Safety and Efficacy of Alternative Tobacco Products in Smoking Cessation: A Scientific Review on E-cigarettes

By Peter Pothula​



Pothula P. Safety and efficacy of alternative tobacco products in smoking cessation: a scientific review on e-cigarettes. HPHR. 2021; 28.


Safety and Efficacy of Alternative Tobacco Products in Smoking Cessation: A Scientific Review on E-cigarettes.


Before visiting a doctor, using the internet & search engines regarding health-related issues became more common practice nowadays. E-cigarettes help in smoking cessation but caused switching to a new smoking habit. In teenagers’ e-cigarettes have a detrimental effect on their health and they are a threat of switching to other drugs. The United States Food and Drug Administration (FDA) cautioned the public about serious lung diseases and deaths associated with vaping. Non-nicotine e-cigarettes may pump toxic chemicals & carcinogens directly into the lungs. Nicotine replacement therapy (NRT) may not give a feeling of active smoking so, people are switching to e-cigarettes. Nicotine causes addiction and may affect brain development. The approved NRT may have side effects but one should not forget that safety & efficacy has been evaluated and approved by the FDA for smoking cessation. It is strictly cautioned to stay away from adulterated vaping products.


Cigarette smoking is injurious to health and smokers try hard to quit the smoking habit but not successful. Many take new year’s resolutions and a few give promises to their loved ones but unsuccessful in quitting the smoking habit. Globally, more than 8 million people are killed by using tobacco products every year (1). The risk of dying from smoking-related diseases, such as cardiovascular disease, chronic obstructive lung disease, and lung cancer, can significantly be reduced by smoking cessation. Naturally, the human body takes 12 hours to clear excess carbon monoxide accumulated after smoking a cigarette (2). Carbon monoxide has a greater affinity for hemoglobin & myoglobin compared to oxygen causing myocardial depression, hypotension, and arrhythmias (3). Carboxyhemoglobin may cause reduced levels of oxygen release results in cardiac decompensation and tissue hypoxia ultimately causing death (3).


Nicotine is extremely addictive and leads to emotional dependence. This dependency may cause withdrawal symptoms upon cessation. The primary reason for unsuccessful cessation was due to withdrawal symptoms (4). Stopping the smoking cycle can lead to withdrawal symptoms such as nicotine cravings, anxiety, irritability, depression, and gain in weight for nicotine-dependent smokers (5).


Many companies came up with nicotine supplementary products helping smokers to quit smoking or in managing nicotine dependency. Nicotine patches and e-cigarettes became popular in curbing cravings and assisting in overcoming nicotine addiction. Nicotine replacement therapy (NRT) provides nicotine in the form of patches, gums, inhalers, or lozenges without any toxic chemicals in tobacco. Many studies showed that NRT doubles the chances of smoking cessation (6, 7).


Protonated nicotine found in the pod mod e-cigarette and instead of smoke the user inhales “vapor” with e-cigarettes (8). As lifestyle changing, many teenagers got addicted to e-cigarettes and likely to start smoking after vaping. The adverse effects of e-cigarettes are unknown but create aerosols with carcinogenic substances and heavy metals (9,10). The current review debates if e-cigarettes are helpful in smoking cessation and whether they are safe compared to active smoking and the NRT.


I have personally observed many friends who switched to e-cigarettes in the practice of quitting active cigarette smoking. Also, I have noticed many college students & early smokers using e-cigarettes/vaping. The main reasons for adopting vaping have been 1. It gives a feel of cigarette smoking 2. As a social status or as a style-making habit in early smokers. Then why e-cigarettes were not promoted under NRT and why these need to be controlled?


  1. Many countries banned e-cigarettes.
  2. San Francisco becomes the first city to ban all sales of vape products (June 2019), to take effect in 2020.
  3. Increase in cases of e-cigarette, or vaping, product use-associated lung injury (EVALI).
  4. Several states and cities impose vaping bans and restrictions amid EVALI outbreaks (11).
  5. The US FDA’s enforcement policy against unauthorized flavored e-cigarette products, including mint & fruit flavors.
  6. Setting the deadline, May 2020 for all e-cigarettes to apply for FDA review (12)

The above observations and several imposed regulations on e-cigarettes made me reviewing the relevant literature and discussing on the safety and efficacy of e-cigarettes.

