THE
STANDARD
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Volume 1, No. 2
Allergies: The Natural Approach
Thomas G. Guilliams Ph.D.
Perhaps one of the most common, recurrent ailments suffered by Americans is allergies. The symptoms of allergic
rhinitis (red, itchy eyes and nose, sneezing, sinus headache and congestion) can be both seasonal, in the case
of "hay fever" or perennial (Fig. 1). Regardless of the particular allergen, the discomfort is
experienced by nearly 20% of Americans (1). While rarely life-threatening, allergic rhinitis
leads to periods of general misery, sleep loss, and lack of productivity in industry as well as education. We
will look here at some of the common causes, treatments, and natural ingredients that help alleviate the many
symptoms associated with allergic rhinitis.
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Fig 1 Airborne Seasonal Allergens and the Weed and Pollen Season
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What triggers an allergic response?
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An allergic reaction can be best thought of as a cascading set of
inflammatory reactions, started by the immune system, in response to
environmental antigens which are usually considered harmless.
--In essence, an allergic response is an overcompensation of the immune
system against relatively harmless airborne substances. Once an allergen
is inhaled it is processed by the immune cells and stimulates a B-cell
mediated IgE response. IgE is one of 5 types of immunoglobulin (antibody)
produced by B-cells; IgA, IgD, IgM, and IgG are the others. Each type of antibody
can bind to antigens or allergens, but differ in the type of responses they
produce once they are bound to antigen. The typical allergic response is
mediated by IgE antibodies when they bind the allergen with one end, and
the IgE receptor of the mast cells or basophils with the other end. This
cross-linking on the surface of the mast cell triggers a multi-step
process leading to degranulation of the mast cell and release of histamine and
other inflammatory mediators (Fig. 2). Once the cascade starts, a whole host
of secondary responses are triggered.
Two phases of responses are triggered by an IgE/allergen cross-linking
event. The first is the release of preformed mediators such as
histamine, proteases, serotonin and Hageman factor from mast cells and basophils.
These chemical mediators are found in preformed vesicles, released by a
calcium dependent process induced by the cross-linking of two or more IgE
receptors. This calcium dependent process may be the most important trigger, as
well as a major key in preventing the cascading allergic response. Once these
chemicals are released, they are responsible for allergic (inflammatory)
processes like vasodilatation, increased vascular permeability, and
increased chemotaxis of other inflammatory cells.
The second phase of the response begins at the same time, as the cell
begins to synthesize lipid-derived mediators. These mediators are derived by
the conversion of phospholipids into arachadonic acid via phospholipase A;
followed by the subsequent conversion of arachodonic acid into
leukotrienes, platelet activating factor (PAF) and prostaglandins (2,5).
This is the identical process involved in a majority of acute and chronic
inflammatory processes. Most of the symptoms associated with allergic rhinitis are a
direct result of both the preformed and lipid derived mediators on the
lining of the upper respiratory tract, and not a property of the
allergen itself (see Fig. 2). Why some people react to some allergens and other
people do not has a lot to do with genetics, geography and exposure
levels.
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Fig 2 Inflammatory Mediators Released by Mast Cells
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Allergens can be classified as perennial or seasonal. Perennial
allergens would include those things such as internal mold spores, dust
and
dust mites, animal dander, and specific chemicals (cleaning agents,
certain
powders). If a patient has allergic rhinitis symptoms lasting more than
2
hours per day for more than 9 months, this would be classified as a
perennial allergic rhinitis. The allergen is most likely something in
their
home or workplace.
Seasonal allergies follow a predictable pattern based on the growing
season.
Figure 1 shows the typical pattern in the Midwestern United States. The
first allergen of the season begins when trees begin to release pollen.
Trees with little or no visible flowers have a higher pollen count since
they rely on the wind rather than insects for pollination. The summer
months
are typically the time for grass pollen allergies. These can come from
commercial crops such as corn pollen, and are often less of a problem in
urban areas where grass pollinates less frequently (if mowed often
enough).
