Natural Foods Merchandiser

Asthma Attack

An estimated 20 million Americans suffer from asthma. The severity of an asthma episode can range from mild to life-threatening, but in general all asthma attacks are characterized by the same primary symptoms: shortness of breath (dyspnea), chest tightness or pain, wheezing and coughing.

An individual in the grip of a severe asthma attack literally cannot breathe. According to the American Academy of Allergy, Asthma and Immunology in Milwaukee, at least 5,000 people die from asthma attacks each year in the United States. The root cause of the problem is inflammation of the bronchial tubes, which results in constriction and narrowing of the airways. Half of all asthma is related to allergies, but viral infection, airborne pollutants, exercise and other factors may trigger asthma attacks.

Treat symptoms and cause
Standard treatments for asthma fall into two main categories: symptomatic remedies for acute attacks, such as bronchodilators (substances that relax the constricted muscles of the bronchial tubes), and longer-term solutions, such as anti-inflammatory medications.

Various herbs have been used for the treatment of both asthma and allergies in traditional healing systems and, in scientific studies, some have demonstrated potent bronchodilating effects. Chief among these herbs is ephedra (Ephedra sinica, also called ma huang), long used in traditional Chinese medicine as a component of herbal formulas for treating asthma, eczema, hay fever and respiratory tract infections. Ephedra is the original source of the powerful alkaloids ephedrine and pseudoephedrine, which in synthetic form are approved by the U.S. Food and Drug Administration for use in asthma and allergy pharmaceuticals (for example, pseudoephedrine is found in the decongestant Sudafed). Safety concerns now limit the sale of dietary supplements containing ephedra in the United States.

Recent research findings suggest that various other dietary supplements may have more to offer in terms of managing asthma. Research on the role of oxidative damage in serious lung conditions has led to promising investigations of the role of antioxidants in asthma management. As well, a growing understanding of the role of inflammation in asthma has encouraged research into the effects of omega-3 fatty acids in reducing asthma incidence and improving symptoms in both children and adults. And clinical research on two ephedra-free Chinese herbal formulas suggests that traditional Chinese medicine has additional contributions to make to asthma treatment.

The role of antioxidants
Research suggests that antioxidant deficiency and the resultant oxidative stress can play a role in the development of asthma.1,2,3 According to this hypothesis, low levels of antioxidants give the body little fighting power to resist inflammation forming in the airways. This then encourages the production of free radicals, which in turn aggravates asthma by increasing oxidative stress in the lungs.2 Once the inflammation process has begun, the oxidative stress creates more inflammation, which leads to more asthma.

That said, increasing the amount of a particular antioxidant in the body doesn't necessarily correlate with improved asthma symptoms. For instance, research suggests that supplementation with vitamin C (a powerful antioxidant) is not necessarily helpful in the treatment of asthma.4 Nonetheless, there is increasing evidence that various other antioxidants may help in asthma management.2,5,6,7

In fact, low levels of numerous antioxidants have been documented in people with asthma.3,6 In one placebo-controlled study involving 56 adults, researchers found significantly decreased levels of the antioxidants coenzyme Q10 and alpha-tocopherol in the plasma and whole blood of people with asthma, compared with controls, but no difference in the levels of beta-carotenes.3 In contrast, another trial showed that asthmatics have lower whole-blood levels of total carotenoids than healthy controls, in spite of similar dietary intakes.6 This study also demonstrated that oral supplementation with 20 mg per day of lycopene for four weeks raised plasma levels of lycopene, which were reflected in higher levels of the antioxidant in the airways. This is important in that it suggests lycopene from orally ingested lycopene supplements does, in fact, reach the lungs.6

Another small, placebo-controlled study suggests that supplementation with lycopene and other antioxidants helps reduce acute airway hyperreactivity in people with exercise-induced asthma.5 For the study, 20 people with EIA were randomly assigned to take either a proprietary mixture of tomato-derived lycopene combined with other carotenoids, tocopherols, phytoene and phytofluene (30 mg per day) or placebo for one week. They then took an exercise challenge to assess lung function; after this, the two groups were switched and the process repeated. According to the results, all placebo recipients had a significant reduction in post-exercise lung function (as measured by forced expiratory volume), but 55 percent of those who took the lycopene mixture were protected against this decline.

