Targeted Nutritional Strategies
Vitamin D plays a crucial role in regulating a broad range of immune processes and anti-inflammatory reactions involved in asthma. Laboratory evidence from several animal models of allergic asthma suggest that vitamin D may play a role in reversing airway remodeling or airway inflammation in the asthmatic lung (Taher 2008; Damera 2009). Evidence also suggests that vitamin D may protect against asthma exacerbations (Majak 2011). Studies among asthma patients found that low or deficient blood levels of vitamin D were associated with several indicators of asthma (Chinellato 2011; Sutherland 2010; Searing 2010).
Observational studies have shown that pregnant women with higher intakes of vitamin D had children with lower risks of wheezing and asthma compared to women with lower intakes of prenatal vitamin D (Devereux 2007; Erkkola 2009; Miyake 2010a). Also, a longitudinal study on children with mild to moderate persistent asthma showed that low vitamin D levels were associated with higher risk of severe asthma exacerbations over a 4-year period (Brehm 2010). Another study found that children who have low vitamin D levels at age 6 are more likely to have asthma at age 14 compared to children with higher vitamin D levels (Hollams 2011).
In order to establish causality, intervention studies registered with the National Institutes of Health (clinicaltrials.gov) are underway to assess the ability of vitamin D to prevent or reduce the risk of asthma. Two randomized controlled clinical trials are ongoing to determine if maternal vitamin D supplementation can prevent childhood asthma (NCT00920621; NCT00856947). A clinical trial on adolescents and adults with asthma will test whether vitamin D supplementation affects the time of the first upper respiratory infection or severe exacerbation (NCT00978315). Another clinical trial on adults will test the effect of adding vitamin D to low-dose controller medications to prevent asthma symptoms and attacks (NCT01248065).
A number of studies have suggested that consuming antioxidants such as vitamins C, E, flavonoids, and selenium, among others reduces the bronchoconstriction associated with asthma.
Vitamin E is a collective name for a group of four tocopherols and four tocotrienols, which possess antioxidant and anti-inflammatory properties. Studies have shown that vitamin E prevents the release of inflammatory cytokines, and specifically inhibits gene expression of IL-4 (Li-Weber 2002).
Studies have shown that asthma patients with higher vitamin E intakes had lower prevalence of wheezing, cough and shortness of breath compared to those with lower intakes (Litonjua 2012). Some studies also report that low maternal vitamin E intake is associated with an increased risk of wheezing in infants and children
(Miyake 2010b; Litonjua 2006), reduced lung function and increased risk of asthma in children 5 years old (Devereux 2006). While one formal review of studies confirmed the protective effect of maternal vitamin E intake on wheezing (Nurmatov 2011), another did not find evidence for an association between dietary intake of vitamin E and the risk of asthma (Gao 2008).
Population based and experimental studies provide evidence for the link between low levels of vitamin C and asthma. An animal model has shown that supplementing with high-dose vitamin C at the time of allergy challenge decreased airway hyper-reactivity and lowered the number of inflammatory cells (Jeong 2010).
One randomized controlled trial demonstrated the role of antioxidants in asthma. Children with persistent asthma who were supplemented with omega-3 fatty acids, vitamin C, or zinc experienced improved lung function. When children received all three nutrients their lung function improved to an even greater extent than it did with the individual nutrients (Biltagi 2009). Another clinical trial of eight asthmatic subjects found that those given 1,500 mg of vitamin C daily for two weeks experienced significantly improved asthma symptom scores compared to subjects receiving placebo (Tecklenburg 2007).
Polyunsaturated Fatty Acids
The two main groups of polyunsaturated fatty acids (PUFAs) include omega-3’s and omega-6’s. Typical sources of omega-3 fatty acids include fish oil, leafy green vegetables, nuts, and flaxseeds. Primary food sources of omega-6 fatty acids include vegetable oils like corn and sunflower oils, and nuts.
The Western diet has seen a decrease in consumption of foods rich in anti-inflammatory omega-3 fatty acids and an increase in pro-inflammatory omega-6 fatty acids, a trend that may have contributed to a rise in asthma and allergic diseases (Black 1997). Observational studies report that higher intake of fish oil may be associated with lower risk of asthma (Laerum 2007; Miyamoto 2007), while higher intake of margarine was associated with asthma (Nagel 2005). Intervention studies also reported a potential benefit for the use of fish oil and omega-3 fatty acid supplements for asthma (Mickleborough 2006; Schubert 2009).
