Breath Pentane Research Articles

Exhaled Breath Analysis Using Selected Ion Flow Tube Mass Spectrometry and Disease Severity in Heart Failure.

Exhaled breath volatile organic compounds (VOCs) are elevated in heart failure (HF). The ability of VOCs to predict long term cardiovascular mortality and morbidity has not been independently verified. In 55 patients admitted with acute decompensated heart failure (ADHF), we measured exhaled breath acetone and pentane levels upon admission and after 48 h of diuresis. In a separate cohort of 51 cardiac patients undergoing cardiopulmonary exercise testing (CPET), we measured exhaled breath acetone and pentane levels before and at peak exercise. In the ADHF cohort, admission acetone levels correlated with lower left ventricular ejection fraction (LVEF, r = -0.297, p = 0.035). Greater weight loss with diuretic therapy correlated with a greater reduction in both acetone levels (r = -0.398, p = 0.003) and pentane levels (r = -0.309, p = 0.021). In patients with above-median weight loss (≥4.5 kg), patients demonstrated significantly greater percentage reduction in acetone (59% reduction vs. 7% increase, p < 0.001) and pentane (23% reduction vs. 2% reduction, p = 0.008). In the CPET cohort, admission acetone and pentane levels correlated with higher VE/VCO2 (r = 0.39, p = 0.005), (r = 0.035, p = 0.014). However, there were no significant correlations between baseline or peak exercise acetone and pentane levels and peak VO2. In longitudinal follow-up with a median duration of 33 months, patients with elevated exhaled acetone and pentane levels experienced higher composite adverse events of death, ventricular assist device implantation, or orthotopic heart transplantation. In patients admitted with ADHF, higher exhaled breath acetone levels are associated with lower LVEF and poorer outcomes, and greater reductions in exhaled breath acetone and pentane tracked with greater weight loss. Exhaled acetone and pentane may be novel biomarkers in heart failure worthy of future investigation.

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Enhancement Acetone Sensing Performances of SnO2 Nanorod Arrays By Decorating Noble Metal Catalysts

Introduction Breath analysis using gas chromatography (GC) to identify more than 200 compounds in the human breath came into practice in the 1970s [1]. Endogenous compounds such as inorganic gases (NO, CO) and VOCs (acetone, ethanol, ammonia, ethane and pentane) in the human breath serve as a biomarker for several diseases [2]. Breath acetone is related to diabetes [3], fasting [4], fat metabolism [5], and other numerous diseases [6].The breath acetone concentration is measured by gas chromatography-mass spectrometry (GC-MS), selected ion flow tube mass spectrometry (SIFT-MS), ion mobility spectrometry (IMS), and proton transfer reaction mass spectrometry (PTR-MS), which are commonly used in the laboratory. As the conventional tools for breath analysis are disadvantageous in terms of cost, portability, and the complexity, so we developed a cheap, and portable breath analyzer.Method The breath acetone analyzer comprised a sampling loop, a packed column, three solenoid valves, a mini-sized pump, and a sensor based on SnO2 nanorod (NR) arrays. SnO2 is one of the metal oxide materials that shows high sensitivity to small amount of gases and has strong durability. The mixed gas was passed through the column for the separation of acetone by the difference of interaction with stationary phase. Acetone is separated from the exhaled breath by the packed column within 100 seconds. The operation temperature of the column is maintained at 30 oC. The separated acetone gas was detected by the SnO2-based sensors.The SnO2 NR arrays were synthesized by using glancing angle deposition method on SiO2 wafers. And various kinds of catalyst such as Au, Pd, Pt were deposit on the surface of SnO2 NR arrays. The tests performed at various temperatures (154 - 434 oC) optimized the operation temperature of the breath acetone analyzer system within the boundary. The breath acetone analyzer was used to detect air balanced acetone gas (50 ppm). At optimized operation temperature, the air balanced acetone gas was used to confirm the detection limits of SnO2 NR arrays-based sensors. The resistance of the SnO2 NR arrays –based sensor was converted to a sensor signal (log(R)) by the breath acetone analyzer. The response of the SnO2 NR arrays sensor was defined as:Sensor Signal: ∆(log(R)) = log(R)max – log(R)min , where log(R)max is the maximum resistance before exposure of the acetone and log(R)min is the minimum resistance at acetone exposure. Results and Conclusions The response of the sensor increased with the operating temperature and decreased after an optimal point. Optimal temperature for bare SnO2 NR, Pd-coated SnO2, Pt-coated SnO2 NR, and Au-coated SnO2 NR were 315 oC, 275 oC, 315 oC and 434 oC, respectively. The Figure 1 shows response of bare and catalysts decorated SnO2 NR arrays for various concentrations of acetone. It exhibits the effect of various metal catalysts on sensing properties. The Au-coated SnO2 NR arrays had superior acetone sensing properties than other sensors. The response of the SnO2 NR array based sensors increased with increasing acetone concentration. Au-coated SnO2 NR array sensors could detect acetone as low as 0.1 ppm at 434 oC, which is sufficient to analyze breath acetone (~ 0.5 ppm for normal cases). Depending on the type of gases, there should be a difference in time due to the difference of interaction between the stationary phase and gas. Therefore, we will conduct experiments with mixed gas samples and confirm selectivity of the device. In conclusion, we demonstrated that Au metal catalyst exhibited the largest enhancement among metal decorated SnO2 NR sensors for the detection of acetone.

