Safety of e-cigarettes still needs to be provedBMJ 2014; 349 doi: https://doi.org/10.1136/bmj.g4597 (Published 15 July 2014) Cite this as: BMJ 2014;349:g4597
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Scientific evidence clearly indicates e-cigarettes are considerably less harmful than tobacco cigarettes
We were dismayed by the approach of Valentine and Nicholson to the issue of e-cigarettes . Of course, unexpected health consequences may occur in the medical profession as it has been also the case with several medications, such as thalidomide, cerivastatin and rofecoxib to name a few. But this cannot be used as a valid argument to oppose e-cigarettes. They suggest e-cigarettes should be quarantined until results from long-term studies are available, while in reality this is not a requirement for any other product approved for human consumption. Even for medications, no regulatory agency is asking for long-term safety data before being approved for use. Although some problems have emerged, such as the recent story with olmesartan , this cannot justify a request to provide long-term studies before approval of medications; it will just be impossible for anyone to cope with the financial cost, while at the same time evolution of new medications will become very slow.
We agree with Valentine and Nicholson that children are frequently exposed to products they find in their homes. That is why household and personal care products, together with medications, are the leading causes of poisonings in children . Until now, there are no documented cases of deaths from exposure to e-cigarette liquids. It is misleading to quote occasional cases of accidental poisoning without providing professional medical reporting. The number of cases is extremely small compared with, for example, household cleaning products. Childproof caps have been now introduced by most producers/distributors and this alone will prevent these rare accidents. Of course, regulation should implement such a requirement. In any case, there has never been proposed that medications or household cleaning products should be banned because of poisonings, nor should this be a reason to restrict the size of packaging of these products. Moreover, it is time to re-evaluate the lethal dose of nicotine, which has historically being set at 40-60mg; this was the result of dubious self-experiments in the 19th century, with a recent review setting the lethal dose at 500-1000mg . Of note, this dose does not take into consideration that voluminous vomiting is the first and most prominent symptom of nicotine ingestion. There are reports of ingesting 1500mg nicotine, with the patient being discharged from the hospital after few hours of observation without any adverse health consequences .
Valentine and Nicholson cite a review by Warren and Singh about the effects of nicotine in promoting cancer . This as well as another review by Grando  referred to laboratory evidence, while there is no clinical study which has verified such findings. On the contrary, there is a wealth of epidemiological data of long-term nicotine intake from snus use. Evidence shows that there is minimal, if any, effect of snus (and the resulting nicotine intake) in cancer incidence [8,9]. In any case, even if a small residual risk remains, it is by far lower compared to the risk of continuing smoking, and is most probably not attributed to the nicotine content in snus. The extensive clinical evidence about snus use clearly supports the important role of tobacco harm reduction products in reducing smoking-related morbidity and mortality.
Evidence that inhalation of e-cigarette aerosols may be of concern for the lung is non-existent. Rather, the opposite may be true. There is now evidence from clinical studies  and research surveys  that smokers with asthma and COPD who switched to regular e-cigarette use benefitted substantially, with improvements in their respiratory symptoms and lung function. Although prospective studies are needed to better define the harm reversal potential of e-cigarettes in patients with already-established lung disease, the available evidence is important because asthma and COPD patients are particularly vulnerable to respiratory irritants and the e-cigarette aerosol does not set off respiratory exacerbations.
A point that has rarely being raised is that, unlike tobacco cigarettes which were developed and marketed for a non-smoker to become a smoker, e-cigarettes are developed and have been endorsed by some scientists strictly as a substitute, for smokers to become e-cigarette users. Thus, it is inappropriate to consider them as a new threat for public health, since they are not promoted as a new habit for everyone (i.e. non-smokers) to adopt. There is currently minimal adoption of e-cigarette use by non-smokers and youth (only 0.5% of non-smoking adolescents has used e-cigarettes in the past 30 days according to the Centers for Disease Control survey , while similar observations were reported in a survey of Korean adolescents ). Besides the recent estimation of the much-reduced risk of e-cigs compared to combustible nicotine containing products , there is also overwhelming evidence that e-cigarettes are by far less harmful compared to tobacco cigarettes . What remains is to objectively quantify the exact reduction in risk; this will be evaluated through long-term studies. However, it is irresponsible to promote risks that are not proven and to deprive smokers of a product which, based on all scientific evidence, is reducing their exposure to health hazards to a large extent.
1. Valentine C, Nicholson P. Safety of e-cigarettes still needs to be proved. BMJ 2014;349:g4597.
2. Graham DJ, Zhou EH, McKean S, Levenson M, Calia K, Gelperin K, et al. Cardiovascular and mortality risk in elderly Medicare beneficiaries treated with olmesartan versus other angiotensin receptor blockers. Pharmacoepidemiol Drug Saf 2014;23:331-339.
3. Swedish Poisons Information Center. Annual Report 2013. Available at: http://www.giftinformation.se/Documents/Annual%20Report%202013.pdf (accessed on July 16, 2014).
4. Mayer B. How much nicotine kills a human? Tracing back the generally accepted lethal dose to dubious self-experiments in the nineteenth century. Arch Toxicol. 2014;88:5-7.
5. Christensen LB, van't Veen T, Bang J. Three cases of attempted suicide by ingestion of nicotine liquid used in e-cigarettes, Clinical Toxicology 2013;51:290.
6. Warren GW1, Singh AK. Nicotine and lung cancer. J Carcinog 2013;12:1.
7. Grando SA. Connections of nicotine to cancer. Nat Rev Cancer 2014;14:419-429.
8. Lee PN. The effect on health of switching from cigarettes to snus - a review. Regul Toxicol Pharmacol 2013;66:1-5.
9. Rodu B, Cole P. Lung cancer mortality: comparing Sweden with other countries in the European Union. Scand J Public Health 2009;37:481-486.
10. Polosa R, Morjaria J, Caponnetto P, Caruso M, Strano S, Battaglia E, et al. Effect of smoking abstinence and reduction in asthmatic smokers switching to electronic cigarettes: evidence for harm reversal. Int J Environ Res Public Health 2014;11:4965-4977.
11. Farsalinos KE, Romagna G, Tsiapras D, Kyrzopoulos S, Voudris V. Characteristics, perceived side effects and benefits of electronic cigarette use: a worldwide survey of more than 19,000 consumers. Int J Environ Res Public Health 2014;11:4356-4373.
12. Centers for Disease Control and Prevention (CDC). Notes from the field: Electronic cigarette use among middle and high school students—United States, 2011–2012. MMWR Morb Mortal Wkly Rep 2013;62:729–730.
13. Lee S, Grana RA, Glantz SA. Electronic cigarette use among Korean adolescents: a cross-sectional study of market penetration, dual use, and relationship to quit attempts and former smoking. J Adolesc Health 2014;54:684-690.
14. Nutt DJ, Phillips LD, Balfour D, Curran HV, Dockrell M, Foulds J, et al. Estimating the Harms of Nicotine-Containing Products Using the MCDA Approach. Eur Addict Res 2014;20:218-225.
15. Farsalinos KE, Polosa R. Safety evaluation and risk assessment of electronic cigarettes as tobacco cigarette substitutes: a systematic review. Ther Adv Drug Safety 2014;5:67-86.
Competing interests: Some studies performed by KF were carried out using funds provided to his institution (Onassis Cardiac Surgery Center) by e-cigarette companies. RP has received lecture fees and research funding from GlaxoSmithKline and Pfizer, manufacturers of stop smoking medications. He has also served as a consultant for Pfizer and Arbi Group Srl (Milano, Italy), the distributor of Categoria™ e-Cigarettes. R.P.’s research on electronic cigarettes is currently supported by LIAF (Lega Italiana AntiFumo).
The great majority of adult smokers wish to stop smoking and a significant and rapidly growing number of people have successfully reduced or stopped inhaling tar, carbon monoxide and many other known carcinogens using e-cigarettes. Strikingly they have found their way to this solution without any help or encouragement from the health service, the medical industry or a significant level of advertising. This laudable example of people ‘taking responsibility for their own health’ should preface any discussion of e-cigarettes.
It is sadly predictable that the response from a significant number of those who make a living from promoting other methods of quitting, or telling us what is good for us, has been hostile. Testimony to the paucity of evidence against e-cigarettes includes such spurious comparisons, as evoked here, of drug addicts leaving methadone lying around the house for their children to swallow! The authors are right that we need to establish what long-term harms are associated with this new method, there will obviously be some, but we should do this in a large randomised comparison of the efficacy and safety of e-cigarettes with other, apparently acceptable, nicotine replacement methods so that people trying to stop smoking and their advisers can make an informed decision about the balance of risk and benefit of all current methods.
A more relevant safety issue is that at present these devices are not subject to the inspection and control that other ingestible substances receive. The majority of longer-term users move from buying the once only cigarette look-alikes sold in convenience stores to devices with a tank they refill with liquids, often bought online. The very low cost of entry to the business of making and selling devices and liquids is a significant concern. Standards should be established for both devices and liquids and enforced though the normal inspection routes for food and electric devices. Seeking to restrict or impede free access will simply drive supply chains underground and give ‘vaping’ the ‘street cred’ with juveniles that it currently lacks. Until society agrees to ban the sale for profit of all addictive substances linked to significant heath risk, such as alcohol and over-the-counter analgesics, it would also be immensely hypocritical.
Competing interests: No competing interests
There is so much wrong in such a short communication, that it is hard to know where to start. I would like to draw out four types of error in this letter:
1. Framing errors. The authors appear to misunderstand the concept of harm reduction. It is not necessary for e-cigarettes to be completely 'safe' - they just need to be very much safer than smoking, and not that dangerous in absolute terms for them to have a valuable public health impact if they function as an appealing alternative to smoking. If the BMA officials had studied the experience of snus (smokeless tobacco) in Scandinavia they would understand this concept. In fact, BMA was one of the organisations that wanted this product banned in the rest of Europe, prompting a number experts in the field to write to the Secretary of State for Health to voice their opposition to a ban with evidence . There is a similar framing error in the authors' approach to acute toxicity of nicotine. Not only is their science obsolete and greatly overstates the toxicity  but their framing is wrong: we do not generally control toxic substances in the home by banning them or limiting container sizes to below sub-lethal doses: imagine having to buy bleach by the cupful. The approach taken is to classify, package and label the products appropriately - something that is easy to do, and the BMA could constructively support instead of trying to reject the product outright on these spurious ground.
2. Loss aversion and accountability for risks created by restrictive policies. The authors appear oblivious to the risks that their own policy prescriptions might create. Many of the restrictions they favour, and their public relations line, will have the effect of denying these products to smokers or persuading them not to try the products - and this comes with consequences. A very much less risky product (e-cigarettes) than the dominant, highly dangerous, incumbent (cigarettes) comes to market and the medical establishment moves in to oppose it. Surely it is obvious that this risks protecting cigarette sales, increasing smoking, denying smokers options that might work for them, and so contribute to more disease and death. In their focus on small or implausible residual risks arising from e-cigarette use, these authors have not symmetrically accounted for the lost opportunities and risks that their ideas might create. I have set out a more detailed account of this argument, and wish to remind the BMA that it should be accountable for additional preventable smoking that arises from its hostile position . As an example, the authors make a wholly unsubstantiated claim that flavours are added to increase appeal children - there is no evidence at all for that. In fact, flavours are important to adults, and particularly important in supporting a long term move away from smoking. To ban flavours risks compromising the appeal of the product to the intended market (smokers) and so leading to more smoking than there otherwise would be. The authors give no reassurance that they have considered this risk, yet it is more plausibly significant in sign and magnitude than any risks they cite.
3.Use of evidence in policymaking The authors want "long term data affirming lack of harm"... but one wonders what would satisfy the authors, and whether this is simply a tactic to create an insurmountable evidential hurdle? What should be done in the meantime? The British doctors survey that demonstrated the effects of smoking unfolded over 50 years . To make good judgements about risks in public health a physician has to look at all the evidence, weight it by its value, and where there is remaining uncertainty to consider the uncertain risks and potential benefits on an even footing. A good evidential picture can be developed starting from the basic physics and chemistry of the processes involved, the toxicology studies on liquids and vapours, the long established and well studied history of nicotine use where there is no tobacco combustion (i.e. in NRT and snus), the absence of significant reported ill-effects or serious incidents, and expert opinion all suggest that the risks arising from e-cigarettes in general are low and the risks of nicotine itself, while finite, are very low. Cherry picking single studies out of context does not alter that. They are also misrepresent the evidence on whether these products are effective at smoking cessation. There is not just 'one study' showing these products to be effective in smoking cessation - there are several trials and impressive survey data. The survey for ASH for example, suggests some 700,000 current British e-cigarette users are now ex-smokers, whilst use among adolescents and non-smokers is very low . Surely the BMA can extract some evidential value from that? What, on the other hand, are the implications of ignoring it?
Missing humility and empathy. I understand modern medical training includes listening skills and recognises the importance of empathy with patients. I would like to commend this approach to the BMA. It is quite possible that millions of smokers are finding something that works for them and gives them immediate gains in welfare and self-esteem and significant improvement in long term health and mortality prognosis - at least that's what many well-informed say users when they describe their experience. The tone from the BMA and the more reactionary elements of the health establishment is that the views and experience of users simply do not matter or are worthless anecdotes. I do not think this is right - not everything can be understood from RCTs and and thousands of user testimonies now point to huge welfare gains from this technology. I would advise any physician minded to take a dismissive view of e-cigarettes developments to look at some testimonies and remind themselves what the profession is all about. There are many available on the internet, and they make inspiring reading .
These issues have been raised before with the BMA and they have promised to consider them , but so far the organisation seems more concerned to defend its earlier positions, even though evidence and experience is increasingly leaving it looking scientifically vacuous, impervious to challenge and criticism and out of touch.
 Martin Jarvis, Peter Hajek, John Britton, Gerry Stimson, Riccardo Polosa, Karl Olov Fagerström, Michael Kunze, Karl Erik Lund, Jacques Le Houezec, Tony Axéll, Lars Ramström, Clive Bates. Letter to the Secretary of State for Health, Tobacco Products Directive and snus, 7 October 2013. Available online at:
Why is the EU banning Europe's most effective anti-smoking strategy?
 Mayer B. How much nicotine kills a human? Tracing back the generally accepted lethal dose to dubious self-experiments in the nineteenth century. Arch Toxicol 2014;88:5–7. doi:10.1007/s00204-013-1127-0
 Bates, C. Turning the tables on public health – let’s talk about the risks *they* create? 3 July 2014
 Doll R, Peto R, Boreham J, et al. Mortality in relation to smoking: 50 years’ observations on male British doctors. BMJ 2004;328:1519. doi:10.1136/bmj.38142.554479.AE
 YouGov for Action on Smoking and Health Use of electronic cigarettes in Great Britain April 2014.
 See examples and links at: Bates C. Where is the humility? Where is the empathy? 30 December 2013.
 Bates C. Letter to Dr Vivienne Nathanson, 25 February 2014, Response from Dr Nathanson, 4 March 2014. Unable to take any more, I write to Dr Nathanson of the BMA. A similar challenge has been made by the campaign group Sense about Science What’s the evidence for banning electronic cigarettes: we asked the BMA why they want them banned in public, 12 December 2013.
Competing interests: No competing interests
Re: Safety of e-cigarettes still needs to be proved
Safety of e-cigarettes still needs to be proved. BMJ 2014; 349: g4597
Although the benefits of e-cigarettes in the removal of toxic carcinogens from tobacco is undisputed, little attention is being given to the other known harmful effects of the nicotine which is present in e-cigarettes. The authors of the above Rapid Response point out the risk of children inadvertently consuming the nicotine contained in an e-cigarette. A far bigger danger is the known toxic effects of nicotine, such as its role in cardiovascular disease, the prevalence of gastroduodenal ulcers, and in toxic amblyopia. Whilst e-cigarettes have a role in helping those who wish to quit smoking, they should still be regarded as only a stage towards total smoking cessation.
Competing interests: No competing interests