A fresh look at tobacco harm reduction: The case for the electronic cigarette

Abstract

Smokers of any age can reap substantial health benefits by quitting. In fact, no other single public health effort is likely to achieve a benefit comparable to large-scale smoking cessation. Surveys document that most smokers would like to quit, and many have made repeated efforts to do so. However, conventional smoking cessation approaches require nicotine addicted smokers to abstain from tobacco and nicotine entirely. Many smokers are unable -- or at least unwilling -- to achieve this goal, and so they continue smoking in the face of impending adverse health consequences. In effect, the status quo in smoking cessation presents smokers with just two unpleasant alternatives: quit or suffer the harmful effects of continuing smoking. But, there is a third choice for smokers: tobacco harm reduction. It involves the use of alternative sources of nicotine, including modern smokeless tobacco products like snus and the electronic cigarette (E-cig), or even pharmaceutical nicotine products, as a replacement for smoking. E-cigs might be the most promising product for tobacco harm reduction to date, because, besides delivering nicotine vapour without the combustion products that are responsible for nearly all of smoking's damaging effect, they also replace some of the rituals associated with smoking behaviour. Thus it is likely that smokers who switch to E-cigs will achieve large health gains. The focus of this article is on the health effects of using an E-cig, with consideration given to the acceptability, safety and effectiveness of this product as a long-term substitute for smoking.

Full text

R E V I E W Open Access
A fresh look at tobacco harm reduction: the case
for the electronic cigarette
Riccardo Polosa
1,2*
, Brad Rodu
3
, Pasquale Caponnetto
1
, Marilena Maglia
1
and Cirino Raciti
1
Abstract
Smokers of any age can reap substantial health benefits by quitting. In fact, no other single public health effort is
likely to achieve a benefit comparable to large-scale smoking cessation. Surveys document that most smokers
would like to quit, and many have made repeated efforts to do so. However, conventional smoking cessation
approaches require nicotine addicted smokers to abstain from tobacco and nicotine entirely. Many smokers are
unable –or at least unwilling –to achieve this goal, and so they continue smoking in the face of impending
adverse health consequences. In effect, the status quo in smoking cessation presents smokers with just two
unpleasant alternatives: quit or suffer the harmful effects of continuing smoking. But, there is a third choice for
smokers: tobacco harm reduction. It involves the use of alternative sources of nicotine, including modern smokeless
tobacco products like snus and the electronic cigarette (E-cig), or even pharmaceutical nicotine products, as a
replacement for smoking. E-cigs might be the most promising product for tobacco harm reduction to date,
because, besides delivering nicotine vapour without the combustion products that are responsible for nearly all of
smoking’s damaging effect, they also replace some of the rituals associated with smoking behaviour. Thus it is likely
that smokers who switch to E-cigs will achieve large health gains. The focus of this article is on the health effects of
using an E-cig, with consideration given to the acceptability, safety and effectiveness of this product as a long-term
substitute for smoking.
Keywords: Tobacco, Harm reduction, Snus, Electronic cigarettes
Introduction
Tobacco smoking is a global pandemic, affecting an
estimated 1.2 billion people, that poses substantial
health burdens and costs. With nearly six million
deaths annually, smoking is the single most important
cause of avoidable premature mortality in the world
[1], mainly from lung cancer, coronary heart disease,
chronic obstructive pulmonary disease and stroke [2,3].
As also underscored by the World Health Organization
(WHO) Framework Convention on Tobacco Control
(FCTC), the key to reducing the health burden of tobacco
in the medium term is to encourage cessation among
smokers [4].
Unfortunately, smoking is a very difficult addiction to
break, even for those with a strong desire to quit. It has
been shown that approximately 80% of smokers who
attempt to quit on their own relapse within the first
month of abstinence, and only about 5% achieve long
term abstinence [5]. Moreover, currently available smoking
cessation medications such as nicotine replacement
therapy, the antidepressant bupropion and the partial
agonist of the α4β2 nicotinic acetylcholine receptor,
varenicline, at best double or triple this quit rate under the
ideal circumstances of an experimental setting but have
had low uptake and inferior efficacy in the community
[6-8]. Furthermore, varenicline and bupropion have
come under increasing scrutiny due to reports of serious
adverse events that include behaviour change, depression,
self-injurious thoughts, and suicidal behaviour [9].
The Tobacco Advisory Group of the Royal College of
Physicians acknowledges that the development of
addiction includes modifications in behaviour together
with changes in brain structure and function that impair
* Correspondence: polosa@unict.it
1
Presidio G. Rodolico –Unità Operativa di Medicina Interna e Medicina
d’Urgenza, Centro per la Prevenzione e Cura del Tabagismo (CPCT), Azienda
Ospedaliero-Universitaria “Policlinico-Vittorio Emanuele”, Università di Catania,
Catania, Italy
2
Institute of Internal Medicine, G. Rodolico Hospital, Azienda
Ospedaliero-Universitaria “Policlinico-Vittorio Emanuele”, Università di Catania,
Catania, Italy
Full list of author information is available at the end of the article
© 2013 Polosa et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.
Polosa et al. Harm Reduction Journal 2013, 10:19
http://www.harmreductionjournal.com/content/10/1/19

the ability to achieve and sustain abstinence. They note
that some of these changes may not be entirely reversible
[10]. Lastly, even tobacco control policies - particularly
when not integrated and well supported by adequate
funding - are not very effective [11].
Consequently, many smokers will keep smoking because,
when given only the options of smoking or completely
giving up nicotine, many will not give it up. Bearing in
mind that nicotine per se does not cause much risk when
separated from inhaling smoke, it is important to consider
that a third option is also available to smokers; the
reduction of smoking-related diseases by taking nicotine
in a low-risk form. Tobacco harm reduction (THR), the
substitution of low-risk nicotine products for cigarette
smoking, is likely to offer huge public health benefits
by fundamentally changing the forecast of a billion
cigarette-caused deaths this century [12].
Value of harm reduction as a tobacco control strategy
The history of THR may be traced back to 1974, with
the publication of a special article in the Lancet by
British tobacco addiction research expert Michael A.H.
