Metabolomic profiles of current cigarette smokers

Hsu, Pei-Chen; Lan, Renny S.; Brasky, Theodore M.; Marian, Cătălin; Cheema, Amrita K.; Ressom, Habtom W.; Loffredo, Christopher A.; Pickworth, Wallace B.; Shields, Peter G.

doi:10.1002/mc.22519

Cited by 54 publications

(41 citation statements)

References 50 publications

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“…Fifth, our study predominantly included middle-aged to older individuals of European ancestry, which may not generalize to other ethnicities or age groups. There is some evidence that metabolomics patterns differ by race 24,25 . Finally, our AF population includes all types of AF, and we may have missed association between the metabolites with specific AF subtypes such as atrial flutter, paroxysmal, persistent, or permanent AF.…”

Section: Discussionmentioning

confidence: 99%

Metabolomic Profiling in Relation to New-Onset Atrial Fibrillation (from the Framingham Heart Study)

Riles

Marcos

et al. 2016

The American Journal of Cardiology

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Previous studies have shown several metabolic biomarkers to be associated with prevalent and incident atrial fibrillation (AF), but the results have not been replicated. We investigated metabolite profiles of 2,458 European ancestry participants from the Framingham Heart Study without AF at the index exam and followed them for 10 years for new-onset AF. Amino acids, organic acids, lipids, and other plasma metabolites were profiled by liquid chromatography-tandem mass spectrometry using fasting plasma samples. We conducted Cox proportional hazard analyses for association between metabolites and new-onset AF. We performed hypothesis generating analysis to identify novel metabolites and hypothesis testing analysis to confirm the previously reported associations between metabolites and AF. Mean age was 55.1±9.9 years, and 53% were women. Incident AF developed in 156 participants (6.3%) in 10 years of follow-up. A total of 217 metabolites were examined, consisting of 54 positively charged metabolites, 59 negatively charged metabolites, and 104 lipids. None of the 217 metabolites met our a priori specified Bonferroni corrected level of significance in the multivariable analyses. We were unable replicate previous results demonstrating associations between metabolites that we had measured and AF. In conclusion, in our metabolomics approach, none of the metabolites we tested were significantly associated with the risk of future AF.

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Section: Discussionmentioning

confidence: 99%

Metabolomic Profiling in Relation to New-Onset Atrial Fibrillation (from the Framingham Heart Study)

Riles

Marcos

et al. 2016

The American Journal of Cardiology

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“…13 Relative changes in plasma MG were reported to correlate with those of various metabolome constituents in smokers, but actual MG concentrations were not reported. 16,17 …”

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confidence: 99%

Plasma Menthol Glucuronide as a Biomarker of Acute Menthol Inhalation

Jatlow

Valentine

Gueorguieva³

et al. 2018

tobacco reg sci

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Objectives Menthol is often added to cigarettes and e-cigarette solutions for its cooling and anti-irritant effects, and may contribute to development of nicotine dependence, particularly in vulnerable populations such as adolescents, and among African Americans. Menthol is rapidly metabolized to menthol glucuronide (MG) with little or no unconjugated menthol measurable in venous blood. Human challenge studies of the effects of inhaled menthol, and of its interactions with nicotine, would benefit from a quantitative measure of acute menthol exposure. Our objective was to determine whether plasma MG concentrations might be a suitable quantitative biomarker of acute menthol exposure following its inhalation. Methods We performed a secondary analysis of plasma MG concentrations obtained during a study of the effects of inhaled menthol on behavioral responses to intravenous nicotine. MG concentrations were followed over time in venous plasma from 48 participants following inhalation of aerosols from e-cigarettes employing solutions containing either of 2 menthol concentrations or placebo. Results Whereas plasma MG concentrations were variable, they showed a dose-dependent increase following menthol inhalation. Conclusions Measurement of plasma MG may be useful to assess inter-individual differences in acute menthol exposure in human challenge studies involving menthol inhalation.