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Review article: breath analysis in inflammatory bowel diseases.

There is an urgent need for cheap, reproducible, easy to perform and specific biomarkers for diagnosis, differentiation and stratification of inflammatory bowel disease (IBD) patients. Technical advances allow for the determination of volatile organic compounds in the human breath to differentiate between health and disease. Review and discuss medical literature on volatile organic compounds in exhaled human breath in GI disorders, focusing on diagnosis and differentiation of IBD. A systematic search in PubMed, Ovid Medline and Scopus was completed using appropriate keywords. In addition, a bibliography search of each article was performed. Mean breath pentane, ethane, propane, 1-octene, 3-methylhexane, 1-decene and NO levels were elevated (P < 0.05 to P < 10(-7)) and mean breath 1-nonene, (E)-2-nonene, hydrogen sulphide and methane were decreased in IBD compared to healthy controls (P = 0.003 to P < 0.001). A combined panel of 3 volatile organic compounds (octene, (E)-2-nonene and decene) showed the best discrimination between paediatric IBD and controls (AUC 0.96). Breath condensate cytokines were higher in IBD compared to healthy individuals (P < 0.008). Breath pentane, ethane, propane, isoprene and NO levels correlated with disease activity in IBD patients. Breath condensate interleukin-1β showed an inverse relation with clinical disease activity. Breath analysis in IBD is a promising approach that is not yet ready for routine clinical use, but data from other gastrointestinal diseases suggest the feasibility for use of this technology in clinical practice. Well-designed future trials, incorporating the latest breath detection techniques, need to determine the exact breath metabolome pattern linked to diagnosis and phenotype of IBD.

Analysis of breath volatile organic compounds as a noninvasive tool to diagnose nonalcoholic fatty liver disease in children

