Flavoring Agents in E-cigarette Liquids: A Comprehensive Analysis of Multiple Health Risks

Abstract

The availability of a wide range of flavored e-cigarettes is one of the primary reasons for vaping initiation and persistent use among adolescents and young people. This plethora of flavors available on the market are crafted using different flavoring agents such as cinnamaldehyde, vanillin, benzaldehyde, ethyl maltol, menthol, and dimethylpyrazine. Recent studies have brought to light the potential risks associated with e-cigarette flavoring agents and their effects on various organ systems, both with and without nicotine. Research has demonstrated that flavoring agents can induce inflammation, endothelial dysfunction, epithelial barrier disruption, oxidative stress, DNA damage, electrophysiological alterations, immunomodulatory effects, and behavioral changes, even independently of nicotine. Notably, these negative outcomes adversely affect cardiovascular system by reducing cell viability, decreasing endothelial nitric oxide synthase, nitric oxide bioavailability, soluble guanylyl cyclase activity and cyclic guanosine monophosphate accumulation, impairing endothelial proliferation and tube formation, and altering vasoreactivity resulting in vascular dysfunction. In the heart, these agents decrease parasympathetic activity, induce depolarization of resting membrane potential, loss of rhythmicity, increase isovolumic relaxation time, and change in ventricular repolarization and ventricular tachyarrhythmias. It is found that the specific response elicited by flavoring agents in different organ systems varies depending on the flavor used, the concentration of the flavoring agent, and the duration of exposure. However, the literature on the effects of flavoring agents is currently limited, emphasizing the need for more preclinical and randomized clinical trials to gain a deeper understanding and provide further evidence of the harmful effects of flavored e-cigarette use. In summary, recent research suggests that flavoring agents themselves can have detrimental effects on the body. To fully comprehend these effects, additional preclinical and clinical studies are needed to explore the risks associated with flavored e-cigarette usage.

Keywords: cardiac electrophysiological alterations; e-cigarette; endothelial dysfunction; epithelial barrier dysfunction; flavor; inflammation; neuro-behavioral changes; vaping.

Figure 1. Effects of flavored e-cigarette aerosol or liquid in different organs based on in vitro and in vivo studies.

The image was created by the authors of this study using BioRender.com.