Transcript Part 4: Update on Peanut Allergy, Update on Probiotics in the

Peanut Allergy
Update
Janice M. Joneja Ph.D., RD
2006
Peanuts and Anaphylaxis
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Peanuts are one of the most frequently cited causes of
life-threatening anaphylactic reactions in Western
countries
Peanuts, tree nuts, fish, and shellfish are the foods
most frequently identified as causes of anaphylaxis,
and of these, peanuts seem to prompt the greatest
concern
The incidence of peanut allergy was reported to have
doubled in American children less than 5 years of age
in the five years between 1998 and 2003
_____________
Sampson 2003
2
Incidence of Peanut Allergy
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One study reported that allergy to peanuts:
Accounts for 28% of food allergies in children
(72% of food allergies were to foods other than
peanut)
 In peanut-allergic individuals, reactivity to peanut
develops:
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Before one year of age in 46%
 Before 15 years of age in 93%
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The true incidence of peanut allergy in any
population is largely a matter of speculation,
based on questionnaires and occasional
epidemiological studies
_____________________
Moneret-Vautrin et al 1998
3
Fatalities Due to Food Allergy
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2001 report of 32 fatal cases of anaphylactic reactions
to foods in USA
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Peanut was responsible for 14 (67%) and possible cause in
a further 6 (55%)
Tree nuts the cause in 7 (33%) and possible cause in a
further 3 (27%)
Two cases thought to be due to milk and fish (1 [19%]
each)
Most of the victims were adolescents or young adults
All but one were known to have food allergy before the
fatal event
All but one were known to have asthma
Peanuts and tree nuts accounted for more than 90% of the
fatalities
_____________
Bock et al 2001
4
Peanut Allergy in Populations
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Allergy to peanut is far less prevalent in China, despite the
high rate of peanut consumption
Allergy to all foods reported to affect only 3.4% – 5.0% of the
residents of a select population in China
Fish, shrimp, crab, and seaweed were the major allergens
In 29 children aged 2 to 12 years with diagnosed food allergy
in the Chinese population studied, none had signs of clinical
allergy to peanut
Peanut allergy in China is virtually non-existent, whereas in
the USA about 3 million people report being allergic to
peanuts
The Chinese-American population living in the USA had an
incidence of peanut allergy similar to that of the general US
population
_____________
Beyer et al 2001
5
Peanut Allergy in the UK
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8 children under 16 years of age died from
food allergy in ten years 1990 -2000 (= 1 death
per 16 million children each year)
Milk caused 4 deaths
No child younger than 13 years died from
eating peanuts
One child died from an overdose of adrenaline
used to treat a mild food reaction
_____________
Pumphrey 2000
6
Incidence of Peanut Allergy in Canadian
Children
The prevalence of peanut allergy in children
kindergarten through Grade 3 in randomly selected
schools in Montreal:
 Between 1.5% and 1.76% of 4339 responding
families
 Study based on:
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Questionnaire
Skin-prick tests
Measurement of peanut-specific IgE in blood
Oral peanut challenge
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Kagan et al 2003
7
Processing of Peanuts and Allergenicity
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Roasting of peanuts has been demonstrated to
increase their allergenicity, compared to the same
variety of peanut when processed by other methods
Roasting gives improved flavour and taste, and is the
method used for processing peanuts and peanut butter
in North America
Roasted peanut is more likely to trigger a severe
anaphylactic reaction than the fried or boiled peanut,
which is the form in which people in countries such
as China consume the food
______________
Maleki et al 2000
8
Effect of Temperature on Allergenicity
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Much higher temperature reached in roasting in comparison to
frying or boiling
Peanut proteins are not degraded at high temperatures, and
retain their potential to trigger an allergic reaction even after
cooking (Class 1 allergens)
Excessively high temperature changes the protein to a more
insoluble form
Increase in insolubility means that less of the protein will
move into solution in the digestive tract, and will be more
protected from digestive enzymes and destruction by gastric
acid than a more soluble form would be
Results in undegraded peanut protein being available as a
continuous source of major allergens in the digestive tract long
after the same protein in a more soluble form would have been
removed from the system
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Kopper et al 2005
9
Allergenicity due to Immune Interaction
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Method of heating the proteins significantly
affects the interaction between the allergen and
the antibodies produced by the allergic
individual
Increases the likelihood of the individual
developing symptoms, and probably the
severity of the symptoms in an allergic
reaction
_________________
Mondoulet et al 2005
10
Factors in Allergenicity of Peanut
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Other factors that might affect the allergenicity
