Selenium, Glutathione Peroxidase, Vitamin C, N-acetyl-cysteine, B2 and Asthma

Selenium and Glutathione Peroxidase

In 1999, as reported in the British medical journal, Lancet, FJ Kelly and associates found lung lining fluid ascorbic acid and alpha-tocopherol (vitamin E) concentrations are low in patients with mild asthma even though blood levels are normal or increased. 

These findings, along with the presence of increased amounts of oxidized glutathione in their airways, indicate that patients with asthma are subject to increased oxidative stress.⁶⁴ 

In a study of asthmatic children, CV Powell and colleagues measured red blood cell GSH-Px, superoxide dismutase(SOD), and plasma concentrations of retinol, vitamin C, alpha tocopherol, and cholesterol levels. 

They observed that children with asthma had significantly reduced red blood cell glutathione peroxidase (GSH-Px) activity when compared to a healthy control group.⁶⁵

This is substantiated by the findings of  research two years later showing decreased levels of selenium in asthmatics. 

Selenium in the form of selenocysteine is incorporated at the four active sites of the enzyme glutathione peroxidase. This enzyme assumes a critical role in protecting against free-radical and oxidative damage (associated with asthma). 

Glutathione peroxidase is especially important in reducing the production of inflammatory prostaglandins and leukotrienes.⁶⁶

J Kadrobova et al. reported that low selenium (Se) levels were observed in patients with asthma when compared to a group of patients without asthma. 

Increased production of reactive oxygen species (ROS), due to inflammatory conditions has also been found in these people, implying the importance of antioxidant properties of Se via the activity of glutathione peroxidase (GPx). 

Plasma and red blood cell Se and red blood cell GPx concentrations were compared in 22 patients with intrinsic asthma with 33 control subjects. 

Compared with controls, Se concentration in plasma and red blood cells and GPx activity were decreased in the intrinsic asthma patients. 

There was a significantly high positive correlation between Se plasma and red blood cell concentrations. The researchers concluded that Se supplementation may be beneficial to patients with intrinsic asthma, who may be at risk of Se deficiency.⁶⁷

Three years later, FJ Kelly reported that asthma is characterized by an imbalance between the amounts of reactive oxygen species (ROS) and available antioxidant defences. 

In the lung, ROS arises from endogenous sources, such as the influx of inflammatory cells, or exogenous sources, such as air pollution and cigarette smoke. When ROS production increases, the redox balance of the airways alters, and this can lead to bronchial hyperactivity and further inflammation. 

The lung, like many other tissues, has a range of antioxidant defences which help to maintain a balanced redox status. These antioxidants are present in the intracellular, the vascular and extracellular respiratory tract lining fluid (RTLF) compartments. 

The reduced glutathione (GSH) content of RTLF is particularly high and new findings are beginning to reveal the role that the RTLF GSH pool plays in defending the lung.⁶⁸ 

CJ Doelman and ABast noted the role vitamin E and selenium play in bronchoconstriction.  

Pulmonary tissue can be damaged in different ways, for instance by xenobiotics (paraquat, butylated hydroxytoluene, bleomycin), during inflammation, ischemia reperfusion, or exposure to mineral dust or to normobaric pure oxygen levels. 

Reactive oxygen species are partly responsible for the observed pulmonary tissue damage. The reactive oxygen species induce bronchoconstriction, elevate mucus secretion, and cause microvascular leakage, which leads to edema formation. 

Reactive oxygen species even induce an autonomic imbalance between muscarinic receptor-mediated contraction and the beta-adrenergic-mediated relaxation of the pulmonary smooth muscle. 

Vitamin E and selenium have a regulatory role in this balance between these two receptor responses. The autonomic imbalance may be involved in the development of bronchial hyperresponsiveness, occurring in lung inflammation.⁶⁹

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Glutathione Levels Affected by Asthma Drugs

A new study shows that glutathione levels are also adversely influenced by asthma drugs. 

HJ Pennings and colleagues reported in 1999, that antioxidant defence in asthmatic patients is decreased. Although inhaled corticosteroids decrease asthmatic inflammation and modulate reactive oxygen species (ROS) generation, little was known of their effect on cellular antioxidant levels. 

Their study was to evaluate the effect of inhaled beclomethasone dipropionate (BDP) on erythrocyte antioxidant levels in stable asthmatic patients. 

Forty patients with stable, mild asthma were treated in a double-blind, placebo-controlled, parallel-group study with BDP 250 microg, two puffs b.i.d. for 6 weeks. At entry and every 2 weeks during treatment, erythrocyte antioxidant levels, haematological parameters, pulmonary function tests and asthma symptoms were determined. 

The results showed that during treatment with BDP, erythrocyte catalase levels increased over 25% in comparison with the placebo. 

Erythrocyte total glutathione levels significantly decreased after 6 weeks treatment with BDP. 

In the BDP-treated patients, blood eosinophil counts were higher in patients who responded with an increase in erythrocyte catalase levels during BDP treatment, as compared to those not responding. 

This study showed that treatment with inhaled bedomethasone dipropionate results in changes in antioxidant levels in erythrocytes of patients with stable, mild asthma. 

This reduction of glutathione in asthma patients using BDP suggests that supplementation with glutathione may offset the negative effect of BDP.⁷⁰

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  Vitamin C, Glutathione, NAC and B2

Glutathione (GSH) levels in blood plasma have been shown to be increased through supplementation with vitamin C and glutathione precursor, N-acetylcysteine (NAC). 

Researchers, studying a 45-month-old girl with an inherited glutathione synthesis deficiency, observed that dosages of vitamin C of 3000mg/day increased white blood cell GSH fourfold and plasma GSH levels eightfold.

NAC supplementation at 800mg/day also increased white blood cell GSH by 350% and plasma levels by 200-500%. 

Based on the improvements seen over a two week period, researchers decided to administer 3000mg of vitamin C for a period of one year.

Glutathione levels remained elevated, the hematocrit increased form a baseline of 25.4% to 32.6%, and the number of immature red blood cells decreased from 11% to 4%. 

These results indicate that vitamin C can decrease cellular damage in patients with hereditary glutathione deficiency.71

The results of the efficacy of vitamin C in improving GSH levels in this study were supported by a previous double-blind study by CJ Johnson, et al.. 

They reported that by supplementing vitamin C at a rate of 500mg per day, in healthy individuals, the average blood cell glutathione concentration increased nearly 50%. A further 5% increase was achieved by increasing vitamin C to 2000mg/day.72

Riboflavin (vitamin B2) supplementation has also been shown to significantly improve glutathione levels. Riboflavin is involved in the regeneration of glutathione.73

These studies suggest roles for vitamin C, N-acetylcysteine and riboflavin in reducing oxidative damage in asthma patients due to glutathione deficiency. 

Further, since these nutrients play a role in glutathione production enhancement, it is suggested that they also play a primary role in Th1/Th2 balance. (see Th1/Th2 Balance in Asthma)

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