HomeENGLISH MAGAZINEE-cigs: those "fruity" liquids are not so harmless after all

E-cigs: those “fruity” liquids are not so harmless after all

E-cigarettes, popular battery-powered devices that simulate the act of smoking a traditional cigarette, dispense a vapor derived from liquid chemicals in a refillable cartridge. The refills typically contain propylene glycol and often flavorings, along with nicotine as active agent. Propylene glycol, a colorless, odorless food additive, is found in numerous processed food and beverages; it is also used as a solvent in several pharmaceuticals. E-cigarette devices and refills are not well regulated, and the long-term health effects of e-cigarette use are not widely known. Nevertheless, flavoring and additive ingredients in e-cigarettes may increase inflammation and impair lung function, according to new research. The choice for flavored liquidi s partciluarly attractive for youngsters. A recent study, published in the American Journal of Physiology–Lung Cellular and Molecular Physiology, already found that short-term exposure to e-cigarettes was enough to cause lung inflammation similar or worse than that seen in traditional cigarette use. Researchers studied several groups of mice that received whole-body exposure to varying chemical combinations four times each day. Each exposure session was separated by 30-minute smoke-free intervals.

  • One group was exposed to cigarette smoke (“cigarette”);
  • One group was exposed to e-cigarette vapor containing propylene glycol and vegetable glycerol, an odorless liquid derived from plant oils (“propylene”);
  • One group was exposed to e-cigarette vapor containing propylene glycol and nicotine (“propylene + nicotine”) and
  • One group was exposed to e-cigarette vapor containing propylene glycol, nicotine and tobacco flavoring (“flavoring”).

The cigarette and e-cigarette groups were compared with a control group that was exposed to medical-grade air. Some of the animals in each group were exposed to short-term cigarette smoke or e-cigarette vapor (three days), while others were exposed for a longer term (four weeks). The research team found an increase in markers of inflammation, mucus production and altered lung function in the propylene, propylene + nicotine and flavoring groups after three days. However, the propylene group showed fewer negative effects with long-term exposure, suggesting the additive alone elicits only a temporary irritation that eventually subsides with continued use.

In addition, two cytokine proteins became elevated on in the flavoring group, suggesting that some of the many flavoring components on the market may not be safe for even short-term use. The condition of the e-cigarette groups in comparison with the cigarette group surprised the researchers. The level of oxidative stress in the flavoring group was equal to or higher than that of the cigarette group. However, respiratory mechanics were adversely affected only in mice exposed to cigarette smoke and not to e-cigarette vapor after prolonged treatment. This because flavoring aldehydes, propylene glycol and nicotine are less “toxic” to oxidized hydrocarbons, tar and the other 700 components of tobacco combustion. Nonetheless, aldehydes promptly react with proteins creating adducts (AGE-like) that might impair extensibility of lung skeletal proteins (e.g. elastine). In addition they may generate oxidative stress through the same mechanism and contribute to the tissue inflammation. The observed detrimental effects in the lung upon e-cigarette vapor exposure in animal models, highlight the need for further investigation of safety and toxicity of these rapidly expanding devices worldwide. Particular concern is toward adolescents that seem to prefer vaping over the traditional “smoking”.

A subsequent study additionally demonstrated that e-cgs flavors impair the cellular ability of white blood cells called neutrophils to porperly face bacterial invasion through their “phagocytosis” response. In these research, scientists proven that cinnamaldehyde (cinnamon flavor) and ethyl vanillin (vanilla flavor) dose-dependently decrease oxidative burst and that benzaldehyde and benzaldehyde propylene glycol acetal (fruity flavors) dose-dependently impair phagocytosis. Isoamyl acetate (a non aromatic banana-like aroma) did not affect either measure of neutrophil function. Though they share a common chemical class, these flavorings have unique functional groups, which may explain their differential activities. For example, cinnamaldehyde is an α,β-unsaturated aldehyde that can covalently bind and modify thiols, including interactions with cysteinyl groups on proteins, whereas vanillin (the sister compound to ethyl vanillin) has been shown to interact with proteins via formation of Schiff bases.  Benzaldehyde shares structural similarity to cinnamaldehyde but lacks the reactive α,β-unsaturated moiety, which may explain why it inhibited neutrophil function to a lesser extent than cinnamaldehyde.

Potential mechanisms underlying decreased oxidative burst observed here could include direct inhibition of key proteins in glycolysis or the pentose phosphate pathway needed for these cells to produce energy from glucose. Cinnamaldehyde and other aldehydes are directly toxic to many kind of cells, either normal and canceous. Proof is that in the ‘70s one potential anticancer drug, that never got in the clinical practice, was a glucose conjugated benzaldehyde derivative, intentionally using a glucide moiety as a trojan horse. The cytotoxic effect of vanillin and its analogous molecules is known from decades of laboratory studies: one of them is a fairly specific inhibitor of NADPH-oxidase of neutrophils, the enzymatic complex that regulates the production of free radicals that neutrophils use to kill bacteria. This supports the data from the previous study on the effects of the vanilla aroma of e-cigs on lung resident neutrophils. The impact of this notion is direct, because the lungs are the first gateway for bacteria from the air we breathe. The local surveillance immune system must always be alert to potential pathogens that eventually arrive in our airways.

Therefore, the use of electronic cigarettes with flavored liquids is a potential for the suppression of our normal defensive barriers against external bacteria. This means a potential higher incidence of bacterial pneumonia among users of these products, not to mention the “lipoid” chemical pneumonia described a few summer years ago, resulting from the use of electronic cigarettes and which caused dozens of deaths among the youngest. It therefore seems that the use of these apparently harmless e-cigarettes, (bragged for not being carcinogenic, but still too early to tell now), is not as harmless as one might think.

  • edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.

Scientific references

Hickman E et al. Chem Res ToxicoL 2019; 32(6):982-985.

Clapp PW et al. AJP Lung Cell Mol. Physiol 2019; 316:L470.

Wang JB, Olgin JE et al. PLoS One. 2018; 13(7):e0198681.

Caruso M, Li Volti G et al. Frontiers Physiol. 2018; 9:1240. 

Muthumalage T et al., Rahman I. Front Physiol. 2017; 8:1130.

Clapp PW et al. AJP Lung Cell Mol Physiol. 2017; 313:L278.

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Dott. Gianfrancesco Cormaci

Medico Chirurgo, Specialista; PhD. a CoFood s.r.l.
- Laurea in Medicina e Chirurgia nel 1998 (MD Degree in 1998) - Specialista in Biochimica Clinica nel 2002 (Clinical Biochemistry residency in 2002) - Dottorato in Neurobiologia nel 2006 (Neurobiology PhD in 2006) - Ha soggiornato negli Stati Uniti, Baltimora (MD) come ricercatore alle dipendenze del National Institute on Drug Abuse (NIDA/NIH) e poi alla Johns Hopkins University, dal 2004 al 2008. - Dal 2009 si occupa di Medicina personalizzata. - Guardia medica presso strutture private dal 2010 - Detentore di due brevetti sulla preparazione di prodotti gluten-free a partire da regolare farina di frumento enzimaticamente neutralizzata (owner of patents concerning the production of bakery gluten-free products, starting from regular wheat flour). - Responsabile del reparto Ricerca e Sviluppo per la società CoFood s.r.l. (Leader of the R&D for the partnership CoFood s.r.l.) - Autore di articoli su informazione medica e salute sul sito www.medicomunicare.it (Medical/health information on website) - Autore di corsi ECM FAD pubblicizzati sul sito www.salutesicilia.it
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