Exhaled Ethane and Antioxidant Vitamin Supplements in Active Smokers

doi:10.1378/chest.110.1.159

Chest

Volume 110, Issue 1, July 1996, Pages 159-164

https://doi.org/10.1378/chest.110.1.159 Get rights and content

To determine the effect of nutritional agents on lipid peroxidation, 10 smokers were given 6 mg beta carotene, 200 IU vitamin E, and 250 mg vitamin C 4 times daily for 3 weeks. Lipid peroxidation was assessed by measuring baseline and postsupplementation levels of exhaled ethane. There was a 29% decrease in mean (±SD) exhaled ethane (4.06±1.49 vs 2.90±1.29 pmol-kg⁻¹ min⁻¹), with individual levels decreasing in 8 of the 10 smokers (p<0.05, Wilcoxon sign rank test). Three nonsmokers had very low baseline levels of ethane that did not change with supplementation. Ethane production correlated with active (packs per day) and lifelong (pack-years) tobacco consumption. Also, a strong correlation was found between the decline in ethane output after micronutrient supplementation and the presupplement FEV₁. Therefore, antioxidant vitamin supplementation resulted in attenuation of smoking-related lipid peroxidation, and the decreases in ethane production appears to be associated with preserved lung function.

Section snippets

Subjects

Twelve current smokers were recruited from staff and patients at the Tucson Veterans Affairs Medical Center. One subject prematurely discontinued the study and another was excluded because he was already taking vitamin supplements. Thus, ten smokers completed the study. None had active illnesses or had taken vitamin supplements for at least 2 months prior to enrollment. Three nonsmoking control subjects were also included. All subjects gave written informed consent prior to participation in the

Population Description/Protocol Compliance

The characteristics of the study population are shown in Table 1. Body weight and dietary habits did not change significantly over the 3-week trial period.

Overall compliance (by pill count) was 92%. After supplementation, beta carotene levels in smokers rose from 9.1±6.1 (SD) to 102.7±61.8 pg/dL (p<0.001), and vitamin E levels rose from 0.988±0.251 to 2.747±0.850 mg/dL (p<0.001). Individual values are shown in Table 2. A linear correlation was present for the changes in beta carotene and

DISCUSSION

Petruzzelli and colleagues³¹ have demonstrated higher levels of thiobarbituric acid-reactive substances in lung parenchyma from smokers vs nonsmokers, indicating pulmonary lipid peroxidation. Others have identified elevated thiobarbituric acid-reactive substances in the plasma and serum of smokers.³² Our previous observation that smokers exhale more ethane than nonsmokers was confirmed in this study, suggesting that peroxidation induced by smoking can be measured noninvasively.²⁸ Other

