Systematic review of biomarker findings from clinical studies of electronic cigarettes and heated tobacco products

BACKGROUND: Worldwide adoption of electronic cigarettes (e-cigarettes) and heated tobacco products (HTPs) has increased exponentially over the past decade. These products have been proposed as non-combustible alternatives to traditional tobacco products such as cigarettes and may thus reduce the negative health consequences associated with tobacco smoke. However, the overall health impact and safety of using these products remains unclear. This review seeks to provide an updated summary of available evidence on changes to levels of tobacco-related biomarkers to aid the overall assessment of the consequences of using e-cigarettes and HTPs. METHODS: A systematic review was conducted through major databases (Medline/PubMed, Scopus, EMBASE) searching for articles directly comparing biomarker levels in humans using e-cigarettes or HTPs and those using combustible cigarettes. We included peer reviewed articles with comparative or longitudinal design and extracted key information for our purpose (type of population, demographics, biomarkers measurements, and health effects). An initial qualitative analysis was performed followed by a summary of findings. RESULTS: A total of 44 studies were included from initial citations. The vast majority of the literature reported reductions in levels of biomarkers of tobacco smoke exposure (BOE), especially nicotine, MHBMA, 3-HPMA, S-PMA, 1-OHP and NNAL, when using e-cigarettes and HTPs compared to combustible cigarettes. There was a slight tendency toward a larger reduction in these biomarkers levels with the use of e-cigarettes, although direct comparisons between e-cigarettes and HTPs were lacking. There was also a trend toward positive changes in levels of biomarkers of biological effect (BOBE) with the use of e-cigarettes and HTPs. CONCLUSIONS: A comparison of levels of biomarkers of tobacco-related exposure collected in clinical studies revealed that the use of e-cigarettes and HTPs could lead to a significant reduction in exposure to harmful substances compared to combusted cigarettes. In tandem, the health status of e-cigarettes and HTP users, indexed by levels of biomarkers of biological effect showed potential for improvement compared to smoking. However, larger and longer-term population-based studies are needed to further clarify these findings.