More evidence for antioxidants comes from a clinical study of a proprietary mixture of bioflavonoids made from the bark of French maritime pine (Pinus maritima), widely known by the trade name Pycnogenol.7 The randomized, placebo-controlled, double-blind study investigated the effects of pine extract in 60 children with mild-to-moderate asthma. The children were randomly assigned to take either pine extract (1 mg/day per pound of body weight) or an identical-looking placebo in divided doses. At the end of the three-month study, children who took the pine extract had significantly greater improvements in lung function and asthma symptoms and were more often able to reduce or discontinue their use of inhalers. Those in the pine extract group also showed a reduction in excretion of urinary leukotrienes, molecules that are associated with the inflammatory process of asthma. Similar results were reported in an earlier clinical trial involving 26 asthmatic adults.8

N-acetyl cysteine (an amino acid derivative with strong antioxidant activity) has also demonstrated beneficial effects in the treatment of a variety of serious lung problems, including chronic obstructive pulmonary disease, pulmonary fibrosis, acute lung injury and flu-related symptoms.1 An animal study conducted in 2002 showed that N-acetyl cysteine supplementation did not immediately reduce bronchospasm in rats exposed to an allergic challenge, but was effective in reducing airway hyperreactivity and the number of eosinophils (inflammatory cells) 24 hours after exposure to the allergen.1 According to the American Lung Association, approximately half of immediate allergic reactions to inhaled allergens are followed by a later reaction that causes more serious injury, airway inflammation and increased hyperreactivity.9 This preliminary animal study suggests that NAC may also be useful as an antioxidant in management of asthma symptoms.

Omega-3 fatty acids
Omega-3 essential fatty acids, a subgroup of polyunsaturated fatty acids, have demonstrated promise not only for ameliorating symptoms of asthma, but also in affecting the inflammatory processes that mediate disease.

In particular, eicosapentaenoic acid and docosahexaenoic acid from fish oil are known to inhibit the formation of pro-inflammatory leukotrienes and prostaglandins and reduce the production of cytokines from inflammatory cells.10 EPA may also produce other leukotrienes that are actually anti-inflammatory in and of themselves.11 One clinical study of 26 adults with asthma suggests that reduction in asthma symptoms after omega-3 supplementation is related to EPA production of 5-series leukotrienes. This study also showed that while a ratio of 1:1 omega-3s and -6s tended to diminish respiratory capacity in study participants, 40 percent of participants experienced significant improvement with a ratio of 1:0.5 omega-3s to omega-6s, which supplied a higher proportion of omega-3s to omega-6s.11

Fish oil supplementation may also be specifically effective against exercise-induced asthma. A small, randomized, double-blind, crossover clinical study published early this year concluded that supplementation with fish oil ameliorated the severity of exercise-induced airway narrowing in 16 people with persistent, mild-to-moderate asthma. The study subjects were randomly assigned to take either placebo or fish oil capsules (providing a daily dose of 3.2 g EPA and 2.0 g DHA) for three weeks before undergoing exercise challenge and pulmonary function tests. The two groups were then switched and the process repeated. Fish oil supplementation improved pulmonary function and significantly reduced concentrations of leukotrienes, prostaglandins and other markers of inflammation. The researchers also reported a more than 31 percent reduction in the use of asthma inhalers among study participants.12

Two controlled studies suggest that omega-3s may have an important role to play in prevention and treatment of childhood asthma. In the first study, 29 children with asthma were randomly assigned to take either placebo or fish oil capsules (300 mg fish oil, delivering 84 mg EPA and 36 mg DHA) for 10 months. Dosage, which was determined by body weight, ranged from 6 to 12 capsules/day. According to the results, children in the fish oil group had significant decreases in asthma scores and improved resistance to allergic challenge after treatment, indicating reductions in airway inflammation.10

The second study investigated the relationship between omega-3 fatty acid plasma concentrations and symptoms of asthma and atopy (allergic eczema) in 18-month-old Australian children. Researchers recruited study participants from a pool of pregnant women at risk of asthma because of family history; at six months of age the babies were randomly assigned to take either placebo or tuna oil supplements (500 mg/day tuna oil; content of EPA and DHA were not specified). A total of 376 children were evaluated at 18 months of age. The researchers reported that higher levels of omega-3 fatty acids in plasma were associated with reductions in some early childhood asthma symptoms, including wheezing and nighttime coughing. The researchers observed statistically significant reductions in wheezing, doctor visits for wheezing, nighttime coughing and bronchodilator use among children with higher plasma levels of omega-3s compared with placebo. However, only 61 percent of children in the study underwent plasma evaluation, a possible source of study bias. The researchers caution that their results may not correlate well with actual chances of developing asthma in later childhood.13

