats treated with antidepressants, are less likely to exhibit
"behavioral despair." CONCLUSIONS: It is concluded that the ketogenic
diet may have antidepressant properties.
Murphy, P., S. S. Likhodii, et al. (2005).
"Effect of the ketogenic diet on the activity level of Wistar rats." Pediatr
Res 57(3): 353-7.
Children, adolescents, and adults
with epilepsy often also show symptoms associated with
attention-deficit/hyperactivity disorder (ADHD). The ketogenic diet, which is
administered to children with epilepsy refractory to drug therapy, seems to
improve behavior in individuals with symptoms of ADHD. The basis for this
improvement is unknown, although it seems to be unrelated to seizure control.
The present research was designed to investigate the effect of two ketogenic
diets on the behavior of normal adult male rats. Two experiments were
conducted. In experiment 1, 36 subjects were placed on one of three diets: a
control diet, a 6.3:1 ketogenic diet, and a 4:1 ketogenic diet. In experiment
2, 20 subjects were placed either on a control diet or on a 4:1 ketogenic diet.
The activity level of each subject was measured using an open field test. Time
spent immobile, grooming, and in exploratory behavior was measured for 600 s.
Subjects were tested once before initiation of the diets and once while on the
diets. No significant group differences were found in activity level before
initiation of the diets. After initiation of the diets, subjects in both
ketogenic groups showed a significantly lower activity level than the rats on
the control diet. The ketogenic diet decreases activity level in an animal
model. This behavioral change may relate to the improved behavior seen when
children with symptoms of ADHD are placed on the diet.
Nyhan, W. L., C. Bay, et al. (1999). "Neurologic
nonmetabolic presentation of propionic acidemia." Arch Neurol 56(9): 1143-7.
BACKGROUND: Patients with propionic
acidemia usually present in the neonatal period with life-threatening
ketoacidosis, often complicated by hyperammonemia. It was thought that the
neurologic abnormalities seen in this disease were exclusively the consequences
of these acute crises. Experience with 2 patients with propionic acidemia
indicates that this disease may present first with prominent neurologic disease
without the life-threatening episodes of ketoacidosis that usually serve as the
alerting signals for a diagnosis of an organic acidemia. OBJECTIVE: To examine
the clinical and metabolic aspects of 2 patients with a phenotype that suggested
disease of the basal ganglia. DESIGN: Examination of patterns of organic acids
of the urine and enzyme assay for propionyl-CoA carboxylase in fibroblasts and
lymphocytes. SETTING: Referral population to a biochemical genetics laboratory.
PATIENTS: Two patients whose prominent features were hypotonia followed by
spastic quadriparesis and choreoathetosis. Both had seizures. One patient was
mildly mentally retarded but grew normally physically. The other had profound
mental retardation and failure to thrive; he also self-mutilated his lower lip.
Self-injurious behavior has not been reported in this disease. MAIN OUTCOME
MEASURES: Clinical description, blood ammonia levels, organic acid levels in
the urine, and enzyme activity. RESULTS: Excretion of metabolites, including
methylcitrate, was typical. Residual activity of propionyl-CoA carboxylase
approximated 5% of the control in each patient. CONCLUSIONS: Propionic acidemia
can present as a pure neurologic disease without acute episodes of massive
ketoacidosis. Hyperammonemia may occur after infancy in some patients,
presenting as Reye syndrome.
Parker, G. and T. Watkins (2002).
"Treatment-resistant depression: when antidepressant drug intolerance may
indicate food intolerance." Aust N Z J Psychiatry 36(2): 263-5.
Pelsser, L. M. and J. K. Buitelaar (2002).
"[Favourable effect of a standard elimination diet on the behavior of
young children with attention deficit hyperactivity disorder (ADHD): a pilot
study]." Ned Tijdschr Geneeskd 146(52):
2543-7.