Nonalcoholic fatty liver disease (NAFLD) is one of the most common complications of childhood obesity. Our objective was to investigate the association of breath volatile organic compounds with the diagnosis of NAFLD in children. Patients were screened with an ultrasound of the abdomen to evaluate for NAFLD. Exhaled breath was collected and analyzed per protocol using selective ion flow tube mass spectrometry (SIFT-MS). Sixty patients were included in the study (37 with NAFLD and 23 with normal liver). All children were overweight or obese. The mean age was 14.1±2.8 years and 50% were female. A comparison of the SIFT-MS results of patients with NAFLD with those with normal liver on ultrasound revealed differences in concentration of more than 15 compounds. A panel of four volatile organic compounds can identify the presence of NAFLD with good accuracy (area under the receiver operating characteristic curve of 0.913 in the training set and 0.763 in the validation set). Breath isoprene, acetone, trimethylamine, acetaldehyde, and pentane were significantly higher in the NAFLD group compared with normal liver group (14.7 ppb vs. 8.9 for isoprene; 71.7 vs. 36.9 for acetone; 5.0 vs. 3.2 for trimethylamine; 35.1 vs. 26.0 for acetaldehyde; and 13.3 vs. 8.8 for pentane, P<0.05 for all). Exhaled breath analysis is a promising noninvasive method to detect fatty liver in children. Isoprene, acetone, trimethylamine, acetaldehyde, and pentane are novel biomarkers that may help to gain insight into pathophysiological processes leading to the development of NAFLD.

Quantification of pentane in exhaled breath, a potential biomarker of bowel disease, using selected ion flow tube mass spectrometry

Inflammatory bowel disease has a relatively large incidence in modern populations and the current diagnostic methods are either invasive or have limited sensitivity or specificity. Thus, there is a need for new non-invasive methods for its diagnosis and therapeutic monitoring, and breath analysis represents a promising direction in this area of research. Specifically, a method is needed for the absolute quantification of pentane in human breath. Selected ion flow tube mass spectrometry (SIFT-MS) has been used to study the kinetics of the O2(+) reaction with pentane. Product ions at m/z 42 and 72 were chosen as characteristic ions useful for the quantification of pentane and the reactivity of these ions with water vapour was characterized. A pilot study has been carried out of pentane in the exhaled breath of patients with Crohn's disease (CD) and ulcerative colitis (UC) and of healthy volunteers. Accurate data on the kinetics of the gas phase reaction of the O2(+•) ions with pentane have been obtained: rate coefficient 8 × 10(-10) cm(3) s(-1) (±5%) and branching ratios into the following product ions C5H12(+•) (m/z 72, 31%); C4H9(+) (m/z 57, 8%); C3H7(+) (m/z 43, 40%), C3H6(+•) (m/z 42, 21%). A method of calculation of absolute pentane concentration in exhaled breath was formulated using the count rates of the ions at m/z 32, 42, 55 and 72. Pentane was found to be significantly elevated in the breath of both the CD (mean 114 ppbv) and the UC patients (mean 84 ppbv) relative to the healthy controls (mean 40 ppbv). SIFT-MS can be used to quantify pentane in human breath in real time avoiding sample storage. This method of analysis can ultimately form the basis of non-invasive screening of inflammatory processes, including inflammatory bowel disease.

457 Role of Interferon γ-Inducible Protein 10 in the Pathogenesis of Non-Alcoholic Steatohepatitis

A S L D A b st ra ct s by mass spectrometry to diagnose NAFLD in overweight/ obese children. Methods: Patients were recruited from the Pediatric Preventive Cardiology and Metabolic Clinic. All patients were screened with an ultrasound of the abdomen to evaluate for the presence of NAFLD. Exhaled breath was collected and analyzed per protocol using selective ion flow tube (SIFTMS) to identify new markers of NAFLD. Results: Sixty patients were included in the study (37 with NAFLD on ultrasound and 23 with normal liver). All children were overweight or obese with a body mass index ≥ 85% for age. The mean age was 15± 3.1 years and 50% were female. A comparison of the SIFT-MS results of patients with NAFLD to those with normal liver on ultrasound revealed differences in concentration of more than 15 compounds. Discriminant analysis via stepwise variable selection of mass scanning ion peak data demonstrated five ion peaks that identified subjects with NAFLD with an accuracy of 90% (-2 log likelihood 0.172; Wilks' Lambda 0.145 (p , 0.0001)). Further analysis revealed that breath isoprene (cholesterol synthesis), acetone (glucose metabolism), trimethyamine (choline metabolism by microbiota), acetaldehyde (ethanol metabolism), and pentane (oxidative stress) were significantly higher in the NAFLD group compared to normal liver group, p value, 0.05 for all (Table). Conclusion: Exhaled breath analysis is a promising noninvasive method to detect fatty liver in obese children. Isoprene, acetone, trimethylamine, acetaldehyde, and pentane are novel biomarkers that may help to gain insight into pathophysiological processes and pathways leading to the development of NAFLD. Future studies are needed to validate our findings.