A lipid extract of New Zealand green mussel (Perna canaliculus), also rich in omega-3s, demonstrated benefits specifically against allergic asthma in a randomized, placebo-controlled, double-blind clinical trial conducted in Russia. For the study, 46 adults with allergic asthma were randomly assigned to take two capsules of either placebo or mussel lipid extract twice daily for eight weeks. Each mussel lipid extract capsule delivered 50 mg omega-3 fatty acids in an unspecified combination of EPA and DHA. The researchers reported that those who took the mussel extract experienced a significant decrease in daytime wheezing and other measures of lung function.14 Earlier in vitro research showed that the mussel extract effectively inhibited the 5-lipooxygenase and cyclooxygenase pathways responsible for the production of pro-inflammatory eicosanoids (inflammatory cells), including leukotrienes and prostaglandins.15

Traditional Chinese medicine
Two Chinese herbal formulas have recently been the subject of controlled clinical studies investigating their effectiveness against allergic asthma. Neither formula contains ephedra. In the first study, researchers compared the effectiveness and safety of a novel herbal formula (dubbed anti-asthma herbal medicine intervention, or ASHMI) with prednisone (an anti-inflammatory corticosteroid drug commonly used to manage asthma).16 ASHMI consists of extracts from reishi mushroom (Ganoderma lucidum), Chinese licorice (Glycyrrhiza uralensis) and the shrub Sophora flavescens. The study participants, 91 adults with moderate-to-severe asthma, were randomly assigned to one of two different treatment regimens: oral treatment with ASHMI (4 capsules three times a day, a total of 3.6 grams of extract) in combination with placebo, or oral prednisone (20 mg given once daily) in combination with placebo. Study subjects were allowed to use beta-2 agonist inhalers as needed but no other medications.

The results showed that ASHMI was comparable to prednisone in improving lung function, asthma symptom scores and degree of inhaler use after four weeks of treatment. (Statistically, improvement was slightly but significantly better in the prednisone group, but both groups improved.) In addition, in the ASHMI group there were significant reductions in the levels of immunoglobulin E, interleukin-5 and interleukin-13, all important markers of allergic response. Both treatments also significantly reduced numbers of eosinophils in peripheral blood.16

The other trial, published in 2005, concluded that a modified version of the traditional Chinese formula Mai Men Dong Tang, or mMMDT, safely and effectively relieved asthma symptoms and improved lung function in children with persistent, mild-to-moderate asthma.17 The mMMDT formula contains five herbs: Mondo grass Ophiopogon japonicus, American ginseng (Panax quinquefolius), Chinese licorice (Glycyrrhiza uralensis), Crowdipper (Pinellia ternata) and Coatbuttons (Tridax procumbens). This double-blind, placebo-controlled study involved a total of 100 children aged 5 to 18 who were randomly assigned to one of three study groups for four months of treatment. The first and second groups received treatment with 80 mg/day or 40 mg/day mMMDT, respectively; the third group took placebo.

According to the results, both mMMDT dosage regimens were significantly more effective than placebo in improving lung function and symptoms scores. Earlier animal research showed that mMMDT significantly decreased concentrations of IL-4 in response to allergen challenge.18

Future challenges
Asthma rates, including rates of allergic asthma, have risen sharply over the past two decades. While the American Lung Association asserts that the incidence of asthma reached a plateau in 2002,9 the need for inexpensive, nontoxic alternatives to conventional pharmaceutical treatments for the condition will continue to grow. With more research, dietary interventions—including supplementation with antioxidants, omega-3 fatty acids and herbs—may play an increasing role in the future management of asthma.

Children, asthma and allergies
Asthma is one of the most common chronic childhood diseases—as many as 9 million Americans under the age of 18 have been diagnosed19—and is probably the most frequent cause of missed school days.20 Asthma appears to have a strong genetic component; approximately 40 percent of children with asthmatic parents will develop asthma themselves.

While the prevalence of asthma increased an estimated 75 percent between 1980 and 1994 in the general U.S. population, asthma rates in children under the age of 5 years rose by a staggering 160 percent during the same time period.19 Among children, asthma is even more likely to be associated with allergy than in adults. The ALA estimates that at least 75 percent to 80 percent of children with asthma have significant allergies.20 The most common asthmatic allergens are indoor inhalant allergens (dust, molds, feathers, pet dander), outdoor inhalant allergens (pollens and molds) and food-derived allergens (milk, soy, eggs, wheat).20

An association between allergic asthma and certain other allergic conditions, such as allergic eczema (also commonly known as atopic eczema), has been well-established in children. Some researchers believe that a large proportion of allergic eczema cases are related to cow's milk allergy. According to research, infants fed formulas made of whole cow's milk or soy protein are more likely to develop atopic eczema or wheezing in early childhood.21

Studies have shown that the use of lactobacillus probiotics in infancy can reduce the incidence of atopic eczema and cow's milk allergy in the early years of life.22,23,24,25 Unfortunately, these results have not been repeated in older children or adults,22 nor have studies been conducted to investigate the effects of probiotics on allergic asthma.