of peanut proteins include:
 Type and variety of the peanut (of which
there are about 14,000)
 Conditions under which the peanut has been
grown
 Degree of maturation of the peanuts
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Chung et al 2003
11
Peanut and Fat Content
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High fat content reduces reactivity to peanut
Study of six people with a known peanut
allergy; reactivity of four of the subjects
significantly increased when the peanut was
included in a lower-fat meal compared to when
the food had a high fat content
Subjects reacted to a dose equivalent to 23
times less peanut with the low-fat recipe
compared to the higher fat meal
_________________
Grimshaw et al 2003
12
Legume Allergy
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There is no evidence to support the thinking that
peanut-allergic individuals should avoid all legumes
In laboratory experiments, cross-reactivity between
peanut and soy is quite frequent, but in clinical trials,
the cross-reactivity is quite uncommon
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One study reports only 2 out of 41 peanut-allergic patients
reacted mildly to other members of the legume family
Avoidance of legumes such as soy, chick peas, lentils,
beans, peas, licorice, carob, and all other members of
the Leguminoceae family, to which peanut belongs, is
only necessary when allergy to the individual foods
has been identified.
_________________________
Bernhisel-Broadbent et al 1989
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Tree Nut Allergy
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Tree nuts are botanically unrelated to peanuts
It is not necessary to avoid tree nuts such as hazelnuts
(filberts), Brazil nuts, walnuts, almonds, macadamia
nuts, pine nuts, pistachios, etc. unless the individual
has an allergy to them
Nuts in a nut mixture are very difficult to distinguish
from each other
Risk of tree nuts, especially nut mixtures, to contain,
or to be contaminated by peanuts
A person who has demonstrated allergy to peanuts is
usually advised to avoid nuts of all types in the
interests of safety
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Peanut and Soy Allergy
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Increase in the incidence of soy allergy, especially in
children
May be the result of exposure to the allergenic protein,
in the form of soy-based infant formulas, in early
infancy when the child is at highest risk for allergic
sensitization
Soy and peanuts contain a similar allergen, exposure to
the soy allergen in infant formula could prime the
child’s immune system to respond to the peanut
allergen, even when he or she shows no signs of allergy
to soy
As a result, the child could exhibit allergic symptoms
on an apparent first exposure to the peanut.
____________
Lack et al 2003
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Progression of Peanut Allergy
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Peanut allergy, like many early food allergies, can be
outgrown
In 2001 pediatric allergists in the U.S. reported that
about 21.5 per cent of children will eventually
outgrow their peanut allergy1
Those with a mild peanut allergy, as determined by
the level of peanut-specific IgE in their blood, have a
50% chance of outgrowing the allergy2
Only about 9% of patients are reported to outgrow
their allergy to tree nuts3
__________________
1Skolnick et al 2001
2Fleischer et al 2003
3Fleischer et al 2005
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Maintaining Tolerance of Peanut
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When there is no longer any evidence of
symptoms developing after a child has
consumed peanuts, it is preferable for that
child to eat peanuts regularly, rather than
avoid them, in order to maintain tolerance to
the peanut
Children who outgrow peanut allergy are at
risk for recurrence, but the risk has been
shown to be significantly higher for those who
continue to avoid peanuts after resolution of
their symptoms
_________________
Fleischer et al 2004
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The Peanut Safe Environment
Important measures for a peanut-safe environment
should include:
 Ensuring that all personnel in a peanut-safe facility
are well-informed about the dangers to the peanutallergic person of accidental contamination
 Clear strategies for maintaining the facility in a
peanut-safe condition, with strict rules about cleaning
 Informing everyone entering the facility to avoid
introducing peanuts into the area, and the reasons for
the restrictions
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The Peanut Safe Environment continued
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Education of the peanut-allergic person concerning
avoidance of their own exposure to peanuts,
including:
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Avoidance of foods likely to contain, or be contaminated
by, peanuts
Being aware of all terms on food labels that would indicate
the possible presence of peanut
Carrying an Epipen of injectable adrenalin, and being
familiar with its use in case of accidental exposure and an
allergic reaction
Wearing a MedicAlert tag or bracelet in case of loss of
consciousness in an allergic reaction
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The Peanut Safe Environment continued
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Informing all staff in the facility about emergency
procedures should anyone in the area develop
symptoms and require medical treatment.