Russell [13]. There are many and varied approaches to
THR. Broadly, these can be categorised into two groups:
(I) non-tobacco interventions aimed at decreasing tobacco
consumption, and (II) alternative tobacco products. THR
empowers smokers to gain control over the consequences
of their nicotine addiction and at its simplest it is non
intrusive and solely educational, therefore having a strong
ethical rationale [14]. The strategy is cost-effective and
accessible today to almost all smokers. Harm reduction is
particularly compelling for nicotine because so many
people have such a strong propensity for using it.
Most scientists and commentators agree that complete
tobacco cessation is the best outcome for smokers, and
any efforts to make available safer products need to be
part of a comprehensive tobacco control strategy aimed at
minimising tobacco use through cessation and prevention
[15]. Opponents of THR often claim that providing safer
alternatives sidetracks smokers from quitting completely.
However, refusing to provide truthful information about
and access to safer alternative sources of nicotine
dissuades smokers from quitting the most harmful
method of obtaining nicotine - inhaling smoke.
Quit rates may be improved by advancing physicians’
understanding of predictors of success in smoking
cessation [16], and some have purported that it may
be better to focus efforts on developing and improving
pharmacologic therapies than to promote safer alternatives
such as smokeless tobacco [17,18]. Currently, however, there
is a growing trend in physicians’indifference or scepticism
towards the efficacy of smoking cessation programs [19].
Moreover, the use of pharmaceutical cessation aids
[20] and behavioural support [21] have led to limited
success in cessation, and it has been argued that the
majority of current smokers will continue to smoke
without acceptable safer alternatives [22]. Therefore,
the case for an effective THR strategy is legitimate.
Avoiding confusion about true health consequences of
nicotine use
When considering harm reduction as a tobacco control
strategy it is important to separate the risk associated
with inhaling smoke from that of taking nicotine. As
Russell noted 30 years ago, "There is little doubt that if
it were not for the nicotine…people would be little more
inclined to smoke than they are to blow bubbles or light
sparklers" [13], "The rapid absorption of nicotine
from snuff confirms its potential as an acceptable
and relatively harmless substitute for smoking"…."Switching
from cigarettes to snuff would substantially reduce the
risk of lung cancer, bronchitis, emphysema, and possibly
coronary heart disease as well, at the cost of a slight
increase in the risk of cancer of the nasopharynx (or oral
cavity in the case of wet snuff)" [23]. Nicotine fulfils all
the criteria of an addictive agent (including psychoactive
effects, drug-reinforced behaviour, compulsive use, relapse
after abstinence, physical dependence, and tolerance) by
stimulating specialized receptors in the brain which
produce both euphoric and sedative effects [24]. Individ-
uals who have emotional dysfunctions or attention deficits
are more likely to start smoking and less likely to quit.
Nicotine has beneficial effects on attention, concentration,
and mood in many smokers; these individuals may be
depending on nicotine as a means of self-medication [25].
Are there important associated adverse health conse-
quences of nicotine intake? The landmark work, Nicotine
Safety and Toxicity, edited by Neal Benowitz, considered
the potentially harmful effects of nicotine as well as its
benefits [26]. After reviewing the evidence, the authors
concluded that nicotine presents little if any cardiovascular
risk, and that nicotine has not been shown to be carcino-
genic. It is has been reported that nicotine may be poten-
tially harmful during pregnancy, but probably less harmful
than continued smoking [27-29].Therearedatasuggesting
that nicotine may be beneficial in treating ulcerative colitis
[30] and Tourette syndrome [31]. Other conditions for
which nicotine is being considered as treatment include
memory impairment, attention deficit disorder, depression,
and Parkinson’s disease [32]. Regarding long-term use, even
though nicotine is a potential toxin, it appears to be
well-tolerated during weeks and months of nicotine
medication therapy without evidence of serious adverse
health effects [10]. Using the multi-criteria decision ana-
lysis method previously used by the Independent Scientific
Committee on Drugs (ISCD) to rank the harms of drugs
used in the UK, a working group of international nicotine
experts convened by the ISCD considered the potential
Polosa et al. Harm Reduction Journal 2013, 10:19 Page 2 of 11
http://www.harmreductionjournal.com/content/10/1/19

harms of a wide range of nicotine containing products
based on sixteen parameters of harm to individuals and
harm to others. Not only conventional cigarettes were
judged to be by far the most harmful form of nicotine
containing product, but e-cigarettes were ranked as
similar in harm to nicotine patches [33]. By and large,
nicotine per se does not cause much risk when separated
from inhaling smoke.
Current tobacco harm reduction products
Pharmaceutical nicotine products have been used as
potential long-term cigarette substitutes. It has been
reported that about 20 percent of smokers who quit
with nicotine gum used it for more than one year,
even though it was available only by prescription [34].
None of the currently available products deliver nicotine to
the brain at a dose and rate similar to smoking. But this
inadequacy is due to a philosophical aversion to nicotine
addiction, not to technical inefficacy; a 1995 study found
that high-dose transdermal nicotine was safe and effective
for heavy smokers [35,36]. To be realistic alternatives, con-
temporary nicotine products need to be as readily available
as cigarettes, competitively priced, socially acceptable and
approved for regular long-term recreational use rather than
as short-term cessation aids [22]. But these products would
also be addictive.
A convincing example of a successful THR strategy is
that of Swedish snus. Snus is a type of finely ground
moist snuff that delivers significant levels of nicotine
(Figure 1). Snus does not produce any of the toxic
combustion products and it is manufactured in a way
that produces low levels of carcinogenic tobacco-specific
nitrosamines (TSNAs) [37,38]. In Sweden, where snus has
progressively replaced cigarette smoking over the past
20 years [35], substantial reductions in smoking preva-
lence have been reported [39]. Although Sweden’s tobacco
control policies have undoubtedly contributed to this
decline, the popularity of snus has played a major role.