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“…The use of menthol in tobacco products is currently not regulated, but the FDA is considering the removal or regulation of menthol in tobacco and restricting its marketing (30). From our previous study using a pre-post experimental design where an individual smoked two cigarettes to assess biomarker changes with smoking, allowing for within-subject replication, MG was the most significant metabolite that rose after each cigarette smoking ( p =6.99E-10, q =8.90E-07) independent of gender, race, and plasma cotinine levels, and baseline MG level was positively correlated with cotinine levels in all smokers ( p= 0.04) and menthol smokers ( p= 0.008) (23). In this study, the associations of the MG boost from the second cigarette were examined, after a 1hr standardized time interval, to various smoking-related variables including topography profiles.…”

Section: Discussionmentioning

confidence: 99%

“…A previously conducted cross-sectional study with a pre-post smoking experimental design was used to determine smoking behavior and novel blood biomarkers before and after smoking cigarettes (23). Subjects ≥18 years of age and who smoked >10 cigarettes/day for at least 5 years with a stable smoking pattern for ≥1 year were recruited through local media.…”

Section: Methodsmentioning

confidence: 99%

“…Recently, an untargeted metabolomics approach by Ultra-Performance Liquid Chromatography-Quadrupole-Time of Flight Mass Spectrometry (UPLC-Q-TOF MS) was used with a pre-post experimental design where dynamic changes of plasma metabolites could be examined in a cross-sectional study of smokers (n=105) who smoked 2 cigarettes one hour apart, we reported that thirty-one novel metabolites were affected by cigarette smoking during this interval, uniquely including MG (23). Here, the study extend our investigation by examining the associations of MG changes during smoking, termed the MG boost, as well as other smoke exposure biomarkers, smokers’ puff profiles, the classification of metabolomic profiles between menthol and non-menthol smokers, and the biological associations of MG in menthol smokers’ plasma with their metabolome.…”

Section: Introductionmentioning

confidence: 99%

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Menthol Smokers: Metabolomic Profiling and Smoking Behavior

Hsu

Lan

Brasky

et al. 2017

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background The use of menthol in cigarettes and marketing is under consideration for regulation by the FDA. However, the effects of menthol on smoking behavior and carcinogen exposure have been inconclusive. We previously reported metabolomic profiling for cigarette smokers, and novelly identified a menthol-glucuronide (MG) as the most significant metabolite directly related to smoking. Here, MG is studied in relation to smoking behavior and metabolomic profiles. Methods A cross-sectional study of 105 smokers who smoked two cigarettes in the laboratory one hour apart. Blood nicotine, MG and exhaled carbon monoxide (CO) boosts were determined (the difference before and after smoking). Spearman's correlation, Chi-Square and ANCOVA adjusted for gender, race and cotinine levels for menthol smokers assessed the relationship of MG boost, smoking behavior, and metabolic profiles. Multivariate metabolite characterization using supervised Partial Least Squares-Discriminant Analysis (PLS-DA) was carried out for the classification of metabolomics profiles. Results MG boost was positively correlated with CO boost, nicotine boost, average puff volume, puff duration, and total smoke exposure. Classification using PLS-DA, MG was the top metabolite discriminating metabolome of menthol vs. non-menthol smokers. Among menthol smokers, forty-two metabolites were significantly correlated with MG boost, which linked to cellular functions such as of cell death, survival, and movement. Conclusion Plasma MG boost is a new smoking behavior biomarker that may provides novel information over self-reported use of menthol cigarettes by integrating different smoking measures for understanding smoking behavior and harm of menthol cigarettes. Impacts These results provide insight into the biological effect of menthol smoking.

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Metabolomic profiles of current cigarette smokers

Cited by 54 publications

References 50 publications

Metabolomic Profiling in Relation to New-Onset Atrial Fibrillation (from the Framingham Heart Study)

Metabolomic Profiling in Relation to New-Onset Atrial Fibrillation (from the Framingham Heart Study)

Plasma Menthol Glucuronide as a Biomarker of Acute Menthol Inhalation

Menthol Smokers: Metabolomic Profiling and Smoking Behavior

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