Evelyn Leigh is a freelance writer and natural products industry consultant based in Boulder, Colo.

1. Blesa S, et al. Effectiveness of oral N-acetylcysteine in a rat experimental model of asthma. Pharmacol Res 2002;45(2):135?40.
2. Misso NL and Thompson PJ. Oxidative stress and antioxidant deficiencies in asthma: potential modification by diet. Redox Report 2005;10(5):247?55.
3. Gazdik F, et al. Decreased levels of coenzyme Q10 in patients with bronchial asthma. Allergy 2002:57:811?4.
4. Ram FS, et al. Vitamin C supplementation for asthma. Cochrane Database Syst Rev 2004;3:CD000993.
5. Neuman I, et al. Reduction of exercise-induced asthma oxidative stress by lycopene, a natural antioxidant. Allergy 2000;55:1184?1189.
6. Wood LG, et al. Airway and circulation levels of carotenoids in asthma and healthy controls. J Am Coll Nutr 2005;24(6):448?55.
7. Lau BHS, et al. Pycnogenol as an adjunct in the management of childhood asthma. J Asthma 2004;41(8):825?832.>
8. Hosseini S, et al. Pycnogenol in the management of asthma. J Med Food 2001;4(4):201?9.
9. [No authors listed] Asthma in Adults Fact Sheet. July 2005 American Lung Association.
10. Nagakura T, et al. Dietary supplementation with fish oil rich in ?-3 polyunsaturated fatty acids in children with bronchial asthma. Eur Respir J 2000;16:861?5
11. Broughton SK, et al. Reduced asthma symptoms with n?3 fatty acid ingestion are related to 5-series leukotriene production. Am J Clin Nutr 1997;65:1011?7.
12. Mickleborough TD, et al. Protective effect of fish oil supplementation on exercise-induced bronchoconstriction in asthma. Chest 2006;129:39?49.
13. Mihrshahi S, et al. Effect of omega-3 fatty acid concentrations in plasma on symptoms of asthma at 18 months of age. Pediatr Allergy Immunol 2004;15:517?522.
14. Emelyanov A, et al. Treatment of asthma with lipid extract of New Zealand green-lipped mussel: a randomised clinical trial. Eur Respir J 2002;20:596?600.
15. Whitehouse MW, et al. Anti-inflammatory activity of a lipid fraction (Lyprinol) from the NZ green-lipped mussel. Inflammopharmacology 1997;5:237?46.
16. Wen M-C, et al. Efficacy and tolerability of antiasthma herbal medicine intervention in adult patients with moderate-severe allergic asthma. J Allergy Clin Immunol 2005;116(3):517?24.
17. Hsu CH, et al. Efficacy and safety of modified Mai-Men-Dong-Tang for treatment of allergic asthma. Pediatr Allergy Immunol 2005;16:76?81.
18. Hsu CH, et al. The mechanisms of anti-asthma formulas in traditional Chinese medicine in the treatment of allergen-induced airway inflammation. J Chin Med 2000;11:111?21.
19. [No authors listed] Asthma Statistics. 2006. American Academy of Allergy, Asthma, & Immunology.
20. [No authors listed] Childhood Asthma Overview. July 2005 American Lung Association.
21. Friedman NJ and Zeiger RS. The role of breast-feeding in the development of allergies and asthma. J Allergy Clin Immunol 2005;115(6):1238?48.
22. Furrie E. Probiotics and allergy. Proc Nutr Soc 2005;64(4):465?9.
23. Kalliomaki M and Isolauri E. Pandemic of atopic diseases?a lack of microbial exposure in early infancy? Curr Drug Targets Infect Disord 2002;2(3):193?9.
24. Kalliomaki M, et al. Probiotics and prevention of atopic disease: 4-year follow up for a randomised placebo-controlled trial. Lancet 2003;361(9372):1869?71.
25. Kalliomaki M and Isolauri E. Role of intestinal flora in the development of allergy. Curr Opin Allergy Clin Immunol 2003;3(1):15?20.

Natural Foods Merchandiser volume XXVII/number 4/p. 44, 46-47

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