Research Paper

Introduction Asthma is a chronic inflammatory disease of the lungs characterized by bronchoconstriction. Asthma causes recurring periods of wheezing, chest tightness, shortness of breath, and coughing (1). As of May 2008, the World Health Organization estimated that 300 million people suffered from asthma. It is the most common chronic disease among children (2). Asthma is a public health problem for all countries regardless of the level of development. Asthma is most common in English speaking countries such as the United States, Australia, United Kingdom and New Zealand and is considered to be a disease of modern living (3). Dietary changes in Western societies has resulted in lower intake of vitamins A, C, and E which are known for their antioxidant properties. Epidemiological evidence shows a correlation of low antioxidant intake and poor lung function (4). There are two types of asthma. Non-allergic(intrinsic) is caused by anxiety, stress, exercise, cold air, and illness. Allergic(extrinsic) is caused by environmental exposure to known allergens such as dust mites, mold, or pollen. Allergic asthma is most common. It is caused by infiltration of inflammatory cells such as mast cells, eosinophils, T lymphocytes, neutrophils, macrophages and epithelial cells in the lining of the airways. These cells are the primary cause of inflammation and generation of reactive oxygen and nitrogen species (5). The inflammation is thought to be Immunoglobin E mediated (1). In healthy lungs, this is normally combated with antioxidants such as gluthione peroxidase, superoxide dismutase, catalase, glutathione, vitamin E, and vitamin C in the lungs. There is increased oxidative stress in asthma as shown by levels of lipid peroxidase products and protein carbonyls. Asthmatic individuals often have an 1

antioxidant /oxidative stress imbalance as a result of their disease which only exasperates the situation to cause more inflammation and tissue damage (4)(6)(11). Many studies have documented details regarding the mechanisms that cause inflammation of airways in asthmatics as a result of reactive oxygen species. Dietary antioxidant intervention is proposed to reduce reactive oxygen species and bronchoconstriction. The purpose of this paper is to determine if intake of dietary antioxidants, in particular vitamin C play a key role in reduction and severity of asthmatic episodes. Studies A study by Tecklenburg et al.(8) examined the effects of ascorbic acid supplementation on exercise induced asthma. Eight subjects diagnosed with asthma took part in the study. Participants served as their own control in the randomized placebo controlled double blind crossover trial. Subjects entered the study with their normal diet and either spent two weeks of ascorbic acid supplementation of 1500mg/day, placebo, or an alternative diet which was not supplemented with ascorbic acid. Following the two week period, they had a week washout period then spent another two weeks on the alternate diet or ascorbic acid supplementation. Subjects were measured at pre and post exercise intervals to their maximum level within each diet group. The purpose of the study was to determine pulmonary function through FEV1 measurements, fraction of exhaled nitric oxide, and urinary concentrations of inflammatory mediators. The diet consisting of ascorbic acid supplements showed decreased oxidative stress and lessened asthmatic symptoms that

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were statistically significant. The placebo and alternate diet did not alter significantly. The study found that that ascorbic acid does attenuate symptoms and lessen severity of bronchoconstriction in exercise related asthma. This was confirmed by the lessened reduction in FEV1 measurement of less than half the drop as compared to placebo and alternate diet. The study was not lengthy and did not have many test subjects. The author noted that further studies should be conducted to determine if diet alone is sufficient to supply adequate antioxidants to reduce exercise induced asthma. The relationship of asthma severity and low antioxidant levels was examined in a study conducted by Misso et al. (7). Evidence shows that bronchoconstriction in asthma occurs as a result of reactive oxygen species that are created in response to environmental triggers. Dietary antioxidant intake was measured by an intake questionnaire and compared to serum concentrations of dietary and non-dietary antioxidants in both severe asthma and mild-moderate asthma. Dietary intake of antioxidants had been reviewed prior to this study but serum non-dietary markers had never been looked at. Ascorbic acid was the primary dietary antioxidant studied and albumin and bilirubin were non-dietary antioxidants measured. Subjects were selected based on severity of asthma and specific parameters were set to ensure diseased state and were referred by Asthma and Allergy Research Institute in Western Australia. Non-asthmatics were recruited from the same community to serve as a control. A total of 53 mid-to-moderate asthmatics, 28 severe asthmatics, and 43 control subjects participated. A trained dietitian administered a semi-quantitative food frequency questionnaire to determine diet antioxidant composition. Plasma antioxidant levels of ascorbic acid, carotene, lycopene, bilirubin, and albumin were 3

taken. Dietary intakes were adjusted for total energy intake and anthropometric measurements were taken as well as activity factors. Sex differences were also accounted for. Of significance, intakes of vitamin C did not differ among the different groups. However, when adjustments for total energy intake were made, vitamin C intakes were lower in all males compared to females and severe asthmatics verses mild-moderate. Plasma ascorbic acid levels, bilirubin, and albumin levels were all lower in severe asthmatics. Overall, males had lower levels of ascorbic acid than females. Severe asthmatics had lower levels of ascorbic acid than mild-moderate. A lower vitamin C level in the presence of increased intake of ascorbic acid in severe asthmatics suggests that oxidative stress may not be fully compensated for. In addition, albumin levels are lower in severe asthmatics. Albumin is an extracellular antioxidant that regulates glutathione levels in the lung. Glutathione is an important antioxidant responsible for removal of reactive oxygen species in the lung. The overall conclusion to this study indicates that ascorbic intake is important to lung function. Levels drop as severity of asthma increases. Larger cohort studies have been suggested. Genetic differences in subjects in relation to ozone exposure and antioxidant supplementation are examined in a study by Romieu et al. (9) The study expanded on a previous randomized double blind study that examined supplementation of antioxidants effects on reactive oxidation species from environmental ozone. One hundred and fifty eight asthmatic children were followed for 12 weeks. Spirometric measurements were taken during this time to determine lung function in relation to ozone levels that were provided from the Mexican government. Subjects were given 250mg/day of vitamin C 4