456 TAK1-Mediated Signaling Regulates AMPK and Autophagy Pathways That Prevent Hepatic Steatosis and Hepatocarcinogenesis in Mice

A S L D A b st ra ct s by mass spectrometry to diagnose NAFLD in overweight/ obese children. Methods: Patients were recruited from the Pediatric Preventive Cardiology and Metabolic Clinic. All patients were screened with an ultrasound of the abdomen to evaluate for the presence of NAFLD. Exhaled breath was collected and analyzed per protocol using selective ion flow tube (SIFTMS) to identify new markers of NAFLD. Results: Sixty patients were included in the study (37 with NAFLD on ultrasound and 23 with normal liver). All children were overweight or obese with a body mass index ≥ 85% for age. The mean age was 15± 3.1 years and 50% were female. A comparison of the SIFT-MS results of patients with NAFLD to those with normal liver on ultrasound revealed differences in concentration of more than 15 compounds. Discriminant analysis via stepwise variable selection of mass scanning ion peak data demonstrated five ion peaks that identified subjects with NAFLD with an accuracy of 90% (-2 log likelihood 0.172; Wilks' Lambda 0.145 (p , 0.0001)). Further analysis revealed that breath isoprene (cholesterol synthesis), acetone (glucose metabolism), trimethyamine (choline metabolism by microbiota), acetaldehyde (ethanol metabolism), and pentane (oxidative stress) were significantly higher in the NAFLD group compared to normal liver group, p value, 0.05 for all (Table). Conclusion: Exhaled breath analysis is a promising noninvasive method to detect fatty liver in obese children. Isoprene, acetone, trimethylamine, acetaldehyde, and pentane are novel biomarkers that may help to gain insight into pathophysiological processes and pathways leading to the development of NAFLD. Future studies are needed to validate our findings.

Breath Pentane as a Potential Biomarker for Survival in Hepatic Ischemia and Reperfusion Injury—A Pilot Study

BackgroundExhaled pentane, which is produced as a consequence of reactive oxygen species-mediated lipid peroxidation, is a marker of oxidative stress. Propofol is widely used as a hypnotic agent in intensive care units and the operating room. Moreover, this agent has been reported to inhibit lipid peroxidation by directly scavenging reactive oxygen species. In this study, using a porcine liver ischemia-reperfusion injury model, we have evaluated the hypothesis that high concentrations of breath pentane are related to adverse outcome and that propofol could reduce breath pentane and improve liver injury and outcome in swine in this situation.Methodology/Principal FindingsTwenty male swine were assigned to two groups: propofol (n = 10) and chloral hydrate groups (n = 10). Hepatic ischemia was induced by occluding the portal inflow vessels. Ischemia lasted for 30 min, followed by reperfusion for 360 min. Exhaled and blood pentane concentrations in the chloral hydrate group markedly increased 1 min after reperfusion and then decreased to baseline. Breath and blood pentane concentrations in the propofol group increased 1 min after reperfusion but were significantly lower than in the chloral hydrate group. A negative correlation was found between breath pentane levels and survival in the chloral hydrate group. The median overall survival was 251 min after reperfusion (range 150–360 min) in the chloral hydrate group. All of the swine were alive in the propofol group.ConclusionsMonitoring of exhaled pentane may be useful for evaluating the severity of hepatic ischemia-reperfusion injury and aid in predicting the outcome; propofol may improve the outcome in this situation.