OBJECTIVE: To determine whether a
standard elimination diet can decrease the ADHD-symptoms in a heterogeneous
group of young children with ADHD. DESIGN: Open, descriptive. METHOD: 40
children, 36 boys and 4 girls, aged 3-7 (average 4.8 years), who met the DSM-IV-criteria
for ADHD, followed their usual diet for two weeks and thereafter for two weeks
an elimination diet, based on the few foods diet (rice, turkey, pear and
lettuce). The behaviour of the child was evaluated at study entry, after the
baseline period and at the end of the diet. Parents completed the 10-item
Conners list, the ADHD Rating Scale and a physical complaints list. The
teachers completed the 10-item Conners list and the ADHD Rating Scale twice, at
the beginning and at the end of the diet. RESULTS: According to the
parent-ratings, 25 children (62%) showed an improvement in behaviour of at
least 50% on both the Conners list and the ADHD Rating Scale at the end of the
elimination diet. Nine children (23%) withdrew from the study because the
parents were unable to stick to the diet or because the child fell ill. Among
the 15 children with both parent and teacher ratings, 10 responded both at home
and in school. CONCLUSION: In young children with ADHD an elimination diet can
lead to a statistically significant decrease in symptoms.
Petrus, M., S. Bonaz, et al. (1996). "Asthmé et
intolérance aux benzoates." Arch Pédiatr 3(10): 984-7.
BACKGROUND: Some foods and drug
additives may induce allergic reactions. CASE REPORT: A girl with a family
history of asthma in both parents developed asthma in her early life. She was
successfully given continuous bronchodilator therapy until the age of 7 years.
At that time, she had more frequent and severe exacerbations (8 within 10
months) despite reinforced continuous treatment. Oral challenges with bisulfite
and sodium benzoate, both additives abundantly ingested by the patient,
revealed heightened sensitivity to administration of sodium benzoate. Avoidance
of this additive was followed by complete and prolonged disappearance of
episodes of coughing and wheezing. CONCLUSION: Adverse reactions to benzoate in
this patient required avoidance of some drugs, some of those classically
prescribed under the form of syrups in asthma.
Pulsifer, M. B., J. M. Gordon, et al. (2001).
"Effects of ketogenic diet on development and behavior: preliminary report
of a prospective study." Dev Med Child Neurol 43(5): 301-6.
The ketogenic diet is increasingly
used for the management of difficult-to-control seizures in children. Here, we
describe the first prospective study of the effects of the diet on development,
behavior, and parenting stress. Participants were 65 children (36 males, 29
females) with intractable seizures, ages 18 months to 14 years 6 months,
enrolled in a prospective study at the Johns Hopkins Hospital, Baltimore, MD,
USA, to study the diet's efficacy. Children were assessed before diet
initiation and at 1-year follow-up. At follow-up, 52% (34 of 65) children
remained on the diet. Mean seizure frequency decreased from 25 per day before
diet initiation to less than two per day 1 year later. At follow-up, mean
developmental quotient showed statistically significant improvement
(p<0.05), with significant behavioral improvements in attention and social
functioning. Parental stress was essentially unchanged. No baseline factor
examined predicted diet adherence, and the primary reason for diet
discontinuation was insufficient seizure control. These preliminary results
support prior anecdotal reports of the beneficial effects of the diet on
cognition and behavior.
Quattrucci, E. and V. Masci (1992). "Nutritional
aspects of food preservatives." Food Addit Contam 9(5): 515-25.
Despite the benefits attributed to
food preservatives, some concern still remains regarding their safety and possible
influence on nutrients. Surprisingly, there is quite a lack of scientific
knowledge in this field. In order to describe a few examples, the effects of
the extensively used sulphite on thiamine, folates, pyridoxal and other
nutrients have been reported. Among its antibrowning effects, inhibition of
ascorbic acid browning is also considered. As far as sorbic acid is concerned,
notwithstanding its easy reaction with protein, probably the acid environment
of the stomach determines the breakdown of the sorbic-protein adducts.
Detoxication of nitrite by tocopherol and ascorbic acid leads, in the last
case, to dehydroascorbic acid and its oxidative products with loss of vitamin
activity. Any oxidizing substance destroys ascorbic acid, vitamin E and free vitamin
A. Phosphates are largely used with different aims, including preservation, in
food processing. Their antimicrobial activity is due to both a direct effect
and an interaction with other antimicrobials. Sequestering capacity of
phosphates and its nutritional implications are discussed. Also mechanisms of
action of organic acids are reported, focusing on sorbic acid effects on single
amino acids and proteins. Finally, the little information available about the
potential impact of food preservatives on nutritional functions is presented.
Rietschel, R. L. (1978). "Contact urticaria from
synthetic cassia oil and sorbic acid limited to the face." Contact
Dermatitis 4(6): 347-9.
A patient with contact urticaria
with skin and respiratory symptoms was found to be sensitive to both sorbic
acid and synthetic oil of cassia. The contact urticaria was only elicitable on
intact skin of the face by open testing. The source of the patient's
contactants was her shampoo and toothpaste.
