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- Material and methods
Background: Because little is known about micronutrient/antioxidant intake and asthma severity, we investigated dietary intake and plasma/serum levels of micronutrients/antioxidants in a group of asthma patients with various degrees of severity, and compared the results with healthy subjects.
Methods: A case control study was carried out on 118 asthma patients and 121 healthy subjects. The severity of the disease was classified by division of patients into four groups. Normal dietary micronutrient/antioxidant intake was estimated from a food frequency questionnaire. Plasma/serum levels of vitamins C, E, and A, selenium, magnesium, zinc, and platelet glutathione peroxidase (GSH-Px) activity were also determined.
Results: No differences in daily micronutrient/antioxidant intake were seen between patients and healthy subjects. The severity of the disease showed no significant relationship with micronutrient/antioxidant intake. There were no differences in plasma/serum levels in any of the micronutrients/antioxidants between healthy subjects and asthmatics. Nor were any differences found between asthma groups in severity in the biochemical measures, except in platelet GSH-Px activity, which was significantly lower in the most severe groups.
Conclusions: In this study, we found no evidence of any association between micronutrient/antioxidant intake or plasma/serum levels of micronutrients/antioxidants and asthma. Reduction of platelet GSH-Px activity in the most severe patients suggests that these patients have a diminished capacity to restore part of the antioxidant defences.
Recent studies suggest that an association may exist between a low intake of certain micronutrients and asthma (1). It has also been hypothesized that a deficient antioxidant capacity may also play a role in the patho-genesis of asthma (2).
Human antioxidant defences include ascorbic acid (vitamin C), α-tocopherol (vitamin E), vitamin A, enzymes such as glutathione peroxidase, and trace elements including selenium and zinc.
Low intake of vitamin C has been associated with wheezing (3, 4), increased risk of bronchial hyperresponsiveness (5), and reduced levels of FEV1 (6, 7). Dietary intake of vitamin E has a positive influence on wheezing (8) and lung function (8). Low dietary intake of vitamin A has been shown to be associated with airflow limitation (9).
Selenium is an essential component of glutathione peroxidase (GSH-Px). It has been suggested that lowered GSH-Px activity due to a low intake of selenium may play a role in asthma (10–13).
Many studies have evaluated the effect of the dietary intake of micronutrients and antioxidants on wheeze (3, 4, 8), lung function (6–9), and bronchial hyperreactivity (5), as assessed by challenge tests. However, neither the presence of wheeze, the demonstration of bronchial hyperresponsiveness, nor low lung function can be used as a substitute for the diagnosis of asthma.
In epidemiologic studies the potential impact of both the severity of the disease and its treatment on the characteristics of asthma patients' diet should also be considered. One example of the possible influence of asthma therapy on the diet is the severe corticosteroid-dependent patient who modifies his/her diet to reduce caloric intake in order to prevent weight gain resulting from the use of systemic corticosteroids. Reduction or modification of dietary intake in these patients can be accompanied by a low intake of micronutrients and antioxidants. Therefore, in order to elucidate the role of dietary factors in asthma, it is important to perform studies on patients with a clearly defined diagnosis of asthma. In addition, only patients with diets not influ-enced by food supplementation or avoidance should be included in the study. In a recent study, we reported that asthma is associated with a decrease in energy intake (14). We also found severe asthma with regular oral corticosteroid therapy to be associated with reduced plasma protein and albumin levels (14).
Although a number of studies have evaluated the possible role of dietary micronutrients/antioxidants in asthma, little is known about the influence of either the severity of the disease and/or its treatment on intake and on the plasma/serum levels of these micronutrients.
The objective of our study was to investigate whether a relationship exists between the dietary intake of micronutrients/antioxidants and asthma. We also studied the effects of asthma severity on plasma/serum levels of vitamins, selenium, magnesium, and zinc, and platelet GSH-Px activity.
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- Material and methods
We investigated differences in dietary micronutrient/antioxidant intake between asthmatics and nonasthmatics. Only patients with clearly defined asthma and with diets not compromised by food supplementation or avoidance were included. The usual dietary intake was measured by an FFQ. FFQs have been found to relate well to more detailed methods of dietary evaluation (21).
The FFQ-estimated intake of vitamin C was correlated with blood concentration (r=0.47). However, we did not find any correlation between dietary nutrient intake and biochemical measurements with the other tested micronutrients/antioxidants. This is in keeping with previous studies, which have generally shown little or no correlation between dietary intake evaluation and biochemical quantification of these micronutrients/antioxidants (21, 23). Significant correlations are more often found in studies in which at least some of the recruited subjects are on supplemented diets (23). However, in our study, these subjects were excluded. Moreover, there are two reasons to explain why plasma/serum levels of micronutrients/antioxidants may not be correlated with dietary intake:
a single plasma/serum measurement of a micronutrient may be a poor marker of long-term intake detected by FFQ
plasma/serum levels of some micronutrients/antioxidants do not always reflect the level of their stores (liver, skeleton, and kidney).