The much steeper decline in smoking prevalence observed
among males than females is likely to be due to greater
snus use in males [40]. Snus prevalence in Swedish males
rose from 10% in 1976 to 23% in 2002 [41]. From the
period 1990–1995 to the period 2002–2007, smoking
prevalence decreased from 26 to 10% among men [42]
Interestingly, the Swedish population prevalence of
tobacco use has remained relatively steady at around
40%, but with 58% of daily tobacco users now taking
snus instead of smoking cigarettes [43]. As a result
of this, tobacco-related mortality in Sweden is among
the lowest in the Western world [44]. Studies provide
quantitative evidence that health risks of using snus
is lower than smoking for lung, oral, and gastric
cancers, for cardiovascular disease, and for all-cause
mortality [45].
The Swedish experience has been replicated in Norway,
which shares a border with Sweden and is culturally
similar [46]. The 2005 California Tobacco Survey shows
that smokers in that state are not receptive to using oral
smokeless tobacco as a substitute for cigarette smoking
[47]. One possible explanation for this phenomenon is
that U.S. smoker’s perceptions of smokeless products are
incorrect; indeed they are sceptical of the idea that snus is
safer than cigarettes [48]. Misleading information dissemi-
nated by government agencies and non-profit health orga-
nizations has made American consumers [49,50] and
health professionals [51] believe that smokeless tobacco is
as harmful as, if not even more harmful than, smoking.
Providing complete and truthful information could make
U.S. smokers more receptive to switching to this much
less harmful alternative.
The issue of abuse liability has been recently used
by opponents of THR to warn about potential risks
of smokeless tobacco products. Hatsukami et al. [52]
concluded that smokeless tobacco appears to have
slightly lower abuse liability, with possibly lower severity
of addiction or dependence compared with smoking and
greater ease of cessation. They also concluded that it may
be possible that switching from cigarettes to smokeless
tobacco would increase the potential for cessation from all
tobacco products. Fagerström and Eissenberg came to
similar conclusions in a recent comparison of dependence
among smokers, smokeless tobacco users and users of
medicinal nicotine [53]. Many former smokers in Sweden
have quit through using snus, suggesting it may be a more
Figure 1 Snus smoke-free tobacco. Snus is an oral tobacco
product that comes in a pouch of some sort, designed to be placed
between the gums and upper lip. Snus is not chewed and requires
no spitting. The standard pouch holds 1 gram of finely ground
tobacco. Snus is regulated as a food in Sweden, and thus held to
strict quality standards. Swedish snus was developed to greatly
reduce TSNA content, and research shows that snus does not
increase the risks of cancer of any type.
Polosa et al. Harm Reduction Journal 2013, 10:19 Page 3 of 11
http://www.harmreductionjournal.com/content/10/1/19

effective cessation aid, and a more attractive long-term
alternative to cigarettes, than pharmaceutical nicotine
because its nicotine delivery and social aspects are similar
to those of smoking [38,39,54]. Three small clinical trials
support the role of smokeless tobacco as a cessation
option for smokers. After reporting reduced TSNA exposure
among smokers given an American snus product or
Ariva (a dissolvable pellet), Mendoza-Baumgart et al.
[55] concluded that this low-nitrosamine smokeless
tobacco product has strong potential as a harm
reduction tool. In 2010 Caldwell et al. [56] tested the
acceptability of Swedish snus, nicotine gum and Zonnic
(a pouch containing 4 milligrams of nicotine embedded in
microcrystalline beads) among naive smokers in New
Zealand. They reported that all three products significantly
reduced craving for cigarettes, and all three enabled
subjects to reduce their smoking significantly, with
Zonnic and snus ranked higher than nicotine gum
for both quitting and reducing smoking. Hence, it is
not surprising that dissolvable tobacco products led
to a significant reduction (approx. 40%) in cigarettes
per day, no significant increases in total tobacco use, and
significant increases in two measures of readiness to quit
in a recent pilot randomized study [57].
The issue of abuse liability has been also used by
anti THR supporters to warn about potential risks of
e-cigarettes. However, in a recent randomized controlled
trial of 300 smokers [58], only 26.9% of those who switched
to e-cigs resulting in complete smoking abstinence were
still using the product by the end of the observational
period (week-52) with the 73.1% of users stopping vaping
as well. That many regular vapers were able to free
themselves also from the behavioral component of
smoking that was being reproduced by vaping the
product under investigation, indicates that the e-cigarettes
are not very "addictive".
Emerging tobacco harm reduction products: electronic
cigarettes
Use of electronic cigarettes (E-cigs) may prove to be an
even more attractive long-term alternative because of their
similarities to smoking, including the hand-to-mouth re-
petitive motion and the visual cue of a smoke-like vapour.
According to the WHO Study Group on Tobacco
Product Regulation, E-cigs are categorized as electronic
nicotine delivery systems (ENDS), devices designed for
the purpose of nicotine delivery to the respiratory
system where tobacco is not necessary for their operation
[59]. Awareness and use of E-cigs has increased exponen-
tially in the past four years. These devices, which are
manufactured and sold by several different companies,
consist of a lithium battery, electronic components, an
atomizer, and a cartridge that holds a liquid solution
composed of water, propylene glycol, flavourings, and
nicotine (Figure 2). Their popularity appears to be related
to the close similarities to smoking, the fact that they can
be used in smoke-free places, the competitive price, and
the perceived potential for harm reduction [60].
Cigarette smokers will keep smoking because of their
addiction and when given the options of smoking or
completely giving up nicotine, many will not give it up.
This rigid dichotomous scheme may be now considered
legacy of the past as many of them would be better off
using nicotine in a low-risk form. E-cigs may be an
additional tool for reducing tobacco related harm
when used to target smokers for whom current cessation
programmes have had only limited success [61]. E-cigs
also may be attractive to inveterate smokers who consider
their tobacco use a recreational habit that they wish to
maintain in a more benign form, rather than a problem to
be medically treated [62].
Toxicological characterization of e-cigarettes
The available evidence indicates that e-cigarettes do not
raise serious health concerns and can be considered a
much safer alternative to conventional smoking [63-66].
