||Last Updated: Aug 4, 2009 - 2:24:45 PM
WE WERE just settling down for our flight when the captain's voice came
over the PA system. "Ladies and gentlemen, I am sorry to disturb you,
but we have a passenger on board who has a severe nut allergy. Could I
ask you please not to open or eat any food that contains nuts for the
duration of the flight? I am sorry for any inconvenience. We hope you
enjoy your flight."
It was no coincidence that at the time I was on my way to a conference
on food allergy in Vienna, Austria. Hazel Gowland, food adviser to the
The Anaphylaxis Campaign in the UK, was travelling for the same reason,
and it was for her benefit that the captain made his request.
While such an announcement may not be an everyday occurrence, most of
us are familiar with the idea that peanuts can trigger a
life-threatening allergic reaction. But peanuts aren't the biggest
concern in every country. Passengers from Greece, where peanut allergy
is rather rare, might have been more concerned about the melon in the
fruit salad. A passenger from the south of Italy might have pushed the
in-flight apple juice to one side for fear that it might trigger a skin
rash and stomach pains, a reaction that would puzzle a compatriot from
Why such regional differences exist is just one of the many mysteries
surrounding food allergies. Why, for example, do some migrants from
east Asia develop an allergy to jackfruit when they move to northern
Europe? Then there's the question of what constitutes an allergic
reaction in the first place, whether there's ever a "safe" level of an
allergen, and what should be done to label foods to warn people that an
allergen may be present.
The Vienna conference, which took place in May this year, is part of an
effort to get to the bottom of some of these mysteries. An
international task force dubbed EuroPrevall, headed by biochemist Clare
Mills at the Institute of Food Research in Norwich, UK, is measuring
the prevalence and variation in food allergies across Europe and also
in Ghana, Australia, India and China. The results are now rolling in,
highlighting some of the regional anomalies and even shedding light on
the basis of some of the food allergies.
One obstacle in interpreting previous research has been that different
teams used different methods to test for food allergies, and much of
the available data comes from subjects self-reporting their allergies
without any medical tests. In 2007, a meta-analysis of more than 900
studies, led by toxicologist Charlotte Madsen of the Technical
University of Denmark in Søborg and Roberto Rona, an epidemiologist at
King's College London, concluded that proven food allergy affects
somewhere between 1 person in 100, and 1 in 20. For the self-reported
surveys, results varied even more widely, from fewer than 1 in 30 to
more than 1 in 3 (The Journal of Allergy and Clinical Immunology, vol
120, p 638). That variation may have been due in part to differences
between the methods used by different studies, but as studies were
conducted in many different situations across Europe it could also have
due to regional differences in the prevalence of food allergies.
The EuroPrevall researchers set out to study the regional differences
more closely. If links could be found between the prevalence of
particular allergies and local eating habits and environmental
conditions, this might shed light on what gives rise to some food
allergies in the first place.
At the Vienna meeting, researchers discussed the patterns emerging from
their research. For adults and children over 3 years old, hazelnuts and
apples turn out to be the most common triggers of food allergies in
Europeans reporting to clinics - not peanut allergy, as many people
might expect. These reports from clinics have also thrown up a
surprising new player: sunflower-seed allergy. Although something of a
rarity, it may become more common as sunflower seeds are increasingly
appearing in food. To make matters worse, the allergen involved seems
to be particularly potent. "The proportion of severe reactions is
higher than for peanut," says Montserrat Fernández Rivas, an
allergologist from the San Carlos Clinical Hospital in Madrid, Spain.
Perhaps most striking are the regional differences. "Peach and melon
allergy is particularly common in the Mediterranean - in Spain and
Greece," says Fernández Rivas. Reports from clinics suggest that
Iceland is a hotspot for fish allergy and Switzerland has a higher rate
of celeriac allergy than elsewhere.
These regional variations are likely to be due in part to differences
in eating habits, causing people to be exposed to different allergens.
But that alone cannot explain a pronounced north-south divide in the
type of apple allergy people experience. In northern Europe, people
react to the uncooked flesh of apples, whereas in the south it's the
skin that sets them off, whether it's cooked or not. What could be the
cause of this strange invisible dividing line that skims across
south-west France, cuts through Italy close to Florence, and continues
eastwards through the middle of the Black Sea?