The fall is the most intense allergy season in the central U.S. due to
the
large amount of weed pollen that becomes airborne. Ragweed and goldenrod
are
among the most common offenders. Interestingly, the common term
"hayfever"
is actually a misnomer since neither hay (alfalfa) nor fevers are
typically
associated with allergies. Finally, there is the issue of fungal spores.
As
one can notice from figure 1, fungal spores are high at all times except
during times of snow cover (typically late Nov through Feb). Fungal
spores
can be kicked up any time a person is walking through grass or leaves,
cutting or stacking wood, or just being in a damp outside location.
Fungal
spores are so ubiquitous and long lasting it may be difficult to
determine
what the offending source is. In these cases, skin testing would be
warranted to determine that indeed the patient is suffering from an
allergen
and is not experiencing infectious sinusitis.
Seasonal allergies are one of the most self-diagnosed and self-treated
conditions. Many people know what will trigger an allergic response and
how
and when to avoid exposure. Over the counter antihistamines and
decongestants are advertised and purchased widely during the common
allergy
seasons. Here are some of the typical treatment options:
The most obvious and beneficial thing that a person can do is
to
avoid the allergen altogether. Spending time in air-conditioned areas,
especially cars, will filter out many of the offending allergens. It is
now
possible to purchase a relatively cheap air-purifier that will recycle
the
air as it filters it, without changing the temperature of the air.
Keeping
the humidity low in their homes is another way a patient can reduce some
of
the common offenders such as mold and dust mites.
Antihistamines are usually the first drugs that most people try
when
seasonal allergies come around. One of the most popular (and typical) is
diphenhydramine (Benadryl), which works by blocking histamine H1
receptors.
By blocking the histamine receptors, antihistamines are excellent at
reducing sneezing, itchy eyes and nose, and slowing the pace of a runny
nose. Antihistamines have little effect on congestion or associated
asthmatic conditions. Of course, one of the major side effects of
antihistamines is drowsiness. In fact, it is because of this side effect
that many of the antihistamines are used as sedatives and hypnotics.
Newer
antihistamines, which do not cross the blood-brain barrier, have little
to
no sedating side effects. Claritin, Seldane, and Hismanal have similar
antihistaminic effects as Benadryl with fewer side effects, but at a
much
greater cost. Seldane has just been pulled from the market by the FDA
for
its complications with the heart. While Hismanal has some of the same
problems as Seldane, the major warning of all of these newer drugs is a
contraindication with the concomitant use of erythromycin (a common
antibiotic) and ketoconazol (a common antifungal).
While antihistamines block many of the effects of histamine, they are
unable
to stop the mast cell from releasing histamine or any of the other
preformed
or lipid-derived mediators. This means that some of the secondary
problems
associated with allergies are unaffected or masked by antihistamines.
Such
problems as nasal congestion and asthma must be addressed by other
means.
Bronchodilators and decongestants are also available by prescription or
over-the-counter. The most common would be ephedrine or pseudoephedrine
(Sudafed) containing products. They work primarily as
a-adrenergic agonists. They reverse congestion by vasoconstricting the
nasal
mucosal blood vessels, reducing swollen membranes, which allows sinus
drainage and improved air conduction. Since both ephedrine and
pseudoephedrine also effect the b-adrenergic receptor, they are capable
of
acting as bronchodilators. Care should be taken when patients with heart
conditions, high blood pressure, or on MAO inhibitors take these drugs.
Another option is steroid drugs. Topical preparations of
glucocorticosteroids are supplied by nasal sprays. The mechanism is
probably
very similar to the anti-inflammatory effects of corticosteroids. They
are
mainly indicated in long-term allergic conditions that are not
responding to
antihistamines.
Allergen immuno-therapy is the subcutaneous injection of
the
offending allergen in increasing doses over several months. Essentially
what
one is doing is to try to stimulate production of other types of
antibodies
(IgG especially) which will proliferate and can bind to the allergen in
the
place of IgE. Since IgG do not have receptors on mast cells, they will
not
stimulate an allergic response. It is not uncommon for many people to
take
"allergy shots" at regular intervals throughout the year.
Because allergies are such a common recurrent condition, many people are
concerned about the perennial high dose of allergy drug use. The
research
into natural ingredients has yielded some excellent results in the
alleviation of allergic symptoms.