Such information should include:
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Familiarity with the use of the Epipen where appropriate
Contacting key care-givers such as parents and guardians
of children, and the person’s doctor or other health
provider
Instructions for transporting the individual to the nearest
hospital in the quickest way possible
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Peanut Oil
Highly refined peanut oil contains barely detectable
amounts of peanut protein, and should be safe for
consumption by most peanut-allergic individuals
 There is no guarantee that any peanut oil is
completely free from peanut protein
 Threshold doses of peanut as low as 100 mcg
reported to elicit (mild) symptoms in test subjects:
may be below level of detection
 A person anaphylactic to peanut is strongly advised to
avoid all types of peanut oil entirely
 Cold-pressed oils (also labelled “pure-pressed”,
“expeller pressed” or “unrefined”) in particular
should
be
avoided.
_________________
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Hourihane et al 1997
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Probiotics, Prebiotics,
Synbiotics
Bacteria as Therapeutic Agents
Microorganisms in the Bowel
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The healthy large bowel sustains a resident microflora
of bacteria, fungi, and other harmless microorganisms
Beneficial effects include:
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Synthesis of vitamins:
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Vitamin K
Biotin
Thiamin
Folic acid
Vitamin B12
Interaction with immune cells to maintain a healthy
epithelium
Positive competition with invading pathogens to resist
disease
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Resident Microflora
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Gut microflora of a breastfed infant is quite different
from that of a formula-fed baby
An individual’s bowel microflora is established at
weaning
Remains stable throughout life unless events
intervene
Individuals in the same household, eating the same
diet, may have a vastly different bowel microflora
After oral antibiotics several microbial species will be
killed, but after about 6 months the previous strains
become re-established and microflora returns to its
pre-antibiotic state
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Bowel Microflora and Allergy
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The type of gut colonization during the first weeks of
life may predispose an individual to atopic disease
The gut microflora influences:
 Resistance to infection
 Immunological environment for subsequent
challenges, including food allergens
 May influence predominance of Th1 or Th2
response
Probiotics may alter the gut microenvironment by
changing the types of microorganisms present and
the cytokines produced by the local immune cells
_________________
Kirjavainen et al 1999
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Probiotic
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Living micro-organisms within a food that is
designed to provide health benefits beyond the
food’s inherent nutritional value
The types of micro-organisms used have
certain characteristics to be of any value:
Have a beneficial effect within the bowel
 Must be capable of living within the human bowel
without causing any harm to the host.
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Thompson 2001
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Probiotic Characteristics
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Probiotic micro-organisms alter the gut
microflora by competitively interacting with
the existing flora by:
Production of antimicrobial metabolites
 Modulating the local immune response to the
indigenous micro-organisms
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Saccharolytic species:
Use carbohydrates as substrate
 Produce beneficial metabolites
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Shanahan 2000
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Possible Use for Probiotics
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Trials in disease situations such as :
Diarrheal diseases
 Re-establishment of normal intestinal microflora
after antibiotic therapy
 Inflammatory bowel diseases
 Fungal disease (e.g. candidiasis)
 Cancers
 Cholesterol lowering
 Prevention of allergic diseases e.g. eczema
 Management of lactose intolerance
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Why Probiotics?
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The desire by consumers to use natural
methods for health maintenance rather than
long-term chemotherapeutic agents (i.e.
antibiotics)
Expectation that food will become a source of
prolonged well-being
Speculation that the probiotic market will
expand rapidly
Depends on the reliability of claims for the
effectiveness of these products in disease
prevention and control
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Micro-organisms Used as Probiotics
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Examples of bacteria:
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Lactobacilli
Bifidobacteria
Strains of enterococci
Requirements for survival of probiotic strains:
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Must be able to survive passage through the hostile
environment of the stomach and upper small intestine
Resist the effects of intestinal secretions
Attach to intestinal cells on reaching the large bowel,
Thrive within its physiological and nutritional milieu.
