Allergies

ALLERGIES

Synopsis:
Background
Allergic Disorders
Nutrient Support for Allergies
Suggested Supplementation
References

 

More than 500 million people worldwide suffer from food allergies. More than 300 million, or about 5% of the global population, now suffer from asthma (Chang 2011). Allergic rhinitis, a risk factor for asthma, affects up to 30% of adults and 40% of children (Wallace 2008).

Some scientists theorize that a potential cause of allergies in the modern world may be over-sanitation. Excess utilization of antibiotics and less frequent exposure to microbes like bacteria and viruses during childhood may impair development of balanced immunity, causing hyper-reactivity to allergens later in life, a phenomenon known as the “hygiene hypothesis” (Fishbein 2012; Jedrychowski 2011).

Patients often report that their conventional medications fail to provide relief (Li 2009; Metcalfe 2010). Also, corticosteroids and beta-2-agonists, drugs frequently used to treat allergic asthma, have potentially deadly side effects over the long-term.

Apart from allergy testing to significantly reduce your allergic symptoms by identifying and avoiding the dietary or environmental culprits driving them, you can also support your body using several natural compounds with immunomodulatory properties that quell allergen-induced inflammatory responses to provide symptom relief.

 

What is an Allergy?

An allergy occurs when your immune system responds aggressively to a harmless environmental substance.

Common inhaled allergens include tree and flower pollen, animal dander, dust and mold. Ingested allergens include medications (penicillin, for example) and foods such as eggs, peanuts, wheat, tree nuts, and shellfish. Nickel, copper, and latex can also cause allergies (AAAAI 2011; Kasper 2005).

These allergens can affect various parts of the body and elicit symptoms in the nasal passages (such as itchy, stuffy and/or runny nose, postnasal drip, facial pressure and pain); mouth area (tingling sensation, swollen mouth and lips, itchy throat); eyes (swollen, itchy, red eyes); respiratory (wheezing, coughing, difficulty breathing, shortness of breath); skin (hives, rashes, swelling); and gastrointestinal (stomach cramps, vomiting, diarrhea). Symptoms can occur within minutes to days after exposure and can range from mild to severe.

The most severe form of allergic reaction is called anaphylaxis. It is a potentially deadly condition that results in respiratory distress and swelling of the larynx, often followed by vascular collapse or shock (Kasper 2005). Anaphylaxis should be treated rapidly because death can occur within minutes or hours after the first symptoms appear. Many people prone to anaphylaxis carry self-injecting epinephrine pens in case of emergencies.

 

What Causes an Allergic Response?

The immune system normally functions to protect the body against viruses, bacteria, fungi, and other pathogens by targeting these substances for destruction upon recognition. However, an allergic response arises when your immune system mistakes harmless substances as potential pathogens and attacks them.

 

Th1 and Th2 Immune Responses in Allergies

T lymphocytes are immune cells that recognize foreign pathogens and also produce cell-signaling cytokine proteins, which facilitate immunological communication. The two main subsets of T cells – Th1 and Th2 – complement one another to produce a comprehensive immune response against invading pathogens.

Th1 cytokines trigger the destruction of pathogens that enter the cells (such as viruses). They are also responsible for cell-mediated immune response and can perpetuate autoimmune reactions. Th2 cytokines destroy extracellular pathogens that invade the blood and other body fluids. An imbalance within the Th1-Th2 paradigm favoring Th2 underlies the increased susceptibility to allergies, called atopy, that some individuals experience (Berger, 2000).

 

 

Allergic Disorders

Epidemiological studies revealed that the prevalence of allergic diseases has increased worldwide over the last few decades (Gupta, 2004; Yuksel, 2008; Asher 2006; Björkstén, 2008). Allergic diseases include atopic dermatitis, allergic rhinitis, asthma, food, drug and insect allergy, urticaria (hives) and angioedema (swelling beneath the skin).

Atopy, the genetic predisposition to producing IgE antibody in response to allergens, increases the risk of developing allergic disorders (Zheng 2011; Johansson 2004). Having one allergic disorder significantly increases the risk of developing other allergic disorders (Simpson 2008). Atopy is the strongest predisposing factor of asthma in children. Epidemiological and experimental studies have shown that atopic disorders typically follow a natural history of manifestation or a progression of clinical signs, beginning with atopic dermatitis in infants and developing to allergic rhinitis and asthma in children (Spergel 2003). This progression, called atopic march, may be influenced by shared genetic and environmental risk factors (Spergel, 2010).

 

Atopic Dermatitis

Atopic dermatitis (AD) is a chronic inflammatory skin disorder that affects at least 15% of children and up to 10% of adults (Pawankar 2011). Studies among children reveal that AD develops very early in life. In fact, around 45% of affected children develop AD in the first 6 months of life, 60 % develop it in the first year, and 85% before their 5th birthday. Further, more than half of affected children will continue to have AD beyond 7 years of age, and more than 40% will experience it through adulthood (Pawankar 2011).

Atopic dermatitis is often the first manifestation of allergic disease and many patients may develop allergic rhinitis and asthma later in life (Spergel 2010). Eczematous rashes are dry, scaly and itchy, and can become infected if left untreated. In infants and young children, the rashes appear on the face, neck, cheeks and scalp. In older children and adults, eczema may appear on the folds of the forearms, the inner elbows and behind the knees. Factors that make the symptoms worse include temperature, humidity, irritants, infections, food, inhalant and contact allergens and emotional stress (Hoare 2000). Atopic dermatitis can affect development, personality, and quality of life of patients and their families.

Patients with atopic dermatitis have reduced skin barrier function. When vital skin lipids are lost, moisture escapes from the skin epidermis (top layer of the skin) and the skin becomes dry, causing cracks and microfissures to develop through which allergens and microbes can easily enter (Pawankar 2011). Soaking baths followed by an application of emollient (moisture-retaining lotion or salve) can help retain moisture and give the patient relief.

Topical corticosteroids are the standard treatment for atopic dermatitis. Low-potency corticosteroids help keep the symptoms under control and high-potency corticosteroids are used in severe flare-ups. Because of their potential adverse effects, high-potency corticosteroids should be used over short periods of time and topically only in areas that are lichenified (areas in which the skin has become leathery and thickened) (Leung 2004).

 

Allergic Rhinitis

Allergic rhinitis is an IgE-mediated inflammation of the nasal mucosa in response to outdoor and indoor allergens, the most common of which are pollens, dust mites, molds and insects. Sensitization and subsequent exposure trigger a release of symptoms that include sneezing, runny or stuffy nose, teary eyes and itchy nose, throat or skin (Meltzer 2009). The nose becomes primed and hyper-reactive on repeated exposure to the allergen, and over time, the amounts of allergen needed to mount an immune response decreases (Pawankar 2011).

Allergic rhinitis is a major respiratory health problem that affects between 10 - 30 % adults and more than 40% of children worldwide. The prevalence of this disease is increasing. Allergic rhinitis negatively affects the patient’s quality of life, school/work performance and social interaction, and creates financial burden (Pawankar 2011). Allergic rhinitis is a risk factor for asthma (Choi 2007), and many patients with it also suffer from atopic dermatitis and conjunctivitis, and co-morbidities that include sinusitis, nasal polyps, upper respiratory infections, sleep disorders and impaired learning in children (Craig 2010). It can also develop 3 to 7 years later among patients with non-allergic rhinitis (Rondón 2009).

Based on frequency and severity of symptoms, allergic rhinitis may be classified into (1) mild intermittent; (2) mild persistent; (3) moderate/severe intermittent; (4) moderate/severe persistent (Bousquet 2008). Based on type of allergen, rhinitis is classified as perennial or seasonal, although patients can respond to both types of triggers. Symptoms can also last up to 4 to 9 months of the year (Meltzer 2009). Risk factors of allergic rhinitis in childhood include a family history of atopy, birth by cesarean section, exposure to cigarette smoke in infancy, endotoxin levels in house dust of inner city homes and pollutants (Sabin 2011).

Conventional treatment of allergic rhinitis usually begins with controlling exposure to the allergen(s), followed by use of intranasal corticosteroid sprays and non-sedating antihistamines. A survey of pediatric allergies in the U.S. (Meltzer 2009) reported that parents and physicians consider nasal allergy medications as insufficient for relieving immediate and long-term symptoms and often have bothersome side effects. Some of the adverse side effects reported include nasal dryness, nose bleeds and drowsiness from antihistamines.