One of the major secondary products of inflammatory
responses
is the formation of a whole host of free radicals. The formation of
these
potentially harmful products is normal, and even helpful at the time and
location of their synthesis; after which they are neutralized by
antioxidants. One of the leading water-soluble antioxidants is ascorbic
acid
(ascorbate) or vitamin C. The use of vitamin C, flavonoids, and other
natural agents as potent antioxidants is beyond the scope of this
article,
but their role in allergic as well as other inflammatory processes have
been
studied for years. The role of supplemental antioxidants in preventative
health will be a topic of a future article.
Among the flavonoids, quercetin is possibly the most
biologically
active. Quercetin is the aglycone (non-carbohydrate portion) of rutin,
quercetrin and other glycoside flavonoids. It is widely distributed in
the
plant kingdom including oak trees (Quercus spp.), onions (Allium cepa)
and
tea (Camellia sinensis). It has effects on many different enzymatic
systems
in the body, most of them via its interaction with the
calcium-regulating
enzyme calmodulin (3).
Quercetin¹s effect on allergies is unmatched by other natural
substances.
It inhibits phospholipase A (responsible for converting phospholipids
into
arachidonic acid), lipoxygenase (responsible for converting arachidonic
acid
into leukotrienes)(4), platelet aggregation, and mast cell and basophil
degranulation (6,7). Quercetin has been shown to bind to
calcium/calmodulin
complexes, preventing the influx of calcium into mast cells and
basophils
(6,11). This inhibition prevents the mast cells from destabilizing and
degranulating, keeping histamine and other preformed mediators from
being
released (13). In fact, quercetin so consistently blocks calcium induced
mast cells destabilization that researchers often use it in experiments
as a
control substance for such activity (7,8,12).
The activity of quercetin has been well known for years, leading to
the
synthesis of similar compounds by pharmaceutical companies. One such
compound, cromyln (the active ingredient in Intal), has been used as a
mast
cell stabilizer for years (10). The only problem is that cromyln cannot
be
absorbed orally and must me delivered as a powder through spinhalers or
an
aerosol inhaler. Even then, only 8% is absorbed in the respiratory tract
(9)
leading to the need to take 2 metered dosages four times per day.
Like most biologically active flavonoids, quercetin¹s pharmacology is
quite interesting. The absorption of quercetin is about 20-52% depending
on
the form (14,15). While this may seem quite low, the elimination of
quercetin and its derivatives is very low, and high plasma levels are
easily
maintained with a regular supply of quercetin in the diet (16). Studies
conducted in rats showed that more than 25% of the absorbed quercetin
was
localized in the lung tissue, an added benefit to combat allergy and
associated asthma (17). While these radioactive studies have not been
repeated in man, it is likely that similar results would be found. It
has
been known for some time that the concomitant administration of
bromelain,
an enzyme derived from the stem of the pineapple plant, can enhance the
absorption of quercetin as well as other flavonoids such as rutin. An
added
benefit included with bromelain is its ability to block inflammatory
pathways (fibrin and kinin) and decrease the viscosity of mucus in the
lungs.
Patients should begin to take quercetin upon the first signs of
allergen
exposure. Since quercetin is prophylactic (stabilizing mast cells rather
than blocking histamine) and will stay in the blood stream, initial
doses
should be 400-600 mg, three times per day, for the first 5-7 days.
Symptom
relief may begin in the first several hours. Once plasma levels are up,
200-400 mg per day should be sufficient through the rest of the allergy
season. Quercetin is extremely safe, and has so many other benefits
(antioxidant, anti-inflammatory, capillary stability etc.) it should
make it
the foundation of any natural approach to allergic rhinitis therapy.
Among the many plants one would propose to be helpful
in
the treatment of allergic rhinitis, the stinging nettle (Urtica dioica
L.)
would probably not be among them. This common plant, often called "itch
weed", is known to cause hives or urticaria (hence the Latin name) due
to
the histamine located in needles under each leaf. For years, the dried
leaves of stinging nettles were used for the symptoms associated with
allergic rhinitis. Finally in 1990 a double-blind, placebo-controlled
study
was done to assess the use of stinging nettle leaf for allergic rhinitis
(18). After one week, stinging nettle was rated higher than placebo.