Significantly, this line marks the southern limit of the birch tree, a
plant whose pollen is one of the causes of hay fever in northern
Europe. Clues for this link lie in the different proteins found in
various parts of the fruit: the flesh harbours an allergenic protein
called Mal d 1, while the skin is relatively rich in Mal d 3. The
structure and composition of the Mal d 1 protein strongly resembles the
allergenic protein Bet v 1 found in birch pollen. This means that
people who suffer from birch pollen allergy may be primed to overreact
to Mal d 1 - explaining the prevalence of the allergy to apple flesh in
A similar cross-reaction explains the allergy to apple skin found in
southern Europe. In this case, a prior sensitisation to the Pru p 3
protein in peaches, which bears a strong similarity to Mal d 3, seems
to be the culprit. What's more, Mal d 1 breaks down when heated while
Mal d 3 is heat resistant, which neatly explains why northern Europeans
are fine with cooked apples and pasteurised apple juice but
apple-allergic people in the south cannot cope with these fruit in any
form (see map).
Other reported cross-reactions include a link between house-dust-mite
faeces and shrimp allergy, and another between mugwort pollen and an
allergy to carrots, celery and sunflower seeds. There are likely to be
many others, since many allergens seem to share similarities in their
amino acid sequences that might confuse the immune system.
In fact, between 2005 and 2008 Mills and Heimo Breiteneder, a molecular
allergist at the Medical University of Vienna, and their colleagues
completed a series of studies showing the majority of allergens
originating in fruit and vegetables belong to just four of the 10,000
or so recognised families of proteins, and most of the animal-food
allergens to just three families (The Journal of Allergy and Clinical
Immunology, vol 115, p 163 and vol 121, p 847). Bet v 1, for example,
causes cross-reactions with several other members of its protein
family, and as a result people who have birch pollen allergy stand a
good chance of being allergic to apple, celery, plums and several other
This also explains why some migrants from east Asia to northern Europe
suddenly develop an allergic reaction to jackfruit once they have come
into contact with birch pollen. The allergen in jackfruit does not on
its own sensitize the immune system, but once birch pollen has done the
job, the immune system may react to jackfruit too.
Get involved: Tell us your food allergies
These numerous examples of cross-reactions raise another question: why
does Bet v 1 cause an allergy to the Mal d 1 protein but not the other
way around? Researchers believe it's because Bet v 1 enters the body
via the lungs, so it is not broken down by digestion and can reach the
bloodstream intact, where it activates the immune system. Mal d 1, on
the other hand, is broken down during digestion, so it loses its
capacity to prime the immune system. Once the immune system has been
stimulated by the Bet v 1, it may then become sensitive to similar
looking proteins like Mal d 1 - sensitive enough to trigger a reaction
when it comes into contact with the mouth.
Cross-reactions are not the end of the story, however. Other
environmental factors probably play a role: for instance, cigarette
smoking has recently been shown to aggravate allergies. Genetics are
also thought to be important.
If the pattern of the various allergies across the world is a confusing
story, the practices and regulations designed to protect vulnerable
people from potentially fatal allergic reactions are no clearer. Even
the apparently sensible precaution of printing warnings on food labels
is fraught with complications.
A study in 2005 by allergy researcher Steve Taylor of the University of
Nebraska in Lincoln showed that of the 200 food products that he
examined labelled "May contain nuts", only 10 per cent actually did,
and many of those contained only minute amounts (Journal of Allergy and
Clinical Immunology, vol 120, p 171). Nor does the absence of a warning
label guarantee that the food is safe for people who are allergic. In
Europe, for example, an examination of various types of chocolate
showed that half of those without a warning contained hazelnut (Food
Additives and Contaminants, vol 24, p 1334).
In a recent study, only 10 per cent of foods labelled with 'May contain
nuts' actually did
Part of the problem with labelling goes back to the practicalities of
industrial production. Since the same machinery may be used to make
many different products, it is often difficult to guarantee that the
foods will not become cross-contaminated. As a result companies play it
safe and put warning labels on products that may not in fact contain
high enough levels of allergen to have any effect. This raises the
danger that people will start ignoring the message, putting themselves
at risk of consuming food that does contain a dangerous level of the
allergen. "The 'may contain' labelling is becoming so devalued," says
Sue Hattersley of the UK's Food Standards Agency.
So what should companies be doing to inform consumers? Individuals are
so diverse that it's hard to define a level that guarantees no one will
have an adverse reaction, so instead they must just try to minimise the
risk. "What level of risk can be considered tolerable?" asks René
Crevel, a toxicologist at food manufacturer Unilever's labs in
Colworth, UK. The threshold level at which some kind of reaction can
occur may be less than a thousandth of a potentially fatal dose, so
where do you draw the line?
There is progress, at least for people who are allergic to gluten in
wheat. A new European guideline, which comes into force in 2012, means
that foods containing less than 20 parts per million of gluten can be
labelled 'gluten free'. And many allergists reckon there is now enough
data to start giving serious thought to a specific limit below which
foods can be deemed free of peanut allergens.