and 50mg/day vitamin E or a placebo and blood measurements of the antioxidants were taken. This study found that supplementation of vitamins C and E lessened ozone related pulmonary function. DNA was taken from blood samples and GSTM1 genotype was determined. GSTM1 null and GSTM1 positive were the two types studied. It was hypothesized that subjects lacking GSTM1(null) might be more susceptible to the effects of oxidation form the ozone and thus have lower pulmonary function. Findings of the study did show that subjects with GSTM1 null genotypes did have a more noticeable protective effect from the antioxidants. GSTM1 serves to protect against oxidative stress by binding of glutathione with reactive oxygen species. It was determined that asthmatic children lacking GSTM1 were more susceptible to the effects of reactive oxygen species and stand to benefit the most from supplementation of antioxidants. Fogarty et al. (10) conducted a study to determine if vitamin C and/or magnesium would allow for reduction in corticosteroid use to control asthma in adults. Ninety-two subjects participated in the double-blind, randomized, parallel-group, placebo-controlled design in a two-phase study. The first phase of the study involved supplementation of vitamin C, magnesium, or placebo for sixteen weeks. The second phase continued with one gram vitamin C for twenty-nine subjects, 450mg magnesium to 31 subjects, and placebo for 32 subjects for a period of ten weeks. Over this time, subjects were asked to lower their inhaled corticosteroid dose by twenty-five percent of their regular maintenance dose in two week increments. The overall goal was a complete withdrawal of inhaled corticosteroids within 8 weeks. Subjects were observed 5

for deteriorated asthma control during this time. Reduction in corticosteroid use was compared in all three groups. A total of ten participants withdrew from the study. One withdrawal was from the vitamin C group, three from magnesium, and six from placebo. Magnesium supplementation results were inconclusive and did not show any evidence of effectiveness. Vitamin C showed a borderline statistically significant effect on inhaled steroid requirements. Vitamin C supplementation may have a modest corticosteroid sparing effect but further studies are needed. Even though some improvement was shown, the study concluded with the statement that any supplemental intervention would be difficult to administer and track results. Summary and Conclusion Of the four original studies, Vitamin C supplementation has shown a modest effect on asthmatic symptoms. All the studies indicated that reactive oxygen species cause oxidative stress and bronchoconstriction in asthmatic airways Vitamin C decreased oxidative stress in short-term studies. Only one study reviewed normal dietary intake of vitamin C. All the others looked at supplementation. The studies were slightly different in nature and focused on different aspects of asthma. The studies were considerably short in duration with the exception of the effects of vitamin supplementation on reduction of corticosteroid use. Of particular interest is the study related to polymorphism of GSTM1. Nutrogenomics provides hopeful dietary treatment of many diseases. Asthma is no exception. In conclusion, studies examined for this paper provide evidence that vitamin C can be of benefit to individuals with asthma. As with any disease state, a balanced diet 6

is key to reducing symptoms of disease and maintaining health. Meeting the DRI requirements for vitamin C with the addition of a supplement could relieve symptoms for asthmatics.

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References 1. Nelms M, Sucher K, Long S. Nutrition Therapy and Pathophysiology. California,

USA: Thompson Brooks Cole, The Thompson Corporation; 2007:720-721 2. World Health Organization. Fact Sheet: available at: http://www.who.int/mediaentre/factsheets/fs307/en/print.html. Accessed April 11, 2009 3. Asthma and Allergy Foundation of America, Asthma Overview, available at: http://www.aafa.org/display.cfm?id=8&sub=14. Accessed April 10, 2009 4. Misso NLA, Brooks-Wildhaber J, Ray S, Vally H, Thompson PJ. Plasma

concentrations of dietary and nondietary antioxidants are low in severe asthma. Eur Repir J. 2005;26:257-264 5. Tsai YC, Chang HW, Chang TT, Lee MS, Chu YT, Hung CH. Effects of All-Trans Retinoic Acid on TH1- an Th2-related chemokines production in monocytes. Inflammation. 2008;31(6):428-433 6. Nadeem A, Masood A, Siddiqui N. Oxidant-antioxidant imbalance in asthma: scientific evidence, epidemiological data and possible therapeutic options. Therapeutic Advances in Respiratory Disease. 2008;2(4):215-235 7. Misso NLA, Thompson PJ. Oxidative stress and antioxidant deficiencies in Asthma: potential modification by diet. Redox Report, Asthma & Allergy Research Institute and Centre for Asthma. 2005;10(5):247-255 8. Tecklenburg SL, Mickleborough TD, Fly AD, Bai Y, Stager JM. Ascorbic acid supplementation attenuates exercise-induced bronchoconstriction in patients with asthma. Respiratory Medicine. 2007;101:1770-1778 9. Romieu I, Sienra-Monge JJ, Ramirez-Aguilar M, Moreno-Marcias H, Reys-Ruiz NI, del Rio-Navarro BE. Genetic polymorphism of GSTM1 and antioxidant supplementation influence lung function in relation to ozone exposure in asthmatic children in Mexico City. Thorax. 2004;59:8-10 10. Fogarty A,Lewis SA, Scriverner SL, Antoniak M, Pacey S, Pringle M, Britton J. Corticosteriod sparing effects of vitamin C and magnesium in asthma: a randomized trial. Respiratory Medicine. 2005;100:174-179 11. Riccion G, D’Orazio N. The role of selenium, zinc, and antioxidant vitamin supplementation in the treatment bronchial asthma: auvant therapy or not? Expert Opin. Investig. Drugs. 2005;14(9):1145-1155

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