We found no evidence of any association between either dietary intake or plasma/serum levels of micronutrients/antioxidants and asthma. Nor did we find evidence that the severity of the disease has any influence on the plasma/serum levels of these substances.
According to our results, no relationship exists between asthma and retinol intake. Troisi et al. (24) found that vitamin E may have a modest effect on the incidence of asthma. We did not find any difference in either vitamin E intake or serum levels between asthma patients and nonasthmatic controls.
Some studies have reported short-term effects of vitamin C in the bronchoprovocation test and improvements in the lung-function test (25), but a beneficial effect of vitamin C was not detected in other studies (26). Olusi et al. (27) and Aderele et al. (28) found significantly higher plasma concentrations of vitamin C in controls than in asthma patients. However, no relationship was detected between vitamin C levels and asthma severity. In contrast, Troisi et al. (24) found no relationship between vitamin C intake and the subsequent development of asthma in women. Nor could Cook et al. (29) find any relationship between plasma vitamin C levels and wheezing.
Selenium is an essential component of glutathione peroxidase (GSH-Px), which reduces hydrogen peroxidase and other organic peroxides to nontoxic substances. Studies performed to determine a possible relationship between selenium levels and asthma have yielded contradictory results. Stone et al. (13) found that patients with asthma have lower concentrations of selenium in plasma and whole blood, but not in platelets, than controls. However, there was no concomitant reduction in GSH-Px activity in whole blood or platelets. In contrast, Flatt et al. (10) found that in whole blood, but not in plasma, selenium concentration and GSH-Px activity were lower in asthmatics than in healthy subjects. Similarly, reduced platelet GSH-Px activity was found by Misso et al. (11) in patients with asthma. Pearson et al. (12) found that aspirin-tolerant asthmatics had higher serum selenium concentrations than either aspirin-intolerant patients or control subjects. However, only aspirin-intolerant patients with asthma were found to have reduced platelet GSH-Px activity. In contrast, Plaza et al. (20) could not find any significant difference between platelet GSH-Px activity in aspirin-intolerant asthmatics and that in either aspirin-tolerant patients or healthy subjects. It has been suggested that GSH-Px levels may reflect the intensity of the inflammatory activity in asthma. Bibi et al. (30) demonstrated a close correlation between asthma severity and erythrocyte GSH-Px activity. Similarly, Pearson & Suarez-Mendez (31) also observed that platelet GSH-Px activity was lower in patients with severe asthma than in those with mild asthma. In keeping with this study, we found that platelet GSH-Px activity was significantly lower in patients with the most severe asthma. Since all these studies were cross-sectional, they could not determine whether the low platelet GSH-Px activity is responsible for asthma severity or is merely the consequence of an increased consumption of antioxidants in patients with a more active inflammatory process. In any case, the restoration of normal GSH-Px activity by increasing selenium intake might be a therapeutic alternative in asthma. Hasselmark et al. (32) found that selenium supplementation improved clinical symptoms in asthma patients, suggesting that the restoration of GSH-Px may improve control of bronchial inflammation.
Although Britton et al. (33) found that dietary intake of magnesium was related to lung function, airway hyperreactivity, and self-reported wheezing in the gen-eral population, we could not find any difference, either in dietary intake or magnesium serum levels, between patients and healthy subjects. Like us, de Valk et al. (34), and Falker et al. (35) did not find any magnesium deficiency in asthmatics with respect to nonasthmatics, nor did the severity of the disease correlate with serum magnesium levels (35).
The statistical power of our study was low to moder-ate (20–40%). Therefore, the lack of statistically signifi-cant differences in micronutrient/antioxidant intake between asthma and controls may have resulted from the study's being underpowered, resulting in a type 1 error.
The possible relationship between asthma and dietary intake of micronutients has been deduced from studies which investigated the prevalence of wheezing (3, 4, 8, 33) or the presence of bronchial hyperresponsiveness (5). However, up to 10% of normal subjects are hyper-responsive to bronchoconstrictor stimuli, and wheezing is more prevalent than asthma in the general population (36).
A reduced intake of vitamins A, E, or C is associated with an increased level of airflow obstruction (6–9). Since subjects with nonasthmatic airflow limitation demonstrate histamine or methacholine airway hyperresponsiveness (37), it may well be that a reduced vita-mins A, E, or C intake may predispose to bronchial hyperresponsiveness, simply by reducing airway diameter rather than by inducing asthma.
If the important question is to know whether or not changes in the diet are associated with asthma, it seems more logical to investigate the relationship of diet and asthma than the association of dietary intake and indicators of asthma such as wheezing and hyperresponsiveness.
In summary, we could not find any association bet-ween micronutrient/antioxidant intake or plasma/serum levels of micronutrients/antioxidants and asthma. Re-duction of platelet GSH-Px activity in the most severe patients suggests that their capacity to restore part of the antioxidant defences is diminished.