Comparison of Safety and Effectiveness of Vapor Products vs. NRT

Nicotine, the addictive compound in cigarettes, cigars, hookah, and other tobacco products, is also found in JUUL products and most e-cigarettes. Nicotine levels are not the same in all e-cigarettes products, and sometimes the quantity of nicotine does not appear on product labels (13). Zero percent nicotine e-cigarettes are claiming 95% safer than cigarette smoking (14). As mentioned on their website, Propylene glycol (PG), Vegetable glycerin (VG) are the ingredients in ezeego cigarettes with different favors optionally including nicotine (14).  The JUUL e-cigarette brand has considerable strengths of nicotine (1-2.4%) compared to some other types of e-cigarettes and cigarettes. It suggests that products like JUUL may have more addictive effects than other e-cigarettes. Earlier, the JUUL manufacturer claimed that its nicotine formulation increases absorption into the blood, 2.7% faster than other e-cigarettes and cigarettes. Shockingly, 63% of JUUL users were between 15-24 years old and they believe that it’s nicotine-free (15).  

A comprehensive analysis indicated that e-cigarettes are less dangerous than smoking a cigarette as there is no nicotine and combustion does not occur, consumers may avoid using a variety of harmful substances typically found in tobacco smoke such as ash, tar, and carbon monoxide (16). Each 5% -JUUL pod contains about 5% nicotine by weight and each 3%- JUUL Pod contains about 3% by weight nicotine (17). Repeated exposure to e-cigarette vapor containing aerosol over a long period presents a significant risk (18). According to the Centers for Disease Control and Prevention (CDC), vaping or e-cigarette associated lung injury caused 2,711 cases of lung illness and 60 deaths in the US nationwide U.S. (19). Several countries, like India, either banned or regulated aromatic e-cigarettes by imposing huge taxes (11) On Jan 02, 2020, the Trump administration put a partial and temporary ban on the sale of vaping cartridges that are flavored with nicotine. (20).


In the US, a decrease (3.5%) in cigarette sales was reported in 2017 compared to 2016; 249 billion cigarette sales in 2017 vs. 258 billion in 2016 (21). Despite the restriction on some flavors, JUUL continued to hold the majority market share in the US. The National Youth Tobacco Survey, 2019 data reported an increase in mint and menthol flavors from 51.2% to in 2018 (22). The decrease or fluctuation in cigarette sales may partially be related to the increased sales of e-cigarettes. However, the increased number of e-cigarette sales raises several questions on its safety especially more concern about younger generations.

Role of e-igarettes in Smoking Cessation

A study in 2016 reported that smoking cessation helped individuals using nicotine e-cigarettes compared to non-nicotine e-cigarettes (22). In 2019, National Health Service, U.K published a report in the New England Journal of Medicine endorsing e-cigarettes to quit active smoking (23). In 2019, another study endorsed e-cigarettes for successful smoking cessation (22). There may be a positive angle in e-cigarettes enhancing chances of smoking cessation, but there is no evidence-based study demonstrating its safety & efficacy of e-cigarettes (22).

Edition 28 – Safety and Efficacy of Alternative Tobacco Products in Smoking Cessation: A Scientific Review on E-cigarettes

Safety Concern

In contrast to tobacco products, e-cigarettes do not produce smoke in the air but produce aerosols. These aerosols can be inhaled or ingested or enter the skin when active or passive smoker exposed. The aerosols emitted from e-cigarettes may contain nicotine. Carbonyl compounds, polyaromatic hydrocarbons, heavy metals, glycols, etc., (18) The exposure and absorption of aerosols into lungs is high as these are liquid particles. The rate of passive inhalation of aerosols is high by non-users. E-cigarette use in a 45‑m3 chamber reported higher amounts of PG, VG, particulate matter, and nicotine compared to controlled sessions (24). They also found a 20% increase in the level of polycyclic aromatic hydrocarbons and a 2.4‑fold increase in aluminum concentrations (24). Shockingly, Ruprecht and colleagues found that nicotine‑free e‑cigarettes produced higher particle levels than e‑cigarettes containing nicotine (25).