Rigg, A. (1997). "Sulphur dioxide in sausages and
other products. ACT Health services. Food survey reports,
www.health.act.gov."
Rowe, K. S. (1988). "Synthetic food colourings
and 'hyperactivity': a double-blind crossover study." Aust Paediatr J
24(2): 143-7.
Of 220 children referred for
suspected 'hyperactivity', 55 were subjected to a 6 week trial of the Feingold
diet. Forty (72.7%) demonstrated improved behaviour and 26 (47.3%) remained
improved following liberalization of the diet over a period of 3-6 months. The
parents of 14 children claimed that a particular cluster of behaviours was
associated with the ingestion of foods containing synthetic colourings. A
double-blind crossover study, employing a single-subject repeated measures
design was conducted, using eight of these children. Subjects were maintained
on a diet free from synthetic additives and were challenged daily for 18 weeks
with either placebo (during lead-in and washout periods) or 50 mg of either
tartrazine or carmoisine, each for 2 separate weeks. Two significant reactors
were identified whose behavioural pattern featured extreme irritability,
restlessness and sleep disturbance. One of the reactors did not have
inattention as a feature. The findings raise the issue of whether the strict
criteria for inclusion in studies concerned with 'hyperactivity' based on
'attention deficit disorder' may miss children who indicate behavioural changes
associated with the ingestion of food colourings. Moreover, for further
studies, the need to construct a behavioural rating instrument specifically
validated for dye challenge is suggested.
Rowe, K. S. and K. J. Rowe (1994). "Synthetic
food coloring and behavior: a dose response effect in a double-blind,
placebo-controlled, repeated-measures study." J Pediatr 125(5 Pt 1): 691-8.
OBJECTIVE: To establish whether
there is an association between the ingestion of synthetic food colorings and
behavioral change in children referred for assessment of
"hyperactivity." PARTICIPANTS: From approximately 800 children
referred to the Royal Children's Hospital (Melbourne) for assessment of
suspected hyperactivity, 200 were included in a 6-week open trial of a diet
free of synthetic food coloring. The parents of 150 children reported
behavioral improvement with the diet, and deterioration on the introduction of
foods noted to contain synthetic coloring. A 30-item behavioral rating
inventory was devised from an examination of the clinical histories of 50
suspected reactors. Thirty-four other children (23 suspected reactors, 11
uncertain reactors) and 20 control subjects, aged 2 to 14 years, were studied.
DESIGN: A 21-day, double-blind, placebo-controlled, repeated-measures study
used each child as his or her own control. Placebo, or one of six dose levels
of tartrazine (1, 2, 5, 10, 20, 50 mg), was administered randomly each morning,
and behavioral ratings were recorded by parents at the end of each 24 hours.
RESULTS: The study identified 24 children as clear reactors (19 of 23
"suspected reactors," 3 of 11 "uncertain reactors," and 2
of 20 "control subjects"). They were irritable and restless and had
sleep disturbance. Significant reactions were observed at all six dose levels.
A dose response effect was obtained. With a dose increase greater than 10 mg,
the duration of effect was prolonged. CONCLUSION: Behavioral changes in
irritability, restlessness, and sleep disturbance are associated with the
ingestion of tartrazine in some children. A dose response effect was observed.
Samuels, A. (1999). "The toxicity/safety of
processed free glutamic acid (MSG): a study in suppression of
information." Account Res 6(4):
259-310.
Schmidt, M. H., P. Mocks, et al. (1997). "Does
oligoantigenic diet influence hyperactive/conduct-disordered children--a
controlled trial." Eur Child Adolesc Psychiatry 6(2): 88-95.
A crossover 'placebo'-controlled,
double-blind design was used to examine the effectiveness of an oligoantigenic
diet in 49 children with hyperactive/disruptive behavior disorder. Effects of
diet were compared with those yielded by stimulant medication
(methylphenidate). The study was conducted in an inpatient unit at the
Department of Child and Adolescent Psychiatry, Central Institute of Mental
Health, Mannheim. Change in behavior was measured in standardized situations by
trained raters, including behavior assessment when testing with CPT and PAT,
during a free play situation, and at school. Twelve children (24%) showed
significant behavioral improvement in two behavior ratings during diet relative
to control diet conditions. Methylphenidate used in 36 children yielded more
responders (44%) than diet. The amount of positive changes in behavior in those
who received both treatments was about the same. Although only effective in a
minority of children, dietary treatment cannot be neglected as a possible
access to treating hyperactive/disruptive children and merits further
investigation.