Increased breath ethane and pentane concentrations in currently unmedicated patients with schizophrenia

Schizophrenia is a common and debilitating mental illness. The disorder is thought to be developmental in origin, with oxidative stress being implicated as possible pathophysiological mechanism. Breath alkanes provide a non-invasive means to assess oxidative stress, with ethane levels reportedly increased in medicated patients with schizophrenia. It is possible, however, that the psychotropic medications used to treat the disorder result in elevated breath ethane levels. We have therefore measured the concentration of ethane and pentane, markers of oxidative stress, in the breath of currently unmedicated patients with schizophrenia. Alveolar breath samples were collected, applied to thermal desorption tubes, and analyzed using a combination of two-stage thermal de-sorption, gas chromatography and mass spectrometry. Compared to healthy controls ethane and pentane levels were found to be elevated in patients with schizophrenia, while levels of butane were normal. Our data support the notion that oxidative stress is increased in schizophrenia and that this is unlikely to be a consequence of antipsychotic medications. In addition, breath alkane analysis may represent a rapid and non-invasive means to monitor oxidative stress occurring in schizophrenia.

Breath analysis by optical fiber sensor for the determination of exhaled organic compounds with a view to diagnostics

Breath analysis constitutes a promising tool in clinical and analytical fields due to its high potential for non-invasive diagnostics of metabolic disorders and monitoring of disease status. An optical fiber (OF) sensor has been developed for determination of volatile organic compounds (ethane, pentane, heptane, octane, decane, benzene, toluene and styrene) in human breath for clinical diagnosis.The analytical system developed showed a high performance for breath analysis, inferred for the analytical signal intensity and stability, linear range, and detection limits ranging from 0.8pmolL−1, for heptane, and to 9.5pmolL−1, for decane. The OF sensor also showed advantageous features of near real-time response and low instrumentation costs, besides showing an analytical performance equivalent to the breath analysis by gas chromatography–mass spectrometry (GC–MS), used as the reference method.

Breath pentane: an indicator for early and continuous monitoring of lipid peroxidation in hepatic ischaemia–reperfusion injury

Lipid peroxidation plays an important role during liver ischaemia-reperfusion injury. Pentane in breath is often used as an index of lipid peroxidation. We observed the changes in levels of breath pentane during the lipid peroxidation process caused by liver ischaemia-reperfusion injury. Ten male swine were anaesthetized with chloral hydrate 0.3-0.5 g kg(-1) min(-1). Total hepatic ischaemia was induced by occluding the portal inflow vessels. Ischaemia lasted 30 min followed by reperfusion for 180 min. Breath samples were sampled from the anaesthesia circuit and blood samples were collected from the inferior vena cava. Pentane concentrations in breath and blood were quantified by means of solid phase microextraction and gas chromatography-mass spectrography technique. Exhaled pentane concentrations (means +/- SE) increased markedly after reperfusion for 1 min (244.13 +/- 33.3 pmol l(-1)) and decreased gradually to initial levels after reperfusion for 60 min. Blood pentane concentrations (means +/- SE) increased significantly after reperfusion for 1 min (333.46 +/- 63.05 pmol l(-1)) and then decreased to basal level. Breath pentane concentrations showed a correlation with blood (r = 0.709, P < 0.05). Breath pentane analysis could provide early, rapid, noninvasive and continuous assessment of lipid peroxidation during hepatic ischaemia-reperfusion injury.