 

Asthma

Asthma is a life-long inflammatory disease characterized by airway hyper-responsiveness and airflow obstruction. In people with asthma, the inner lining of the airways become inflamed and the muscles surrounding the airways tighten up. Mucus glands in the airways secrete thick mucus. Together, these changes cause the airway to narrow and leads to difficulty breathing, shortness of breath, cough and wheezing.

Between 60% and 70% of asthma cases in children are allergic or atopic. Children with allergies have a 30% increased risk of developing asthma (Pawankar 2011). Genes play an important role in the susceptibility to develop asthma and several candidate genes have been identified in this regard (Zhang 2008). Other factors that affect the development and severity of asthma include indoor allergen exposures, outdoor pollens, viral upper respiratory infections, exercise, foods, occupational history of the child and parents, environmental smoke, pollution and exposure to day care.

Inhaled corticosteroids are anti-inflammatory medications for the treatment of persistent asthma. However, clinical control deteriorates within weeks to months once corticosteroid treatment is discontinued. The most effective long-term medications are long-acting inhaled beta-agonists (Pawankar 2011), but they come with potentially serious adverse effects (Chang, 2011).

 

Food Allergy

Food allergy is a global health burden; it is estimated to affect up to 10% of the population (Sicherer 2011).

The most common food allergens include cow’s milk, eggs, peanuts, tree nuts, seafood, soy and wheat. Symptoms of food allergy, which may occur following ingestion, inhalation or contact, are mediated by IgE and non-IgE reactions. Upon sensitization of an allergen, IgE synthesis increases and elevated numbers of cytokines are produced in the serum and intestinal fluids (Yu, 2012). IgE-mediated reactions occur within minutes to hours of exposure and include symptoms like angioedema (swelling of the inner layers of the skin), nausea and vomiting, swelling of the throat, hives, swelling and itchiness of the mouth area, diarrhea and wheezing. Symptoms of non-IgE mediated reactions can occur hours to days later and may include constipation, atopic eczema, protein-induced enterocolitis syndrome, allergic proctitis or rectal inflammation and Heiner syndrome (a pulmonary disease) (Bahna 2003).

The health of the gastrointestinal system plays a pivotal role in food allergies and food sensitivities. The gastrointestinal system acts as a semipermeable barrier, allowing only usable molecules into the bloodstream after food has been broken down. Studies have shown that allergen challenge in sensitized individuals can cause the intestinal walls to become more permeable (Troncone 1994; Pizzuti 2011). When the intestinal wall has been weakened by infection or inflammation, the barrier function is compromised, allowing large molecules to pass through the intestinal wall and into the bloodstream (Moneret-Vautrin 2005; Yu 2012). Allergic sensitization can occur as the immune system responds to these abnormally large molecules, causing digestive complaints such as upset stomach or diarrhea, or symptoms such as joint pain and headaches (Moneret-Vautrin 2005).

Healthy individuals host 100 trillion symbiotic bacteria that include Lactobacillus, Clostridium, Bacteroidetes, Proteobacteria and Bifidobacteria (Frank 2007). Enteric bacteria modulate intestinal morphology; they also produce short chain fatty acids, vitamins, ferment dietary fiber, and shape mucosal immunity (Kelly 2005; Kelly 2007). Animal models have shown that enhancing or restoring intestinal commensal bacteria through supplementation (i.e. supplemental probiotics) (Sudo 2002) can induce tolerance and prevent allergy. Evidence also suggests that a healthy population of intestinal bacteria can help reduce intestinal permeability (Vinderola 2004; Gun 2005).

Probiotic bacteria include Lactobacilli, Bifidobacteria, and Bacillius coagulans. Saccharomyces boulardii is a probiotic yeast (Casas 2000; Pelto 1998; Goldin 1998; Cross 2001). Also, prebiotics, such as fructooligosaccharides, may be included to encourage the growth of beneficial bacteria (Bouhnik 1999). Consuming plenty of dietary fiber each day supports intestinal microbiota as well (O’Keefe 2011).

 

IgG-Mediated “Food Sensitivities”

A number of innovative doctors advocate an elimination diet based on quantitative IgG antibody testing for the relief of a wide array of patient complaints (Russel 2010). This involves assessing levels of IgG antibodies in a patient’s blood using an ELISA method and then instructing the patient to eliminate any foods to which high levels of IgG4 antibodies are detected.

Innovative doctors suggest that this method can be effective for relieving ambiguous symptoms, such as headaches, fatigue, and mood imbalances when other causes cannot be identified. The postulated link is that IgG’s, particularly IgG4, facilitate a delayed reaction to foods, which is often referred to as a “food sensitivity”. These hypothesized IgG4-mediated “food sensitivities” are not the same as true IgE-mediated food allergies, and although some prominent alternative medical practitioners believe these to be separate & distinct phenomena, others disagree.

 

Vitamin D

In recent years, there has been an increased interest in the role that vitamin D plays in the immune system and, in particular, allergic diseases. It is known that vitamin D receptors are found in multiple tissues and cells in the human body, including mononuclear cells, T lymphocytes and dendritic cells, which are important in the recognition of antigens. Vitamin D also has multiple cytokine-modulating effects and can decrease proliferation of both Th1 and Th2 cells, and lower the production of interleukins and interferons (Searing 2010). This vitamin has also been shown to have a role in airway remodeling, which may be important in understanding and treating asthma (Clifford 2009). Molecular studies also provide evidence that vitamin D can modulate inflammatory responses, enhance antimicrobial peptide activity and promote the integrity of the permeability barrier of the skin (Searing 2010).

Epidemiological studies revealed that Vitamin D deficiency is associated with an increased incidence of asthma and allergy symptoms (Weiss 2008; Litonjua, 2009; Freishtat, 2010), higher IgE responses to food and environmental allergens in children and adults (Sharief 2011) and severity of atopic dermatitis (Peroni, 2011). Similarly, children with well-controlled asthma were found to have higher levels of vitamin D (Chinellato 2011) and adults with chronic urticaria (hives) have lower vitamin D levels than controls (Thorp 2010). A randomized controlled trial involving 45 atopic dermatitis patients provided evidence for the beneficial effect of vitamin D and E supplementation on clinical manifestations. Symptom scores significantly improved in the treatment groups for vitamin D and vitamin E was associated with more favorable symptom scores (Javanbakht 2011).

On the role of vitamin D in preventing asthma and atopic diseases, studies demonstrated that a woman’s high intake of vitamin D during pregnancy lowers the risk of her child developing wheezing (Camargo 2007) or rhinitis at age 5 (Erkkola 2009). This correlation was found in different populations, regardless of the amount of vitamin D intake. A prospective follow-up study showed conflicting results.

A recent longitudinal study demonstrated vitamin D as a predictor of asthma or atopy in later years. The study, involving 689 children from a cohort unselected for asthma or atopy who were examined at age 6 and again at age 14, showed that among male children, inadequate levels of vitamin D is a risk factor for developing atopy, bronchial hyperresponsiveness and asthma. More importantly, vitamin D levels at age 6 were predictive of atopy/asthma-associated phenotypes at age 14 years (Hollams 2011).

 

Vitamin E

Vitamin E is a fat-soluble vitamin that acts as a free-radical scavenger. It protects cell membranes and prevents damage to membrane-associated enzymes. Research suggests that vitamin E inhibits the activation of neutrophils – cells that contribute to respiratory inflammation in asthmatics (Centanni 2001). Studies also indicate that vitamin E can influence and halt the proliferation of mast cells in culture (Zingg 2007; Kempna. 2004 ), suggesting a role for vitamin E in modulating allergies, atherosclerosis, cancer and other diseases in which mast cells play a role.