Schoenthaler, S., W. Doraz, et al. (1986). " The
impact of a low food additive and sucrose diet on academic performance in 803
Schulte-Korne, G., W. Deimel, et al. (1996).
"[Effect of an oligo-antigen diet on the behavior of hyperkinetic
children]." Z Kinder Jugendpsychiatr Psychother 24(3): 176-83.
The influence of an oligoantigenic
diet on different dimensions of the behavior of 21 children diagnosed as having
attention-deficit hyperactivity disorder (ADHD) was examined. Treatment effects
were assessed with three subjective measures (two questionnaires and an
interview) and three objective measures (two attention tests and actometer).
The study was divided into three phases: baseline, diet and provocation, each
lasting three weeks. A crossover design was used. A significant effect was
found for the subjective measures, but not for the objective measures. The
results are discussed in terms of possible types of effects, e. g. rater
effects and environmental effects. It may be that the oligoantigenic diet
influences only certain dimensions of hyperactivity.
Scottish Food Co-ordination Committee "A survey
of the level of sulphur dioxide preservatives in minced meat in Scotland
1988-1992."
Settipane, G. A., F. H. Chafee, et al. (1976).
"Significance of tartrazine sensitivity in chronic urticaria of unknown
etiology." J Allergy Clin Immunol 57(6): 541-6.
Of 38 patients with chronic
urticaria of unknown etiology who were evaluated for food and drug additive
sensitivity, 53% (20/38) had urticaria for 1 yr or more. Total eosinophil
counts were not elevated in most patients, and the frequency of atopy was found
to be similar to that in a general population. Of these 38 patients, 10 (26%)
had a personal history of aspirin intolerance, but elimination of aspirin did
not relieve the urticaria. In a double-blind crossover challenge with 0.22 mg
of tartrazine and a control, tartrazine sensitivity was found in 8% (3/38) of
patients with chronic urticaria and 20% (2/10) of patients with aspirin
intolerance.
Speer, S. (1958). Management of Childhood Asthma.
Springfield, Charles C Thomas.
Steel, R. J. (1997). "Thiamine deficiency in a
cat associated with the preservation of 'pet meat' with sulphur dioxide." Aust
Vet J 75(10): 719-21.
A cat with allergic dermatitis was
fed a diet of fresh meat and a multi-vitamin supplement for 38 days to exclude
food allergy as a cause of its dermatopathy. The cat died as a result of acute
thiamine deficiency, which was caused by inactivation of thiamine by the
preservative, sulphur dioxide. The continuing undeclared usage of sulphites in
the Australian pet food industry is discussed.
Steinman, H. A., M. Le Roux, et al. (1993).
"Sulphur dioxide sensitivity in South African asthmatic children." S
Afr Med J 83(6): 387-90.
Sulphur dioxide (SO2) is a well-known
precipitant of asthmatic attacks. Many foodstuffs are preserved with SO2 and
other sulphites. In this study 37 asthmatic children attending the Allergy
Clinic at the Red Cross Children's Hospital were challenged with SO2 in apple
juice in a dose similar to that commonly ingested in soft-drinks containing
this preservative. The responses of these children were compared with the
responses of 22 asthmatics challenged with apple juice alone. Sixteen out of 37
children (43.2%) challenged with SO2 reacted with a fall in forced expiratory
volume in 1 second (FEV1) of more than 10% compared with none of the 22 control
asthmatic children challenged with apple juice alone (P = 0.0016). Girls were
found to be more sensitive than boys. A 20% or more fall in FEV1 occurred in 8
(21.6%) of the children challenged with SO2 compared with none in the control
group (P = 0.039). There was an individual variability in the responses of
sensitive individuals to the SO2 challenge. Reactions occurred in spite of
maintenance medication and occurred within 5-30 minutes of challenge. Since
sulphite sensitivity is common in asthmatic children, ingestion of sulphites
should be avoided.
Steinman, H. A. and E. G. Weinberg (1986). "The
effects of soft-drink preservatives on asthmatic children."