Detailed toxicology characterization of e-cigarette
liquid and vapour using gas chromatography mass
spectrometry (GC-MS) demonstrates that their primary
components are water, propylene glycol (PG), glycerin, and
nicotine [67]. In an independent study, Laugesen tested
E-cig mist for over 50 priority-listed cigarette smoke
toxicants and found none [64]. This report only revealed
traces (8.2 ng/g) of TSNAs in the “high”nicotine cartridge
of a Ruyan brand E-cig. However, it must be noted that
this amount is equal to the quantity reported to be present
in a nicotine medicinal patch [61] (Table 1).
FDA-commissioned testing of e-cigarette cartridge fluids
found diethylene glycol in one of the 18 e-cigarette
cartridges tested [68]. Formaldehyde, acetaldehyde, and
acroleine (potentially toxic carbonyl compounds) have been
detected in e-cigarette vapour in 12 brands of e-cigarettes
but at levels substantially lower than in cigarette smoke.
These compounds may be formed by the oxidation of
propylene glycol or glycerol when in contact with the
heating coil.
Cahn and Siegel [61] reviewed the results of 16 laboratory
analyses of E-cig liquid, including the FDA’sReportnoted
above . TSNAs were reported in two studies, but at trace
levels, which are similar to those found in a nicotine patch,
and, most importantly, about 500-fold to 1400-fold
lower than TSNA levels measured in regular cigarettes
(E-cigs containing only 0.07–0.2% of the TSNAs
present in cigarettes) (Table 1).
It must be however noted that the e-cigarette industry
is now adopting improved manufacturing standards.
According to American e-liquid Manufacturing Standards
Association (AESMA), liquids produced before 2013
Polosa et al. Harm Reduction Journal 2013, 10:19 Page 4 of 11
http://www.harmreductionjournal.com/content/10/1/19

were largely inaccurate, whereas newest products have
substantially improved in term of purity, consistency
and accuracy of nicotine content.
For example, [69] in a recent analysis of 20 refill
liquids of 10 of the most popular brands have shown
that the nicotine content in the bottles corresponded
closely to the labels on the bottles with levels of nicotine
degradation products being 1–2% for most samples. Also,
this analysis did not detect ethylene glycol nor diethylene
glycol; for several brands the levels of impurities were
above the level set for nicotine products in the European
Pharmacopoeia, but below the level likely to cause harm.
E-cigarette vapour contains a number of potentially
toxic compounds. Testing on some devices has found
tobacco-specific nitrosamines (TSNAs) [70]) and poly-
cyclic aromatic hydrocarbons present in cartridge fluid,
but generally in very low levels, similar to those in
nicotine replacement therapy [64,68,71].
Cadmium, lead and nickel have also been detected in
vapour but in trace levels only, comparable with levels
found in Nicorette inhaler [72]. Metal and silicate parti-
cles were detected in fluid and vapour from e-cigarette
cartomisers obtained from one manufacturer over
several years, leading to exposure to amounts of these par-
ticles equal to or higher than users of tobacco cigarettes
might typically experience [73].
In essence, these products appear to be much safer
than tobacco cigarettes and comparable in toxicity to
conventional nicotine replacement products. Of note, re-
tailers have already sold hundreds of thousands of E-cigs
with no evidence that these products have endangered
anyone when used as directed. Although there is no
indication that E-cigs are any more an immediate threat
to public health and safety than traditional cigarettes,
which are readily available to the public, the current data
is insufficient to conclude that E-cigs are safe in absolute
terms, and further studies are needed to comprehensively
assess their safety, particularly in the long term.
E-cigarette studies
The E-cig is a very hot topic that has generated consider-
able global debate, with authorities wanting to ban it or at
least regulate it. Consequently, a formal demonstration
supporting the efficacy and safety of these devices in clinical
trials would be of utmost importance.
Table 1 Summary data of maximum tabacco-specific
nitrosamine levels in various cigarettes and
nicotine-delivery products includine electronic
cigarettes (ng/g, except for nicotine gum and patch
that are ng/gum piece and ng/patch) –Modified by
Khan Z et al.J Public Health Policy 2011
Product NNN NNK NAT NAB
Nicorette gum (4 mg) 2.00 ND ND ND
NicoDerm CQ patch (4 mg) ND 8.00 ND ND
Electronic cigarettes 3.87 1.46 2.16 0.69
Swedish snus 980.00 180.00 790.00 60.00
Winston (full) 2200.00 580.00 560.00 25.00
Marlboro (full) 2900.00 960.00 2300.00 100.00
Camel (full) 2500.00 900.00 1700.00 91.00
Marlboro (ultra-light) 2900.00 750.00 1100.00 58.00
NNN, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone;
NNK, N’-nitrosonornicotine.
NAT, N’-nitrosoanatabine; NAB, N’-nitrosoanabasine.
ND, Not detected.
Figure 2 Structure of a standard entry model electronic-cigarette (e-Cigarette). The e-Cigarette is a battery-powered electronic nicotine
delivery device (ENDD) resembling a cigarette designed for the purpose of providing inhaled doses of nicotine by way of a vaporized solution. The
product provides a flavor and physical sensation similar to that of inhaled tobacco smoke, while no smoke or combustion is actually involved in its
operation. It is composed of the following key components: (1) the inhaler –also known as ‘cartridge’(a disposable plastic mouthpiece - resembling a
tobacco cigarette’s filter containing an absorbent material saturated with a liquid solution of propylene glycol and vegetable glycerin in which it may
be dissolved nicotine); (2) the atomizing device (the heating element that vaporizes the liquid in the mouthpiece and generates the mist with each
puff); (3) the battery component (the body of the device - resembling a tobacco cigarette –which houses a lithium-ion re-chargeable battery to
power the atomizer). The body of the device also houses an electronic airflow sensor to automatically activate the heating element upon inhalation
and to light up a red LED indicator to signal activation of the device with each puff. The LED indicator also signals low battery charge.
Polosa et al. Harm Reduction Journal 2013, 10:19 Page 5 of 11
http://www.harmreductionjournal.com/content/10/1/19

One of the earliest clinical trials of electronic cigarettes
was conducted at the University of Auckland, New
Zealand. Forty adult smokers of 10 or more cigarettes
per day were randomized to use an E-cig containing
16 mg of nicotine or 0 mg of nicotine (placebo), a
Nicorette nicotine inhalator, or their own brand cigarette.
The 16 mg E-cig alleviated desire to smoke after overnight
abstinence, was well tolerated and exhibited a pharmacoki-
netic profile more like the Nicorette inhalator than a
tobacco cigarette [74]. In a small preliminary study of
16 smokers comparing two brands of E-cigs to the
participants’own brand, Eissenberg reported that 10
puffs from either brand delivered little to no nicotine
compared with 10 puffs from the regular brand [75].
A response to this letter pointed out that each puff
from an electronic cigarette delivers approximately
10% of the nicotine found in a puff of cigarette smoke
[76]. Therefore E-cigs users need to take more puffs than
smokers to raise blood nicotine levels. Final results of
Eissenberg’s study for 32 participants confirmed that no
measurable levels of nicotine or carbon monoxide were
detected in E-cigs users. However, both brands effectively
suppressed nicotine abstinence symptoms [77]. Recently
Vansickel and Eissenberg studied blood nicotine levels
and among subjects who used E-cigs according to a stand-
ard protocol after 12 hours of abstinence [78]. All subjects
were former smokers who had quit smoking 11 months
earlier and were veteran vapers. Blood nicotine levels
increased from 2 nanograms per milliliter (ng/ml) at base-
line to 10 ng/ml within 5 minutes of the first puff, and to
16 ng/ml at the end of the ad lib period of use. These
levels are very similar to those produced by cigarette
smoking, suggesting that a learning curve effect has to be
taken into account when discussing clinical studies with
E-cigs. Canadian researchers examined the reinforcing
effects of E-cigs with and without nicotine on 11 volunteers.
Participants reported a reduction in craving, regardless of
the nicotine content [79]. Our recent smoking cessation
study with a plastic nicotine-free inhalator, suggests
that E-cigs can serve as an effective smoking replacement
for some smokers, even if no nicotine is present [80].
Japanese researchers conducted a safety assessment of
E-cigs with 32 smokers and found that following the
treatment, no abnormal changes in blood pressure,
hematological data, or blood chemistry and no severe
adverse events were observed [62]. In a prospective
proof-of-concept study, we monitored for 6 months
possible modifications in smoking habits of 40 smokers
not willing to quit who experimented with a 7.4 mg
nicotine/cartridge E-cig [60]. Combined sustained
smoking reduction and smoking abstinence was shown in
22/40 (55%) participants, with an overall 88% fall in
cigs/day. Mouth and throat irritation, and dry cough
were common, but diminished substantially by the
end of the study. Participants’perception and acceptance
of the product was good.
That these results could be maintained for at least
24 months by adopting newer more efficient models as
improved smoking sensation aids [81] indicates that
these products have potential for efficient long-term
substitution for smoking.
In a recent prospective 12-month randomized control
design study (ECLAT study) we have just collected the
data of E-cigs with 7.2 mg, 5.4 mg and 0 mg nicotine
cartridges to measure smoking reduction or abstinence
in 300 smokers unwilling to quit Declines in cig/day use
and eCO levels were observed at each study visits in
all three study groups (p,0.001 vs baseline), with no
consistent differences among study groups. Smoking
reduction was documented in 22.3% and 10.3% at week-12
and week-52 respectively. Complete abstinence from
tobacco smoking was documented in 10.7% and 8.7%
at week-12 and week-52 respectively. A substantial
decrease in adverse events from baseline was observed and
withdrawal symptoms were infrequently reported during
the study [58].
In another recent randomized controlled trial, Bullen
and coll. [82,83] randomised 657 adult smokers wanting
to quit to 16 mg nicotine e-cigarettes (as needed), 21 mg
nicotine patches (one per day), or placebo e-cigarettes
(no nicotine, as needed) in a 4:4:1 ratio. Participants,
who all lived in Auckland, New Zealand, could access
the national Quitline (a telephone counselling service),
but received no additional support. At 6 months,
7.3% participants in the nicotine e-cigarettes group had
achieved biochemically verified abstinence, compared with
5.8% participants in the patches group, and 4.1% in the
placebo e-cigarettes group. However, the statistical
power was insufficient to conclude superiority of nicotine
e-cigarettes to patches or to placebo e-cigarettes. As for
other clinical studies with e-cigarettes, adverse events
were very mild.
Several surveys [84-86] paint a picture of the typical
e-cig consumer as a long-term smoker who tried
repeatedly to quit. The median age of respondents
ranges from late 30s to mid 40s. The percentage of
respondents using e-cigs as a complete replacement
for smoking ranged from 31% to 79%. Etter and
Bullen found that 77% of daily users were former
smokers, and 19% who were still daily smokers re-
duced their cigarettes per day from 25 to 15. The
most-used flavour was tobacco, but 61% preferred
various fruit flavours, coffee, vanilla, and chocolate [86].
Over 90% of respondents reported that their health
has improved. When asked the main reason why they
chose to use an e-cig, 64.6% selected “to continue to
have a ‘smoking’experience, but with reduced health
risks.”[85].
Polosa et al. Harm Reduction Journal 2013, 10:19 Page 6 of 11
http://www.harmreductionjournal.com/content/10/1/19

Discussion
E-cigs might be the most promising product for tobacco
harm reduction to date. E-cigs deliver a nicotine vapour
without the combustion products that are responsible for
nearly all of smoking’s damaging effects (Figure 3).
Temperatures of approximately 1.000 °C are generated
with each puff of a lit cigarette, and thousands of toxic
chemicals are produced during the combustion process
[87]. In contrast, E-cigs use vaporization, rather than com-
bustion, and the low operating temperature of the atomizer
(up to 160 °C, depending on the model) does not emit
cigarette toxicants [64]. Therefore, the health risks are
likely to be similar to those from smokeless tobacco, which
has approximately 1% of the mortality risk of smoking
[49]. E-cigs may contain nicotine, which contributes to
nicotine addiction and helps sustain tobacco use. However,
if sufficient numbers of smokers can transfer their nicotine
dependence to a less-harmful delivery method, millions of
lives could be saved. The positive aspects of E-cigs appear
to outweigh the negative aspects (Table 2).