According to various studies and literature reviews, e-cigarette use during pregnancy may cause problems to the fetus, infant, and brain development in the child (26). E-cigarette users and passive smokers may be exposed to different aerosols including toxic chemicals, mostly carcinogens. The adverse events (AEs) associated with vaping were unclear until cases of EVALI came into the picture.

Nicotine Replacement Therapy (NRT)

The US FDA has approved over-the-counter nicotine patches, chewing gums, and lozenges. Nicotrol, a prescribed brand and approved only for use in adults is available as a nasal spray and oral inhaler (27).

Edition 28 – Safety and Efficacy of Alternative Tobacco Products in Smoking Cessation: A Scientific Review on E-cigarettes

Role of NRT in Smoking Cessation

Several studies and meta-analyses evidenced the role of NRT in successful smoking cessation. Nicotine replacement therapy is a successful method to promote prolonged smoking abstinence for smokers that are unintentional or unwilling to attempt sudden cessation (34). There is good evidence that NRT can double the chances of successful cancelation, at least among those motivated to leave (35).

Smoking Concern

Nicotine doses may be lethal if they are more than 40-60 mg. The NRT provides 2-4 mg of nicotine into circulation therefore there is no risk of fatality (36). Though there is no evidence that NRT possesses carcinogenic or genotoxic effects (37). Several limited studies have shown a possible risk of vascular incidents in people using NRT, including case reports (38-44). Besides, there are other effects associated with tobacco, as an anti-depressant, so smoking cessation may cause depression (37). The NRT is believed to be enhancing the effects of certain medicines (45). Healthcare professionals should consider the patient’s history and concomitant medications before prescribing the NRT. We can’t conclude here that NRT is not safe and effective in helping in smoking cessation.  There are equal benefits and risks with e-cigarettes and the NRT. So, what is an appropriate alternative to quitting active smoking?


Nowadays, dependency on the internet and search engines has become a common practice before visiting a physician for medical advice. It’s more common among younger generations to research before making any decision regarding education, life, food/ restaurants, smoking, alcohol consumption, sex, etc., They rely on the reports that appear handy according to their expectations. The internet search related to e-cigarettes & smoking cessation will give a laundry list of results especially portraying one randomized clinical trial that was conducted on 886 subjects (23).


To a common man, it is very difficult to interpret these study results and to understand the outcome. In the e-cigarette group, of 69 participants who stopped smoking for 1 year, 80% were still using e-cigarettes and in the NRT group, only 9% were still using one of the products (46). This is a clear indication that though e-cigarettes helped in smoking cessation but caused switching to a new smoking habit. There was no significant safety information from the randomized clinical trial to conclude its safety. However, EVALI cases changed the perspective on e-cigarettes. It was believed that vitamin E in the e-cigarette causes EVALI and other products in the e-cigarettes were under investigation. So, CDC recommends all e-cigarette users refrain from using e-cigarettes and other vaping products (47).  Till January 07, 2020, a total of 2602 EVALI cases were reported to the CDC within the US including 57 fatalities (48).


Nicotinate e-cigarettes pump nicotine into the bloodstream via the lungs and stimulate epinephrine production which in turn stimulates the nervous system leading to an increase in blood pressure & heart rate. According to the research, e-cigarettes may be less harmful compared to cigarette smoking however, there is no difference in getting addicted to nicotine (49). Vaping process produces some potentially toxic chemicals and carcinogens which will be pumped directly into the lungs. In certain e-cigarettes, heating coils are made up of high levels of nickel and chromium. Like cigarettes, a few e-cigarettes contain low levels of cadmium that can cause breathing problems (50, 51).