Sulphites, used extensively as
preservatives in foods and soft drinks, are known to precipitate asthma attacks
in 5-10% of susceptible children. Among children attending the Allergy Clinic
at the Red Cross War Memorial Children's Hospital, Cape Town, many were found
to be sensitive to sulphites. The basis of asthma therapy is modification of
the environment and avoidance of precipitating factors. Medical personnel
counselling parents of asthmatic children should be aware of this factor. A
list of soft drinks containing sulphites and other preservatives is included.
Studdert, V. P. and R. H. Labuc (1991). "Thiamin
deficiency in cats and dogs associated with feeding meat preserved with sulphur
dioxide." Aust Vet J 68(2):
54-7.
Thiamin deficiency was diagnosed in
cats and dogs being fed fresh minced meat, which contained sulphur dioxide as a
preservative and less than 0.5 mg/kg thiamin. Thiamin in the meat and in added
dietary ingredients, including a supplementary vitamin mixture, was destroyed
by the sulphur dioxide.
Swain, A., V. Soutter, et al. (1985).
"Salicylates, oligoantigenic diets, and behaviour." Lancet 2(8445): 41-2.
Swain AR, Soutter VL, et al. (2002). Friendly Food.
Swanson, J. M. and M. Kinsbourne (1980). "Food
dyes impair performance of hyperactive children on a laboratory learning
test." Science 207(4438):
1485-7.
Forty children were given a diet
free of artificial food dyes and other additives for 5 days. Twenty of the
children had been classified as hyperactive by scores on the Conners Rating
Scale and were reported to have favorable responses to stimulant medication. A
diagnosis of hyperactivity had been rejected in the other 20 children. Oral
challenges with large doses (100 or 150 milligrams) of a blend of FD & C
approved food dyes or placebo were administered on days 4 and 5 of the
experiment. The performance of the hyperactive children on paired-associate
learning tests on the day they received the dye blend was impaired relative to
their performance after they received the placebo, but the performance of the
nonhyperactive group was not affected by the challenge with the food dye blend.
Timberlake, C. M., A. K. Toun, et al. (1992).
"Precipitation of asthma attacks in Melanesian adults by sodium
metabisulphite." P N G Med J 35(3):
186-90.
Seven Melanesian asthmatic patients
were challenged with substances that have been shown to precipitate asthma
attacks in asthma patients in developed countries. Patients were challenged in
a double-blind fashion using placebo and active substances. The active
substances were tartrazine, sodium metabisulphite, aspirin and betel nut. All 7
patients were challenged with tartrazine and sodium metabisulphite; 5 were
challenged with aspirin also, but only 2 were challenged with betel nut. Asthma
attacks were precipitated by sodium metabisulphite in 3 patients. No other
substances precipitated asthma. As sodium metabisulphite is a common food
additive, these results suggest that processed foods introduced into developing
countries may have an important role in precipitating asthma attacks in
susceptible persons.
Towns, S. J. and C. M. Mellis (1984). "Role of
acetyl salicylic acid and sodium metabisulfite in chronic childhood
asthma." Pediatrics 73(5):
631-7.
The role of a commonly ingested food
additive, the preservative sodium metabisulfite (MBS), and aspirin (ASA), in
chronic asthma has been studied in 29 children. After 1 week on a strict
elimination diet, all 29 children were challenged, in a single-blind fashion,
in the pulmonary function laboratory on three consecutive days with placebo,
MBS (capsule form and solution), and ASA. Children with a positive response to
MBS were prescribed a diet that excluded foods containing MBS. Patients with a
positive response to ASA were prescribed a diet excluding medications
containing aspirin and natural salicylates. After 3 months on these restricted
diets, the children were reassessed to determine whether there had been any
therapeutic response. There was a 66% (19/29) incidence of positive challenge
(greater than 20% decrease in forced expiratory volume in one second) with MBS
and a 21% (6/29) incidence of positive challenge with ASA. None of the children
reacted to MBS in capsule form (maximum dose = 100 mg), but 19/29 reacted to
MBS in solution with 30 mL of 0.5% citric acid. After 3 months on the
restricted diet, four of 19 children on the MBS-free diet and one of six on the
salicylate-free diet had objective signs of improvement, namely, reduction in
asthma medications and/or improvement in lung function. Unfortunately,
compliance with the restrictive diet during this 3-month period was poor,
particularly with the ASA-sensitive children.(ABSTRACT TRUNCATED AT 250 WORDS)
Trindade, V. M., A. M. Brusque, et al. (2002).