Evidence suggests that supplementation with beneficial bacteria – probiotics – may modulate components of the immune response and inflammatory processes (Feleszko 2007; Lomax 2009). Therefore, as asthma and allergy are intrinsically tied to inflammation, scientists have been interested in studying the effects of probiotics in people with asthma or other allergic diseases.
Probiotics have reliably shown positive effects in allergic rhinitis – a condition with allergic inflammation, similar to asthma. However, a clear therapeutic role of probiotics in adults with asthma needs to be further elucidated (Vliagoftis 2008). Although, probiotics have been shown to be effective among children with asthma (Chen 2010).
Studies have shown that people with chronic or severe asthma may suffer from a selenium deficiency (Qujeq 2003; Allam 2004; Rubin 2004). Several studies have examined the use of selenium supplementation in asthma. One study found a decrease in corticosteroid use when patients were supplemented with 200 mcg daily (Gazdik 2002), while another study found significant clinical improvement with 100 mcg daily (Allam 2004). A 2007 study of 26 selenium deficient, asthmatic patients revealed improvements in asthma-related quality of life and lung function measurements when deficiency was corrected with 200 mcg of selenium daily for 16 weeks (Voicekovska 2007). Another randomized controlled study revealed improvements in quality of life with no change in objective lung function measures (Shaheen 2007).
Large studies found that higher maternal intakes of zinc during pregnancy may protect against childhood wheezing and asthma (Litonjua 2006; Devereux 2006). Another study demonstrated that low levels of zinc in the sputum were associated with more episodes of wheezing, severe asthma and decreased lung function (Jayaram 2011). Also, a study found that allergic mice exposed to cockroach allergen and supplemented with zinc had significantly lower cytokines in their airways, lower blood IgE levels, and decreased airway hyper-responsiveness (Morgan 2011).
Laboratory studies indicate that magnesium can relax bronchial smooth muscles. (Gourgoulianis 2001).
In a randomized, placebo-controlled trial, patients with mild to moderate asthma who received 340 mg of magnesium daily for 6.5 months were found to have significantly lower bronchial reactivity, improved lung function, better asthma control and quality of life compared to the placebo group (Kazaks 2010). Two other trials among children with mild to moderate persistent asthma found similar benefits with magnesium supplementation (Bede 2003; Gontijo-Amaral 2007).
A recent comprehensive review of 16 clinical trials confirmed the benefit and safety of using intravenous magnesium sulfate in severe exacerbations (Song 2012).
Curcumin, a yellow pigment in the spice turmeric (found in curry powder), inhibits nuclear factor kappa-B (Nf-kB), a protein involved in the production of inflammatory cytokines (Oh 2011). This was demonstrated in a laboratory animal model of asthma where treatment with curcumin reduced airway hyper-responsiveness, prevented the activation of Nf-kB, and reduced the number of leukocytes (white blood cells) in lung fluid (Oh 2011).
Researchers looking at the effects of lycopene (the red pigment found in tomatoes and some fruits) on asthma patients found that more than half of the patients supplemented with lycopene were significantly protected from exercise-induced asthma (Neuman 2000). In animal models, lycopene supplementation suppressed the release of cytokines associated with the allergic response, suppressed the influx of eosinophils and mucus-secreting cells into the lung tissue and airways (Hazlewood 2011), and suppressed airway hyper-responsiveness and inflammatory mediators (Lee 2008).
Flavonoids are polyphenols (found in fruits, vegetables, red wine, and tea) that have antioxidant and anti-inflammatory properties. Flavonoids have been associated with improved lung function (Garcia 2005). The following flavonoids/ flavonoid-containing plants have been studied in the context of asthma:
- Quercetin. Part of quercetin’s chemical structure is similar to cromolyn, a mast cell stabilizer sometimes used to treat asthma (Weng 2012). In one study, a high dietary intake of the flavonoids quercetin (found in wine, tea, and onions), naringenin (found in oranges and grapefruit), and hesperetin (found in oranges and lemons) was associated with a lower prevalence of asthma (Knekt 2002). Several animal models of asthma have demonstrated the anti-inflammatory properties of quercetin. In one study, a single-dose oral administration of quercetin caused significant broncodilation, both in culture and in vivo (Joskova 2011). In another study, oral administration of quercetin significantly reduced levels of the inflammatory cytokines IL-5 and IL-4 as well as inhibited mucus production in the lungs (Rogerio 2010). In yet another animal model, quercetin significantly inhibited all asthmatic reactions when it was administered before an asthma-inducing substance (Park 2009).
