Journal of Epidemiology
Online ISSN : 1349-9092
Print ISSN : 0917-5040
ISSN-L : 0917-5040
Metabolomics profiles alterations in cigarette smokers and heated tobacco product users
Sei HaradaHideki OhmomoMinako MatsumotoMizuki SataMiho IidaAya HirataNaoko MiyagawaKazuyo KuwabaraSuzuka KatoRyota TokiShun EdagawaDaisuke SugiyamaAsako SatoAkiyoshi HirayamaMasahiro SugimotoTomoyoshi SogaMasaru TomitaAtsushi ShimizuTomonori OkamuraToru Takebayashi
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JOURNAL OPEN ACCESS Advance online publication
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Article ID: JE20230170


Background: Heated tobacco products (HTPs) have gained global popularity, but their health risks remain unclear. Therefore, the current study aimed to identify plasma metabolites associated with smoking and HTP use in a large Japanese population to improve health risk assessment.

Methods: Metabolomics data from 9,922 baseline participants of the Tsuruoka Metabolomics Cohort Study (TMCS) were analyzed to determine the association between smoking habits and plasma metabolites. Moreover, alterations in smoking-related metabolites among HTP users were examined based on data obtained from 3,334 participants involved from April 2018 to June 2019 in a follow-up survey.

Results: Our study revealed that cigarette smokers had metabolomics profiles distinct from never smokers, with 22 polar metabolites identified as candidate biomarkers for smoking. These biomarker profiles of HTP users were closer to those of cigarette smokers than those of never smokers. The concentration of glutamate was higher in cigarette smokers, and biomarkers involved in glutamate metabolism were also associated with cigarette smoking and HTP use. Network pathway analysis showed that smoking was associated with the glutamate pathway, which could lead to endothelial dysfunction and atherosclerosis of the vessels.

Conclusions: Our study showed that the glutamate pathway is affected by habitual smoking. These changes in the glutamate pathway may partly explain the mechanism by which cigarette smoking causes cardiovascular disease. HTP use was also associated with glutamate metabolism, indicating that HTP use may contribute to the development of cardiovascular disease through mechanisms similar to those in cigarette use.

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© 2023 Sei Harada et al.

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