Several studies provide evidence on the relationship between vitamin E intake and asthma or allergic diseases. A Japanese prospective study reported that low maternal vitamin E intake during pregnancy was associated with increased likelihood of wheezing in children younger than 2 years of age (Miyake 2010). A Scottish birth cohort study reported that low alpha-tocopherol intake during the first trimester of pregnancy was associated with an increased risk of wheezing and asthma in 5-year old children (Devereux 2006). A case-control study reported that childhood asthma is associated with low dietary vitamin E intake (Hijazi et al, 2000), and a 10-year prospective study of adult-onset asthma also reported similar findings (Troisi 1995). In a clinical study of atopic dermatitis, patients randomly selected to orally receive 400 IU of vitamin E daily for 8 months reported remarkable improvement in facial erythema (redness) and lichenification (scaling and thickening of the skin). Eczematous lesions were also reportedly healed as a result of decreased itch sensation (Tsoureli-Nikita 2002).

Animal models have shown that supplementation with high dose vitamin E reduced proliferation of splenic lymphocytes, the production of IL-4, IL-5 and total serum IgE levels. Sneezing and nasal allergic response were also suppressed in the treatment group (Zheng 1999). In a randomized controlled trial, patients with seasonal allergic rhinitis who received vitamin E supplementation during hay fever season experienced improvement in their symptoms (Shahar, 2004).

 

Vitamin C

Vitamin C (ascorbic acid) increases the function of many immune cells, including T cells, phagocytes (which destroy pathogenic organisms), and others. As an antioxidant, ascorbic acid can protect cells from reactive oxygen species known to cause tissue damage and disease. Vitamin C has anti-histamine properties (Johnston CS, 1996) that can help relieve allergy symptoms, but the evidence is still controversial.

Early studies demonstrated that 2 grams of vitamin C improve pulmonary function one hour after ingestion, compared with a placebo (Bucca 1990) and another study found a fivefold increase in bronchial hyperreactivity among those with the lowest intake of vitamin C (Soutar 1997).

An animal model showed that high dose vitamin C supplementation significantly decreased inflammation in the lungs (Chang 2009).

 

Magnesium

Magnesium is utilized by every cell in the body and participates in energy metabolism and protein synthesis. Magnesium participates in at least 350 enzymatic processes within the body. Evidence from animal models indicates that magnesium plays a role in immune response, and that deficiency leads to increased inflammation (Laires 2008).

Results from randomized clinical trials showed that children and adults who were hospitalized for severe, acute asthma benefited from using intravenous (IV) magnesium sulfate (Ciarallo 1996; Devi 1997; Gürkan 1999; Ciarallo 2000). One of these studies used a higher dose of magnesium sulfate (40 mg/kg) and observed a faster and more prolonged improvement in pulmonary function (Ciarallo 2000). But, one randomized study found no evidence that IV magnesium sulfate can treat moderate to severe asthma (Scarfone 2000).

A randomized study found that taking 200 - 290 mg of magnesium for 16 weeks significantly reduced the use of bronchodilators in children with mild to moderate asthma (Bede 2003). Similar beneficial effects of 12-week magnesium supplementation were found in a small study involving children with moderate persistent asthma treated with inhaled fluticasone (Gontijo-Amaral 2007). More recently, long term treatment with oral magnesium (170 mg twice a day for 6.5 months) in adults with mild to moderate asthma showed improvement in objective measures of bronchial reactivity and in subjective measures of asthma control and quality of life (Kazaks 2010).

 

Fish oil and Fatty Acids

Fish oils contain the omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). EPA and DHA exert anti-inflammatory and antithrombotic (anti-clotting) effects (Calder 2005) because omega-3 fatty acids compete with arachidonic acid, which serves is converted into pro-inflammatory eicosanoids (Leaf 2002; Connor 2001; Calder 2001). Studies suggest that fish oils reduce the production of inflammatory cytokines such as interleukin-1, IL-2, and tumor necrosis factor, which are all involved in the allergic response. Additionally, lower levels of omega-3 fatty acids in the blood are associated with delayed-type hypersensitivity skin reactions in elderly malnourished subjects (Cederholm 1994).

In one study, an ointment containing DHA and EPA produced satisfactory results in 64 patients with refractory dermatitis (Watanabe 1999). A systematic review of maternal supplementation with omega-3 polyunsaturated fatty acids (n-3 PUFA) found evidence that they reduced the prevalence of childhood asthma, but supplementation during lactation did not prevent asthma or food allergy (Klemens 2011). Intake of n-6 PUFA among 1,002 pregnant Japanese females showed a tendency towards lesser allergic rhinitis in the children (Miyake 2007).

 

Butterbur

The perennial shrub Butterbur (Petasites hybridus) is known to inhibit plasma histamine, leukotrienes, and the priming of mast cells in response to allergens (Thomet 2002; Shimoda 2006). Traditional Chinese Medicine has used Butterbur to treat asthma, migraine stress and gastric ulcer (Lee 2011). Petasin, a pharmacological compound extracted from the plant, has been commercialized as Ze 339 and approved in Switzerland as an anti-allergic drug to treat seasonal allergic rhinitis.

A randomized controlled study found Ze 339 effective in improving asthma scores compared to placebo (Schapowal 2004). Other studies found the effect of Ze 339 comparable to cetirizine (Schapowal 2002) and fexofenadine (antihistamine drugs) (Schapowal 2005; Lee 2004). A systematic review of 6 randomized controlled trials found that butterbur extract is effective as a non-sedative antihistamine for intermittent allergic rhinitis as well (Guo 2007). Ze 339 reduced allergic airway inflammation in the lungs of asthmatic animals and inhibited the production of Th2 cytokines, interleukins and RANTES (Regulated upon Activation, Normal T-cell Expressed, and Secreted), which facilitates infiltration of white blood cells during the inflammatory response (Brattström 2010).

Extracts from the Japanese butterbur (Petasites japonicus), which contains a profile of active compounds similar to Petasites hybridus, inhibited eosinophil infiltration and reduced mucus secretion in an animal model of asthma. In cell culture studies, the extract inhibited the release of interleukins triggered by house dust mites (Lee et al., 2011), suggesting that butterbur can suppress the pathogenesis of airway inflammation.

 

Quercetin

Quercetin, one of the most common flavonoids found in a variety of foods such as red wine, green tea, and apples, has been studied for its ability to reduce the symptoms of allergies. It has been shown to inhibit leukotrienes, mast cells, and the release of histamine (Chirumbolo 2010), which makes it a good candidate for anti-allergy therapy. Evidence also demonstrated that quercetin blunts the inflammatory response of immune cells upon antigen recognition (Huang et al, 2010).

In an animal model of peanut allergy, quercetin completely stopped peanut-induced anaphylactic reactions after challenge. Histamine levels in quercetin-treated rats were significantly lower than the positive control group (Shishehbor 2010). In guinea pigs sensitized with ovalbumin, a relatively low dose of quercetin reduced the hyperactivity of airways and caused significant bronchodilation (Joskova 2011). Quercetin microemulsion treatment exhibited anti-inflammatory properties in a similarly designed murine model (Rogerio et al, 2010).

Patients with nasal allergies treated with nasal spray containing quercetin and Artemisia abrotanum L experienced rapid and significant relief of nasal symptoms that was comparable to antihistamine preparations (Remberg 2004). In two independent randomized controlled studies among patients with pollen allergies, taking 100 mg of a quercetin-related compound for 8 weeks, significantly reduced nasal symptoms compared to placebo group (Kawai 2009; Hirano 2009).

 

Stinging Nettle

Urtica dioica acquired the common name ‘stinging nettle’ because the leaves, flowers, seeds and root contain different chemicals such as histamine, formic acid, acetic acid and other irritants that cause mildly painful stings, itchiness or numbness on contact (Anderson 2003).

Historically, stinging nettle has been used to treat allergic rhinitis, but very few clinical studies have been conducted. In an open trial of 69 patients with allergic rhinitis, 58% of subjects who took 600 mg freeze-dried nettle leaf reported a relief in symptoms of rhinoconjunctivitis, and 48% found it more effective than over-the-counter medications (Mittman 1990). Long-term use of the stinging nettle extract, IDS 30, was shown to have anti-inflammatory effects and to be effective in preventing chronic colitis in animal models (Konrad 2005).

Recently, data from bioassay experiments revealed that bioactive constituents in nettle extract inhibit histamine receptors, inhibits enzymes involved releasing cytokines and chemokines that cause allergy symptoms, and reduces the production of allergy-specific prostaglandins. For the first time, these results provided a mechanistic understanding of the role of nettle extracts in reducing allergy and other inflammatory responses (Roschek 2009).

