Many thousands of people in the UK have already stopped smoking with the help of an e-cigarette. There's growing evidence that they can be effective.
Using an e-cigarette can help you manage your nicotine cravings. To get the best out of it, make sure you're using it as much as you need to and with the right strength of nicotine in your e-liquid.
A major UK clinical trial published in found that, when combined with expert face-to-face support, people who used e-cigarettes to quit smoking were twice as likely to succeed as people who used other nicotine replacement products, such as patches or gum. You will not get the full benefit from vaping unless you stop smoking cigarettes completely. Getting expert help from your local stop smoking service gives you the best chance of quitting smoking for good.
Moreover, it has been reported that the heating process itself can lead to the formation of new decomposition compounds of questionable toxicity. Numerous in vivo and in vitro studies have been performed to better understand the impact of these new inhalable compounds on human health.
Results of toxicological analyses suggest that e-cigarettes can be safer than conventional cigarettes, although harmful effects from short-term e-cigarette use have been described.
Worryingly, the potential long-term effects of e-cigarette consumption have been scarcely investigated. In this review, we take stock of the main findings in this field and their consequences for human health including coronavirus disease COVID Electronic nicotine dispensing systems ENDS , commonly known as electronic cigarettes or e-cigarettes , have been popularly considered a less harmful alternative to conventional cigarette smoking since they first appeared on the market more than a decade ago.
Both the electronic devices and the different e-liquids are easily available in shops or online stores. Effect of the heating process on aerosol composition.
Main harmful effects documented. Several compounds detected in e-cigarette aerosols are not present in e-liquid s and the device material also seems to contribute to the presence of metal and silicate particles in the aerosols. The heating conditions especially on humectants, flavourings and the low-quality material used have been identified as the generator of the new compounds in aerosols.
Some compounds generated from humectants propylene glycol and glycerol and flavourings, have been associated with clear airways impact, inflammation, impairment of cardiovascular function and toxicity. In addition, some of them are carcinogens or potential carcinogens.
The e-liquid typically contains humectants and flavourings, with or without nicotine; once vapourised by the atomiser, the aerosol vapour provides a sensation similar to tobacco smoking, but purportedly without harmful effects [ 3 ]. However, it has been reported that the heating process can lead to the generation of new decomposition compounds that may be hazardous [ 4 , 5 ].
The levels of nicotine, which is the key addictive component of tobacco, can also vary between the commercially available e-liquids, and even nicotine-free options are available. For this particular reason, e-cigarettes are often viewed as a smoking cessation tool, given that those with nicotine can prevent smoking craving, yet this idea has not been fully demonstrated [ 2 , 6 , 7 ]. However, are they risk-free? Is there sufficient toxicological data on all the components employed in e-liquids?
Do we really know the composition of the inhaled vapour during the heating process and its impact on health? Can e-cigarettes be used to curb tobacco use? In the present review, we have attempted to clarify these questions based on the existing scientific literature, and we have compiled new insights related with the toxicity derived from the use of these devices.
One of the first studies in humans involved the analysis of 9 volunteers that consumed e-cigarettes , with or without nicotine, in a ventilated room for 2 h [ 8 ]. Pollutants in indoor air, exhaled nitric oxide NO and urinary metabolite profiles were analysed. The results of this acute experiment revealed that e-cigarettes are not emission-free, and ultrafine particles formed from propylene glycol PG could be detected in the lungs. The study also suggested that the presence of nicotine in e-cigarettes increased the levels of NO exhaled from consumers and provoked marked airway inflammation; however, no differences were found in the levels of exhaled carbon monoxide CO , an oxidative stress marker, before and after e-cigarette consumption [ 8 ].
A more recent human study detected significantly higher levels of metabolites of hazardous compounds including benzene, ethylene oxide, acrylonitrile, acrolein and acrylamide in the urine of adolescent dual users e-cigarettes and conventional tobacco consumers than in adolescent e-cigarette -only users Table 1 [ 9 ].
Moreover, the urine levels of metabolites of acrylonitrile, acrolein, propylene oxide, acrylamide and crotonaldehyde, all of which are detrimental for human health, were significantly higher in e-cigarette -only users than in non-smoker controls, reaching up to twice the registered values of those from non-smoker subjects Table 1 [ 9 ].
In line with these observations, dysregulation of lung homeostasis has been documented in non-smokers subjected to acute inhalation of e-cigarette aerosols [ 10 ]. Little is known about the effect of vaping on the immune system.
Interestingly, both traditional and e-cigarette consumption by non-smokers was found to provoke short-term effects on platelet function, increasing platelet activation levels of soluble CD40 ligand and the adhesion molecule P-selectin and platelet aggregation, although to a lesser extent with e-cigarettes [ 11 ]. As found with platelets, the exposure of neutrophils to e-cigarette aerosol resulted in increased CD11b and CD66b expression being both markers of neutrophil activation [ 12 ].