"Ganglioside alterations in the central nervous system of rats chronically
injected with methylmalonic and propionic acids." Metab Brain Dis 17(2): 93-102.
Neurological dysfunction and
structural cerebral abnormalities are commonly found in patients with
methylmalonic and propionic acidemia. However, the mechanisms underlying the
neuropathology of these disorders are poorly understood. We have previously
demonstrated that methylmalonic and propionic acids induce a significant
reduction of ganglioside N-acetylneuraminic acid in the brain of rats subjected
to chronic administration of these metabolites. In the present study, we
investigated the in vivo effects of chronic administration of methylmalonic
(MMA) and propionic (PA) acids (from the 6th to the 28th day of life) on the
distribution and composition of gangliosides in the cerebellum and cerebral
cortex of rats. Control rats were treated with the same volumes of saline. It
was first verified that MMA and PA treatment did not modify body, cerebellum,
or cortical weight, nor the ganglioside concentration in the cerebral cortex of
the animals. In contrast, a significant reduction in total ganglioside content
in the cerebellum of approximately 20-30% and 50% of control levels occurred in
rats injected with MMA and PA, respectively. Moreover, chronic MMA and PA
administration did not interfere with the ganglioside pattern in the cerebral
cortex, whereas the distribution of individual gangliosides was altered in the
cerebellum of MMA- and PA-treated animals. Rats injected with MMA demonstrated
a marked decrease in GM1 and GD3, whereas chronic PA treatment provoked a
significant reduction of all ganglioside species, with the exception of an
increase in GM2. Since gangliosides are closely related to the dendritic
surface and other neural membranes, indirectly reflecting synaptogenesis, these
ganglioside abnormalities may be associated with the brain damage found in
methylmalonic and propionic acidemias.
Uhlig, T., A. Merkenschlager, et al. (1997).
"Topographic mapping of brain electrical activity in children with
food-induced attention deficit hyperkinetic disorder." Eur J Pediatr
156(7): 557-61.
In 15 children suffering from food
induced attention deficit hyperkinetic syndrome, topographic EEG mapping of
brain electrical activity was carried out following avoidance and ingestion of
previously identified provoking foods. A crossover design was used and
recordings were interpreted independently by two investigators, one of whom was
blind to the order of testing. During consumption of provoking foods there was
a significant increase in betal activity in the frontotemporal areas of the
brain. This investigation is the first one to show an association between brain
electrical activity and intake of provoking foods in children with food-induced
attention deficit hyperactivity disorder. CONCLUSIONS: These data support the
hypothesis that in a subgroup of children with attention deficit hyperactivity
disorder certain foods may not only influence clinical symptoms but may also
alter brain electrical activity.
Weiss, B., J. H. Williams, et al. (1980).
"Behavioral responses to artificial food colors." Science 207(4438): 1487-9.
Twenty-two young children, maintained
on a diet that excluded certain foods, were challenged intermittently with a
blend of seven artificial colors in a double-blind trial. Parents' observations
provided the criteria of response. One child that responded mildly to the
challenge and one that responded dramatically were detected. The latter, a
34-month-old female, showed a significant increase in aversive behaviors. These
results further confirm previous controlled studies.
Wyse, A. T., A. M. Brusque, et al. (1998).
"Inhibition of Na+,K+-ATPase from rat brain cortex by propionic
acid." Neuroreport 9(8):
1719-21.
Buffered propionic acid was injected
Sorbates:
* Fisher AA. Cutaneous reactions to sorbic acid and
potassium sorbate. Cutis. 1980 Apr;25(4):350, 352, 423. [there are many more
like this without abstracts]
* J Am Acad Dermatol. 1986 Feb;14(2 Pt 1):234-41.
Sorbic acid-induced erythema and edema.Soschin D, Leyden JJ. Sorbic acid
concentrations as low as 0.1% produced transient erythema with edema and flare
after open or closed application to human skin. Multiple areas of the body were
tested. Reactions were most intense on the face but also could be produced on
the back, forearm, and deltoid areas. Sorbic acid-induced erythema, edema, and
flare were not associated with mast cell degranulation. Pretreatment of skin with
topical steroids to induce vasoconstriction resulted in a diminished response
to sorbic acid. Aspirin blocked the erythematous component, suggesting that
prostaglandins are important mediators. Systemic steroids, antihistamines, and
hydroxyzine failed to influence sorbic acid-induced erythema and edema.