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Citation Excerpt :
Increased oxidative stress, and hence elevated breath ethane levels, may also relate to decreased dietary intake of antioxidants. Indeed, it has been previously reported that supplementation with vitamin E can reduce breath ethane levels (Do et al., 1996). Such a possibility was not investigated in this study, although anti-oxidant intake is reported to be normal in schizophrenia (Strassnig et al., 2005).
Oxidative stress has been reported to be elevated in mental illness. Preliminary evidence suggests this phenomenon can be assessed non-invasively by determining breath levels of the omega-3 polyunsaturated fatty acid (PUFA) oxidation product ethane. This study compares alkane levels in chronic, medicated, patients with schizophrenia or bipolar disorder with those in healthy controls. Both ethane and butane levels were significantly increased in patients with schizophrenia or bipolar disorder, although elevated butane levels were likely due to increased ambient gas concentrations. Ethane levels were not correlated with symptom severity or with erythrocyte omega-3 PUFA levels. Our results support the hypothesis that oxidative stress is elevated in patients with schizophrenia and bipolar disorder leading to increased breath ethane abundance. This does not appear to be caused by increased abundance of omega-3 PUFA, but rather is likely due to enhanced oxidative damage of these lipids. As such, breath hydrocarbon analysis may represent a simple, non-invasive means to monitor the metabolic processes occurring in these disorders.
The in vitro effects of cigarette smoke on fatty acid metabolism are partially counteracted by simvastatin
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Statins enhance the synthesis of long-chain polyunsaturated fatty acids (LC-PUFAs) from their precursors both in vitro and in vivo. In particular, an increased conversion of linoleic acid (LA) and of alpha-linolenic acid to their derivatives is observed in cultured cells. On the contrary, cigarette smoke (CS) negatively and dose-dependently affects the LC-PUFA production.
To evaluate the effects of CS alone or with simvastatin, on [1-¹⁴C] LA metabolism in THP-1 cells.
CS inhibits LA conversion; after co-incubation, simvastatin nullifies the effects of CS, maintaining LA conversion comparable to controls. However, at the highest CS concentration, simvastatin is unable to counteract the effects of CS. Changes of LA conversion reflect the modulation of desaturase activities by simvastatin and CS.
CS decreases PUFA conversion and its effects are modulated by the opposite effect of statins. It can be speculated that statin treatments in smoking patients may provide some beneficial effects on PUFA metabolism in addition to lowering cholesterol levels.
Diagnostic potential of breath analysis - Focus on volatile organic compounds
2004, Clinica Chimica Acta
Breath analysis has attracted a considerable amount of scientific and clinical interest during the last decade. In contrast to NO, which is predominantly generated in the bronchial system, volatile organic compounds (VOCs) are mainly blood borne and therefore enable monitoring of different processes in the body. Exhaled ethane and pentane concentrations were elevated in inflammatory diseases. Acetone was linked to dextrose metabolism and lipolysis. Exhaled isoprene concentrations showed correlations with cholesterol biosynthesis. Exhaled levels of sulphur-containing compounds were elevated in liver failure and allograft rejection. Looking at a set of volatile markers may enable recognition and diagnosis of complex diseases such as lung or breast cancer. Due to technical problems of sampling and analysis and a lack of normalization and standardization, huge variations exist between results of different studies. This is among the main reasons why breath analysis could not yet been introduced into clinical practice. This review addresses the basic principles of breath analysis and the diagnostic potential of different volatile breath markers. Analytical procedures, issues concerning biochemistry and exhalation mechanisms of volatile substances, and future developments will be discussed.
Environmental factors and membrane polyunsaturated fatty acids in schizophrenia
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There is accumulating evidence of reductions in red blood cell membrane essential fatty acids in patients with schizophrenia. The mechanisms that may underlie these reductions have yet to be determined. It is possible that the observed membrane fatty acid deficits are associated with the development of schizophrenia. Alternatively, the membrane fatty acid deficits may be due to environmental factors, such as smoking and variations in diet, which may not be associated specifically with the pathophysiology of schizophrenia. Patients with schizophrenia smoke cigarettes at very high rates. Cigarette smoke contains many pro-oxidants that contribute directly to oxidative stress. Polyunsaturated fatty acids (PUFAs) are very susceptible to oxidative effects of free radicals. Thus, smoke-induced oxidative stress could plausibly account for reductions in membrane fatty acid in schizophrenia. Recent studies provide conflicting evidence for smoking effects on membrane fatty acid deficits. Likewise, the effects of diet on membrane PUFAs in schizophrenia are not entirely clear. Essential PUFAs need to be consumed in diet. Thus, differences in membrane PUFAs observed between patients and control subjects may be due to dietary variation. Few studies that have examined dietary effects differ in their interpretation of the effects of diet on membrane PUFAs. Thus, the jury is still out whether smoking or dietary effects are the primary causes of membrane PUFA deficits in patients with schizophrenia. Future studies will need to systematically examine the potential effects of smoking and diet, as well as other environmental factors such exercise, to definitively establish whether or not PUFA abnormalities are inherent to schizophrenia.
Long-term administration of N-acetylcysteine decreases hydrogen peroxide exhalation in subjects with chronic obstructive pulmonary disease
2001, Respiratory Medicine
Patients with chronic obstructive pulmonary disease (COPD) exhale more hydrogen peroxide (H₂O₂) and lipid peroxidation products than healthy subjects. This may reflect oxidative stress in the airways that plays important role in the development and progression of COPD. N-acetylcysteine (NAC), a mucolytic drug, possesses antioxidant properties as it is a precursor of reduced glutathione that together with glutathione peroxidase may decompose H₂O₂and lipid peroxides.
We aimed to determine the effect of NAC, 600 mg effervescent tablets (Fluimucil), once a day for 12 months, and placebo on the concentration of H₂O₂and thiobarbituric acid reactive substances (TBARs) in expired breath condensate and serum levels of two lipid peroxidation products (TBARs, lipid peroxides) in patients with COPD.
The study was performed as a double-blind, double-dummy comparison between active drug and placebo in two parallel groups. Forty-four outpatients with stable COPD (22 in the NAC group and 22 in the placebo group) completed the study. Specimens of expired breath condensate and serum were collected at the randomization visit and then every 3 months over 1 year. The concentration of TBARs and H₂O₂in expired breath condensate was measured spectrofluorimetrically by the thiobarbituric acid and homovanillic acid methods, respectively. Serum levels of lipid peroxides were determined spectrophotometrically after extraction with butanol and pyridine.
Initially, H₂O₂exhalation did not differ between the placebo and NAC groups up to 6 months of treatment. After this the significant differences were observed. After 9 and 12 months of treatment NAC group exhaled 2·3-fold (0·17± 0·33 μ $M$ vs. 0·41±0·26 μ $M$ , P<0·04) [median=0·01μ $M$ , quartile range (qr)=0·22 vs. median=0·15 μ $M$ , qr=0·43] and 2·6-fold (0·15±0·23 μ $M$ vs. 0·40± 0·25 μ $M$ , P<0·05) median=0·00μ $M$ , qr=0·23 vs. median=0·36 μ $M$ , qr=0·51] less H₂O₂than placebo receivers, respectively. No significant effect of NAC administration on TBARs exhalation and serum levels of TBARs and lipid peroxides were noted over the whole treatment period. Also no significant associations between exhaled H₂O₂and concentrations of lipid peroxidation products were noted in both treatment groups at any time-point.
These results indicate that long-term oral administration of NAC attenuates H₂O₂formation in the airways of COPD subjects and prove anti-oxidant action of drug. However, further studies are necessary to estimate the clinical significance of this finding.
Methods for measuring ethane and pentane in expired air from rats and humans
2000, Free Radical Biology and Medicine
Numerous studies in animals and humans provide evidence that ethane and pentane in expired air are useful markers of in vivo lipid peroxidation. The measurement of breath hydrocarbons, being noninvasive, is well suited for routine use in research and clinical settings. However, the lack of standardized methods for collecting, processing, and analyzing expired air has resulted in the use of a wide variety of different methods that have yielded highly disparate results among investigators. This review outlines the methods that we have developed and validated for measuring ethane and pentane in expired air from rats and humans. We describe the advantages of these methods, their performance, as well as potential errors that can be introduced during sample collection, concentration, and analysis. A main source of error involves contamination with ambient-air ethane and pentane, the concentrations of which are usually much greater and more variable than those in expired air. Thus, it appears that the effective removal of ambient-air hydrocarbons from the subject’s lungs before collection is an important step in standardizing the collection procedure. Also discussed is whether ethane or pentane is a better marker of in vivo lipid peroxidation.