The NRT may be associated with withdrawal symptoms with the most common adverse events like headache, skin rash, throat pain mouth, etc., However, in a study conducted on smoking cessation, nicotine gum and transdermal nicotine showed relieving withdrawal symptoms and 2-fold success rates compared to placebo. over placebo in trials of smoking cessation (52). In intensive Care Unit (ICU) patients, the NRT did not affect mortality or Serious adverse events but exhibited long-time alive with no delirium, sedation, and coma compared to placebo (53, 54). But Also, NRT is recommended for preventing withdrawal symptoms or treating aggressive activity in ICU-admitted smoking patients, regardless of its potential side-effects and in the presence of incoherent safety and effectiveness evidence (52).


Nicotine activates the nervous system and activates the brain stimulating the production of dopamine which reinforces rewarding behaviors. The pleasure gained by nicotine’s interaction causes some people to be addicted to nicotine (56). The NRT has been approved therapy by the FDA for smoking cessation. Then why people who intend to quit smoking are switching to e-cigarettes rather than NRT?


A nicotine patch may keep a person away from nicotine from active smoking, but it does not make them fully satisfied as they are missing some activity of keeping something between the lips & puffing. This psychological feeling makes people switching to e-cigarettes as the vapors give the smoker the ‘experience’. NRT products may have side effects but one should not forget that safety & efficacy has been evaluated and approved by the FDA for smoking cessation.


The internet searches provide a laundry list of articles saying that e-cigarettes help in smoking cessation compared to NRT. There is no smoking cessation but switching to another addiction of e-smoking. There is no evidence that nicotine-free or tetrahydrocannabinol -free e-cigarettes are safe (57). What are the long-term effects of sucking a battery and inhaling vapors? Benefits should be overweighed. E-cigarettes emulate cigarettes by having a smoking experience. There is no doubt. This might also help smokers adapt to new cigarette behaviors, but not to discourage them directly. The NRT may not help in long-term smoking cessation as 93% of over-the-counter NRT users started smoking within 6 months. However, adding some other antidepressants with the NRT enhanced long-term success rates (58,59).


Mentally, placebo plays a powerful role. When a person wants to stop smoking and decides to put a patch on his neck or upper arm, the placebo effect may give a dissatisfactory feeling compared to the smoking e-cigarette.  The mind of a smoker is fulfilled when they do it, light it up, inhale it, take it deep, and release it. Which gives smokers a new way of satisfying themselves. Nevertheless, it should be remembered that increased use of non-smoking tobacco products leads to serious health problems such as cancer and heart diseases (60).


In adults, brain development during 13-19 years of age is critical. As nicotine affects the brain’s function it not only leads to nicotine addiction but also makes them switch to other drugs.  Nicotine may affect attention and focus further causing problems in impulse control (61). More research is required if vaping is as effective as FDA-approved smoking cessation aids. Also, the CDC is monitoring the safety of chemical compounds used in vaping nicotine and non-nicotine e-cigarettes (52). It is advised to wait until CDC & FDA confirm the safety of various vaping compounds used in e-cigarettes.


E-cigarettes may help in smoking cigarettes but not in smoking cessation. They are switching to other smoking addictions. As the US FDA cautioned the public about various serious lung diseases and deaths associated with deaths, it is advised to not use adulterated vaping products. It is highly recommended to use FDA-approved aids for smoking cessation.

Conflicts of Interest

Opinions expressed within the content are solely the author’s based on the literature data. The author has no conflicts of interest to generate this article.


