Changes in human biomarkers of exposure after complete switching from cigarettes to e-cigarettes or exclusive e-cigarette use: a systematic review and biomarker-specific meta-analysis.

BACKGROUND: Combustible cigarette smoking remains a major preventable cause of premature mortality worldwide, and the public-health relevance of electronic cigarettes depends substantially on whether switching from cigarettes lowers exposure to toxicants associated with smoking-related disease. We systematically reviewed the human biomonitoring evidence and quantified changes in biomarkers of exposure after complete switching from cigarettes to e-cigarettes or exclusive e-cigarette use after cigarette smoking.

METHODS: PubMed, Scopus and Web of Science Core Collection were searched from inception to 28 May 2026 for human studies reporting biomarkers of exposure or potential harm in relation to e-cigarette use, dual use or switching. Study characteristics, biomarker data and a pragmatic risk-of-bias and funding assessment were extracted in duplicate. Meta-analysis was restricted to biomarkers of exposure with at least two compatible estimates for complete switching or exclusive e-cigarette use after cigarette smoking; dual-use evidence was synthesised narratively. Effects were expressed as ratios of means comparing post-switch with baseline or reference cigarette-smoking levels and pooled using random-effects models with restricted maximum likelihood estimation.

RESULTS: Sixty studies were included. Six publications, representing seven study-level sources, contributed 47 biomarker-specific effects across ten biomarkers. Complete switching or exclusive e-cigarette use after cigarette smoking was associated with lower levels of every pooled biomarker. Approximate reductions were 61% for NNAL, 92% for NNN, 72% for 3-HPMA, 84% for the acrylonitrile metabolite CEMA, 77% for HMPMA, 82% for MHBMA, 90% for S-PMA, 79% for exhaled carbon monoxide, 77% for carboxyhaemoglobin and 76% for 1-OHP. Between-study heterogeneity was substantial for most biomarkers (I² 57-99%), and 95% prediction intervals lay entirely below 1.0 only for NNN, CEMA and carboxyhaemoglobin; the pooled values are therefore central estimates rather than precise expectations for any individual future study. Narrative evidence was broadly consistent: exclusive e-cigarette use was generally associated with lower exposure than cigarette smoking, whereas reductions among dual users were smaller and depended on cigarette displacement. Biomarkers of potential harm were more heterogeneous and were not pooled. Many switching studies were short-term, product-specific and industry-funded.

CONCLUSIONS: Complete switching from cigarettes to e-cigarettes or exclusive e-cigarette use after cigarette smoking is associated with substantially lower biomarkers of exposure to tobacco- and combustion-related toxicants. Exposure reductions appear greatest when cigarette smoking is fully displaced. These findings describe reduced exposure to measured toxicants; they do not, by themselves, establish reduced disease risk or long-term safety.