Nonetheless, websites that provide information about
the health risks of smokeless tobacco, have conflated
these risks with the risks of smoking, misleading the public
and smokers into believing that there is no potential for
harm reduction by switching from smoked to smokeless
products [49]. Yet, evidence continues to emerge that snus
is an effective harm-reduction strategy [88]. Similar
deceptive advice is being given to smokers who might be
thinking about switching to E-cigs [89]. Foulds et al. [90]
found that 78% of E-cig users they interviewed had not
used any tobacco in the prior 30 days, but they still ad-
vised smokers to use proven treatments (e.g. counselling
and FDA-approved drugs). This is a bizarre advice, in view
of the fact that the subjects they interviewed had tried to
quit smoking an average of nine times before taking up
use of an E-cig, and two-thirds had tried to quit with an
FDA-approved smoking cessation medication [90].
With the excuse of safeguarding public health and
guiding regulatory strategies, extensive research on product
design, toxicant exposure, abuseliability,youthinitiation,
and influence on cessation efforts has been advocated [91].
Thus it appears that the same tactics that are being
used to keep less hazardous products such as snus
from being widely adopted by smokers are being used
Developed by the Consumer Advocates for Smoke-free Alternatives Association –CASAA.org
Figure 3 Medical Infograph. This Infograph compares the potential health risks of cigarette smoke with the health risks of vapor. Since
e-cigarette liquid contains only propylene glycol, vegetable glycerin, flavorings, and nicotine, the resulting vapor is unlikely to present any more
disease risk than medicinal nicotine products -- the risk of nicotine addiction. The many more toxic and carcinogenic ingredients in tobacco
smoke are linked to numerous health problems.
Polosa et al. Harm Reduction Journal 2013, 10:19 Page 7 of 11
http://www.harmreductionjournal.com/content/10/1/19

to combat switching to E-cigs. None of the toxicological
testing conducted in E-cigs has shown that users or
bystanders are exposed to harmful levels of toxins or
carcinogens. Any danger of toxicant contamination
can be averted by forcing manufacturers to adopt a
similar regulatory framework as for dietary supplements,
provided that no claims are made about prevention or
treatment of disease [92]. Under dietary supplement regu-
lation, manufacturers must show that a product is not
dangerous before introduction. Compliance with national
good manufacturing practice policies would ensure that
e-liquids are produced in a quality manner, do not contain
contaminants or impurities, are accurately labelled, and
are held under conditions to prevent adulteration. With
regard to marketing and safety of e-cigarettes' electronics,
batteries, and spare parts, these components are already
regulated by existing directives.
There is no evidence that large numbers of non-
smokers are purchasing or will purchase E-cigs and
become addicted to nicotine. E-cigs eliminate exposure to
the smoke toxicants responsible for nearly all smoking-
related diseases. Thus even if 50% of the non-smoking
population should decide to addict itself to nicotine
via an E-cig, the associated disease risks, if any, would be
minimal. Thus, “abuse liability”is a moot point in
this context.
Furthermore, E-cigs represent a middle ground between
nicotine maintenance using the most deadly of deliv-
ery mechanism, smoking, and the nicotine abstinence
demanded by the tobacco control community [93].
Fears that smokers who “might have quit altogether”
will instead switch to snus or E-cigs is further evidence
that the tobacco control community believes that total
abstinence is something that all smokers will eventually
embrace, and perhaps come to love. However, research
shows that many smokers are dependent on the beneficial
effects of nicotine to combat symptoms of underlying
conditions [10] and that long-term nicotine abstinence may
result in long-term discomfort for many smokers [94].
Summary
The dream of a tobacco-free, nicotine-free world is
just that—a dream. Nicotine’s beneficial effects include
correcting problems with concentration, attention and
memory, as well as improving symptoms of mood
impairments. Keeping such disabilities at bay right now
can be much stronger motivation to continue using
nicotine than any threats of diseases that may strike
years and years in the future.
Nicotine’s beneficial effects can be controlled, and the
detrimental effects of the smoky delivery system can be
attenuated, by providing the drug via less hazardous
delivery systems. Although more research is needed,
e-cigs appear to be effective cigarette substitutes for
inveterate smokers, and the health improvements
enjoyed by switchers do not differ from those enjoyed
by tobacco/nicotine abstainers.
It is of paramount importance that government and
trusted health authorities provide accurate and truthful
information about the relative risks of smoking and
Table 2 Positive and negative aspects of e-cigarettes
Positive Negative
Beneficial effects on health (improved exercise tolerance, and less cough) Small percent of the population is sensitive to propylene
glycol (dry mouth and throat)
No tobacco smoke odor or bad breath Some flavors (e.g. piña colada) have a lingering smell
Much less toxic than conventional cigarettes Trace amounts of contaminants and metals present in
some products
Mimics the “throat hit”sensation of inhaling smoke “Throat hit”sensation dependent on hardware used and
liquid composition
Replicates gestures or actions associated with smoking behavior Equipment is heavier than traditional cigarette and puffing
technique requires some training
Facilitates smoking abstinence Not all users manage to quit smoking or reduce consumption
of conventional cigarettes
Relieves withdrawal symptoms and craving for conventional cigarettes Relief of withdrawal symptoms varies, affected by quality of
equipment and nicotine strength of liquid
No risk to bystanders. Due to few studies on potential risk to bystanders, some communities
are outlawing indoor use
No ash, dirt, or burned clothes Environmental concern about safe disposal of cartridges
and batteries
Accessible prices (in the long run cheaper than conventional cigarettes) The intricacies of their use and maintenance may hinder
widespread adoption
Much improved self-regulatory framework by e-cigarettes industry Impending medicinal regulation in many countries
Polosa et al. Harm Reduction Journal 2013, 10:19 Page 8 of 11
http://www.harmreductionjournal.com/content/10/1/19

alternatives to smoking. If the public continues to be
misled about the risks of THR products, millions of
smokers will be dissuaded from switching to these much
less hazardous alternatives. One of us recently wrote
that, “It’s time to be honest with the 50 million Americans,
and hundreds of millions around the world, who use
tobacco. The benefits they get from tobacco are very
real. It’s time to abandon the myth that tobacco is
devoid of benefits, and to focus on how we can help
smokers continue to derive those benefits with a safer
delivery system”[95].
In the absence of regulatory standards, it is important
that currently marketed products are of high quality.
For example, the hardware should be reliable and
should produce vapour consistently. The liquids should be
manufactured under sanitary conditions and use pharma-
ceutical grade ingredients, and labels should contain a list
of all ingredients and an accurate and standardized
description of the nicotine content.
According to a recent article by CDC researchers, the
proportion of U.S. adults who have ever used electronic
cigarettes more than quadrupled from 0.6% in 2009 to 2.7%
in 2010 with an estimated number of current electronic
cigarette users of about 2.5 million [96]. Although rigorous
studies are required to establish THR potential and long
term safety of electronic cigarettes, these figures clearly
suggest that smokers are finding these products helpful. If
they were ineffective one would not expect the market to
take off as it is. Most importantly, even if this THR
product proves to be effective for only 25% of the
smoking population, it could save millions of lives
world-wide over the next ten years.
Competing interests
R.P. is Professor of Medicine and he is supported by the University of
Catania, Italy. He has received lecture fees and research funding from
GlaxoSmithKline and Pfizer, manufacturers of stop smoking mediactions. 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). B.R.’s
research is supported by unrestricted grants from tobacco manufacturers to
the University of Louisville, and by the Kentucky Research Challenge Trust
Fund. P.C. and C.R. are Assistant Professors and they are supported by the
University of Catania, Italy. M.M is researcher and she is supported by the
University of Catania, Italy. They have no relevant conflict of interest to
declare in relation to this work.
Authors’contributions
All authors revised the article critically for important intellectual content and
approved its final version.
Author details
1
Presidio G. Rodolico –Unità Operativa di Medicina Interna e Medicina
d’Urgenza, Centro per la Prevenzione e Cura del Tabagismo (CPCT), Azienda
Ospedaliero-Universitaria “Policlinico-Vittorio Emanuele”, Università di Catania,
Catania, Italy.
2
Institute of Internal Medicine, G. Rodolico Hospital,
Azienda Ospedaliero-Universitaria “Policlinico-Vittorio Emanuele”, Università
di Catania, Catania, Italy.
3
Department of Medicine, School of Medicine,
University of Louisville, Louisville, KY, USA.
Received: 12 November 2012 Accepted: 24 September 2013
Published: 4 October 2013
References
1. World Health Organization (WHO): Tobacco Fact Sheet N339 2011.
2. Doll R, Peto R, Boreham J, Sutherland I: Mortality in relation to smoking:
50 years' observations on male British doctors. BMJ 2004,
328(7436):1519–1528.
3. US Department of Health and Human Services: The health consequences of
smoking: a report of the surgeon general. Atlanta, GA: US 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; 2004.
4. World Health Organization (WHO): WHO Framework Convention on Tobacco
Control. Geneva: WHO Press; 2003. ISBN: 9241591013.
5. Hughes JR, Keely J, Naud S: Shape of the relapse curve and long-term
abstinence among untreated smokers. Addiction 2004, 99:29–38.
6. Casella G, Caponnetto P, Polosa R: Therapeutic advances in the treatment
of nicotine addiction: present and future. Ther Adv Chronic Dis 2010,
1(3):95–106.
7. NIH State-of-the-Science Conference Statement on Tobacco Use:
Prevention, Cessation, and Control. Ann Intern Med 2006, 145:839–844.
8. Etter JF, Burri M, Stapleton J: The impact of pharmaceutical company
funding on results of randomized trials of nicotine replacement therapy
for smoking cessation: a meta-analysis. Addiction 2007, 102(5):815–822.
9. Hays JT, Ebbert JO: Adverse effects and tolerability of medications for the
treatment of tobacco use and dependence. Drugs 2010,
70(18):2357–2372.
10. Tobacco Advisory Group of the Royal College of Physicians: Harm reduction
in nicotine addiction: Helping people who can’t quit. London: Royal College of
Physicians; 2007.
11. Bridgehead International, EQUIPP: Europe Quitting: Progress and Pathways.
London; 2011. Equip Report available at: http://www.ersnet.org/images/
stories/weekly/EQUIP_REPORT_COMPLETE.PDF.
12. Sweanor D, Alcabes P, Drucker E: Tobacco harm reduction: how rational
public policy could transform a pandemic. Int J Drug Pol 2007, 18:70–74.
13. Russell MAH: Realistic goals for smoking and health: a case for safer
smoking. Lancet 1974, 1:254–258.
14. Chapman S: Public health advocacy and tobacco Control: making smoking
history. Oxford: Blackwell; 2007.
15. Stratton K, Shetty P, Wallace R, et al:Clearing the smoke: assessing the science
base for tobacco harm reduction. Washington, DC: Institute of Medicine
National Academies Press; 2001.
16. Caponnetto P, Polosa R: Common predictors of smoking cessation in
clinical practice. Respir Med 2008, 102(8):1182–1192.
17. Bullen C, McRobbie H, Thornley S, et al:Working with what we have
before getting into bed with the tobacco industry. N Z Med J 2006,
119(1240):U2139.
18. Jorenby DE, Fiore MC, Smith SS, et al:Treating cigarette smoking with
smokeless tobacco: a flawed recommendation. Am J Med 1998,
104:499–500.
19. Vogt F, Hall S, Marteau TM: General practitioners’and family physicians’
negative beliefs and attitudes towards discussing smoking cessation
with patients: a systematic review. Addiction 2005, 100(10):1423–1431.