 

Spirulina

The term “spirulina” refers to the dried biomass of a species of cyanobacterium called Arthrospira platensis. It is widely consumed by humans as a dietary supplement and even used as a food source for some aquatic species and poultry.

Spirulina is a source of a variety micronutrients and phytonutrients; it is also, by weight, a good source of non-animal protein (Deng 2010). Studies have shown that spirulina exerts a number of favorable biologic effects in both humans and animals when it is consumed as a food or a supplement (Deng 2010). Additionally, the United States Pharmacopeial Convention (USP) recently assigned a safety rating of “Class A” to spirulina, meaning that data support a high level of confidence regarding the safety of spirulina when used as a dietary supplement (Marles 2011).

Several trials have examined the role of spirulina in modulating the biology of allergic response. Administered at 2,000 mg per day, spirulina was shown by Mao et al (2005) to shift the T-cell profile away from Th2 in allergic rhinitis patients by inhibiting IL-4 signaling. Upon analyzing their results, the scientists stated “this… human feeding study …demonstrates the protective effects of Spirulina towards allergic rhinitis.”

In a similarly designed clinical trial, Cingi and colleagues (2008) corroborated Mao’s findings by showing that “spirulina consumption significantly improved the symptoms and physical findings [in allergic rhinitis patients] compared with placebo including nasal discharge, sneezing, nasal congestion and itching”.

To better explore the mechanisms by which spirulina blunts allergic reactions, Chen et al (2005) studied its biological effects in a murine model of allergic rhinitis. They found that spirulina lowered IgE levels and, correspondingly, attenuated degranulation of nasal mast cells, resulting in suppressed histamine levels in serum. Very similar findings were reported by Remirez (2002) as well.

 

Probiotics

In order to prevent the development of childhood allergic diseases, an infant’s immune system must mature from a Th2- to a Th1-dominated response through microbial contact soon after birth. In comparison with the time before antibiotics and common presence of infectious diseases, along with the widespread use of antimicrobial agents in consumer products like soap, individuals in modern times have reduced contact with microbes. In the theory known as the “hygiene hypothesis”, scientists speculate that an antiseptic environment results in a lack of microbial stimulation to the gut immune system and causes an increase in allergic disease (Penders 2007; Pan 2010). In fact, studies have shown that non-allergic children have higher levels of Bidifobacteria and Lactobacilli compared to allergic children (Kalliomaki 2001). The presence of these ‘harmless’ probiotic bacteria in the intestinal biota seem to correspond with protection against allergy.

Many randomized trials, clinical and experimental studies and meta-analyses have been conducted on the efficacy of probiotics on the treatment or prevention of allergic diseases.

Randomized controlled trials (RCTs) showed that using probiotics provided significant clinical benefits to children with allergic rhinitis. Lactobabillus casei decreased the frequency and severity of nose and eye symptoms and improved the quality of life for children who were sensitized to house dust mites (Wang 2004; Peng 2005). Among preschool children with seasonal allergic rhinitis, L. casei was also found to reduce symptoms and the number of episodes, and lessen the use of relief medications. The effect, however, was not statistically significant for asthma (Giovannini 2007). Similar positive effects were observed among children with pollen-sensitized allergic rhinitis who were treated with oral Bacillus clausii spores (Ciprandi et al, 2005).

Studies that examined the effects of probiotics at the level of the immune system also showed some positive effects. Supplementation with L. gasseri significantly reduced serum IgE specific to Japanese cedar pollen in children with seasonal allergies (Morita 2006).

Positive effects were also observed among patients who received Bifidobacterium longum BB536 supplement (Xiao 2006). Moreover, BB536 seems to suppress Th-2 cell attraction and activation, suggesting it may be effective in blunting the IgE-mediated allergic response (Iwabuchi 2009). In a 28-week clinical trial, BB536 favorably modulated intestinal microbiotia, lessening the burden of allergens, in subjects with cedar pollen allergies (Odamaki 2007). In an experimental model, a BB536 DNA oligodeoxynucleotide, shunted the cytokine profile in favor of Th1 and suppressed IgE levels, both markers of and contributors to a lessened allergic response (Takahashi 2006).

In two randomized controlled trials studying the clinical effects of L. plantarum No. 14 (LP14), eosinophil counts decreased immediately after intake in the group that took LP14, and the percentage of Th1 helper T cells increased after 6 weeks. LP14 also strongly induced the gene expression of Th1-type cytokines, indicating that probiotics are clinically effective in the management of seasonal allergic disease.(Nagata 2010).

A review of 13 randomized, controlled trials on the effectiveness of probiotics in the treatment or prevention of atopic dermatitis found that, regardless of IgE sensitization, Lactobacillus rhamnosus GG (LGG) and other probiotics were effective in preventing AD. Probiotics also reduced the severity of AD in half of the trials evaluated, although there was no significant change observed in the inflammatory markers (Betsi 2008).

In terms of preventing allergies, a meta-analysis of six studies reported significant benefits in infants at high risk of allergy who used probiotic supplements containing L. rhamnosus. A recent study (Berni 2011) demonstrated that infants with suspected cow’s milk allergy who were given partially hydrolyzed infant food supplemented with LGG had a higher probability of acquiring tolerance to cow’s milk protein at 6 and 12 months compared with infants who were not given LGG supplementation. In addition, skin patch test responses were negative in all infants who acquired tolerance.

Clinical improvements have been reported among patients with allergic rhinitis and IgE-sensitized atopic eczema, but studies on the efficacy of probiotics in the management of asthma remain inconsistent. Possible reasons include differences in study designs, types of probiotics used and duration of probiotic supplementation, which limits the comparability of results (Ozdemir 2010).

 

 

Initial strategies to reduce allergy symptoms should include:

• Avoid known allergens as much as possible’
• Ensure that your environment is kept clean; regular vacuuming and use of an air purifier may help;
• Work with a qualified healthcare practitioner to identify allergens that you react to (using IgE antibody testing).  
• Quantitative IgG antibody testing can be clinically effective for food allergies – alternative practitioners could advise you on elimination diets

 

In addition, the following natural compounds may help ease allergy symptoms:

• Vitamin D: 5000 – 8000 IU daily; depending upon blood levels of 25-OH-vitamin D
• Natural Vitamin E: 100 – 400 IU alpha-tocopherol and 200 mg gamma-tocopherol daily
• Vitamin C: 1000 – 2000 mg daily
• Magnesium: 140 – 500 elemental milligrams of highly-absorbable magnesium
• Fish oil (with olive polyphenols): providing 1400 mg EPA and 1000 mg DHA daily
• Butterbur: standardized extract: 75 – 150 mg daily
• Quercetin (providing quercetin glycoside derivatives and free quercetin): 250 – 500 mg daily
• Stinging nettle (leaf); standardized extract: 500 – 1500 mg daily
• Spirulina: 1000 – 2000 mg daily
• Probiotics

 

American Academy of Allergy, Asthma and Immunology. Allergies. Available at http://www.aaaai.org/conditions-and-treatments/allergies.aspx. Accessibility verified December 17, 2011.

Anderson BE, Miller CJ, Adams DR. Stinging nettle dermatitis. Am J Contact Dermat. 2003 Mar;14(1):44-6.

Anthoni S et al. Milk protein IgG and IgA: the association with milk-induced gastrointestinal symptoms in adults. World J Gastroenterol. 2009 Oct 21;15(39):4915-8.

Asher MI, Montefort S, ISAAC Phase Three Study Group, et al. Worldwide time trends in the prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and eczema in childhood: ISAAC Phases One and Three repeat multicountry cross-sectional surveys. Lancet. 2006 Aug 26;368(9537):733-43.

Atkinson W et al. Food elimination based on IgG antibodies in irritable bowel syndrome: a randomised controlled trial. Gut. 2004 Oct;53(10):1459-64.

Bahceciler NN, Cobanoglu N. Subcutaneous versus sublingual immunotherapy for allergic rhinitis and/or asthma. Immunotherapy. 2011 Jun;3(6):747-56.

Bahna SL. Clinical expressions of food allergy. Ann Allergy Asthma Immunol. 2003 Jun;90(6 Suppl 3):41-4.

Bede O, Surányi A, Pintér K, Szlávik M, Gyurkovits K. Urinary magnesium excretion in asthmatic children receiving magnesium supplementation: a randomized, placebo-controlled, double-blind study. Magnes Res. 2003 Dec;16(4):262-70.

Bellanti JA. Cytokines and allergic diseases: clinical aspects. Allergy Asthma Proc 1998 Dec;19(6):337-41.

Bentz S et al. Clinical relevance of IgG antibodies against food antigens in Crohn's disease: a double-blind cross-over diet intervention study. Digestion. 10;81(4):252-64. Epub 2010 Jan 30.

Berger A. Th1 and Th2 responses: What are they? BMJ 2000;321:424.1.

Berni Canani R, Nocerino R, Terrin G, et al. Effect of Lactobacillus GG on tolerance acquisition in infants with cow's milk allergy: A randomized trial. J Allergy ClinImmunol. 2011 Nov 10.

Betsi GI, Papadavid E, Falagas ME. Probiotics for the treatment or prevention of atopic dermatitis: a review of the evidence from randomized controlled trials. Am J ClinDermatol. 2008;9(2):93-103.

Björkstén  B, Clayton T, et al. ISAAC Phase III Study Group. Worldwide time trends for symptoms of rhinitis and conjunctivitis: Phase III of the International Study of Asthma and Allergies in Childhood. Pediatr Allergy Immunol. 2008 Mar;19(2):110-24.

Bouhnik Y, Vahedi K, et al. Short-chain fructo-oligosaccharide administration dose-dependently increases fecal bifidobacteria in healthy humans. J Nutr 1999;129:113–6 .

Bousquet J, Khaltaev N, Cruz AA, Denburg J, et al. Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen). Allergy. 2008 Apr;63Suppl 86:8-160.

Boyle RJ, Ismail IH, Kivivuori S, et al. Lactobacillus GG treatment during pregnancy for the prevention of eczema: a randomized controlled trial.Allergy. 2011 Apr;66(4):509-16.

Branum AM, Lukacs SL. Food allergy among U.S. children: trends in prevalence and hospitalizations. NCHS Data Brief. 2008 Oct;(10):1-8.

Brattström  A, Schapowal A, Maillet I, et al. Petasites extract Ze 339 (PET) inhibits allergen-induced Th2 responses, airway inflammation and airway hyperreactivity in mice. Phytother Res. 2010 May;24(5):680-5.

Bucca C, Rolla G, et al. Effect of vitamin C on histamine bronchial responsiveness of patients with allergic rhinitis. Ann Allergy . 1990 Oct; 65(4):311–4.

Calder PC. N-3 polyunsaturated fatty acids, inflammation and immunity: pouring oil on troubled waters or another fishy tale? Nutr Res . 2001;21:309–41.

Calder PC. Polyunsaturated fatty acids and inflammation. BiochemSoc Trans . 2005 Apr; (pt 2): 423–7.

Calderon MA, Penagos M, Sheikh A, et al. Sublingual immunotherapy for allergic conjunctivitis: Cochrane systemic review and meta-analysis. Clin Exp Allergy. 2011 Sep;41(9):1263-72.

Camargo CA, RifasShiman SL, Litonjua AA, et al. Maternal intake of vitamin D during pregnancy and risk of recurrent wheeze in children at 3 y of age. Am J ClinNutr 2007;85:788–795

Casas IA , DobrogoszWJ. Validation of the probiotic concept: Lactobacillus reuteri confers broad-spectrum protection against disease in humans and animals. Microbial Ecology in Health and Disease 2000;12:247–85.

CederholmTE et al. Low levels of essential fatty acids are related to impaired delayed skin hypersensitivity in malnourished chronically ill elderly people. Eur J Clin Invest. 1994 Sep;24(9):615-20.

Centanni S, Santus P, Di Marco F, et al. The potential role of tocopherol in asthma and allergies: modification of the leukotriene pathway. Biodrugs . 2001;15(2):81–6.

Chang HH, Chen CS, Lin JY. High dose vitamin C supplementation increases the Th1/Th2 cytokine secretion ratio, but decreases eosinophilic infiltration in bronchoalveolar lavage fluid of ovalbumin-sensitized and challenged mice. J Agric Food Chem. 2009 Nov 11;57(21):10471-6.

Chang, Christopher, 2011. Asthma in Children and Adolescents: A Comprehensive Approach to Diagnosis and Management. Clinical Reviews in Allergy and Immunology. Doi: 10.1007/s12016-011-8261-3.

Chen LL et al. [Experimental study of spirulinaplatensis in treating allergic rhinitis in rats]. Zhong Nan Da XueXueBao Yi Xue Ban. 2005 Feb;30(1):96-8.

Chinellato I, Piazza M, Sandri M, et al. Vitamin D serum levels and markers of asthma control in Italian children. J Pediatr 2011;158:437–441.

Chirumbolo S, Marzotto M, Conforti A, et al.Bimodal action of the flavonoid quercetin on basophil function: an investigation of the putative biochemical targets. ClinMol Allergy. 2010 Sep 17;8:13.

Choi IS et al. Effects of dehydroepiandrosterone on Th2 cytokine production in peripheral blood mononuclear cells from asthmatics. Korean J Intern Med. 2008 Dec;23(4):176-81.

Choi SH, Yoo Y, Yu J, et al. Bronchial hyperresponsiveness in young children with allergic rhinitis and its risk factors. Allergy. 2007 Sep;62(9):1051-6.

Ciarallo L, Brousseau D, Reinert S. Higher-dose intravenous magnesium therapy for children with moderate to severe acute asthma. Arch PediatrAdolesc Med. 2000 Oct;154(10):979-83.

Ciarallo L, Sauer AH, Shannon MW. Intravenous magnesium therapy for moderate to severe pediatric asthma: results of a randomized, placebo-controlled trial. J Pediatr. 1996;129(6):809–14.

Cingi C et al. The effects of spirulina on allergic rhinitis. Eur Arch Otorhinolaryngol. 2008 Oct;265(10):1219-23. Epub 2008 Mar 15.

Ciprandi G, Vizzaccaro A, Cirillo I, Tosca MA. Bacillus clausii effects in children with allergic rhinitis. Allergy. 2005 May;60(5):702-3.

Clifford RL, Knox AJ. Vitamin D-a new treatment for airway remodelling in asthma?. Br J Pharmacol 2009;158:1426–1428.

Connor WE. N-3 Fatty acids from fish and fish oil: panacea or nostrum? Am J ClinNutr. 2001;74:415 – 6.

Cox L, Wallace D. Specific allergy immunotherapy for allergic rhinitis: subcutaneous and sublingual. Immunol Allergy Clin North Am. 2011 Aug;31(3):561-99.

Craig TJ, Sherkat A, Safaee S. Congestion and sleep impairment in allergic rhinitis. Curr Allergy Asthma Rep. 2010 Mar;10(2):113-21.

Cross ML, Gill HS. Can immunoregulatory lactic acid bacteria be used as dietary supplements to limit allergies? Int Arch Allergy Immunol . 2001 Jun;125(2):112–9.

Deng R, Chow TJ. Hypolipidemic, antioxidant, and antiinflammatory activities of microalgae Spirulina. CardiovascTher. 2010 Aug;28(4):e33-45.

Devereux G, Turner SW, Craig LCA, et al. Reduced maternal vitamin E intake during pregnancy is associated with asthma in 5-year-old children. Am J RespirCrit Care Med. 2006;174;499-507.

Devi PR, Kumar L, Singhi SC, Prasad R, Singh M. Intravenous magnesium sulfate in acute severe asthma not responding to conventional therapy. Indian Pediatr. 1997;34(5):389–97.

Dillon JS. Dehydroepiandrosterone, dehydroepiandrosterone sulfate and related steroids: their role in inflammatory, allergic and immunological disorders. Curr Drug Targets Inflamm Allergy. 2005 Jun;4(3):377-85.

Erkkola M, Kaila M, Nwaru BI, et al. Maternal vitamin D intake during pregnancy is inversely associated with asthma and allergic rhinitis in 5-year-old children. ClinExp Allergy 2009;39:875–882.

Fischbach F. A manual of Laboratory and Diagnostic Tests . 5th ed. Philadelphia , Pa : Lippincott-Raven; 1996.

Fishbein AB, FuleihanRL. The hygiene hypothesis revisited: does exposure to infectious agents protect us from allergy? CurrOpinPediatr. 2012 Feb;24(1):98-102.

Food and Agriculture Organization, World Health Organization (FAO/WHO). Report of Joint FAO/WHO expert consultation on evaluation of health and nutritional properties of probiotics in food including powder milk with live lactic acid bacteria. FAO/WHO Report no. 10-1-2001.WHOINT; Córdoba,Argentina.

Frank DN, Amand ALS, Feldman RA, et al. Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proceedings of the National Academy of Sciences of the United States of America. 2007;104(34):13780–13785.

Freishtat RJ, Iqbal SF, Pillai DK, et al. High prevalence of vitamin d deficiency among inner-city African American youth with asthma in Washington, DC. J Pediatr 2010;156:948– 952.

Garg A et al. Chemistry and pharmacology of the Citrus bioflavonoid hesperidin. Phytother Res. 2001 Dec;15(8):655-69.

GerasimovSV, VasjutaVV, MyhovychOO, Bondarchuk LI. Probiotic supplement reduces atopic dermatitis in preschool children: a randomized, double-blind, placebo-controlled, clinical trial. Am J ClinDermatol. 2010;11(5):351-61.

Giovannini M, Agostoni C, Riva E et al.; Felicita Study Group. A randomized prospective double blind controlled trial on effects of long-term consumption of fermented milk containing Lactobacillus casei in pre-school children with allergic asthma and/or rhinitis. Pediatr Res. 2007 Aug;62(2):215-20.

Goldin BR. Health benefits of probiotics. Br J Nutr1998;80:S203–S207 .

Gontijo-Amaral C, Ribeiro MA, GontijoLS, Condino-Neto A, Ribeiro JD. Oral magnesium supplementation in asthmatic children: a double-blind randomized placebo-controlled trial. Eur J ClinNutr. 2007 Jan;61(1):54-60. Epub 2006 Jun 21.

Guex JJ et al. Quality of life improvement in Latin American patients suffering from chronic venous disorder using a combination of Ruscusaculeatus and hesperidin methyl-chalcone and ascorbic acid (quality study). IntAngiol. 2010 Dec;29(6):525-32.

Gun F, Salman T, et al. Effect of probiotic supplementation on bacterial transaction in thermal injury. Surg Today . 2005;35(9):760–4.

Guo R, Pittler MH, Ernst E. Herbal medicines for the treatment of allergic rhinitis: a systematic review. Ann Allergy Asthma Immunol. 2007 Dec;99(6):483-95.

Gupta R, Sheikh A, Strachan DP, Anderson HR. Burden of allergic disease in the UK: secondary analyses of national databases. ClinExp Allergy. 2004 Apr;34(4):520-6.

Gürkan  F, Haspolat K, Bosnak M, et al. Intravenous magnesium sulphate in the management of moderate to severe acute asthmatic children nonresponding to conventional therapy. Eur J Emerg Med. 1999;6(3):201–5.

Hansen I, Klimek L, Mosges R, Hormann K. Mediators of inflammation in the early and the late phase of allergic rhinitis. CurrOpin Allergy ClinImmunol. 2004 Jun;4(3):159-63.

Hijazi N, Abalkhail B, et al. Diet and childhood asthma in a society in transition: A study in urban and rural Saudi Arabia . Thorax . 2000 Sep;55(9):775–9.

Hirano T, Kawai M, Arimitsu J, et al. Preventative effect of a flavonoid, enzymatically modified isoquercitrin on ocular symptoms of Japanese cedar pollinosis. Allergol Int. 2009 Sep;58(3):373-82. Epub 2009 May 25.

Hoare C, Li Wan Po A, Williams H. Systematic review of treatments for atopic eczema. Health Technol Assess. 2000;4(37):1-191.

Hollams EM, Hart PH, Holt BJ, et al. Vitamin D and atopy and asthma phenotypes in children: a longitudinal cohort study. EurRespir J. 2011 Dec;38(6):1320-7. Epub 2011 May 12.

Huang RY, Yu YL, Cheng WC, et al. Immunosuppressive effect of quercetin on dendritic cell activation and function. J Immunol. 2010 Jun 15;184(12):6815-21. Epub 2010 May 17.

Inoue K, Takano H, Shiga A, et al. Effects of volatile constituents of a rosemary extract on allergic airway inflammation related to house dust mite allergen in mice. Int J Mol Med. 2005 Aug;16(2):315-9.

Iwabuchi N et al. Suppressive effects of Bifidobacteriumlongum on the production of Th2-attracting chemokines induced with T cell-antigen-presenting cell interactions. FEMSImmunol Med Microbiol. 2009 Apr;55(3):324-34.

Jang AH, Kim TH, Kim GD, et al. Rosmarinic acid attenuates 2,4-dinitrofluorobenzene-induced atopic dermatitis in NC/Nga mice. IntImmunopharmacol. 2011 Sep;11(9):1271-7. Epub 2011 Apr 17.

Javanbakht MH, Keshavarz SA, Djalali M, et al. Randomized controlled trial using vitamins E and D supplementation in atopic dermatitis. J Dermatolog Treat. 2011 Jun;22(3):144-50. Epub 2010 Jul 24.

Jedrychowski W et al. Wheezing and asthma may be enhanced by broad spectrum antibiotics used in early childhood. Concept and results of a pharmacoepidemiology study. J PhysiolPharmacol. 2011 Apr;62(2):189-95.

Johansson SG, Bieber T, Dahl R, et al. Revised nomenclature for allergy for global use: Report of the Nomenclature Review Committee of the World Allergy Organization, October 2003. J Allergy ClinImmunol. 2004 May;113(5):832-6.

Johnston CS, Solomon RE, Corte C. Vitamin C depletion is associated with alterations in blood histamine and plasma free carnitine in adults. J Am CollNutr . 1996 Dec;15(6):586–91.

Joskova M, Franova S, Sadlonova V. Acute bronchodilator effect of quercetin in experimental allergic asthma. BratislLekListy. 2011;112(1):9-12.

Kalliomaki M, Kirjavainen P, Eerola E, et al. Distinct patterns of neonatal gut microflora in infants in whom atopy was and was not developing. J Allergy ClinImmunol 2001;107:129–34.

Kasper DL, Braunwald DE , et al. Harrison 's Principles of Internal Medicine . 16th ed. New York : McGraw-Hill Professional; 2005.

Kasperska-Zajac AE et al. Dehydroepiandrosterone in therapy of allergic diseases. Recent Pat Inflamm Allergy Drug Discov. 2009 Nov;3(3):211-3.

Kawai M, Hirano T, Arimitsu J, et al.Effect of enzymatically modified isoquercitrin, a flavonoid, on symptoms of Japanese cedar pollinosis: a randomized double-blind placebo-controlled trial. Int Arch Allergy Immunol. 2009;149(4):359-68. Epub 2009 Mar 17.

Kazaks AG, Uriu-Adams JY, Albertson TE, Shenoy SF, Stern JS. Effect of oral magnesium supplementation on measures of airway resistance and subjective assessment of asthma control and quality of life in men and women with mild to moderate asthma: a randomized placebo controlled trial. J Asthma. 2010 Feb;47(1):83-92.

Kelly D, Conway S. Bacterial modulation of mucosal innate immunity. Molecular Immunology. 2005;42(8):895–901.

Kelly D, King T, Aminov R. Importance of microbial colonization of the gut in early life to the development of immunity. Mutation Research. 2007;622(1-2):58–69.

Kempna P, Reiter E, Arock M, Azzi A, Zingg JM. Inhibition of HMC-1 mast cell proliferation by vitamin E: involvement of the protein kinase B pathway. J BiolChem 2004;279:50700-9.

Klemens CM, Berman DR, Mozurkewich EL. The effect of perinatal omega-3 fatty acid supplementation on inflammatory markers and allergic diseases: a systematic review. BJOG. 2011 Jul;118(8):916-25.

Konrad A, Mähler M, Arni S, et al. Ameliorative effect of IDS 30, a stinging nettle leaf extract, on chronic colitis. Int J Colorectal Dis. 2005 Jan;20(1):9-17.

