E-cigarettes are less dangerous than smoking, but they are not harmless; long-term health effects remain debated

AFFIRMATION COMPLETE: Budding research on e-cigarettes also suggests that these flavors contain terpenes that may be more damaging to the lungs than other flavors are. Other studies have indicated that while e-cigarettes may have milder effects on the lungs, they are just as bad - if not worse - for the cardiovascular system, raising risks of heart disease and high blood pressure.

SUMMARY

This Daily Mail article reports on the Food and Drug Administration (FDA)’s decision to regulate e-cigarette advertising. Originally meant as a tool to help smokers quit smoking, e-cigarettes have instead made their way into children’s hands. With “more than 2 million US teenagers” now using e-cigarettes, the FDA has labelled vaping an epidemic. While e-cigarette manufacturers have denied targeting their products at children, it is also clear that many e-cigarettes have been designed with packaging and flavours which appeal to teenagers.

E-cigarettes are relatively new, therefore their long-term impact on health is not well-established. A study has reported that toxic and potentially carcinogenic substances are present within e-cigarette vapour, although fewer than in combustible cigarettes^[1]. Besides toxic chemicals, the nicotine in many e-cigarettes also presents another health issue. Aside from addiction – potentially acting as a gateway to future drug use – nicotine is also associated with cardiovascular problems (e.g. high blood pressure). These findings have led health authorities and professionals to express significant concerns about the popularity of e-cigarette among teenagers^[2].

In general, reviewers agreed that e-cigarettes cause harm to the lungs and cardiovascular systems. However, opinions differed as to the degree of harm to both systems, and the safety of e-cigarettes relative to combustible cigarettes.

SCIENTISTS’ FEEDBACK

Irfan Rahman, Professor, Department of Environmental Medicine, University of Rochester:
E-cigarettes are not a safer alternative to tobacco smoking. We have published several papers on human, mouse, and cell-based studies using flavors and nicotine including vaping, showing that e-cigarettes are damaging to oral and lung tissues/cells^[3,4,5,6].

Neal Benowitz, Professor Emeritus, School of Medicine, University of California San Francisco:
I think it is reasonable to conclude that there may be some harm to the cardiovascular system and lungs from e-cigarette smoking, but in my opinion far less than that of cigarette smoking. E-cigarette flavors contain lots of different chemicals. Some e-liquids contain terpenes, others do not. I am not aware of data showing that terpenes are more damaging to lungs than other flavors. I disagree with the statement that e-cigarettes are just as bad for the cardiovascular system. With e-cigarettes, the nicotine-like effects (on blood pressure, for instance) are just a small fraction of the cardiovascular risk. The combustion products (e.g. conventional cigarettes) are the ones producing major risk chemicals^[7,8].

Sukhwinder Sohal, Lecturer, School of Health Sciences, University of Tasmania:
These claims are correct based on available scientific evidence. We also reported damaging effects of e-cigarettes on lungs in a recently published study^[9]. Proteins which cells secrete in response to e-cigarettes and IQOS are also part of the cancer pathology. So I wouldn’t be surprised if these devices lead to lung cancer.

Martin Chaumont, Physician, Department of Cardiology, Erasme University Hospital:
As reported by the US National Academies of Science, Engineering and Medicine, nearly all the data (short and mid-term exposure) show that e-cigarettes are far less dangerous than combustible cigarettes to the respiratory and cardiovascular systems^[10]. This is because vaping (in real-life settings) does not produce significant amounts of carbonyls (combustion by-products) and carbon monoxide, which are both present in the smoke of combustible cigarettes. These compounds, rather than nicotine, are the main factors leading to cancer, atherosclerotic disease and chronic obstructive pulmonary disease in smokers. Of course, as there are no controlled human data on long-term e-cigarette toxicity, we will have to monitor carefully potential side effects.There are many ways to vape, which can significantly modulate its health effects^[10]. The variety of devices and e-liquids available is extraordinary, presenting formidable challenges to scientists. In order to accurately estimate vaping’s toxicity, several factors have to be considered, such as power of the device, nicotine concentration, total amount of e-liquid vaped per days, and flavors. For instance, vaping at a high wattage with a large amount of strongly flavored e-liquid per day could be harmful for the lungs. In contrast, vaping less e-liquid at low/mid-wattage could be safe. To the best of my knowledge, there are no data giving clear cut-offs in vaping methods to distinguish safety and toxicity of vaping.It is true that some data show certain flavors to be more damaging to the lungs than others^[3]. Flavors are one of the largest question marks in this field since there has been little work examining them. However, it seems that some flavors are more toxic than others. It is unknown if the amount of these flavors present in e-liquid is sufficient to cause toxicity in real-life vaping conditions^[11]. Studies are in progress.It is true that most data has shown e-cigarettes to be less harmful to the lungs than combustible cigarettes. This is mainly due to the lack of carbonyls, which are present in tobacco smoke. However, the physico-chemical properties of propylene glycol/glycerol could drive another form of toxicity, for instance at the level of small airways^[12]. Studies are in progress.However, it is not true that e-cigarettes are “just as bad, if not worse” than combustible cigarettes for the cardiovascular system. E-cigarettes containing nicotine do increase heart rate and blood pressure. But these are the effects of nicotine, rather than the effects of the e-cigarette itself. Furthermore, while nicotine is a strongly addictive alkaloid, it does not cause major cardiovascular toxicity. This is known from data on non-combustible nicotine (such as nicotine replacement therapy^[13] and snus^[14]). It is the tar from tobacco combustion (carbonyls) that causes most of the cardiovascular toxicity^[8].In conclusion, vaping is certainly far less dangerous than tobacco smoking. However, extreme vaping conditions (such as the use of high power, high e-liquid amount consumed per day, certain flavors) likely produce other kinds of toxicity, which we should carefully monitor.

