{"doi":"10.1093/ntr/ntab134","title":"Changes in Biomarkers of Cigarette Smoke Exposure After 6 Days of Switching Exclusively or Partially to Use of the JUUL System with Two Nicotine Concentrations: A Randomized Controlled Confinement Study in Adult Smokers","abstract":"<jats:title>Abstract</jats:title><jats:sec><jats:title>Introduction</jats:title><jats:p>Evidence suggests that cigarette smokers who switch to electronic nicotine delivery systems (ENDS) reduce their exposure to harmful toxicants and carcinogens. It is unclear if dual-use is associated with decreases in exposure to toxicants.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>This parallel-group confinement study assessed changes in biomarkers of exposure (BOEs) over six days among healthy adult smokers who were randomized into 1 of 11 study groups: eight JUUL-brand System (JUUL) groups (4 JUUL flavors [Virginia Tobacco, Menthol, Mint, Mango] × 2 nicotine concentrations [5.0% or 3.0% by weight]); Dual-Use group used preferred JUUL flavor (5.0% nicotine) and ≤50% usual brand (UB) cigarettes/day; UB Cigarette group and one group abstained from all tobacco/nicotine product use (Abstinence group). Urine and blood analysis assessed changes in primary BOE endpoints (NNAL, 3-HPMA, MHBMA, S-PMA COHb) and secondary BOE endpoints (NNN, HMPMA, CEMA, 1-OHP, O-toluidine, 2-NA, 4-ABP) among 279 adult smokers.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>In JUUL groups, median percent reductions in primary BOEs (Day 6–Baseline) were 90%–≥100% of Abstinence; there were no significant differences between JUUL groups and Abstinence. All reductions in JUUL groups were substantially and statistically significantly greater than reductions in the UB Cigarette group (ps &amp;lt; 0.025). Median reductions in primary BOEs in the Dual-Use group were 43%–55% of Abstinence. Similar results were observed for secondary BOEs.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>This study suggests that the use of JUUL as a complete or partial substitute (i.e., dual-use with ≥50% reduction in cigarette consumption) for combustible cigarettes can substantially reduce exposure to multiple toxins associated with cigarette smoking.</jats:p></jats:sec><jats:sec><jats:title>Implications</jats:title><jats:p>This study adds to the growing body of evidence supporting the utility of ENDS products as potentially reduced-harm alternatives to cigarettes for adult smokers. Adult smokers who switched completely from cigarette smoking to use of the JUUL System (“JUUL”) in two nicotine concentrations (5.0% and 3.0%) and four flavors significantly reduced their exposure to multiple classes of cigarette-related toxicants. Additionally, smokers who used JUUL and continued smoking but reduced their daily cigarette consumption by ≥50% (dual users) also significantly reduced their toxicant exposure compared to cigarette smoking.</jats:p></jats:sec>","journal":"Nicotine &amp; Tobacco Research","year":2021,"id":593650,"datarank":0.6010999777848708,"base_score":4.007333185232471,"endowment":4.007333185232471,"self_citation_contribution":0.6010999777848708,"citation_network_contribution":0.0,"self_endowment_contribution":0.6010999777848708,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":54,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":2,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1519451,"name":"Nicholas I Goldenson","orcid":null,"position":1,"is_corresponding":false},{"id":1519452,"name":"Patrick C Bailey","orcid":null,"position":2,"is_corresponding":false},{"id":1285073,"name":"Stephanie Chan","orcid":"0000-0001-7147-1916","position":3,"is_corresponding":false},{"id":1032016,"name":"Saul Shiffman","orcid":"0000-0002-9639-490X","position":4,"is_corresponding":false},{"id":1381778,"name":"Gal Cohen","orcid":"0000-0002-4367-1491","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Changes in Biomarkers of Cigarette Smoke Exposure After 6 Days of Switching Exclusively or Partially to Use of the JUUL System with Two Nicotine Concentrations: A Randomized Controlled Confinement Study in Adult Smokers","abstract":"<jats:title>Abstract</jats:title><jats:sec><jats:title>Introduction</jats:title><jats:p>Evidence suggests that cigarette smokers who switch to electronic nicotine delivery systems (ENDS) reduce their exposure to harmful toxicants and carcinogens. It is unclear if dual-use is associated with decreases in exposure to toxicants.