Additionally, increased oxidative stress, vascular endothelial damage, impaired endothelial function, and changes in vascular tone have all been reported in different human studies on vaping [ 13 , 14 , 15 , 16 , 17 ].
In this context, it is widely accepted that platelet and leukocyte activation as well as endothelial dysfunction are associated with atherogenesis and cardiovascular morbidity [ 18 , 19 ]. In line with these observations the potential association of daily e-cigarettes consumption and the increased risk of myocardial infarction remains controversial but benefits may occur when switching from tobacco to chronic e-cigarette use in blood pressure regulation, endothelial function and vascular stiffness reviewed in [ 20 ].
Nevertheless, whether or not e-cigarette vaping has cardiovascular consequences requires further investigation. Indeed, computed tomography CT scan revealed local inflammation that impaired gas exchange caused by aerosolised oils from e-cigarettes [ 21 ].
However, most of the reported cases of lung injury were associated with use of e-cigarettes for tetrahydrocannabinol THC consumption as well as vitamin E additives [ 20 ] and not necessarily attributable to other e-cigarette components. Beyond airway disease, exposure to aerosols from e-liquids with or without nicotine has also been also associated with neurotoxicity in an early-life murine model [ 23 ].
Results from in vitro studies are in general agreement with the limited number of in vivo studies. For example, in an analysis using primary human umbilical vein endothelial cells HUVEC exposed to 11 commercially-available vapours, 5 were found to be acutely cytotoxic, and only 3 of those contained nicotine [ 24 ]. In addition, 5 of the 11 vapours tested including 4 that were cytotoxic reduced HUVEC proliferation and one of them increased the production of intracellular reactive oxygen species ROS [ 24 ].
Three of the most cytotoxic vapours—with effects similar to those of conventional high-nicotine CS extracts—also caused comparable morphological changes [ 24 ].
Endothelial cell migration is an important mechanism of vascular repair than can be disrupted in smokers due to endothelial dysfunction [ 25 , 26 ]. In a comparative study of CS and e-cigarette aerosols, Taylor et al. In contrast, while CS extract reduced epithelial barrier integrity determined by the translocation of dextran from the apical to the basolateral side of the cell layer , e-cigarette aerosol did not, suggesting that only CS extract negatively affected host defence [ 28 ].
Moreover, Higham et al. In a comparative study, repeated exposure of human gingival fibroblasts to CS condensate or to nicotine-rich or nicotine-free e-vapour condensates led to alterations in morphology, suppression of proliferation and induction of apoptosis, with changes in all three parameters greater in cells exposed to CS condensate [ 29 ]. All this evidence would suggest that e-cigarettes are potentially less harmful than conventional cigarettes Fig. Importantly, however, most of these studies have investigated only short-term effects [ 10 , 14 , 15 , 22 , 27 , 28 , 29 , 31 , 32 ], and the long-term effects of e-cigarette consumption on human health are still unclear and require further study.
Comparison of the degree of harmful effects documented from e-cigarette and conventional cigarette consumption. Human studies, in vivo mice exposure and in vitro studies. All of these effects from e-cigarettes were documented to be lower than those exerted by conventional cigarettes, which may suggest that e-cigarette consumption could be a safer option than conventional tobacco smoking but not a clear safe choice.
Beyond flavour, one of the major issues in the e-liquid market is the range of nicotine content available. The mislabelling of nicotine content in e-liquids has been previously addressed [ 8 , 34 ]. Of note, several studies have detected nicotine in those e-liquids labelled as nicotine-free [ 5 , 35 , 36 ]. One study detected the presence of nicotine 0. Among the 17 samples tested in this latter study 14 were identified to be counterfeit or suspected counterfeit.
A third study detected nicotine in 7 of 10 nicotine-free refills, although the concentrations were lower than those identified in the previous analyses 0.
Not only is there evidence of mislabelling of nicotine content among refills labelled as nicotine-free, but there also seems to be a history of poor labelling accuracy in nicotine-containing e-liquids [ 37 , 38 ]. A comparison of the serum levels of nicotine from e-cigarette or conventional cigarette consumption has been recently reported [ 39 ].
Blood samples were collected 1, 2, 4, 6, 8, 10, 12 and 15 min after the first puff, and nicotine serum levels were measured by liquid chromatography-mass spectrometry LC—MS. The results revealed higher serum levels of nicotine in the conventional CS group than in the e-cigarette group In this line, a study compared the acute impact of CS vs.
Both increased markers of oxidative stress and decreased NO bioavailability, flow-mediated dilation, and vitamin E levels showing no significant differences between tobacco and e-cigarette exposure reviewed in [ 20 ]. Inasmuch, short-term e-cigarette use in healthy smokers resulted in marked impairment of endothelial function and an increase in arterial stiffness reviewed in [ 20 ].
Similar effects on endothelial dysfunction and arterial stiffness were found in animals when they were exposed to e-cigarette vapor either for several days or chronically reviewed in [ 20 ]. In contrast, other studies found acute microvascular endothelial dysfunction, increased oxidative stress and arterial stiffness in smokers after exposure to e-cigarettes with nicotine, but not after e-cigarettes without nicotine reviewed in [ 20 ].