  1. WHO (2019). Retrieved online:
  2. Benefits of Quitting Smoking Over Time. Retrieved online:
  3. I., Carbon monoxide poisoning. J R Soc Med. 2001;94(6):270‐272.
  4. Cosci, F., Pistelli, F., Lazzarini, N., Carrozzi, L., Nicotine dependence and psychological distress: outcomes and clinical implications in smoking cessation. Psychol Res Behav Manag. 2011; 4:119‐128.
  5. Kim, S.S., Fang, H., McKee, S.A., Ziedonis, D., Prospective Evaluation of Factors Predicting Nicotine Withdrawal Symptoms Among Korean Americans. J Smok Cessat. 2014;10.1017
  6. Hartmann‐Boyce, J., Chepkin, S.C., Ye, W., Bullen, C., Lancaster, T., Nicotine replacement therapy versus control for smoking cessation. Cochrane Database of Systematic Reviews 2018, Issue 5.
  7. Martin, T., Is the Nicotine Patch a Good Way to Stop Smoking? [health site]: Verywell Mind, 2019.
  8. Spindle, T.R., Eissenberg, T., Pod Mod Electronic Cigarettes—An Emerging Threat to Public Health. JAMA Netw Open.2018;1(6): e183518.
  9. Sareen, S., et al., E-cigarettes, and youth: Patterns of use, potential harms, and recommendations, Preventive Medicine 2020; Volume 133,
  10. E-Cigarette Use Among Youth and young adults: Report of the surgeon general. Rockville: E-Cigarette Use Among Youth, 2016. CDC:
  11. Feuer, W., Massachusetts lawmakers approve a bill banning flavored tobacco and levying a 75% excise tax on e-cigarettes. [Online] Health and science, November 21, 2019.
  12. Drug Watch:
  13. Maciej L. G., Tomasz, K., Michal, G., Jakub, K., Leon, K., Nicotine Levels in Electronic Cigarettes. : Nicotine & Tobacco Research, 2013, Vol. 15.
  14. Zero Nicotine:
  15. Truth Initiative:
  16. Raub, J.A., Mathieu-Nolf, M., Hampson, N.B., Thom, S.R. Carbon monoxide poisoning — a public health perspective. Toxicology2000;145: 1-14.
  17. Discover More About JUULpods & Flavors:
  18. Strongin, R.M., E-Cigarette Chemistry and Analytical Detection. Annu Rev Anal Chem (Palo Alto Calif). 2019;12(1):23‐39.
  19. Stephen S.H., Who Thought Sucking on a Battery Was a Good Idea? Vaping is a health crisis that’s only just begun. Retrieved from:
  20. NPR:
  21. CDC:
  22. Truth initiative:
  23. Peter, H., Anna, P.H., Dunja, P., Randomized Trial of E-Cigarettes versus Nicotine-Replacement Therapy.: New England Journal of Medicine, 2019, Vol. 380, pp. 629-637
  24. Schober, W., et al., Use of electronic cigarettes (e-cigarettes) impairs indoor air quality and increases FeNO levels of e-cigarette consumers. International Journal of Hygiene and Environmental Health2014;217(6):628–37
  25. Ruprecht, A.A., De, M.C., Pozzi, P., Munarini, E., Mazza, R., Angellotti, G., Turla, F., Boffi, R., Comparison between particulate matter and ultrafine particle emission by electronic and normal cigarettes in real-life conditions. 2014;100: e24–e27.
  26. CDC:
  27. FDA:
  28. Nicotine Patch:
  29. Nicotine Gum:
  30. Nicotine Lozenge:
  31. Molander, L., Lunell, E., Fagerström, K.O., Reduction of tobacco withdrawal symptoms with a sublingual nicotine tablet: a placebo-controlled study. Nicotine Tob Res. 2000;2(2):187-91.
  32. Nicotine Oral inhaler Product Label:
  33. Nicotine Nasal spray Product Label:
  34. Moore, D., Aveyard, P., Connock, M., Wang, D., Fry-Smith, A., Barton, P., Effectiveness, and safety of nicotine replacement therapy assisted reduction to stop smoking: systematic review and meta-analysis. BMJ. 2009;338: b1024.
  35. Tonnesen, P., et al., Higher dosage nicotine patches increase one-year smoking cessation rates: results from the European CEASE trial. Collaborative European Anti-Smoking Evaluation European Respiratory Society. Eur Resp J 1999; 13(2):238–46
  36. Benowitz, N.L., Pharmacologic aspects of cigarette smoking and nicotine addiction. New Engl J Med 1988; 319(20):1318–30
  37. Lavelle, C., Birek, C., Scott, D.A., Are nicotine replacement strategies to facilitate smoking cessation safe? J Can Dent Assoc. 2003;69(9):592-7.