E-cigarettes were originally developed as a smoking cessation aid. They work by heating a liquid (also called e-liquid, e-juice) within a cartridge, producing a vapour that is inhaled like conventional cigarettes. Like other smoking cessation aids such as nicotine patches, e-cigarette liquid commonly (but not always) includes nicotine.

E-cigarette liquid also contains many other chemicals, especially for flavoured versions designed to make vaping more pleasant. Some of these chemicals can also undergo changes upon heating, producing various by-products, not unlike combustible cigarettes. However, a study has shown that the toxic by-products in e-cigarette vapour are fewer in number and lower in concentration^[1]. This suggests that they would cause less harm to smokers than combustible cigarettes, and therefore serve as a useful harm reduction tool.

However, less harm does not equate to being harmless. People who smoke e-cigarettes will still be exposed to more toxic chemicals and carcinogens than those who do not smoke at all. The effect of these chemicals on health in the long run is still unknown. This is the main issue driving the debate and concern about e-cigarettes’ health effects: its growing popularity in people who would otherwise not be smoking, such as teenagers.

Consistent with the finding of toxic chemicals in e-cigarette vapour^[1], a study by Rubinstein et al. found significantly higher levels of various chemicals such as acrylonitrile and acrylamide in the urine of adolescents using e-cigarettes compared to non-smoking adolescents^[15]. Acrylonitrile has been classified as a possible carcinogen (cancer-causing substance) by the International Agency for Research on Cancer, while acrylamide has been linked to neurological damage^[16].

Experiments using human and mouse cells grown in culture medium also showed that e-cigarette vapour can cause changes in DNA and prevent DNA from being repaired after damage^[17,18]. Such DNA changes can be a precursor to cancer, although it is also important to keep in mind that these in vitro tests may not reflect exactly what happens in a human body, as discussed in this Guardian article.

The ill-effects of conventional cigarette smoking on the respiratory tract is well-established, but no conclusive evidence yet links e-cigarette use to respiratory disorders^[10]. Some studies conducted on human lung cells and mice found that e-cigarette vapour caused oxidative stress and inflammatory responses^[3,4]. A study involving a telephone survey on adults about e-cigarette use found an association between e-cigarette use and diagnosis of asthma and/or chronic obstructive pulmonary disease (COPD)^[19]. An ongoing study in the US also found wheezing to be associated with e-cigarette use^[20], although the study did not take into account certain factors that could have contributed to wheezing (such as diet and physical activity levels). Furthermore, neither of these studies prove that a cause-and-effect relationship between vaping and respiratory disorders exists.

On the flip side, a study conducted in Italy evaluated COPD symptoms in smokers who had switched to e-cigarettes. This study showed that COPD symptoms were significantly improved as a result of reduced combustible cigarette consumption^[21]. This is in keeping with the idea of e-cigarettes as a harm reduction tool. However, the study did not evaluate whether complete cessation of smoking (with combustible cigarettes or e-cigarettes) would improve COPD symptoms as well – if not better – nor how e-cigarettes would compare next to other smoking cessation aids such as nicotine patches (which do not contain the toxic chemicals found in e-cigarette vapour) in alleviating COPD symptoms.

The Italian study illustrates e-cigarettes’ potential as a smoking cessation aid, and how it could improve the health of heavy smokers by allowing them to switch to a relatively less toxic form of smoking. However, the success of e-cigarettes in helping people to actually quit smoking is still debated among researchers – a systematic literature review^[22] showed how some studies found an improvement in quitting, while others did not.