Laires MJ, Monteiro C. Exercise, magnesium and immune function. Magnes Res. 2008 Jun;21(2):92-6.

Leaf A. On the reanalysis of the GISSI-Prevenzione. Circulation . 2002;105:1874 – 1875.

Lee DK, Gray RD, Robb FM, et al. A placebo-controlled evaluation of butterbur and fexofenadine on objective and subjective outcomes in perennial allergic rhinitis. ClinExp Allergy 2004; 34:646–64.

Lee J, Jung E, Koh J, Kim YS, Park D. Effect of rosmarinic acid on atopic dermatitis.JDermatol. 2008 Dec;35(12):768-71.

Lee JS, Yang EJ, Yun CY, et al. Suppressive effect of Petasites japonicas extract on ovalbumin-induced airway inflammation in an asthmatic mouse model. J Ethnopharmacol. 2011 Jan;133(2):551-7.

Lee JS, Yang EJ, Yun CY, Kim DH, Kim IS. Suppressive effect of Petasitesjaponicus extract on ovalbumin-induced airway inflammation in an asthmatic mouse model. J Ethnopharmacol. 2011 Jan 27;133(2):551-7. Epub 2010 Oct 26.

Leung DY, Nicklas RA, Li JT, et al. Disease management of atopic dermatitis: an updated practice parameter. Joint Task Force on Practice Parameters. Ann Allergy Asthma Immunol. 2004 Sep;93(3 Suppl 2):S1-21.

Li XM. Complementary and alternative medicine in pediatric allergic disorders. CurrOpin Allergy ClinImmunol. 2009 Apr;9(2):161-7.

Lin SY et al. Sublingual immunotherapy. OtolaryngolClin North Am. 2011 Jun;44(3):753-64, x-xi.

Litonjua AA. Childhood asthma may be a consequence of vitamin D deficiency. CurrOpin Allergy ClinImmunol 2009;9:202–207.

Mainardi T, Kapoor S, Bielory L. Complementary and alternative medicine: herbs, phytochemicals and vitamins and their immunologic effects. J Allergy ClinImmunol. 2009 Feb;123(2):283-94; quiz 295-6.

Mao TK et al. Effects of a Spirulina-based dietary supplement on cytokine production from allergic rhinitis patients. J Med Food. 2005 Spring;8(1):27-30.

Marles RJ et al. United States pharmacopeia safety evaluation of spirulina. Crit Rev Food SciNutr. 2011 Aug;51(7):593-604.

Meltzer EO, Blaiss MS, DereberyMJ, et al. Burden of allergic rhinitis: results from the Pediatric Allergies in America survey. J Allergy ClinImmunol. 2009 Sep;124(3 Suppl):S43-70. Epub 2009 Jul 9.

Metcalfe A, Williams J, McChesney J, et al. Use of complementary and alternative medicine by those with a chronic disease and the general population—results of a national population based survey. BMC Complement Altern Med. 2010;10:58.

Mitchell N et al. Randomised controlled trial of food elimination diet based on IgG antibodies for the prevention of migraine like headaches. Nutr J. 2011 Aug 11;10:85.

Mittman P. Randomized, double-blind study of freeze-dried Urticadioica in the treatment of allergic rhinitis. Planta Med. 1990 Feb;56(1):44-7.

Miyake Y, Sasaki S, Tanaka K, et al; Osaka Maternal and Child Health Study Group. Fish and fat intake and prevalence of allergic rhinitis in Japanese females: the Osaka Maternal and Child Health Study. J Am CollNutr. 2007 Jun;26(3):279-87.

Miyake Y, Sasaki S, Tanaka K, Hirota Y. Consumption of vegetables, fruit, and antioxidants during pregnancy and wheeze and eczema in infants. Allergy. 2010 Jun 1;65(6):758-65.

Moneret-Vautrin DA, Morisset M. Adult food allergy. Curr Allergy Asthma Rep . 2005 Jan;5(1):80–5.

Morita H, He F, Kawase M, Kubota A, et al.Preliminary human study for possible alteration of serum immunoglobulin E production in perennial allergic rhinitis with fermented milk prepared with Lactobacillus gasseriTMC0356. MicrobiolImmunol. 2006;50(9):701-6.

Moroi M, Uchi S, Nakamura K, et al. Beneficial effect of a diet containing heat-killed Lactobacillus paracaseiK71 on adult type atopic dermatitis. J Dermatol. 2011 Feb;38(2):131-9. doi: 10.1111/j.1346-8138.2010.00939.

Nagata Y, Yoshida M, Kitazawa H, Araki E, Gomyo T. Improvements in seasonal allergic disease with Lactobacillus plantarum No. 14. BiosciBiotechnolBiochem. 2010;74(9):1869-77.

O’Keefe SJ et al. Effect of fiber supplementation on the microbiota in critically ill patients. World J GastrointestPathophysiol. 2011 Dec 15;2(6):138-45.

Odamaki T et al. Influence of BifidobacteriumlongumBB536 intake on faecalmicrobiota in individuals with Japanese cedar pollinosis during the pollen season. J Med Microbiol. 2007 Oct;56(Pt 10):1301-8.

Oh H, Park CS, AhnHJ, Park YS, Kim HM. Effect of Perillafrutescens var. acutaKudo and rosmarinic acid on allergic inflammatory reactions. ExpBiol Med (Maywood). 2011 Jan;236(1):99-106.

Osakabe N, Takano H, Sanbongi C, et al. Anti-inflammatory and anti-allergic effect of rosmarinic acid (RA); inhibition of seasonal allergic rhinoconjunctivitis (SAR) and its mechanism. Biofactors. 2004;21(1-4):127-31.

Ozdemir O. Various effects of different probiotic strains in allergic disorders: an update from laboratory and clinical data. ClinExpImmunol. 2010 Jun;160(3):295-304.

Pan SJ, Kuo CH, Lam KP, et al.Probiotics and allergy in children--an update review. Pediatr Allergy Immunol. 2010 Jun;21(4 Pt 2):e659-66.

Pawankar R, Canonica G, Holgate S, Lockey R. (eds). World Health Organization (WAO) White Book on Allergy. 2011.

Pelto L, Ioslauri E, et al. Probiotic bacteria down-regulate the milk-induced inflammatory response in milk-hypersensitive subjects but have an immunostimulatory effect in healthy subjects . ClinExp Allergy. 1998 Dec;28(12):1474–9.

Penders J, Stobberingh EE, van den Brandt PA, Thijs C. The role of the intestinal microbiota in the development of atopic disorders. Allergy. 2007 Nov;62(11):1223-36.

Peng GC, Hsu CH. The efficacy and safety of heat-killed Lactobacillus paracasei for treatment of perennial allergic rhinitis induced by house-dust mite. Pediatr Allergy Immunol. 2005 Aug;16(5):433-8.

Peroni DG, Piacentini GL, Cametti E, Chinellato I, Boner AL. Correlation between serum 25-hydroxyvitamin D levels and severity of atopic dermatitis in children. Br J Dermatol 2011;164:1078–1082.

Pizzuti D, Senzolo M, Buda A, et al. In vitro model for IgE mediated food allergy. Scand J Gastroenterol. 2011 Feb;46(2):177-87. Epub 2010 Oct 28.

Randomized trial: maternal vitamin D supplementation to prevent childhood asthma (VDAART). ClinicalTrials.gov: NCT00920621.

Remberg P, Bjork L, Sterner O. Characteristics, clinical effect profile and tolerability of a nasal spray preparation for Artemisia abrotanum L for allergic rhinitis. Phytomedicine . 2004 Jan;11(1):36–42.

Remirez D et al. Role of histamine in the inhibitory effects of phycocyanin in experimental models of allergic inflammatory response. Mediators Inflamm. 2002 Apr;11(2):81-5.

Rogerio AP, Dora CL, Andrade EL, et al. Anti-inflammatory effect of quercetin-loaded microemulsion in the airways allergic inflammatory model in mice. Pharmacol Res. 2010 Apr;61(4):288-97.

Rolinck-Werninghaus C, Staden U, et al. Specific oral tolerance induction with food in children: transient or persistent effect on food allergy? Allergy . 2005 Oct;60(10):1320–2.