P-712 Breath pentane as a marker of lipid peroxidation duringradiotherapy of lung cancer patients

P-712 Breath pentane as a marker of lipid peroxidation duringradiotherapy of lung cancer patients

The Effects of Exercise on Markers of Lipid Peroxidation in Renal Dialysis Patients Compared with Control Subjects

The purpose of this study was to compare the susceptibility to exercise-induced lipid peroxidation of patients on chronic maintenance dialysis (CMD) and non-CMD control subjects. Cross-sectional comparison of exercise-induced changes in breath ethane and pentane flux between patients on CMD (group A) and an age-, gender-, medical diagnosis-, smoking-, and ethanol consumption-matched comparison group (group B). Breath ethane and pentane were measured at rest before exercise, during cardiopulmonary exercise stress testing (CPX) at lactic acidosis threshold (Vo2lat), and 5 minutes after CPX. Group comparisons of clinical characteristics reveal that the groups were similar in terms of age, ethnicity, comorbid diagnoses, prevalence of medication use, BMI, measurements of aerobic exercise capacity, cigarette smoking and ethanol consumption behaviors. All subjects successfully completed the CPX protocol achieving Vo2lat. There were significant differences in breath ethane flux between group A and B subjects, with greater pre-exercise, Vo2lat, and postexercise ethane levels in group A compared with group B subjects, and significant group differences, with lower breath ethane/pentane flux ratios at rest, Vo2lat, and recovery with lower ratios in group B than group A subjects. This study shows that patients on CMD have greater lipid peroxidation compared with control subjects at rest and during and after physical exercise. In addition, compared with control subjects, patients on CMD preferentially peroxidize n-3 polyunsaturated fatty acids at rest and during physical exercise and recovery. The lipid peroxidation profile may result in an unfavorable endoperoxide shift and should be evaluated further, along with modalities to reduce oxidative stress among patients on CMD.

Validation of a method for collection and assay of pentane in the exhaled breath of the horse

Oxidative stress refers to an imbalance between the production of oxidising free radicals and the antioxidant defenses of the cell, and is associated with many pathogenic processes. Oxidative damage to cellular lipids results in the evolution of pentane and ethane gas, and detection of these hydrocarbons in the exhaled breath can be used to monitor in vivo oxidative stress. The aim of this study was to validate a gas chromatography (GC) method for measurement of breath pentane in the horse. The GC-system developed showed good specificity for discrimination of pentane from other breath hydrocarbons, and was sensitive to 0.5 ppb pentane. Pentane was detected in the exhaled breath of five horses investigated on two occasions. The results of this preliminary study demonstrate that breath pentane can be measured in the horse, and further work is now justified to investigate the feasibility of applying this method for monitoring in vivo oxidative stress in the horse.

Antioxidant vitamin supplementation in Crohn’s disease decreases oxidative stress: a randomized controlled trial

Objective We showed previously that patients with Crohn’s disease (CD) had increased oxidative stress and lower antioxidant vitamins compared with healthy controls. This is despite inactive or mildly active disease and maintenance therapy. The aim of this study was to evaluate in these patients the effects of antioxidant vitamin supplementation on oxidative stress. Methods This is a randomized controlled trial where stable but oxidatively stressed CD subjects (n = 57) were supplemented with vitamins E (800 IU) and C (1000 mg) or their placebo for 4 wk. Oxidative stress measured by breath pentane and ethane output, plasma lipid peroxides, and F2-isoprostane was assessed at baseline and at 4 wk. Disease activity was also monitored by measuring CD activity index and plasma orosomucoid. Results During supplementation, plasma vitamin C and α-tocopherol increased and all indices of oxidative stress decreased significantly. Disease activity remained stable. Conclusions In this population, vitamin E and C supplementation resulted in a significant reduction in oxidative stress. This suggests that patients with inactive or mildly active CD can be oxidatively stressed and have increased requirement in antioxidant vitamins.