In women smokers, a study found a significant difference in stiffness after smoking just one tobacco cigarette, but not after use of e-cigarettes reviewed in [ 20 ]. It is well known that nicotine is extremely addictive and has a multitude of harmful effects. Nicotine has significant biologic activity and adversely affects several physiological systems including the cardiovascular, respiratory, immunological and reproductive systems, and can also compromise lung and kidney function [ 41 ].
In addition to its toxicological effects on foetus development, nicotine can disrupt brain development in adolescents and young adults [ 44 , 45 , 46 ]. Several studies have also suggested that nicotine is potentially carcinogenic reviewed in [ 41 ] , but more work is needed to prove its carcinogenicity independently of the combustion products of tobacco [ 47 ].
In this latter regard, no differences were encountered in the frequency of tumour appearance in rats subjected to long-term 2 years inhalation of nicotine when compared with control rats [ 48 ]. Assuming that a conventional cigarette contains 0. We would argue that further studies with chronic administration of low doses of nicotine are required to clearly evaluate its impact on carcinogenicity. In the aforementioned study exposing human gingival fibroblasts to CS condensate or to nicotine-rich or nicotine-free e-vapour condensates [ 29 ], the detrimental effects were greater in cells exposed to nicotine-rich condensate than to nicotine-free condensate, suggesting that the possible injurious effects of nicotine should be considered when purchasing e-refills.
The lethal dose of nicotine for an adult is estimated at 30—60 mg [ 52 ]. Thus, devices with rechargeable refills are another issue of concern with e-cigarettes , especially when e-liquids are not sold in child-safe containers, increasing the risk of spilling, swallowing or breathing.
These data overall indicate that the harmful effects of nicotine should not be underestimated. Despite the established regulations, some inaccuracies in nicotine content labelling remain in different brands of e-liquids. Consequently, stricter regulation and a higher quality control in the e-liquid industry are required. In this particular aspect, again the composition of the e-liquid varies significantly among different commercial brands [ 4 , 35 ].
The most common and major components of e-liquids are PG or 1,2-propanediol, and glycerol or glycerine propane-1,2,3-triol. In fact, they are widely used as alimentary and pharmaceutical products [ 2 ].
In an analysis of 54 commercially available e-liquids , PG and glycerol were detected in almost all samples at concentrations ranging from 0. With regards to toxicity, little is known about the effects of humectants when they are heated and chronically inhaled. Studies have indicated that PG can induce respiratory irritation and increase the probability of asthma development [ 55 , 56 ], and both PG and glycerol from e-cigarettes might reach concentrations sufficiently high to potentially cause irritation of the airways [ 57 ].
In vitro, aerosols from glycerol only-containing refills showed cytotoxicity in A and human embryonic stem cells, even at a low battery output voltage [ 59 ].
PG was also found to affect early neurodevelopment in a zebrafish model [ 60 ]. Another important issue is that, under heating conditions PG can produce acetaldehyde or formaldehyde Although, assuming 15 puffs per e-cigarette unit, carbonyls produced by PG or glycerol heating would be below the maximum levels found in a conventional cigarette combustion Table 2 [ 51 , 62 ].
Nevertheless, further studies are required to properly test the deleterious effects of all these compounds at physiological doses resembling those to which individuals are chronically exposed. Although PG and glycerol are the major components of e-liquids other components have been detected. Of note, the analysis identified formaldehyde, acetaldehyde and acrolein [ 4 ], 3 carbonyl compounds with known high toxicity [ 63 , 64 , 65 , 66 , 67 ]. While no information was given regarding formaldehyde and acetaldehyde concentrations, the authors calculated that one puff could result in an acrolein exposure of 0.
Assuming 40 mL per puff and 15 puffs per e-cigarette unit according to several manufacturers [ 4 ], each e-cigarette unit would generate approximately 1. However, given that e-cigarette units of vaping are not well established, users may puff intermittently throughout the whole day.
In a similar study, acrolein was found in 11 of 12 aerosols tested, with a similar content range approximately 0. In the same study, both formaldehyde and acetaldehyde were detected in all of the aerosols tested, with contents of 0.
It is important to point out that the levels of these toxic products in e-cigarette aerosols are significantly lower than those found in CS: 9 times lower for formaldehyde, times lower for acetaldehyde and 15 times lower for acrolein Table 2 [ 62 , 68 ]. Other compounds that have been detected in aerosols include acetamide, a potential human carcinogen [ 5 ], and some aldehydes [ 69 ], although their levels were minimal.
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There is no sure way to flush the body of nicotine quickly, but people may try maintaining a healthy lifestyle so that their body works efficiently. It is not yet clear whether people who vape clear nicotine from their systems more rapidly than regular smokers. Giving up nicotine can be difficult, but it is worth the challenge. The American Lung Association report that in there were Hence, more people are enjoying the benefits of living a nicotine-free life every day.
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