- Proanthocyanidin. Proanthocyanidin is the main constituent of Pycnogenol®, an extract from the French maritime pine bark. Proanthocyanidin is a powerful antioxidant that neutralizes free radicals (Cos 2004). A randomized, placebo-controlled trial found that children with mild to moderate asthma who received Pycnogenol® for 4 weeks in addition to daily and/or rescue inhalers had significantly improved lung function and asthma symptoms compared to the placebo group. Also, the treatment group was able to reduce or discontinue use of rescue medication(s) more often than the control group (Lau 2004). Similar results were found in a more recent trial among adults with stable, controlled asthma who used Pycnogenol® as an adjunct compared to inhaled corticosteroid only or placebo (Belcaro 2011).
- Ginkgo biloba. A flavonoid-rich extract of leaves of the Ginkgo biloba tree appears to be an effective asthma therapy (Mahmoud 2000; Li 1997; Tang 2007). In one study, ginkgo biloba extract was added to corticosteroids for 2 weeks. Researchers found that the sputum of patients on the ginkgo therapy had significantly less inflammatory cells compared to the drug-only or placebo groups, suggesting that ginkgo extract may relieve the airway inflammation associated with asthma (Tang 2007). In an animal model of asthma where an allergy challenge was followed by treatment with ginkgo, the extract inhibited the release of eosinophils in the lung tissue and mucus-secreting cells in the airways (Chu 2011).
Butterbur (Petasites hybridus) is a perennial shrub used since ancient times to treat a variety of conditions. Four substances - petasin, isopetasin, S-petasin and S-isopetasin - isolated from the plant can inhibit leukotrienes (inflammatory mediators associated with asthma) (Thomet 2002).
A few research teams have examined butterbur’s effectiveness for asthma with encouraging results. In one open label trial of 64 adults and 16 children and adolescents, asthma patients were treated for two months with butterbur extract, followed by an optional two-month treatment period. Data showed that all the measured symptoms improved throughout the study, and 40% of patients were able to reduce their intake of traditional asthma medications (Danesch 2004). Another study found that butterbur therapy, in conjunction with inhaled corticosteroids, reduced asthma symptoms (Lee 2004).
Results from a laboratory animal model showed potential for S-petasin as a therapeutic agent for asthma. S-petasin, administered under the skin of allergen-challenged asthmatic animals, significantly slowed the production of inflammatory cells and mediators as well as relaxed the bronchial tubes, suggesting that S-petasin has both anti-inflammatory and bronchodilator properties (Shih 2009). An animal model testing butterbur extract observed similar anti-inflammatory effects on asthmatic mice (Brattström 2010).
Evidence suggests that compounds within the gum resin of the Boswellia serrata tree modulate the inflammatory process that drives asthma symptoms. Boswellia serrata inhibits leukotriene synthesis by blocking activity of the 5-lipoxygenase enzyme (5-LOX) (Siddiqui 2011). Moreover, it suppresses other enzymes (prostaglandin E synthase-1 and the serine protease cathepsin G) that, like 5-LOX, normally generate inflammatory compounds within the body (Abdel-Tawab 2011).
Two clinical trials have investigated the action of Boswellia serrata extract alone or in combination with other natural anti-inflammatory agents among people with asthma. First, 40 asthmatic subjects were randomized to receive either 300 mg of boswellia serrata extract or placebo three times daily for six weeks (Gupta 1998). While improvement was seen in only 27% of subjects receiving placebo, 70% of those receiving Boswellia serrata extract experienced improvements in symptoms such as breathlessness, wheezing, and number of attacks. Those in the boswellia group also exhibited decreased eosinophil count and lower erythrocyte sedimentation rate (ESR) – both measures of inflammation. In the second trial, 63 asthma patients took either a combination of boswellia, curcumin, and licorice root or placebo three times daily for four weeks (Houssen 2010). The herbal combination caused a significant decline in levels of an LTC4 (an inflammatory leukotriene) and two markers of oxidative stress – malondialdehyde and nitric oxide. The scientists stated that a combination of boswellia, curcumin, and licorice root “has a pronounced effect in the management of bronchial asthma.”
Tylophora indica (Tylophora asthmatica)
Tylophora indica (T. indica) is a vine whose leaves have been studied as a potential therapy for asthma symptoms. In studies published in the late 60’s and early 70’s, T. indica relieved asthma symptoms more effectively than a control (Shivpuri 1969; Shivpuri 1972; Mathew 1974). Unfortunately, no newer studies have rigorously evaluated T. indica as an asthma treatment. However, investigators recently pooled the data from the older trials and found that the treatment effect remained significant after adjustment for variables (Clark 2010). They concluded that “…Tylophora indica showed potential to improve lung function…”.