Unfortunately this study was based on diary entries of symptoms and
overall
patient ratings. These studies should be expanded to include more
patients,
longer intervals, and more objective measurements.
A recent article studying the use of stinging nettle leaf extracts in
the
treatment of rheumatoid arthritis (another inflammatory process) may
explain
the mechanism. An extract of stinging nettle leaves was shown to inhibit
both lipoxygenase and cyclooxygenase activity (19). These two enzymes
are
responsible for converting arachidonic acid into the inflammatory
prostaglandins and leukotrienes. This and possibly a negative feedback
effect from oral histamine (from the nettle leaf) contribute to the
overall
activity of nettle leaf in allergic symptom relief.
While other botanical products have been used for allergic rhinitis
over
the years, most of these work as anti-allergic agents due to the high
amount
of quercetin in them. Among them, garlic, onion, and green tea are the
most
popular.
Asthma is one of the most common allergy associated ailments. It
can
be triggered by the same events as allergies (IgE-allergen interaction)
and
results in the constriction of the bronchioles and increased production
of
bronchial mucus. While several of the mast cell preformed mediators play
significant roles in asthma, increasing research has been targeted at
leukotriene and PAF-induced asthma (20,21,22).
These lipid-derived mediators are responsible for drawing eosinophils (by chemotaxis) to the lungs,
which perpetuate the response by releasing more PAF.
Several botanical constituents, including quercetin (23) and bilobide B
from Ginkgo biloba (24), have been shown to inhibit the synthesis or
effect of PAF. There is continued research to find other botanical ingredients
that will address this area of allergy and asthma.
Ephedra (Ephedra sinica Stapt.) or Ma Huang has been used in
Chinese medicine for thousands of years (29). The ephedra plant contains
2
to 3% alkaloids, mostly ephedrine and pseudoephedrine. These alkaloids
were
discovered and synthetically produced in the late 1920's and their use
has
been wide in over-the-counter and prescription medications for asthma,
hay
fever and related conditions. See the discussion under "Treatment
Options:
Drugs" above for mechanisms.
Ephedra has come under scrutiny of late by the FDA, primarily due to
its
formulation with caffeine-containing products and its promotion as a
stimulant weight-loss product. Restrictions will be recommended, and
possibly mandated on the use, dose, and combination use of ephedra in
the
near future. Extracts of ephedra (Ma Huang) is safe in short-term use
(1-2
weeks) as a bronchodilator. Longer use of ephedra should be monitored
closely and should be accompanied by adrenal stimulating herbs like
licorice
(Glycyrriza glabra L.), Siberian Ginseng (Eleutherococcus senticosus
Maxim.), and Dandelion Root (Taraxacum officinalle Wiggers). Ephedra
extracts contain 6-8% ephedrine and should be dosed at 200-400 mg 2 or 3
times daily. Each individual reacts differently to ephedra and smaller
and
less frequent doses should be attempted prior to increasing dosing.
NAC: N-Acetyl Cysteine (NAC) may be one of the best
expectorant/mucolytic
agents, although it has been forgotten in recent years. NAC is gaining
interest as an antioxidant that acts by itself and as a "recharger" of
the
body's own glutathione (25). As disulfide reducing agents, both NAC and
glutathione can decrease the viscosity of mucus, which is increased by
disulfide bridging of sulfur proteins in mucus. Recently, the mucolytic
mechanism is being reassessed by research suggesting a "mucoregulating"
action for NAC (27,28). NAC has been used quite frequently in an
assortment
of lung conditions including COPD, bronchitis, and asthma (26).
As we finish editing this article, we are looking at one of the worst
allergy seasons in decades. Just one more El Niño effect, we are told.
As
the seasons approach, patients will begin stocking up on prescription,
over-the-counter, and natural products to combat the inevitable symptoms
they will face. This information should help you direct your patients to
the
best natural treatment options for the coming season.
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What triggers an allergic response?
The Alergens