Antioxidant Status of Young Children: Response to an Antioxidant Supplement

Objective To study oxidative stress indicators in healthy young children and their response to a commercially available fruit- and vegetable-based antioxidant supplement. Design Healthy children were randomly assigned to a placebo and a supplement (commercial antioxidant supplement produced from dried fruit and vegetable extracts and fortified with antioxidants, resembling a gummy-type candy). The placebo and the supplement were taken in 2 doses per day for 21 days. Subjects Participants were 39 children (26 boys and 13 girls) aged 5 to 10 years. Research was conducted at Primary Children's Medical Center and the University of Utah, Salt Lake City. Main outcome measures Breath and urine samples were collected on days 1 and 21 and assayed for breath pentane and urine 8-hydroxydeoxyguanosine, malondialdehyde, nitrites, and 8-isoprostane as noninvasive indicators of oxidative stress. Urine oxygen radical absorbance capacity was measured at days 1 and 21 as an indirect indicator of the antioxidant capacity of the body. Three-day food records were collected at the beginning and end of the study to measure intake of dietary fruit; vegetable; and antioxidant vitamins A, C, and E. Statistical analysis Descriptive statistics, repeated measures analysis of variance, paired t tests, and Pearson r correlations. Results Markers of oxidative stress were not significantly different between the placebo and supplement groups at day 1 or day 21. The oxidative stress indicators of the healthy children in this study appear to be similar to those of healthy adults and were not changed by antioxidant supplementation. The diet record analyses indicated that mean fruit and vegetable intakes (2.75 servings/day) were similar to the national average intake for children in the United States. Applications/conclusions This research presents original information on the subject of oxidative stress in healthy children. The results of this study may be useful as reference baseline markers to use in conjunction with clinical dietary evaluations and for future research with healthy children and with children in disease states who are subject to elevated levels of oxidative stress. J Am Diet Assoc. 2002; 102:1652-1657.

Lycopene, tomatoes, and the prevention of coronary heart disease.

Coronary heart disease (CHD) is one of the primary causes of death in the Western world. The emphasis so far has been on the relationship between serum cholesterol levels and the risk of CHD. More recently, oxidative stress induced by reactive oxygen species (ROS) is also considered to play an important part in the etiology of this disease. Oxidation of the circulating low-density lipoprotein (LDL(ox)) is thought to play a key role in the pathogenesis of atherosclerosis and CHD. According to this hypothesis, macrophages inside the arterial wall take up the LDL(ox) and initiate the process of plaque formation. Dietary antioxidants such as vitamin E and beta-carotene have been shown in in vitro studies to prevent the formation of LDL(ox) and their uptake by microphages. In a recent study, healthy human subjects ingesting lycopene, a carotenoid antioxidant, in the form of tomato juice, tomato sauce, and oleoresin soft gel capsules for 1 week had significantly lower levels of LDL(ox) compared with controls. The antioxidant effects of lycopene have also been shown in four other human trials, including one where lycopene consumption reduced the levels of breath pentane. However, in one recent study, dietary supplementation with beta-carotene but not with lycopene was shown to inhibit LDL oxidation. The sources of lycopene used in most of these studies were either tomato products or lycopene extracted from tomatoes containing other carotenoids in various proportions. Therefore, it is not possible to attribute the effects solely to lycopene. Mechanisms other than the antioxidant properties of lycopene have also been shown to reduce the risk of CHD. Lycopene was shown to inhibit the activity of an essential enzyme involved in cholesterol synthesis in an in vitro and a small clinical study suggesting a hypocholesterolemic effect. Other possible mechanisms include enhanced LDL degradation, LDL particle size and composition, plaque rupture, and altered endothelial functions. Recent epidemiological studies have also shown an inverse relationship between tissue and serum levels of lycopene and mortality from CHD, cerebrovascular disease, and myocardial infraction. However, the most impressive population-based evidence comes from a multicenter case-control study where subjects from 10 European countries were evaluated for relationship between antioxidant status and acute myocardial infarctions. After adjusting for a range of dietary variables, only lycopene levels but not beta-carotene were found to be protective. At present, the role of lycopene in the prevention of CHD is strongly suggestive. Although the antioxidant property of lycopene may be one of the principal mechanism for its effect, other mechanisms may also be responsible. Controlled clinical and dietary intervention studies using well-defined subject populations and disease end points must be undertaken in the future to provide definitive evidence for the role of lycopene in the prevention of CHD. Mechanistic studies must also be initiated to understand the mode of lycopene action.