Rondón  C, Doña I, Torres MJ, Campo P, Blanca M. Evolution of patients with nonallergic rhinitis supports conversion to allergic rhinitis. J Allergy ClinImmunol. 2009 May;123(5):1098-102.

Roschek B Jr, Fink RC, McMichael M, Alberte RS. Nettle extract (Urticadioica) affects key receptors and enzymes associated with allergic rhinitis. Phytother Res. 2009 Jul;23(7):920-6.

Russel L et al. What’s Really Making You Sick? Life Extension Magazine September 2010.

Sabin BR, Saltoun CA, Avila PC. Advances in upper airway diseases and allergen immunotherapy. J Allergy ClinImmunol. 2011 Feb;127(2):342-50.

Sanbongi C, Takano H, Osakabe N, et al. Rosmarinic acid in perilla extract inhibits allergic inflammation induced by mite allergen, in a mouse model. ClinExp Allergy. 2004 Jun;34(6):971-7.

Saylor BW. Treatment of allergic and vasomotor rhinitis with hesperidin chalcone sodium. Arch Otolaryngol. 1949 Dec;50(6):813-20.

Scarfone RJ, LoiselleJM, Joffe MD, et al. A randomized trial of magnesium in the emergency department treatment of children with asthma. Ann Emerg Med. 2000;36(6):572–8.

Schapowal A. Butterbur Ze339 for the treatment of intermittent allergic rhinitis: dose-dependent efficacy in a prospective, randomized, double-blind, placebo-controlled study. Arch Otolaryngol Head Neck Surg 2004; 130: 1381–1386.

Schapowal A. Randomised controlled trial of butterbur and cetirizine for treating seasonal allergic rhinitis. BMJ 2002; 324:144–146.

Schapowal A. Treating intermittent allergic rhinitis: a prospective, randomized, placebo and antihistamine-controlled study of butterbur extract Ze 339. Phytother Res 2005; 19:530–537.

Searing DA, Leung DY. Vitamin D in atopic dermatitis, asthma and allergic diseases. Immunol Allergy Clin North Am. 2010 Aug;30(3):397-409.

Shahar, E., Hassoun, G., and Pollack, S. (2004). Effect of vitamin E supplementation on the regular treatment of seasonal allergic rhinitis. Ann. Allergy Asthma Immunol. 92, 654–658.

Sharief S, Jariwala S, Kumar J, Muntner P, Melamed ML. Vitamin D levels and food and environmental allergies in the United States: results from the National Health and Nutrition Examination Survey 2005–2006. J Allergy ClinImmunol 2011;127:1195–1202.

Shimoda H, Tanaka J, Yamada E, et al. Anti type I allergic property of Japanese butterbur extract and its mast cell degranulation inhibitory ingredients. J Agric Food Chem 2006; 54:2915–2920.

Shishehbor F, Behroo L, GhafouriyanBroujerdnia M, Namjoyan F, Latifi SM. Quercetin effectively quells peanut-induced anaphylactic reactions in the peanut sensitized rats. Iran J Allergy Asthma Immunol. 2010 Mar;9(1):27-34.

Sicherer SH. Food allergy. Mt Sinai J Med. 2011 Sep-Oct;78(5):683-96. doi: 10.1002/msj.20292.

Simpson CR, Newton J, Hippisley-Cox J, Sheikh A. Incidence and prevalence of multiple allergic disorders recorded in a national primary care database. J R Soc Med. 2008 Nov;101(11):558-63.

Soutar A, Seaton A, et al. Bronchial reactivity and dietary antioxidants. Thorax . 1997 Feb;52(2):166–70.

Spergel JM. Epidemiology of atopic dermatitis and atopic march in children. Immunol Allergy Clin North Am. 2010 Aug;30(3):269-80.

Spergel JM, Paller AS. Atopic dermatitis and the atopic march. J Allergy ClinImmunol. 2003 Dec;112(6 Suppl):S118-27.

Sudo N, Yu XN, Aiba Y, et al. An oral introduction of intestinal bacteria prevents the development of a long-term Th2-skewed immunological memory induced by neonatal antibiotic treatment in mice. Clinical and Experimental Allergy. 2002;32(7):1112–1116

Takahashi N et al. Oral administration of an immunostimulatory DNA sequence from Bifidobacteriumlongum improves Th1/Th2 balance in a murine model. BiosciBiotechnolBiochem. 2006 Aug;70(8):2013-7.

Takano H, Osakabe N, Sanbongi C, et al.Extract of Perillafrutescens enriched for rosmarinic acid, a polyphenolic phytochemical, inhibits seasonal allergic rhinoconjunctivitis in humans.ExpBiol Med (Maywood). 2004 Mar;229(3):247-54.

Thomet OA, Schapowal A, Heinisch IV, Wiesmann UN, Simon HU. Anti-inflammatory activity of an extract of Petasiteshybridus in allergic rhinitis. IntImmunopharmacol. 2002 Jun;2(7):997-1006.

Thorp WA, Goldner W, Meza J, Poole JA. Reduced vitamin D levels in adult subjects with chronic urticaria. J Allergy ClinImmunol 2010;126:413.

Troisi RJ, Willett WC, Weiss ST, et al. A prospective study of diet and adult-onset asthma. Am J RespirCrit Care Med. 1995;151:1401-1408.

Troncone  R, Caputo N, Florio G, Finelli E. Increased intestinal sugar permeability after challenge in children with cow’s milk allergy or intolerance. Allergy. 1994;49(3):142–146.

Tsoureli-Nikita E, Hercogova J, Lotti T, Menchini G. Evaluation of dietary intake of vitamin E in the treatment of atopic dermatitis: a study of the clinical course and evaluation of the immunoglobulin E serum levels. Int J Dermatol. 2002 Mar;41(3):146-50.

Vinderola CG, Medici M, Perdigon G. Relationship between interaction sites in the gut, hydrophobicity, mucosal immunomodulating capacities and cell wall protein profiles in indigenous and exogenous bacteria. J ApplMicrobiol . 2004;96(2):230–43.

Wallace DV, Dykewicz MS, Bernstein DI, et al. The diagnosis and management of rhinitis: An updated practice parameters. J Allergy ClinImmunol 2008; 122: S1-S84

Wang MF, Lin HC, Wang YY, Hsu CH. Treatment of perennial allergic rhinitis with lactic acid bacteria. Pediatr Allergy Immunol 2004: 15: 152–8.

Watanabe T, Kuroda Y. The effect of a newly developed ointment containing eicosapentaenoic and docosahexaenioc acid in the treatment of atopic dermatitis. J Med Invest . 1999 Aug;46(3–4):173–7.

Weiss ST, Litonjua AA. Childhood asthma is a fat-soluble vitamin deficiency disease. ClinExp Allergy 2008;38:385–387.

Wenzel SE et al. Nebulized dehydroepiandrosterone-3-sulfate improves asthma control in the moderate-to-severe asthma results of a 6-week, randomized, double-blind, placebo-controlled study. Allergy Asthma Proc. 2010 Nov-Dec;31(6):461-71.

Xiao JZ, Kondo S, Yanagisawa N, et al. Probiotics in the treatment of Japanese cedar pollinosis: a double-blind placebo-controlled trial. ClinExp Allergy. 2006 Nov;36(11):1425-35.

Yu LC. Intestinal epithelial barrier dysfunction in food hypersensitivity. J Allergy (Cairo). 2012;2012:596081.

Yuksel H, Dinc G, Sakar A, et al. Prevalence and comorbidity of allergic eczema, rhinitis, and asthma in a city in western Turkey. J InvestigAllergolClinImmunol. 2008;18(1):31-5.

Zhang J, ParéPD, SandfordAJ. Recent advances in asthma genetics. Respir Res. 2008 Jan 15;9:4.

Zheng K, Adjei A, Shinjo M, et al. Effect of dietary vitamin E supplementation on murine nasal allergy. Am. J. Med. Sci. 1999. 318, 49–54.

Zheng T, Yu J, Oh MH, Zhu Z. The atopic march: progression from atopic dermatitis to allergic rhinitis and asthma. Allergy Asthma Immunol Res. 2011 Apr;3(2):67-73.

Zingg JM. Vitamin E and mast cells. VitamHorm 2007;76:393-418.