  38. Compendium of Pharmaceuticals and Specialties (CPS). 36th edition. 2001; p. 647–8 and 1027–32, Canadian Association of Pharmacists.
  39. Arnaot, M.R., Treating heart disease. Nicotine patches may not be safe. BMJ 1995; 310(6980):663–4.
  40. Dacosta, A., et al. Myocardial infarction and nicotine patch: a contributing or causative factor? Eur Heart J 1993; 14(12):1709–11.
  41. Fredrickson, P.A., et al. High dose transdermal nicotine therapy for heavy smokers: safety, tolerability and measurement of nicotine and cotinine levels. Psychopharmacology 1995; 122(3):215–22
  42. Jackson, M., Cerebral arterial narrowing with nicotine patch. Lancet 1993; 342(8865):236–7.
  43. Ottervanger, J.P., Festen J.M, de Vries A.G, Stricker B.H. Acute myocardial infarction while using the nicotine patch. Chest 1995; 107(6):1765–6.
  44. Mathew, T.P., Herity, N.A. Acute myocardial infarction soon after nicotine replacement therapy. QJM 2001; 94(9):503–4.
  45. MedlinePlus Health Information, Drug Information, Nicotine (systemic). Available from: URL: druginfo/uspdi/202407.html (accessed July 24, 2002).
  46. Smoking Cessation:
  47. EVALI:
  48. Brian, A. K., Christopher, M.J., Grant T. B., and Peter A. B., The EVALI and Youth Vaping Epidemics — Implications for Public Health. N Engl J Med 2020; 382:689-691
  49. Levine, A., Huang, Y., Drisaldi, B., et al. Molecular mechanism for a gateway drug: epigenetic changes initiated by nicotine prime gene expression by cocaine. Sci Transl Med.2011;3(107):107-109.
  50. Sleiman, M., Logue, J.M., Montesinos, V.N., et al. Emissions from electronic cigarettes: Key parameters affecting the release of harmful chemicals. Environ Sci Technol.2016;50(17):9644-9651.
  51. Hess, C.A., Olmedo, P., Navas-Acien, A., et al. E-cigarettes as a source of toxic and potentially carcinogenic metals. Environ Res.2017; 152:221-225.
  52. Fagerström, K.O., Schneider, N.G., Lunell, E., Effectiveness of nicotine patch and nicotine gum as individual versus combined treatments for tobacco withdrawal symptoms. Psychopharmacology (Berl). 1993;111(3):271‐277.
  53. Melanie, K., Andrew, A.U., Hayden, J.M., Nicotine replacement therapy for agitation and delirium management in the intensive care unit: a systematic review of the literature. : Journal of intensive care, 2016, Vol. 4.47.
  54. Ben de, J., Anne, S.S., Arriette, K.G.,, The safety and efficacy of nicotine replacement therapy in the intensive care unit: a randomized controlled pilot study..: Annals of Intensive Care, 2018, Vol. 70.
  55. Safety of nicotine replacement therapy in critically ill smokers: a retrospective cohort study. : Anaesth Intensive Care., 2016, Vol. 44.
  56. Vaping devices:
  57. Flori Sassano, M., Eric S. D., James E.K., Evaluation of e-liquid toxicity using an open-source high-throughput screening assay. : Plos Biology, 2018.
  58. Millstone, K., (2007-02-13). “Nixing the patch: Smokers quit cold turkey”. News Service. Archived from the original on 2018-12-25. Retrieved 2011-02-21.
  59. Lancaster, T., Stead, L.F., “Mecamylamine (a nicotine antagonist) for smoking cessation”. The Cochrane Database of Systematic Reviews 2000;(2): CD001009
  60. Conquer cancer the asco foundation. Cancer.Net. Retrieved online:
  61. S. Department of Health, and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease, Prevention and Health Promotion, Office on Smoking and Health. E-Cigarette Use Among Youth And Young Adults: A Report of the Surgeon General — Executive Summary.; 2016. Accessed February 21, 2017

About the Authors

Peter Pothula

Peter Pothula, PhD at Biopharmaceutical Company is an experienced healthcare professional with a strong background in Pharmacovigilance, Medical writing, & Project management with a passion for safety in drug development / post-marketing use. 

* Correspondence: