Myth: Alternative nicotine products are as dangerous as smoking

Snus

2019: Snus: a compelling harm reduction alternative to cigarettes

• “Use of snus confers a significant harm reduction benefit which is reflected in the comparatively low levels of tobacco-related disease in Sweden compared with the rest of Europe [where snus is, inexplicably, banned].”
• Citation: Clarke, E., Thompson, K., Weaver, S. et al. Snus: a compelling harm reduction alternative to cigarettes. Harm Reduct J 16, 62 (2019). doi:10.1186/s12954-019-0335-1
• Acknowledgement: The review was funded by Imperial Brands Plc.

HnB / HTP

• See also “Vaping” for studies that include both

2018: Carbonyl emissions from a novel heated tobacco product (IQOS): comparison with an e-cigarette and a tobacco cigarette

• The IQOS heated tobacco product emits substantially lower levels of carbonyls than a commercial tobacco cigarette (Marlboro Red) but higher levels than a Nautilus Mini e-cigarette.
• PDF Version
• Citation: Farsalinos KE, Yannovits N, Sarri T, Voudris V, Poulas K, Leischow SJ. Carbonyl emissions from a novel heated tobacco product (IQOS): comparison with an e-cigarette and a tobacco cigarette. Addiction. 2018 Nov;113(11):2099-2106. doi: 10.1111/add.14365. Epub 2018 Jul 10. PMID: 29920842.
• Acknowledgement: P30 CA015083/CA/NCI NIH HHS/United States

Vaping

Flavors

2019: High Content Screening in NHBE cells shows significantly reduced biological activity of flavoured e-liquids, when compared to cigarette smoke condensate

• Our results clearly show a lower toxicity of e-liquids, including flavoured e-liquids, when compared to CSC (cigarette smoke condensate).
• PDF Version
• Citation: Lukasz Czekala, Liam Simms, Matthew Stevenson, Edgar Trelles-Sticken, Paul Walker, Tanvir Walele, High Content Screening in NHBE cells shows significantly reduced biological activity of flavoured e-liquids, when compared to cigarette smoke condensate, Toxicology in Vitro, Volume 58, 2019, Pages 86-96, ISSN 0887-2333, doi:10.1016/j.tiv.2019.03.018.
• Acknowledgement: This work was funded and supported by Fontem Ventures B.V., part of Imperial Brands Group PLC.

2018: Do flavouring (flavoring) compounds contribute to aldehyde emissions in e-cigarettes?

• Aldehyde emissions from all flavoured liquids were 79–99.8% lower than smoking and lower than commonly measured indoor levels and occupational and indoor safety limits.
• PDF Version
• Citation: Farsalinos, K. E., & Voudris, V. (2018). Do flavouring compounds contribute to aldehyde emissions in e-cigarettes? Food and Chemical Toxicology, 115, 212–217. doi:10.1016/j.fct.2018.02.059
• Acknowledgement: The study was funded by Public Health England.

2015 An approach to ingredient screening and toxicological risk assessment of flavours (flavors) in e-liquids

• Individual flavours or groups of flavours were added to the tobacco rod and the resultant smoke was analysed for priority smoke constituents and tested in several in vitro tests as well as 90-day rat inhalation studies. In general, addition of the flavours had no effect on, or reduced the levels of most of the measured smoke constituents.
• PDF Version
• Citation: S. Costigan, C. Meredith, An approach to ingredient screening and toxicological risk assessment of flavours in e-liquids, Regulatory Toxicology and Pharmacology, Volume 72, Issue 2, 2015, Pages 361-369, ISSN 0273-2300, doi:10.1016/j.yrtph.2015.05.018.
• Acknowledgement: This work was joint funded by Nicoventures and British American Tobacco (BAT), and the authors are full time employees of Nicoventures and British American Tobacco (BAT).

2013: Comparison of the Cytotoxic Potential of Cigarette Smoke and Electronic Cigarette Vapour Extract on Cultured Myocardial Cells

• Overall, EC vapor extracts showed significantly higher cell viability compared to CS extract, based on a realistic-use rather than a standardized comparative level of exposure. This supports the concept that ECs may be useful as tobacco harm reduction products
• PDF Version
• Citation: Farsalinos, K.E.; Romagna, G.; Allifranchini, E.; Ripamonti, E.; Bocchietto, E.; Todeschi, S.; Tsiapras, D.; Kyrzopoulos, S.; Voudris, V. Comparison of the Cytotoxic Potential of Cigarette Smoke and Electronic Cigarette Vapour Extract on Cultured Myocardial Cells. Int. J. Environ. Res. Public Health 2013, 10, 5146-5162. doi:10.3390/ijerph10105146
• Acknowledgement: Funding: The study was funded in part by the Greek Association of E-cigarette Businesses (SEEHT). Role of the funding source: The study was investigator-initiated and investigator-driven. The sponsor funded the expenses of the laboratory (ABICH S.r.l, Verbania, Italy) where the experiments were performed. The sponsor had no involvement in the study design, data collection, analysis and interpretation, writing or approving the manuscript and decision to submit the manuscript for publication. No author has received any financial or other compensation for this study.

Cancer / Tumors

2021: Effect of an electronic nicotine delivery system with 0, 8, or 36 mg/mL liquid nicotine versus a cigarette substitute on tobacco-related toxicant exposure: a four-arm, parallel-group, randomised, controlled trial

• Use of an ENDS with cigarette-like nicotine delivery can reduce exposure to a major pulmonary carcinogen, NNAL, even with concurrent smoking
• Citation: Caroline O Cobb, Jonathan Foulds, Miao-Shan Yen, Susan Veldheer, Alexa A Lopez, Jessica M Yingst, Christopher Bullen, Le Kang, Thomas Eissenberg, Sophia I. Allen, Phoebe Brosnan, Christopher Bullen, Nadia Chowdhury, Caroline O. Cobb, Thomas Eissenberg, Jonathan Foulds, Jacob T. Graham, Erin Hammett, Sharilee Hrabovsky, Breianna L. Hummer, Le Kang, Courtney Lester, Alexa A. Lopez, John P. Richie, Christopher Sciamanna, Shumei Sun, Thokozeni Lipato, Susan Veldheer, Miao-Shan Yen, Jessica M. Yingst, Effect of an electronic nicotine delivery system with 0, 8, or 36 mg/mL liquid nicotine versus a cigarette substitute on tobacco-related toxicant exposure: a four-arm, parallel-group, randomised, controlled trial, The Lancet Respiratory Medicine, Volume 9, Issue 8, 2021, Pages 840-850, ISSN 2213-2600, doi:10.1016/S2213-2600(21)00022-9.
• Acknowledgement: Funding: National Institutes of Health, US Food and Drug Administration.

2021: Comparison of biological and transcriptomic effects of conventional cigarette and electronic cigarette smoke exposure at toxicological dose in BEAS-2B cells

• In conclusion, our study indicated that the cytotoxicity of e-cigarette was far less than conventional cigarette at equivalent nicotine content in BEAS-2B cells.
• PDF Version
• Citation: Lilan Wang, Yao Wang, Jianwen Chen, Xue-Min Yang, Xing-Tao Jiang, Peiqing Liu, Min Li, Comparison of biological and transcriptomic effects of conventional cigarette and electronic cigarette smoke exposure at toxicological dose in BEAS-2B cells, Ecotoxicology and Environmental Safety, Volume 222, 2021, 112472, ISSN 0147-6513, doi:10.1016/j.ecoenv.2021.112472.
• Acknowledgement: At the time of the study, XM Yang and XT Jiang are employees of Shenzhen RELX Tech. This work was supported by the National Natural Science Foundation of China (31970699), the Guangdong Basic and Applied Basic Research Foundation (2021A1515010766 and 2019A1515011030), the Guangdong Provincial Key Laboratory of Construction Foundation (2019B030301005), the Key-Area Research and Development Program of Guangdong Province (2020B1111110003), and the National Major Special Projects for the Creation and Manufacture of New Drugs (2019ZX09301104).

2020: Cancer potencies and margin of exposure used for comparative risk assessment of heated tobacco products and electronic cigarettes aerosols with cigarette smoke

• Even if they should not be considered as risk-free products, HTPs and ECs lead to an appreciable risk reduction in comparison to cigarettes, both for cancer and non-cancer diseases. According to the current knowledge, and more specifically to the data presented here, HTPs and ECs might be considered as an acceptable reduced risk substitute for cigarettes for legal-age smokers who would otherwise continue smoking cigarettes.
• PDF Version
• Citation: Rodrigo, G., Jaccard, G., Tafin Djoko, D. et al. Cancer potencies and margin of exposure used for comparative risk assessment of heated tobacco products and electronic cigarettes aerosols with cigarette smoke. Arch Toxicol 95, 283–298 (2021). https://doi.org/10.1007/s00204-020-02924-x
• Acknowledgement: All authors are employees of Philip Morris International. Philip Morris International is the sole source of funding and

sponsor of this research.

2020: Tobacco-Specific Nitrosamines (NNAL, NNN, NAT, and NAB) Exposures in the US Population Assessment of Tobacco and Health (PATH) Study Wave 1 (2013–2014)

• Among established, every day, exclusive tobacco product users, the geometric mean urinary NNAL concentration was highest for smokeless tobacco users, followed by all types of combustible tobacco product users, then poly tobacco users, and lowest in e-cigarette product users.
• PDF Version
• Citation: Baoyun Xia, PhD, Benjamin C Blount, PhD, Tonya Guillot, MPH, Christina Brosius, MPH, Yao Li, BS, Dana M Van Bemmel, PhD MPH, Heather L Kimmel, PhD, Cindy M Chang, PhD MPH, Nicolette Borek, PhD, Kathryn C Edwards, PhD, Charlie Lawrence, PhD, Andrew Hyland, PhD, Maciej L Goniewicz, PhD PharmD, Brittany N Pine, BS, Yang Xia, PhD, John T Bernert, B Rey De Castro, ScD, John Lee, BS, Justin L Brown, MPH, Stephen Arnstein, MS, Diane Choi, BS, Erin L Wade, BS, Dorothy Hatsukami, PhD, Gladys Ervies, PhD, Angel Cobos, BS, Keegan Nicodemus, BS, Dana Freeman, BS, Stephen S Hecht, PhD, Kevin Conway, PhD, Lanqing Wang, PhD, Tobacco-Specific Nitrosamines (NNAL, NNN, NAT, and NAB) Exposures in the US Population Assessment of Tobacco and Health (PATH) Study Wave 1 (2013–2014), Nicotine & Tobacco Research, Volume 23, Issue 3, March 2021, Pages 573–583, https://doi.org/10.1093/ntr/ntaa110
• Acknowledgement: This manuscript is supported with Federal funds from the National Institute on Drug Abuse, National Institutes of Health, and the Center for Tobacco Products, Food and Drug Administration, Department of Health and Human Services, under contract to Westat (contract nos. HHSN271201100027C and HHSN271201600001C) and through an interagency agreement between the FDA Center for Tobacco Products and the Centers for Disease Control and Prevention. Maciej L. Goniewicz receives fees for serving on an advisory board from Johnson & Johnson and grant support from Pfizer

2020: Effect of Pod e-Cigarettes vs Cigarettes on Carcinogen Exposure Among African American and Latinx Smokers

• This randomized clinical trial found that the use of NSPS (nicotine salt pod system) e-cigarettes for replacing cigarettes led to significant reduction in a primary pulmonary carcinogen, NNAL, for African American and Latinx smokers. There were also significant reductions in cigarettes smoked per day, co, and respiratory symptoms and no increase in nicotine exposure. Furthermore, about one-fourth of participants randomized to e-cigarettes were able to fully cease use of combustible cigarettes at week 6. Reduction in cigarettes and biomarkers of exposure in this study suggest potential of NSPS e-cigarettes as a harm reduction strategy for members of the 2 largest minority groups in the US who face significant health disparities.
• PDF Version
• Citation: Pulvers K, Nollen NL, Rice M, et al. Effect of Pod e-Cigarettes vs Cigarettes on Carcinogen Exposure Among African American and Latinx Smokers: A Randomized Clinical Trial. JAMA Netw Open. 2020;3(11):e2026324. doi:10.1001/jamanetworkopen.2020.26324
• Acknowledgement: Drs Pulvers and Nollen and Ms Rice were supported by grant No. 5SC3GM122628 from the National Institutes of Health (NIH). Drs Schmid and Ahluwalia were supported in part by grant No. P20GM130414, from the NIH-funded Center of Biomedical Research Excellence (COBRE). Dr Schmid was partially supported by Institutional Development Award No. U54GM115677 from the National Institute of General Medical Sciences of the NIH, which funds Advance Clinical and Translational Research (Advance-CTR).

2020: Comparison of the chemical composition of aerosols from heated tobacco products, electronic cigarettes and tobacco cigarettes and their toxic impacts on the human bronchial epithelial BEAS-2B cells

• We first report that HTP (Heated Tobacco Product) delivers slightly less nicotine and emits much lower amounts of carbonyl and PAH compounds than tobacco cigarettes.
• However, HTP emissions still contain carcinogenic compounds (e.g. formaldehyde, acetaldehyde and benzo[a]pyrene) and the amounts of carbonyls and PAHs in HTP aerosols are higher than in e-cig vapours (vapor).
• In accordance with the levels of toxic compounds in each aerosol, HTP aerosol exhibits reduced cytotoxicity compared to cigarette smoke but higher than e-cig vapours.
• HTP and e-cig have the potential to increase oxidative stress and inflammatory response, in a manner very similar to that of cigarette smoke, but only after a more intensive exposure. In addition, our data support that e-cig use at higher power settings emit higher carbonyl and PAH compounds and, consequently, generate more oxidative stress.
• Finally, this study contributes to a better understanding of HTP and e-cig emission properties and their related toxicological impacts and provides important data needed for risk assessment purposes, by demonstrating that HTP might be less harmful than tobacco cigarettes but considerably more harmful than e-cig.
• PDF Version
• Citation: Romain Dusautoir, Gianni Zarcone, Marie Verriele, Guillaume Garçon, Isabelle Fronval, Nicolas Beauval, Delphine Allorge, Véronique Riffault, Nadine Locoge, Jean-Marc Lo-Guidice, Sébastien Anthérieu, Comparison of the chemical composition of aerosols from heated tobacco products, electronic cigarettes and tobacco cigarettes and their toxic impacts on the human bronchial epithelial BEAS-2B cells, Journal of Hazardous Materials, Volume 401, 2021, 123417, ISSN 0304-3894, doi:10.1016/j.jhazmat.2020.123417
• Acknowledgement: This work was supported by the French Institute of Cancer (INCa) and the French Institute for Public Health Research (IResP): Contracts n°INCa_11505 and n°INCa_13648.

2020: Five-Day Changes in Biomarkers of Exposure Among Adult Smokers After Completely Switching From Combustible Cigarettes to a Nicotine-Salt Pod System

(PDF 9 pages) The results of this study concorded with evidence that complete switching from combustible cigarettes to vapor products may reduce exposure to key carcinogens and other toxicants known to be associated with tobacco-related diseases.

2018: Measurements of electronic cigarette-generated particles for the evaluation of lung cancer risk of active and passive users

(PDF 23 pages) In this study, we have demonstrated that no clinically relevant, product-related safety findings were observed for smokers of Combustible Cigarettes (CC) switching to an Electronic Vapor Product (EVP) for 12 weeks under real-life settings… EVP use was associated with significant decreases in exposure to nicotine and other chemicals such as benzene and acrolein, typically found in CC smoke. Changes were also observed in the level of WBC, haemoglobin, RBC and LDL cholesterol, which although minor, were consistent with those observed after smoking cessation.

2017: Comparative tumor promotion assessment of e‐cigarette and cigarettes using the in vitro Bhas 42 cell transformation assay

Results from this study suggest that e‐cigarettes may have reduced tumor promoter activity compared to conventional cigarettes and therefore may provide a safer alternative to cigarettes.

• COI: BAT

2017: Comparing the cancer potencies of emissions from vapourised nicotine products including e-cigarettes with those of tobacco smoke

Samples of a prototype heat-not-burn device have lower cancer potencies than tobacco smoke by at least one order of magnitude, but higher potencies than most e-cigarettes. Mean lifetime risks decline in the sequence: combustible cigarettes >> heat-not-burn >> e-cigarettes (normal power)≥nicotine inhaler.

2017: Nicotine, Carcinogen, and Toxin Exposure in Long-Term E-Cigarette and Nicotine Replacement Therapy Users

Long-term NRT-only and e-cigarette–only use, but not dual use of NRTs or e-cigarettes with combustible cigarettes, is associated with substantially reduced levels of measured carcinogens and toxins relative to smoking only combustible cigarettes.

2017: Comparing the cancer potencies of emissions from vapourised nicotine products including e-cigarettes with those of tobacco smoke

(PDF 8 pages) -Most e-cigarette analyses indicate cancer potencies <1% that of tobacco smoke and <10% that of a heat-not-burn prototype, although a minority of analyses indicate higher potencies. -Optimal combinations of device settings, liquid formulation and vaping behaviour normally result in e-cigarette emissions with much less carcinogenic potency than tobacco smoke. -Article in Lung Disease News: E-Cigarettes Carry Much Less Risk of Lung Cancer Than Cigarette Smoke, Study Finds

2016: Have combustible cigarettes met their match? The nicotine delivery profiles and harmful constituent exposures of second-generation and third-generation electronic cigarette users

Compared with cigarettes, G2 and G3 e-cigarettes resulted in significantly lower levels of exposure to a potent lung carcinogen and cardiovascular toxicant.

2016: Exposure to Nicotine and Selected Toxicants in Cigarette Smokers Who Switched to Electronic Cigarettes: A Longitudinal Within-Subjects Observational Study

(PDF 8 pages) After switching from tobacco to e-cigarettes, nicotine exposure remains unchanged, while exposure to selected carcinogens and toxicants is substantially reduced.

2016: The mutagenic assessment of an electronic-cigarette and reference cigarette smoke using the Ames assay in strains TA98 and TA100

(PDF 10 pages) -In the presence and absence of metabolic activation, e-cigarette ACM and aerosol were deemed non-mutagenic in tester strains TA98 and TA100, under the test conditions described previously, despite clear positive control responses. Conversely, 3R4F cigarette smoke TPM and freshly generated whole smoke were clearly positive. -In the case of freshly generated cigarette smoke, a positive response in both strains was observed within 24 min, whereas e-cigarette aerosols remained negative up to 3 h.

2016: Patients with lung cancer: Are electronic cigarettes harmful or useful?

Based on current knowledge, for patients with lung or other forms of cancer who would otherwise continue to smoke, e-cigarettes offer an alternative way to quit smoking while they undergo medical treatment. The option to switch to e-cigarettes should be considered by healthcare practitioners with patients with cancer who would otherwise continue to smoke.

2015: Development of an in vitro cytotoxicity model for aerosol exposure using 3D reconstructed human airway tissue; application for assessment of e-cigarette aerosol

(PDF 11 pages) -Despite being tested with a more intense puffing regime, e-cigarette aerosol showed no acute cytotoxicity in this study when compared with traditional 3R4F reference cigarette smoke. -Under the study conditions cigarette smoke demonstrated a dose-dependent response that resulted in near-complete cell death after a 6 h exposure period. In contrast, e-cigarette aerosol showed no decrease in tissue viability following a 6 h exposure, despite appropriate positive control responses. Furthermore, cytotoxicity appears to be unaffected by different e-cigarette formulations as tested in this study.

2014: Levels of selected carcinogens and toxicants in vapor from electronic cigarettes

(PDF 16 pages) Results: The levels of potentially toxic compounds in e-cigarette vapor is from 9 to 450-fold lower than those in the smoke from conventional cigarettes, and in many cases comparable to the trace amounts present in pharmaceutical preparation (Note: Reference product was a medicinal nicotine inhaler.). Our findings support the idea that substituting tobacco cigarettes with electronic cigarettes may substantially reduce exposure to tobacco-specific toxicants.

2014: Evaluation of Toxicant and Carcinogen Metabolites in the Urine of E-Cigarette Users Versus Cigarette Smokers

(PDF 6 pages) Conclusion: “With respect to the compounds analyzed here, e-cigarettes have a more favorable toxicity profile than tobacco cigarettes.”

Cardiovascular

Re-examining the Association Between E-Cigarette Use and Myocardial Infarction: A Cautionary Tale

There is no reliable evidence that e-cigarette use is associated with ever having had a myocardial infarction among never smokers.

Biomarkers of Inflammation and Oxidative Stress Among Adult Former Smoker, Current E-Cigarette Users Results from Wave 1 PATH Study

Exclusive e-cigarette users have biomarker concentrations that are similar to those of former smokers who do not currently use tobacco, and lower than those of exclusive cigarette smokers.

2021: Increased Expression of Proatherogenic Proteins in Immune Cell Subtypes in Tobacco Cigarette Smokers But Not in Electronic Cigarette Vapers

-In this study, we showed that tobacco cigarette smoking, but not electronic-cigarette vaping, is associated with increased expression of major proteins in the toll-like receptor 4 (TLR4) inflammasome-interleukin (IL)-6 signalling axis in monocyte subtypes and T cells. -These findings implicate the non-nicotine, pro-oxidant toxicants in tobacco cigarette smoke as instigators of increased expression of key proteins in the TLR4-inflammasome-IL-6 axis that contribute to atherogenesis.

2020: Expression of Key Inflammatory Proteins Is Increased in Immune Cells From Tobacco Cigarette Smokers But Not Electronic Cigarette Vapers: Implications for Atherosclerosis

TCIGs but not ECIGs are associated with increased expression of key proteins in the TLR4–inflammasome–IL‐6 signaling axis, supporting the notion that ECIGs may represent a harm reduction approach to those addicted to TCIGs who are unwilling or unable to quit.

2020: Effects of electronic cigarette on platelet and vascular function after four months of use

-Electronic Cigarette vaping for four months has a neutral effect on platelet aggregation of healthy smokers. Continuation of tobacco cigarette smoking further deteriorates platelet function during 4 months of use. -Electronic cigarette vaping improves arterial elastic properties and oxidative stress after 4 months of use. Tobacco cigarette smoking causes further impairment of arterial elasticity and oxidative stress during 4 months of use

2020: Differential Effects of Tobacco Cigarettes and Electronic Cigarettes on Endothelial Function in Healthy Young People

-Endothelial dysfunction, as measured by flow mediated vasodilation(FMD) is a predictor of future atherosclerosis and adverse cardiovascular events, and is impaired in tobacco cigarette (TC) smokers. -FMD was significantly impaired after smoking one TC, but not after vaping an equivalent "dose"(estimated plasma nicotine) of an e-cigarette (EC), consistent with the notion that non-nicotine constituents in TC smoke mediate the impairment.

2020: Association of electronic cigarette use with lead, cadmium, barium, and antimony body burden: NHANES 2015-2016

PDF Version In this study, blood lead levels, and urinary cadmium, barium, and antimony levels were similar between participants who ever-used e-cigarettes and participants who did not, and therefore, e-cigarette use was not a major source of heavy metals.

2019: Cardiovascular Effects of Switching From Tobacco Cigarettes to Electronic Cigarettes

TC smokers, particularly females, demonstrate significant improvement in vascular health within 1 month of switching from TC to EC. Switching from TC to EC may be considered a harms reduction measure. 2019: Global Forum on Nicotine (GFN) The effect of electronic nicotine delivery systems (ends) and new tobacco products on the risk of cardiovascular disease in people with high tobacco dependence -Switching to ENDS/NTPs and nicotine delivery with cigarette smoke’s harmful effects elimination does not interrupt blood oxygen transport function which allows to avoid vessel endothelial damage. The obtained results show significantly less harmful influence of ENDS/NTPs on cardio-vascular function if compared to tobacco smoke and confirm the possibility to consider them as harm reduction products for smokers who do not want or are not ready to quit smoking completely. -Poster that goes with the study -2017 Article about this study

2019: Electronic cigarettes and cardiovascular health: what do we know so far?

Though they may not be as harmless as previously proposed, it seems likely that on the spectrum of tobacco products, ECs are less harmful than TCs, and there is increasing evidence that ECs may help promote TC cessation. As such, ECs may be helpful for risk reduction

2017: A comparative assessment of e-cigarette aerosols and cigarette smoke on in vitro endothelial cell migration - PubMed (nih.gov) Exposure to 3R4F extract (20h) induced concentration-dependent inhibition of endothelial cell migration, with complete inhibition at concentrations >20%. E-cigarette extracts did not inhibit migration, even at double the 3R4F extract nicotine concentration, allowing cells to migrate into the wounded area. Our data demonstrate that e-cigarettes do not induce the inhibition of endothelial cell migration in vitro when compared to 3R4F. 2017: Electronic cigarette smoking increases of arterial stiffness and oxidative stress to a lesser extent than a single normal cigarette: an acute and chronic study Electronic cigarette smoking causes a smaller increase of arterial stiffness and oxidative stress, compared to a single normal cigarette in an acute setting. Replacement of normal cigarettes by a moderate nicotine concentration electronic cigarette results in improved aortic elasticity and oxidative stress within 1 month.

2016: Cigarette smoke but not electronic cigarette aerosol activates a stress response in human coronary artery endothelial cells in culture (PDF 5 pages) -Human coronary artery endothelial cells show a biological response to cigarette smoke. -This response was not seen following exposure to e-cigarette aerosol. -Using e-cigarettes instead of cigarettes may reduce immediate cardiovascular harms.

2016: Cardiovascular toxicity of nicotine: Implications for electronic cigarette use (must pay to view PDF) -Studies of nicotine medications and smokeless tobacco indicate that the risks of nicotine without tobacco combustion products (cigarette smoke) are low compared to cigarette smoking, but are still of concern in people with cardiovascular disease. -Electronic cigarettes deliver nicotine without combustion of tobacco and appear to pose low-cardiovascular risk, at least with short-term use, in healthy users.

2013: Chronic Idiopathic Neutrophilia in A Smoker, Relieved after Smoking Cessation with the Use of Electronic Cigarette: a Case Report (PDF 7 pages) -A male Caucasian patient, born in 1977, presented in September 2005 with asymptomatic elevation of white blood cell and neutrophil count, and mildly-elevated C-reactive protein levels. He was a smoker since 1996 and was treated with 20 mg/day of simvastatin since 2003 due to hyperlipidemia. Clinical examination, and laboratory and imaging investigations ruled out any infectious, haematological, rheumatological, or endocrine conditions. He was followed-up regularly and was advised to stop smoking. He had 2 unsuccessful attempts to quit smoking; one was unassisted and the second was performed with the use of both varenicline and nicotine replacement therapy (patches). During the subsequent 6.5 years, his leukocyte and C-reactive protein levels were repeatedly elevated; the condition was consistent with chronic idiopathic neutrophilia. In February 2012, he started using electronic cigarettes and he managed to quit smoking within 10 days. After 6 months, laboratory examination showed normalized leukocyte count and C-reactive protein levels, confirmed immediately by a second laboratory and by repeated tests after 1 and 2 months. -Smoking cessation with the use of electronic cigarette led to reversal of chronic idiopathic neutrophilia. The daily use of electronic cigarette may help preserve the beneficial effects of smoking cessation.

2012: Acute effects of electronic and tobacco cigarette smoking on complete blood count -Active and passive tobacco cigarette smoking increased white blood cell, lymphocyte, and granulocyte counts for at least one hour in smokers and never smokers. Active and passive tobacco cigarette smoking increase the secondary proteins of acute inflammatory load for at least one hour. -It is concluded that acute active and passive smoking [vaping] using the e-cigarettes tested in the current study does not influence CBC indices in smokers and never smokers. The results demonstrated that CBC indices remained unchanged during the control session and the active and passive e-cigarette smoking [vaping] sessions.

2010: A clinical laboratory model for evaluating the acute effects of electronic “cigarettes”: nicotine delivery profile and cardiovascular and subjective effects (PDF 15 pages) -Heart rate increased from an average (SD) of 65.7 (10.4) bpm at baseline to a peak of 80.3 (10.9) bpm five minutes after the first administration under the tobacco cigarette condition. No significant changes in heart rate were observed for the e-cigarette or sham conditions. -Under these acute testing conditions, neither of the electronic cigarettes exposed users to measurable levels of nicotine or CO, although both suppressed nicotine/tobacco abstinence symptom ratings.

Oral Health

2020: Impact of Electronic Cigarettes on Oral Health: a Review (PDF 8 pages) -Several self-reported and randomized studies suggest that e‑cigarettes are a harm-reduction strategy that may improve the oral and general health of smokers and may contribute to smoking cessation. -Based on the available literature, it is possible to recommend the use of e‑cigarettes as a temporary alternative for harm reduction and as an aid to smoking cessation.

2019: A Comparison of Flavorless Electronic Cigarette-Generated Aerosol and Conventional Cigarette Smoke on the Planktonic Growth of Common Oral Commensal Streptococci (PDF 22 pages) -A potential implication of these results is that flavorless E-liquids and their generated aerosol induce less tooth decay and periodontal disease than traditional cigarette smoke. -A case for improving oral health (and overall health) could be made by federal health regulatory agencies for promoting the use of electronic nicotine delivery systems over the use of traditional cigarettes as a means of harm reduction.

2019: Impact of cigarette smoking and vaping on the outcome of full-mouth ultrasonic scaling among patients with gingival inflammation: a prospective study Periodontal inflammatory parameters are worse in cigarette-smokers than individuals vaping electronic cigarettes and never-smokers following FMUS (full-mouth ultrasonic scaling). Public Health

2021: Metabolomic Analysis Identified Reduced Levels of Xenobiotics, Oxidative Stress, and Improved Vitamin Metabolism in Smokers Switched to Vuse Electronic Nicotine Delivery System Our results suggest reduced toxicant exposure, reduced oxidative stress, and potential beneficial changes in vitamin metabolism within 5 days in smokers switching to Vuse ENDS.

2020: E-cigarettes and their impact on health: from pharmacology to clinical implications Despite many areas of ambiguity, current evidence suggest that e-cigarettes are less harmful than combustible products, but this only applies to smokers who completely switched to e-cigarettes. Thus, e-cigarettes still hold a great potential to reduce incidences of tobacco-related diseases and could be a part of the strategy to reduce the damage caused by smoking. Therefore, mechanisms should be developed to protect young people from using e-cigarettes but support smokers in their decisions to quit smoking with e-cigarettes.

2018: Characterization of the Spatial and Temporal Dispersion Differences Between Exhaled E-Cigarette Mist and Cigarette Smoke (PDF 7 pages) For both product categories, the particle concentrations registered following each puff were in the same order of magnitude. However, for e-cigarettes the particle concentration returned rapidly to background values within seconds; for conventional cigarettes it increased with successive puffs, returning to background levels after 30–45 minutes. Unlike for the e-cigarette devices tested, such temporal variation was dependent on the room ventilation rate. Particle size measurements showed that exhaled e-cigarette particles were smaller than those emitted during smoking conventional cigarettes and evaporated almost immediately after exhalation, thus affecting the removal of particles through evaporation rather than displacement by ventilation.

2017: Potential deaths averted in USA by replacing cigarettes with e-cigarettes -Compared with the Status Quo, replacement of cigarette by e-cigarette use over a 10-year period yields 6.6 million fewer premature deaths with 86.7 million fewer life years lost in the Optimistic Scenario. Under the Pessimistic Scenario, 1.6 million premature deaths are averted with 20.8 million fewer life years lost. The largest gains are among younger cohorts, with a 0.5 gain in average life expectancy projected for the age 15 years cohort in 2016. -The tobacco control community has been divided regarding the role of e-cigarettes in tobacco control. Our projections show that a strategy of replacing cigarette smoking with vaping would yield substantial life year gains, even under pessimistic assumptions regarding cessation, initiation and relative harm.

2012: Comparison of the effects of e-cigarette vapor and cigarette smoke on indoor air quality -Comparisons of pollutant concentrations were made between e-cigarette vapor and tobacco smoke samples. Pollutants included VOCs, carbonyls, PAHs, nicotine, TSNAs, and glycols. -Non-cancer risk analysis revealed “No Significant Risk” of harm to human health for vapor samples from e-liquids. -With regard to cancer risk analysis, no vapor sample from e-liquids exceeded the risk limit for either children or adults.

Respiratory System

2021: Cigarette smoke preparations, not electronic nicotine delivery system preparations, induce features of lung disease in a 3D lung repeat-dose model We show that 1-h daily exposure of normal human bronchial epithelial NHBE cultures over a 10-day period to combustible cigarette whole smoke-conditioned media (WS-CM) increased expression of oxidative stress markers, cell proliferation, airway remodeling, and cellular transformation markers and decreased mucociliary function including ion channel function and airway surface liquid. Conversely, aerosol conditioned media (ACM) from ENDS with similar nicotine concentration (equivalent-nicotine units) as WS-CM and nicotine alone had no effect on those parameters. PDF COI: RAI

2020: Benefits of e-cigarettes in smoking reduction and in pulmonary health among chronic smokers undergoing a lung cancer screening program at 6 months Pulmonary health, assessed with self-reported measures, clinical evaluations and the Leicester Cough Questionnaire, improved in participants who stopped smoking compared to their own baseline. Moreover, participants in this group [nicotine e-cigarettes] showed the lowest level of exhaled carbon monoxide, and the lowest level of dependence compared to the nicotine-free e-cigarette and control conditions.

2020: Exclusive e-cigarette users report lower levels of respiratory symptoms relative to dual e-cigarette and cigarette users Findings suggest that differences in respiratory symptoms between dual and exclusive e-cigarette users appear to be attributable to combustible cigarette smoking, rather than more intense or frequent e-cigarette use across groups.

2020: SACCHARIN TRANSIT TIME IN EXCLUSIVE E-CIGARETTES AND HEATED TOBACCO PRODUCTS USERS: A CROSS-SECTIONAL STUDY Ex-smokers who have switched to exclusive regular use of combustion-free nicotine delivery systems (i.e. ECs/e-cigarettes and HTPs/heated tobacco products) exhibit similar saccharin transit time as never and former smokers. This suggests that combustion-free nicotine delivery technologies are unlikely to have detrimental effects on MCC (mucociliary clearance) function

2020: COPD smokers who switched to e-cigarettes: health outcomes at 5-year follow up The present study suggests that EC use may ameliorate objective and subjective COPD outcomes, and that the benefits gained appear to persist long term. EC use for abstinence and smoking reduction may ameliorate some of the harm resulting from tobacco smoking in COPD patients.

2020: Vaping effects on asthma: results from a web survey and clinical investigation Almost all of the asthmatics who previously smoked would recommend switching to e-cig, and vaping did not worsen their asthma symptoms. Furthermore, switching from tobacco smoking to e-cigs showed a significant improvement in asthma control and quality of life, not showing, in the period studied, to affect pulmonary function tests.

2019: The effect of e-cigarette aerosol emissions on respiratory health: a narrative review. (PDF 18 pages) -Expert opinion: There is growing evidence to support the relative safety of E-Cigarette (EC) emission aerosols for the respiratory tract compared to tobacco smoke. -This review article shows that although some potential effects on respiratory cell types can be shown in vitro, and low levels of chronic irritation of the respiratory tract can be anticipated at certain levels of vaping, these effects are much less than those of smoking. The clinical evidence confirms that ECs are unlikely to raise significant health concerns for the respiratory tract under normal conditions of use. -Promoting further access to ECs may offer an opportunity to reduce or prevent some of the otherwise inevitable burden of respiratory morbidity and mortality caused by tobacco smoking -...we are now confident that current vaping products are much less harmful than conventional cigarettes as well as earlier EC designs.

2018: Health effects in COPD smokers who switch to electronic cigarettes: a retrospective-prospective 3-year follow-up (PDF 10 pages) The present study suggests that EC use may ameliorate objective and subjective COPD outcomes and that the benefits gained may persist long-term. EC use may reverse some of the harm resulting from tobacco smoking in COPD patients.

2017: E-cigarettes in patients with COPD: current perspectives (PDF 8 pages) Although ECs are not risk free, they are much less harmful than conventional tobacco smoking. The emerging clinical evidence suggests that ECs are unlikely to raise significant health concerns for the respiratory tract under normal conditions of use, even in smokers with preexisting lung disease. In particular, recent studies in COPD and chronic asthma suggest that substitution of conventional tobacco cigarettes for ECs can ameliorate subjective and objective disease-related outcomes and exacerbation rates as well as improving success in abstaining from smoking long term.

2017: Reduced biological effect of e-cigarette aerosol compared to cigarette smoke evaluated in vitro using normalized nicotine dose and RNA-seq-based toxicogenomics (PDF 16 pages) -Here, we assessed the transcriptional response of a primary 3D airway model acutely exposed to e-cigarette aerosol and cigarette (3R4F) smoke. -Based on equivalent or higher nicotine delivery, an acute exposure to e-cigarette aerosol had a reduced impact on gene expression compared to 3R4F smoke exposure in vitro. -Therefore, we can conclude that the data strongly supports the adverse effect of acute exposure to cigarette smoke on MucilAir™ cells with functional enrichment for cancer, inflammation and fibrosis genes. In contrast, RNA-seq-based toxicogenomics showed a reduced impact of e-cigarette aerosols acute exposure on MucilAir™ cells compared with 3R4F reference cigarette at equivalent or higher dose of nicotine exposure. COI: BAT

2017: Electronic cigarette vapor alters the lateral structure but not tensiometric properties of calf lung surfactant While both e-cigarette vapor and conventional cigarette smoke affect surfactant lateral structure, only cigarette smoke disrupts surfactant interfacial properties. The surfactant inhibitory compound in conventional cigarettes is tar, which is a product of burning and is thus absent in e-cigarette vapor.

2016: Evidence for harm reduction in COPD smokers who switch to electronic cigarettes (EC’s) (PDF 10 pages) These findings suggest that ECs use may aid smokers with COPD reduce their cigarette consumption or remain abstinent, which results in marked improvements in annual exacerbation rate as well as subjective and objective COPD outcomes.”

2016: Changes in the Frequency of Airway Infections in Smokers Who Switched to Vaping: Results of an Online Survey (PDF 3 Pages) 941 responses were received. Overall, 29% of responders reported no change in respiratory symptoms, 5% reported worsening, and 66% reported an improvement.

2016: Changes in breathomics from a 1‐year randomized smoking cessation trial of electronic cigarettes Smokers invited to switch to electronic cigarettes who completely abstained from smoking showed steady progressive improvements in their exhaled breath measurements and symptom scores. FeNo and eCO normalization is highly supportive of improved respiratory health outcomes and adds to the notion that quitting from tobacco smoking can reverse harm in the lung.

2016: Respiratory infections and pneumonia: potential benefits of switching from smoking to Vaping (PDF 4 pages) -Also, given that the propylene glycol in EC aerosols is a potent bactericidal agent, switching from smoking to regular vaping is likely to produce additional lung health benefits. -In conclusion, smokers who quit by switching to regular ECs use can reduce risk and reverse harm from tobacco smoking. -Innovation in the e-vapour category is likely not only to further minimise residual health risks, but also to maximise health benefits.

2016: Persisting long term benefits of smoking abstinence and reduction in asthmatic smokers who have switched to electronic cigarettes This prospective study confirms that EC use ameliorates objective and subjective asthma outcomes and shows that these beneficial effects may persist in the long term. EC use can reverse harm from tobacco smoking in asthma patients who smoke. The evidence-based notion that substitution of conventional cigarettes with EC is unlikely to raise significant respiratory concerns, can improve counseling between physicians and their asthmatic patients who are using or intend to use ECs.

2014: Effect of Smoking Abstinence and Reduction in Asthmatic Smokers Switching to Electronic Cigarettes: Evidence for Harm Reversal (PDF 13 pages) -The e-cig may help smokers with asthma to reduce their cigarette consumption or remain abstinent and hence reduce the burden of smoking-related asthma symptoms. The positive findings observed with e-cigs allows us to advance the hypothesis that these products may be valuable for smoking cessation and/or tobacco harm reduction also in asthma patients who smoke. -By substantially reducing number of cigarettes smoked per day and exposure to their hazardous toxicants, e-cigs may not only improve asthma symptoms and pulmonary function but may also confer an overall health advantage in smokers with asthma. Therefore, e-cig use in asthmatic smokers unable or unwilling to quit should be exploited as a safer alternative approach to harm-reversal (i.e., specific reversal of asthma-related outcomes) and, in general, to harm-reduction (i.e., overall reduction of smoke-related diseases).

Toxic

2021: Screening of different cytotoxicity methods for the assessment of ENDS toxicity relative to tobacco cigarettes All tests showed reduced cell viability following 1R6F smoke exposure and slight or no reduction with ENDS at 24 hours.

2020: Association of electronic cigarette use with lead, cadmium, barium, and antimony body burden: NHANES 2015-2016 (PDF 23 pages) -Blood lead levels, and urinary cadmium, barium, and antimony levels were similar between participants who used e-cigarettes and participants who did not. -However, participants with a smoking history were more likely to have higher blood lead and urinary cadmium than participants who neither used e-cigarettes nor cigarettes.

2018: NASEM report on E-Cig Health Effects evaluates the available evidence of health effects related to the use of E-cigarettes: Public Health Consequences of E-Cigarettes (750 pages) Report At A Glance Comparisons of using e-cigarettes vs smoking: There is conclusive evidence that completely substituting e-cigarettes for combustible tobacco cigarettes reduces users’ exposure to numerous toxicants and carcinogens present in combustible tobacco cigarettes. There is substantial evidence that except for nicotine, under typical conditions of use, exposure to potentially toxic substances from e-cigarettes is significantly lower compared with combustible tobacco cigarettes. There is substantial evidence that completely switching from regular use of combustible tobacco cigarettes to e-cigarettes results in reduced short-term adverse health outcomes in several organ systems. There is moderate evidence that risk and severity of dependence are lower for e-cigarettes than combustible tobacco cigarettes. There is moderate evidence from randomized controlled trials that e-cigarettes with nicotine are more effective than e-cigarettes without nicotine for smoking cessation. While the overall evidence from observational trials is mixed, there is moderate evidence from observational studies that more frequent use of e-cigarettes is associated with an increased likelihood of cessation. There is moderate evidence that second-hand exposure to nicotine and particulates is lower from e-cigarettes compared with combustible tobacco cigarettes. There is limited evidence for improvement in lung function and respiratory symptoms among adult smokers with asthma who switch to e-cigarettes completely or in part (dual use). There is limited evidence for reduction of chronic obstructive pulmonary disease (COPD) exacerbations among adult smokers with COPD who switch to e-cigarettes completely or in part (dual use). There is limited evidence suggesting that switching to e-cigarettes will improve periodontal disease in smokers.

2018: Comparison of Nicotine and Toxicant Exposure in Users of Electronic Cigarettes and Combustible Cigarettes (PDF 16 Pages) In this population-based cohort study of 5105 participants, current exclusive e-cigarette users had greater concentrations of biomarkers of nicotine, tobacco-specific nitrosamines, volatile organic compounds, and metals compared with never tobacco users. However, these concentrations were lower than those observed in current exclusive cigarette smokers and dual users of both products.

2018: Chemical Composition of myblu™ Pod-System E-Cigarette Aerosols: A Quantitative Comparison with Conventional Cigarette Smoke (PDF 1 page) -Testing of the myblu™ aerosols indicate low or no detectable levels of the toxicants tested. Over all the e-cigarettes yielded <1μg/puff of the toxicants tested compared to the reported cigarette yield of 381μg/puff. Of the 51 toxicants tested, eight were detected in the e-cigarette aerosols but at substantially lower levels than reported in cigarette smoke. -Findings from several recent clinical studies indicate that smokers who have switched to e-cigarettes have significantly lower exposure to carcinogens and toxicants found in cigarette smoke, with reductions largely indistinguishable from complete smoking cessation or use of licensed nicotine replacement products.

2017: Trace Metals Derived from Electronic Cigarette (ECIG) Generated Aerosol: Potential Problem of ECIG Devices That Contain Nickel (PDF 17 pages) -In general, the findings of this study suggest that the concentrations of most trace metals extracted from cigarette smoke exceed the concentrations of trace metals extracted from ECIG-generated aerosol. -Only Ni in the ECIG-generated aerosol was higher than control (smoke). The most probable source of Ni in this aerosol is the core assembly. -From this study, it is unlikely that the ECIG-generated aerosol contains enough of the other trace metals to induce significant pathology.

2017: Benzene formation in electronic cigarettes (PDF 10 pages) The risks from benzene will be lower from e-cigarettes than from conventional cigarettes.

2016: Royal College of Physicians - Nicotine without Smoke (PDF 206 pages) -Provision of the nicotine that smokers are addicted to without the harmful components of tobacco smoke can prevent most of the harm from smoking. -The hazard to health arising from long-term vapour inhalation from the e-cigarettes available today is unlikely to exceed 5% of the harm from smoking tobacco. -In the interests of public health it is important to promote the use of e-cigarettes, NRT and other non-tobacco nicotine products as widely as possible as a substitute for smoking…

2016: A randomised, parallel group study to evaluate the safety profile of an electronic vapour product over 12 weeks (PDF 14 pages) In this study, we have demonstrated that no clinically relevant, product-related safety findings were observed for smokers of Combustible Cigarettes (CCs) switching to an Electronic Vapor Product (EVP) for 12 weeks under real-life settings. EVP use was associated with significant decreases in exposure to nicotine and other chemicals such as benzene and acrolein, typically found in CC smoke. Changes were also observed in the level of WBC, haemoglobin, RBC and LDL cholesterol, which although minor, were consistent with those observed after smoking cessation.

2016: Tobacco Consumption and Toxicant Exposure of Cigarette Smokers Using Electronic Cigarettes (PDF 28 pages) Smokers using ECs over 4 weeks maintained cotinine levels and experienced significant reductions in carbon monoxide, NNAL, and two out of eight measured VOC metabolites. Those who switched exclusively to ECs for at least half of the study period significantly reduced two additional VOCs.

2016: Reductions in biomarkers of exposure, impacts on smoking urge and assessment of product use and tolerability in adult smokers following partial or complete substitution of cigarettes with electronic cigarettes (PDF 16 pages) -Subjects switching to e-cigarettes had significantly lower levels (29 %–95 %) of urinary BoEs after 5 days. Nicotine equivalents declined by 25 %–40 %. -All groups experienced significant decreases in exhaled CO (27 %–89 %).

2016: Electronic cigarette aerosol induces significantly less cytotoxicity than tobacco smoke (PDF 16 pages) Under the conditions tested, Vype ePen e-cigarette aerosol was significantly less cytotoxic than reference 3R4F cigarette smoke.

2014: Safety evaluation and risk assessment of electronic cigarettes as tobacco cigarette substitutes: a systematic review (PDF 20 pages) Conclusion: “Existing evidence indicates that E-cigarette (EC) use is by far a less harmful alternative to smoking. There is no tobacco and no combustion involved in EC use; therefore, regular vapers may avoid several harmful toxic chemicals that are typically present in the smoke of tobacco cigarettes. Indeed, some toxic chemicals are released in the EC vapor as well, but their levels are substantially lower compared with tobacco smoke, and in some cases (such as nitrosamines) are comparable with the amounts found in pharmaceutical nicotine products. Surveys, clinical, chemistry and toxicology data have often been mispresented or misinterpreted by health authorities and tobacco regulators, in such a way that the potential for harmful consequences of EC use has been largely exaggerated. It is obvious that some residual risk associated with EC use may be present, but this is probably trivial compared with the devastating consequences of smoking. Moreover, ECs are recommended to smokers or former smokers only, as a substitute for conventional cigarettes or to prevent smoking relapse; thus, any risk should be estimated relative to the risk of continuing or relapsing back to smoking and the low efficacy of currently approved medications for smoking cessation should be taken into consideration…..”

2014: Comparison of select analytes in aerosol from e-cigarettes with smoke from conventional cigarettes and with ambient air No significant contribution of tested HPHC classes was found for the e-cigarettes.

2013: Cytotoxicity evaluation of electronic cigarette vapor extract on cultured mammalian fibroblasts (ClearStream-LIFE): comparison with tobacco cigarette smoke extract This study indicates that EC vapor is significantly less cytotoxic compared to tobacco CS.

Weight

2018: Lack of Substantial Post-Cessation Weight Increase in Electronic Cigarettes Users (PDF 13 pages) -Within the study limitations, EC use may help smokers attenuate cigarette consumption or remain abstinent, as well as reduce their post-cessation weight increase. The potential role of the e-vapour category for harm minimization in relation to tobacco and/or food abuse requires confirmation from larger prospective studies. Moreover, the observed lack of post-cessation weight gain in those who reduced substantially cigarette consumption by switching to ECs (i.e., dual users) is an interesting finding and calls for further research investigating the role of nicotine in weight control. Meanwhile, these preliminary findings should be communicated to smokers and particularly to weight-conscious smokers intending to quit. -By combining substantial reduction of smoking with prevention of post-cessation weight gain, EC-based interventions may promote an overall improvement in quality of life. Considering that the negative effects of weight increase could overshadow the health benefits of smoking abstinence, it is important to stimulate more research in this area.”

2017: Could Vaping be a New Weapon in the Battle of the Bulge? -Obesity is set to overtake tobacco smoking in many countries as the primary cause of several high-cost diseases. Tobacco smoking mitigates weight gain through nicotine’s effect on the brain and metabolism. -There have been some reports among vapers that vaping is helping to mitigate weight gain after stopping smoking and or vaping is helping them to control their weight. There are several potential mechanisms by which vaping, in addition to the direct effects of nicotine, could facilitate weight control, these include taste perception, physical mouthfeel, and sensation and behavioral replacement.

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2021: Interventions for preventing weight gain after smoking cessation

• There was moderate‐certainty that NRT reduced weight at end of treatment and moderate‐certainty that the effect may be similar at 12 months, although the estimates are too imprecise to assess long‐term benefit.

2021: Clinical Pharmacology of Electronic Nicotine Delivery Systems (ENDS): Implications for Benefits and Risks in the Promotion of the Combusted Tobacco Endgame

• “If smokers used ENDS to quit smoking, even if they continued to use ENDS, we expect that there would be an enormous benefit to public health.”
• Summary of paper by Dr. Colin Mendelsohn
  • Nicotine
    • Nicotine per se is not harmless, but is much less harmful than combusted tobacco use. The effects of nicotine include ’pleasure, arousal and stimulation, and reduction of anxiety and mood stabilization’
    • Vapers and smokers take in the same amount of nicotine into the body each day
    • Daily intake of nicotine is much the same for users of high powered devices with 3-6mg/ml for MTL as for low powered pod devices with 60mg/ml nicotine for MTL
    • Experienced users take in more nicotine than new vapers, so satisfaction increases over time
    • E-liquids with high levels of propylene glycol deliver more nicotine than those with lower levels with the same nicotine concentration.
    • Of the nicotine that is inhaled from an e-cigarette, more than 90% is retained by the smoker so very little is released into the surrounding air.
    • One 5% JUUL pod delivers a similar amount of nicotine to smoking around 18 cigarettes.
    • The rate of rise of nicotine in the blood is similar for cigarettes and e-cigarettes, but in general peak levels of nicotine are lower with e-cigarettes.
  • Safety of vaping
    • ENDS products expose users to much lower levels of toxicants compared with cigarette smoking. Based on the far lower number and levels of potential toxins in ENDS aerosol, it is predicted that toxicity will be much lower than that of smoking, but toxicity will likely differ by device.
    • High powered devices have a greater health risk. The clouds are larger and the higher temperatures create more toxic chemicals. Devices with high concentrations of nicotine salt generate smaller, cooler clouds with less toxin exposure.
    • Although no smoking or vaping is preferred, switching to less harmful e-cigarettes long-term would likely reduce smoking-related disease risk and would be an acceptable alternative compared with regular use of tobacco cigarettes.
    • Dripping” (ie, dripping drops of the e-liquid directly onto the heating element and then inhaling the produced vapor) can lead to high liquid heating temperatures and generation of harmful more chemicals.
    • Long-term harm is unknown because the products have not been used for long-enough
• PDF Version
• Citation: Benowitz, N.L., St.Helen, G. and Liakoni, E. (2021), Clinical Pharmacology of Electronic Nicotine Delivery Systems (ENDS): Implications for Benefits and Risks in the Promotion of the Combusted Tobacco Endgame. The Journal of Clinical Pharmacology, 61: S18-S36. doi:10.1002/jcph.1915
• Acknowledgement: Preparation of this review was supported in part by National Institutes of Health grants DA039264 from the National Institute on Drug Abuse and U54HL147127 from the National Heart Lung and Blood Institute. Data presented in figures were collected at the Clinical Research Center at Zuckerberg San Francisco General Hospital (NIH/NCRR UL1 RR024131)