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: Presented in part at the American Federation for Clinical Research Western regional meeting, February 1995.

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Chest

Clinical Investigations: Smoking and CancerExhaled Ethane and Antioxidant Vitamin Supplements in Active Smokers

Section snippets

Subjects

Population Description/Protocol Compliance

DISCUSSION

Lancet

J Nutr

Lancet

Prev Med

Am J Clin Nutr

Lancet

Chest

Anal Biochem

Am J Clin Nutr

Oxidants and antioxidants: state of the art

Am J Med

Increase in circulating products of lipid peroxidation (F2 isoprostanes) in smokers: smoking as a cause of oxidative damage

N Engl J Med

Free-radical chemistry of smoke and its toxicological implications

Environ Health Perspect

Free-radicals produced in cigarette smoke

Nature

Cigarette smoke and the involvement of free radical reactions in chemical carcinogenesis

Br J Cancer

Oxidative DNA damage estimated by 8-hydroxydeoxyguanosine excretion in humans: influence of smoking, gender, and body mass index

Carcinogenesis

Cigarette smoking, emphysema, and damage to alpha 1-proteinase inhibitor

Am J Physiol (Lung Cell Mol Physiol)

Inactivation of human alpha-1-proteinase inhibitor by cigarette smoke: effect of smoke phase and buffer

Am Rev Respir Dis

Oxidants spontaneously released by alveolar macrophages of cigarette smokers can inactivate the active site of alpha 1-antitrypsin, rendering it ineffective as an inhibitor of neutrophil elastase

J Clin Invest

Cellular defenses against damage from reactive oxygen species

Physiol Rev

Clinical Investigations: Smoking and Cancer
Exhaled Ethane and Antioxidant Vitamin Supplements in Active Smokers