Impact of Nicotine-Free Electronic Cigarettes on Cardiovascular Health: A Systematic Review

Background: The cardiovascular effects of nicotine-containing e-cigarettes are well-established; however, far less is known about nicotine-free formulations, which are often perceived as safer alternatives. Yet, these products generate complex aerosols that may still pose toxicological risks. Methods: Following the PRISMA 2020 guidelines, we systematically searched PubMed, Scopus, Web of Science, and the Cochrane Library up to 27 August 2025. Eligible studies included human and animal research on nicotine-free e-cigarettes evaluating vascular, hemodynamic, arrhythmic, oxidative, or inflammatory outcomes. Owing to the heterogeneity of the studies, the findings were synthesized qualitatively. Results: Nine studies met the inclusion criteria. Human trials consistently demonstrated acute vascular impairments, including endothelial dysfunction, oxidative stress, increased arterial stiffness, and transient blood pressure elevations. Experimental models corroborated these findings and further revealed systemic inflammation, mitochondrial injury, and developmental cardiotoxicity. Conclusions: Nicotine-free e-cigarettes produce reproducible acute cardiovascular effects. Although the long-term outcomes remain uncertain, preclinical evidence highlights biologically plausible mechanisms, including mitochondrial dysfunction and proarrhythmogenic potential. Until large-scale longitudinal studies have been conducted to clarify their risk profile, nicotine-free products should not be regarded as risk-free.