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>This parallel-group confinement study assessed changes in biomarkers of exposure (BOEs) over six days among healthy adult smokers who were randomized into 1 of 11 study groups: eight JUUL-brand System (JUUL) groups (4 JUUL flavors [Virginia Tobacco, Menthol, Mint, Mango] × 2 nicotine concentrations [5.0% or 3.0% by weight]); Dual-Use group used preferred JUUL flavor (5.0% nicotine) and ≤50% usual brand (UB) cigarettes/day; UB Cigarette group and one group abstained from all tobacco/nicotine product use (Abstinence group). Urine and blood analysis assessed changes in primary BOE endpoints (NNAL, 3-HPMA, MHBMA, S-PMA COHb) and secondary BOE endpoints (NNN, HMPMA, CEMA, 1-OHP, O-toluidine, 2-NA, 4-ABP) among 279 adult smokers.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>In JUUL groups, median percent reductions in primary BOEs (Day 6–Baseline) were 90%–≥100% of Abstinence; there were no significant differences between JUUL groups and Abstinence. All reductions in JUUL groups were substantially and statistically significantly greater than reductions in the UB Cigarette group (ps &amp;lt; 0.025). Median reductions in primary BOEs in the Dual-Use group were 43%–55% of Abstinence. Similar results were observed for secondary BOEs.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>This study suggests that the use of JUUL as a complete or partial substitute (i.e., dual-use with ≥50% reduction in cigarette consumption) for combustible cigarettes can substantially reduce exposure to multiple toxins associated with cigarette smoking.</jats:p></jats:sec><jats:sec><jats:title>Implications</jats:title><jats:p>This study adds to the growing body of evidence supporting the utility of ENDS products as potentially reduced-harm alternatives to cigarettes for adult smokers. Adult smokers who switched completely from cigarette smoking to use of the JUUL System (“JUUL”) in two nicotine concentrations (5.0% and 3.0%) and four flavors significantly reduced their exposure to multiple classes of cigarette-related toxicants. Additionally, smokers who used JUUL and continued smoking but reduced their daily cigarette consumption by ≥50% (dual users) also significantly reduced their toxicant exposure compared to cigarette smoking.</jats:p></jats:sec>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":2,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"34161586","pmcid":"PMC8570669","openalex_id":null,"authors":[],"funders":[{"funder_name":"JUUL System","grant_id":"","title":null},{"funder_name":"Juul Labs, Inc.","grant_id":"","title":null}],"total_grants":2,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"hybrid","license":"cc-by-nc-nd","oa_locations":[{"url":"https://academic.oup.com/ntr/article-pdf/23/12/2153/41091012/ntab134.pdf","host_type":"publisher"},{"url":"http://academic.oup.com/ntr/advance-article-pdf/doi/10.1093/ntr/ntab134/38967591/ntab134.pdf","host_type":"publisher"},{"url":"http://europepmc.org/pmc/articles/PMC8570669","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/8570669","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC8570669","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC8570669?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":[],"mesh_terms":["Humans","Nicotine","Smoking","Adult","Tobacco Products","Biomarkers","Smokers","Electronic Nicotine Delivery Systems"],"keywords":[],"sdg_mappings":[],"linked_datasets":[{"doi":"10.6084/m9.figshare.19976927.v1","title":"Additional file 1 of A randomised, crossover, clinical study to assess nicotine pharmacokinetics and subjective effects of the BIDI® stick ENDS compared with combustible cigarettes and a comparator ENDS in adult smokers","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.19976927","title":"Additional file 1 of A randomised, crossover, clinical study to assess nicotine pharmacokinetics and subjective effects of the BIDI® stick ENDS compared with combustible cigarettes and a comparator ENDS in adult smokers","publisher":"figshare","resource_type":"JournalArticle"}],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-27T11:48:43.213257Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}