In summary, short-term use of e-cigarettes certainly appears to be less harmful than using combustible cigarettes, suggesting that e-cigarettes could be a useful harm reduction tool. However, a clear picture of long-term health effects from vaping has yet to emerge, since e-cigarettes are relatively new. Recent studies show that dangerous chemicals are present in e-cigarettes and that short-term exposure to e-cigarette vapours are detrimental to DNA integrity and cellular stress. These findings strongly indicate that vaping is unlikely to be completely harmless. Ultimately, people who do not smoke in the first place would be better off not picking up a vaping habit at all.

NOTES & REFERENCES

• 1 – Goniewicz et al. (2014). Levels of selected carcinogens and toxicants in vapour from electronic cigarettes. Tobacco Control.
• 2 – Drazen et al. (2019). The Dangerous Flavors of E-Cigarettes. New England Journal of Medicine.
• 3 – Lerner et al. (2015). Vapors Produced by Electronic Cigarettes and E-Juices with Flavorings Induce Toxicity, Oxidative Stress, and Inflammatory Response in Lung Epithelial Cells and in Mouse Lung. PLoS One.
• 4 – Lerner et al. (2017). Electronic cigarette aerosols and copper nanoparticles induce mitochondrial stress and promote DNA fragmentation in lung fibroblasts. Biochemical and Biophysical Research Communications.
• 5 – Sundar et al. (2016). E-cigarettes and flavorings induce inflammatory and pro-senescence responses in oral epithelial cells and periodontal fibroblasts. Oncotarget.
• 6 – Lei et al. (2017). Myofibroblast differentiation and its functional properties are inhibited by nicotine and e-cigarette via mitochondrial OXPHOS complex III. Scientific Reports.
• 7 – Benowitz et al. (2016). Cardiovascular toxicity of nicotine: Implications for electronic cigarette use. Trends in Cardiovascular Medicine.
• 8 – Benowitz et al. (2017). Cardiovascular effects of e-cigarettes. Nature Reviews Cardiology.
• 9 – Singh Sohal et al. (2019). IQOS exposure impairs human airway cell homeostasis: direct comparison with traditional cigarette and e-cigarette. European Respiratory Journal Open Research.
• 10 – The National Academies of Sciences, Engineering, and Medicine. (2018). Public health consequences of e-cigarettes. Retrieved from: https://doi.org/10.17226/24952
• 11 – Clapp et al. (2019). Cinnamaldehyde in flavored e-cigarette liquids temporarily suppresses bronchial epithelial cell ciliary motility by dysregulation of mitochondrial function. American Journal of Physiology Lung Cellular and Molecular Physiology.
• 12 – Chaumont et al. (2019). Fourth generation e-cigarette vaping induces transient lung inflammation and gas exchanges disturbances: results from two randomized clinical trials. American Journal of Physiology Lung Cellular and Molecular Physiology.
• 13 – Ford et al. (2005). Nicotine Replacement Therapy and Cardiovascular Disease. Mayo Clinic Proceedings.
• 14 – Wallenfeldt et al. (2001). Carotid and femoral atherosclerosis, cardiovascular risk factors and C‐reactive protein in relation to smokeless tobacco use or smoking in 58‐year‐old men. Journal of Internal Medicine.
• 15 – Rubinstein et al. (2018). Adolescent Exposure to Toxic Volatile Organic Chemicals From E-Cigarettes. Pediatrics.
• 16 – Pennisi et al. (2013). Neurotoxicity of Acrylamide in Exposed Workers. International Journal of Environmental Research and Public Health.
• 17 – Ganapathy et al. (2017). Electronic cigarette aerosols suppress cellular antioxidant defenses and induce significant oxidative DNA damage. PLoS One.
• 18 – Lee et al. (2018). E-cigarette smoke damages DNA and reduces repair activity in mouse lung, heart, and bladder as well as in human lung and bladder cells. PNAS.
• 19 – Wills et al. (2016). E-cigarette use and respiratory disorder in an adult sample. Drug and Alcohol Dependence.
• 20 – Li et al. (2019). Association of smoking and electronic cigarette use with wheezing and related respiratory symptoms in adults: cross-sectional results from the Population Assessment of Tobacco and Health (PATH) study, wave 2. Tobacco Control.
• 21 – Polosa et al. (2016). Evidence for harm reduction in COPD smokers who switch to electronic cigarettes. Respiratory Research.
• 22 – Kalkhoran et al. (2016). E-cigarettes and smoking cessation in real-world and clinical settings: a systematic review and meta-analysis. The Lancet Respiratory Medicine.