Even if the food industry does find a better way to label foods, there
will always be the danger of an accidental exposure to high
concentrations of an allergen. "The main risk is from caterers and
restaurants," says Frans Timmermans of the Netherlands Anaphylaxis
Network. "In the UK most deaths are from curries, weddings, parties,
and not knowing what satay and pesto are," says Gowland, my fellow
passenger on the Vienna flight. "Otherwise, it's often down to not
knowing in the first place that they were allergic."
Some people with a severe food allergy are afraid of even a passing
exposure to an allergen, and this has led some to ask for bans of
potentially dangerous foods in public areas such as schools, to reduce
the risk. Some American high schools, for example, are now banning food
products containing peanuts. In one instance, a school bus was
evacuated and then taken out of service to be decontaminated after a
single peanut escaped from its wrapper. "People in favour of various
bans feel it is just easier to have the food eliminated," says Scott
Sicherer, an allergist at the Mount Sinai School of Medicine in New
Others believe that such measures are out of proportion to the real
danger. Writing in the medical journal BMJ last year, medical
sociologist Nicholas Christakis of Harvard Medical School in Boston
observed that efforts by US schools to prevent students being exposed
to peanuts "represent a gross overreaction to the magnitude of the
threat" (BMJ, vol 337, p 1384). According to Timmermans, parents can
sometimes become so worried about the possible threat to their children
that they cause the children themselves psychological distress.
But what of my flight: was the captain right to ask that no nut
products be consumed on the plane? Timmermans says he is surprised by
the request. His daughter, who is also highly allergic to peanuts,
would be able to sit next to someone eating a peanut dish without
experiencing a reaction, he says, though he admits it would make her
Others are more sympathetic. "I have no problem with pilots making this
announcement," says Taylor. "Nut-allergic passengers can be at risk of
rather scary and uncomfortable reactions from the food of others." It
may seem extreme and inconvenient to fellow passengers but, for Gowland
and her fellow sufferers, the risk is too real to ignore.
Get involved: Tell us your food allergies
How to test for allergies
There are three main methods to test for an allergic reaction:
The skin-prick test: A drop of a solution containing the suspected
allergen is placed on the skin of the subject's forearm, which is then
pricked with a needle. A positive reaction is indicated by itchiness
and a reddening of the skin, or a white swelling.
Blood tests: High levels of allergen-specific antibodies in the blood
indicate an allergy.
Food challenges: Research teams from the EuroPrevall task force are
using a chocolate dessert which can be spiked with an allergen without
a noticeable change in flavour. Each team feeds its subjects increasing
amounts of the dessert at 20-minute intervals, containing allergen
doses ranging from 3 micrograms to 3 grams, until the subject reacts -
for example with a skin rash or swelling. The placebo, identical except
that it contains no allergen, is administered in the same way but on a
What is a food allergy?
Our immune system is meant to protect the body from invading parasites,
bacteria and other foreign substances. Sometimes it overreacts to what
should be a perfectly innocuous food or other substance, causing an
Most people who suffer from a food allergy have immunoglobulin E (IgE)
antibodies that are primed to respond to the allergen involved. In the
presence of the allergen, the IgE antibodies activate mast cells around
blood vessels and in the skin. Histamine released by these cells causes
small blood vessels to dilate, giving rise to the well-known symptoms
such as itching and swelling in the mouth, skin rash, itchy or runny
nose or diarrhoea.
The most dangerous result is anaphylaxis, a whole-body reaction which
can end in a catastrophic fall in blood pressure combined with
breathing difficulties, sometimes resulting in death.
Not all food allergies are mediated by IgE. Perhaps the best known of
this other group is coeliac disease, an allergy to proteins present in
the gluten of wheat, barley and rye. It is caused by an overreaction by
the immune system's T-cells, which damages the lining of the gut.
Sufferers endure diarrhoea, loss of weight and potentially malnutrition.
True food allergies should not be confused with "food intolerances".
Rather than being caused by an overenthusiastic immune system, milk
intolerance, for example, results from a lack of the enzyme the body
needs to break down lactose, the main sugar in milk. Symptoms include
nausea, abdominal pain and, once again, diarrhoea.
While the symptoms of an allergic reaction to foods can be treated,
there is no accepted therapy to prevent the reactions in the first
There may be hope, for those with a peanut allergy at least. A team
from Addenbrooke's Hospital in Cambridge, UK, recently exposed four
children to a daily dose of peanut flour, starting with just 5
milligrams. This year they reported that by the end of the six-month
trial the children were able to tolerate 10 whole peanuts a day
(Allergy, vol 64, p 1218).
If you or a friend or family member have a peanut allergy, please do
not try this at home.
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