* J Am Optom Assoc. 1986 Mar;57(3):188-9. Sorbic acid
revisited.Josephson JE, Caffery B. 135 patients wearing hydrogel lenses were
prescribed a care system of sorbic acid preserved surfactant, Lensept and
Bausch and Lomb Sensitive Eyes Saline (sorbic acid 0.10%). Fifteen percent of
patients presented with an adverse ocular response to their care system. The
etiology was attributed to sorbic acid as the use of nonpreserved saline
eliminated the signs and symptoms. This incidence of reaction is similar to
those published earlier on thimerosal preserved saline and sorbic acid
preserved saline.
* Laryngoscope. 2000 Feb;110(2 Pt 1):312-7. Long-term
use of preservatives on rat nasal respiratory mucosa: effects of benzalkonium
chloride and potassium sorbate.Cho JH, Kwun YS, Jang HS, Kang JM, Won YS, Yoon
HR. Department of Otolaryngology-Head and Neck Surgery, College of Medicine,
The Catholic University of Korea, Seoul.
OBJECTIVES: The preservatives benzalkonium chloride
(BZC) and potassium sorbate (PS) are widely used, not only for nasal drops, but
also for eyedrops and cosmetics. However, there have been many case reports
that consider lesions such as dermatitis or conjunctivitis to be the results of
irritation induced by BZC or PS. METHODS: We evaluated the histological changes
after the long-term administration of BZC or PS on rat nasal respiratory
mucosa. Forty rats were used for the BZC group and 40 rats for PS group.
Animals in each group were divided into four subgroups The first subgroup
received a low-concentration preservative solution that was commonly used for
nasal sprays. The second subgroup received a high-concentration preservative
solution that was reported to induce dermatitis in humans. The third and fourth
subgroups received a steroid mixed preservative solution of low and high
concentrations, respectively. The control group was administrated normal
saline. After each group received 1, 2, and 4 weeks of topical administration,
the symptomatic and histological changes on H&E stain were observed.
RESULTS: Sneezing and nasal rubbing with forelegs were observed in almost all
subgroups by the seventh day of treatment. The preservatives induced nasal
lesions, including intraepithelial glandular formation, inflammatory cell
infiltration, vascular hyperplasia, and edematous change. The symptomatic and
histological changes were pronounced with the prolonged duration of
administration. Similar results were observed in the steroid mixed-solution
groups. In the PS steroid mixed-solution group, however, symptoms and nasal
lesions were reduced with the prolonged duration of administration. CONCLUSION:
It is our finding that even a low-concentration solution of preservative can
lead to nasal lesion. Hence there is a strong need to develop both a
preservative that can be safely and widely used and a nasal spray without
preservatives.
* Contact Dermatitis. 2005 Sep;53(3):176-7.
Occupational contact dermatitis from potassium sorbate in milk transformation
plant.Le Coz CJ, Abensour M. Unité de Dermato-Allergologie, Dermatologie
Professionnelle et Photobiologie, Clinique Dermatologique des Hôpitaux
Universitaires de Strasbourg, Strasbourg, France. christophe.lecoz@wanadoo.fr
* Contact Dermatitis. 1978 Dec;4(6):347-9. Contact
urticaria from synthetic cassia oil and sorbic acid limited to the face.
Rietschel RL. A patient with contact urticaria with skin and respiratory
symptoms was found to be sensitive to both sorbic acid and synthetic oil of
cassia. The contact urticaria was only elicitable on intact skin of the face by
open testing. The source of the patient's contactants was her shampoo and
toothpaste.
* Contact Dermatitis. 1982 Jan;8(1):1-6. Perioral
contact urticaria from sorbic acid and benzoic acid in a salad dressing.Clemmensen
O, Hjorth N. Contact urticaria was observed in a kindergarten in 18 of 20
children following the intake and accidental perioral application of a
mayonnaise salad cream. In healthy adult controls, stinging tests and closed 20
minute patch test with the salad dressing were positive in 9 out of 12 and 4
out of 10 cases respectively. Twenty minute patch tests with the different
components of the salad dressing were positive only so sorbic acid (SA) and
benzoic acid (BA). Urticaria was provoked by inunction of the salad dressing
periorally in two healthy boys. Serial 20 minute closed patch testing with
varying concentrations of SA in 91 patients and BA in 41 patients gave almost
identical results: positive reactions in two thirds of the patients with the
highest concentrations.
Date of last update January 2009
