Natural Support for Allergies
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).
Although many epidemiological studies over the past decade have clearly identified a link between vitamin D levels and asthma and/or atopic diseases, such studies have limitations and cannot establish causality. A clinical trial examining whether maternal supplementation with 4,000 IU of vitamin D daily can reduce the incidence of asthma in their offspring during the first three years of life is currently underway. This trial will provide stronger evidence regarding the role of vitamin D in preventing allergies (Randomized trial: maternal vitamin D supplementation to prevent childhood asthma (VDAART). ClinicalTrials.gov: NCT00920621.)
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 (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 antihistamine 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 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).
Life Extension suggests that the omega-6 to omega-3 ratio should be kept below 4 to1 for optimal health. More information on testing and optimizing your omega-6 to omega-3 ratio can be found in the Life Extension Magazine article entitled “Optimize Your Omega-3 Status”.
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 trialss 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, 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).
Hesperidin Methyl Chalcone
Chemically similar to quercetin, the flavonoid hesperidin has been studied in a variety of contexts in both experimental models and in human clinical trials (Garg 2001). Its chalcone form was specifically studied in 99 atopic individuals in 1949. At daily doses ranging from 100 – 600 mg, hesperidin methyl chalcone provided complete relief of allergic symptoms in 35% of study participants; another 34% of the subjects achieved partial symptom relief (Saylor 1949). More recently, hesperidin methyl chalcone has emerged as an effective treatment for chronic venous disorders (Guex 2010). Today, innovative doctors frequently suggest hesperidin methyl chalcone to patients with allergic symptoms and report clinical effectiveness.
Rosmarinic acid is a flavonoid found in various herbs such as basil, sage, mint, rosemary and Perilla frutescens. It is reported to have antioxidant, anti-inflammatory, anti-microbial, and anti-tumor effects (Mainardi 2009; Jang 2011). Rosmarinic acid can also inhibit pro-inflammatory cytokines and chemokines and stabilize mast cells (Osakabe 2004; Takano 2004). In animal models, cell cultures, and human studies, rosmarinic acid has shown potential as a natural therapeutic agent for asthma and allergic diseases.
Researchers demonstrated that daily treatment with rosmarinic acid from perilla leaf extract given orally to mice prevented allergic asthma caused by dust mite allergen. The investigators concluded that oral administration of perilla-derived rosmarinic acid may treat allergic asthma effectively by attenuating the production of cytokines and allergy-specific antibodies (Sanbongi 2004). In another study, volatile rosemary extract significantly suppressed cytokines, eosinophils and neutrophils in mice models of allergic asthma induced by house dust mites (Inoue 2005). Similarly, rosmarinic acid effectively suppressed cytokines, chemokines and IgE levels in murine models of atopic dermatitis (Jang 2011). It was also able to alleviate symptoms related to allergic rhinitis and allergic rhinoconjunctivitis in allergen-sensitized animal models (Oh 2011).
Oral supplementation with rosmarinic acid in patients with allergic rhinoconjunctivitis significantly relieved symptoms and inhibited eosinophils in nasal lavage fluid (Osakabe 2004). Another study demonstrated that perilla leaf extract enriched with rosmarinic acid is effective among humans suffering from seasonal allergic symptoms (Takano 2004). In this study, rosmarinic acid inhibited the eye-related symptoms associated with seasonal allergies. In a randomized study on atopic dermatitis, patients given topical rosmarinic emulsions applied to the elbows twice a day for 8 weeks reported improvement in skin dryness and redness and general symptomatic relief (Lee 2008).
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).
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 2,000mg 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
Dehydroepiandrosterone (DHEA) and its metabolites are naturally present in humans and exert an array of actions throughout human physiology. DHEA has been studied in numerous contexts, and it is from these studies that the realization that DHEA possess considerable immunomodulatory action has arisen.
With respect to its immunological properties, DHEA has been shown to promote balance between Th1 and Th2 cytokines and combat inflammatory responses (Dillon 2005; Kasperska-Zajac 2009). Accordingly, researchers have carried these findings forward and examined the impact of DHEA on allergic reactions in clinical trials.
In once trial, immune cells were taken from subjects with asthma and cultured with or without DHEA. When DHEA was included, those immune cells produced less inflammatory cytokines and other allergic mediators, leading the investigators to conclude that “DHEA may be a useful therapy for asthma” (Choi 2008). Another group (Wenzel 2010) showed that nebulized (inhaled) DHEA-sulfate (DHEA-s; a major metabolite of DHEA) improved symptoms in patients with asthma.
Several lines of evidence support an anti-inflammatory role of DHEA in atopic individuals (Kasperska-Zajac 2009), but levels of DHEA decline with advancing age. Supplementation with DHEA can restore blood levels of DHEA-s to youthful ranges. Individuals interested in reading more about DHEA should consult Life Extension’s Male and Female Hormone Restoration Therapy protocols.