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Forms of Probiotic Agents
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Examples of food supplements containing
live culture:
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Yogurts
Fermented milks
Fortified fruit juice
Powders
Capsules
Tablets
Sprays
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Prebiotics
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Non-digestible food ingredients that selectively
stimulate a limited number of bacteria, to
improve health
Examples:
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Fructo-oligosaccharides (FOS)
Lactulose
Galacto-oligosaccharides (GOS)
Provided in:
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Beverages and fermented milks
Health drinks and spreads
Cereals, confectionery, cakes
Food supplements
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Synbiotics
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Combine prebiotics and probiotics
Prebiotic substrate should enhance survival of
probiotic bacteria
Example:
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Bifidobacteria + fructo-oligosaccharide (FOS)
In order to establish the new species, need to
continue to provide live culture, and
appropriate substrate
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Probiotics and Lactose Intolerance
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Lactobacilli, bifidobacteria and Streptococcus
thermophilus, assist in reducing the symptoms of
lactose intolerance
Produce the enzyme beta-galactosidase (lactase) in
yogurt
Microbial lactase breaks down lactose
The fermented milk itself delays gastrointestinal
transit, thus allowing a longer period of time in which
both the human and microbial lactase enzyme can act
on the milk lactose.
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Microflora and Lactose Intolerance
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Lactose tolerance in people who are deficient in
lactase may be improved by continued ingestion of
small quantities of milk
Does not improve or affect the production of lactase
in the brush border cells of the small intestine
Continued presence of lactose in the colon contributes
to the establishment and multiplication of bacteria
capable of synthesizing the beta-galactosidase
enzyme over time
Resident micro-organisms will break down the
undigested lactose in the colon
Reduces the osmotic imbalance within the colon that
is the cause of much of the distress of lactose
intolerance
_________________
de Vrese et al 2001
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Clinical Trials of Probiotics
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Not all probiotics have been tested in clinical
studies with regard to allergy prevention or
treatment
L. bulgaricus seemed to have no effect on
immune parameters, whereas it was associated
with lower frequency of allergies
L. acidophilus consumption accelerated
recovery from food allergy symptoms
These effects have also been observed in
infants with eczema and cow's milk allergy
using infant formulas supplemented with
L. rhamnosus.
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Trials on Probiotics and Eczema Prevention
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Pregnant women took capsules containing Lactobacillus
rhamnosus GG (LGG) during the last two to four weeks of
pregnancy
The newborn infants were given the same microorganism
from birth to six months
Breast-feeding mothers continued to take the capsules
during lactation
The babies were given the bacteria mixed with water by
spoon
Subjects taking the probiotic had a reduced risk of
developing atopic dermatitis (eczema) compared to controls
up to 4 years of age
Other studies found no reduced incidence of eczema in
babies treated with probiotics
_________________
Kalliomaki et al 2003
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Prebiotics and Eczema
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A few preliminary studies suggested increased
bifidobacteria may be associated with a decreased
incidence of atopic dermatitis
Stool of infants fed formula containing
oligosaccharides (FOS and GOS) in comparison to
infants not fed the test formula had:
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Increased numbers of bifidobacteria and lactobacilli
Increased amount of short chain fatty acids
Increased proportion of acetate
Decreased proportion of propionate
Lower stool mean pH
This is closer to that seen in breast-fed infants
compared to infants fed control formula
_______________
Ben XM et al 2004
____________
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Knol et al 2005
Effects of Probiotics on Intestinal Functions and
Immune Responses
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Probiotics have effects on a number of intestinal
functions and immune responses that may be
beneficial in food allergy management, such as:
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Repair of intestinal barrier function
Repair of tight junctions
Enhanced mucin production
Effects on dendritic cell function
Skewing of T cells towards Th1 rather than Th2
Exclusion of pathogens by competition for substrate
Suppression of intestinal inflammation
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Saxelin et al 2005
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Status of Probiotics as Therapy
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Great care must be taken in transferring data from
laboratory and experimental animal studies into
human use
Applies also to the use of known probiotics, some of
which are already present in human nutrition, such as
yoghurt
Not all strains of bacteria in use as probiotics are
completely harmless
Their immune-modifying effects and possible
antiallergic and anti-cancer actions require large
clinical studies
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