20. Polosa R, Benowitz NL: Treatment of nicotine addiction: present
therapeutic options and pipeline developments. Trends Pharmacol Sci
2011, 32(5):281–289.
21. Mottillo S, Filion KB, Bélisle P, Joseph L, et al:Behavioural interventions for
smoking cessation: a meta-analysis of randomized controlled trials.
Eur Heart J 2009, 30(6):718–730.
22. Britton J: Smokeless tobacco: friend or foe? Addiction 2003, 98:1199–1201.
discussion 1204–1197.
23. Russell MAH, Jarvis MJ, Devitt G, Feyerabend C: Nicotine intake by snuff
users. BMJ 1981, 283:814–817.
24. CDC, USDHHS: Tobacco use compared to other drug dependencies. In
The Health Consequences of Smoking: Nicotine Addiction. Rockville, MD: A
Report of the Surgeon General Volume Chapter V. U.S. Department of
Health and Human Services, Centers for Disease Contro; 1988.
25. Gehricke JG, Loughlin SE, Whalen CK, et al:Smoking to self-medicate
attentional and emotional dysfunctions. Nicotine Tob Res 2007,
9(Suppl 4):S523–S536.
Polosa et al. Harm Reduction Journal 2013, 10:19 Page 9 of 11
http://www.harmreductionjournal.com/content/10/1/19

26. Benowitz N: Nicotine Safety and Toxicity. Oxford (UK): Oxford University
Press; 1998.
27. Coleman T, Chamberlain C, Cooper S, et al:Efficacy and safety of nicotine
replacement therapy for smoking cessation in pregnancy: systematic
review and meta-analysis. Addiction 2011, 106(1):52–61.
28. Forinash AB, Pitlick JM, Clark K, et al:Nicotine replacement therapy effect
on pregnancy outcomes. Ann Pharmacother 2010, 44(11):1817–1821.
29. Osadchy A, Kazmin A, Koren G: Nicotine replacement therapy during
pregnancy: recommended or not recommended? J Obstet Gynaecol Can
2009, 31(8):744–747.
30. McGrath J, McDonald JW, Macdonald JK: Transdermal nicotine for
induction of remission in ulcerative colitis. Cochrane Database Syst Rev
2004, 18(4):CD004722.
31. Silver AA, Shytle RD, Philipp MK, et al:Transdermal nicotine and
haloperidol in Tourette's disorder: a double-blind placebo-controlled
study. J Clin Psychiatry 2001, 62(9):707–714.
32. Mihailescu S, Drucker-Colín R: Nicotine, brain nicotinic receptors, and
neuropsychiatric disorders. Arch Med Res 2000, 31(2):131–144.
33. Multi-criteria Decision Analysis: A new approach to evaluating the harm
caused by nicotine delivery products. http://www.drugscience.org.uk/external-
resources/nicotine-mcda-briefing/.
34. Henningfield JE: Nicotine medications for smoking cessation. N Engl J
Med 1995, 333(18):1196–1203.
35. Dale LC, Hurt RD, Offord KP, Lawson GM, Croghan IT, Schroeder DR: High
dose nicotine patch therapy: percentage of replacement and smoking
cessation. JAMA 1995, 274:1353–1358.
36. Österdahl B-G, Jansson C, Paccou A: Decreased levels of tobacco specific
N-nitrosamines in moist snuff on the Swedish market. J Agric Food Chem
2004, 52:5085–5088.
37. St Helen G, Novalen M, Heitjan DF: Reproducibility of the nicotine
metabolite ratio in cigarette smokers. Cancer Epidemiol Biomarkers Prev
2012, 21(7):1105–1114.
38. Norberg M, Lundqvist G, Nilsson M: Changing patterns of tobacco use in a
middle-aged population: the role of snus, gender, age, and education.
Glob Health Action 2011, 4: doi:10.3402/gha.v4i0.5613.
39. Stegmayr B, Eliasson M, Rodu B: The decline of smoking in northern
Sweden. Scand J Public Health 2005, 33(4):321–324.
40. Foulds J, Ramström L, Burke M, et al:Effect of smokeless tobacco (snus)
on smoking and public health in Sweden. Tob Control 2003, 12:349–359.
41. Ten years of Swedish public health policy –Summary report. Swedish National
Institute of Public Health 2013. http://www.fhi.se/en/.
42. Furberg H, Lichtenstein P, Pedersen NL, et al:Cigarettes and oral snuff use
in Sweden: Prevalence and transitions. Addiction 2006, 101(10):1509–1515.
43. Ramström LM, Foulds J: Role of snus in initiation and cessation of
tobacco smoking in Sweden. Tob Control 2006, 15:210–214.
44. Peto R, Lopez AD, Boreham J, Thun M: Mortality from smoking in developed
countries 1950–2000: Sweden. 2nd edition. 2006. http://www.ctsu.ox.ac.uk/
deathsfromsmoking/download%20files/Country%20presentations/Sweden/
Sweden%20data.pdf.
45. Roth D, Roth AB, Liu X: Health risks of smoking compared with Swedish
snus. Inhal Toxicol 2005, 17:741–748.
46. Lund KE, Scheffels J, McNeill A: The association between use of snus and
quit rates for smoking: results from seven Norwegian cross-sectional
studies. Addiction 2011, 106:162–167.
47. Timberlake DS: Are smokers receptive to using smokeless tobacco as a
substitute? Prev Med 2009, 49(2–3):229–232.
48. Bahreinifar S, Sheon NM, Ling PM: Is snus the same as dip? Smokers’
perceptions of new smokeless tobacco advertising. Tob Control.
doi:10.1136/tobaccocontrol-2011-050022.
49. Phillips CV, Wang C, Guenzel B: You might as well smoke; the misleading
and harmful public message about smokeless tobacco. BMC Public Health
2005, 5:31.
50. O'Connor RJ, McNeill A, Borland R, et al:Smokers' beliefs about the
relative safety of other tobacco products: findings from the ITC
collaboration. Nicotine Tob Res 2007, 9(10):1033–1042.
51. Peiper N, Stone R, van Zyl R, et al:University faculty perceptions of the
health risks related to cigarettes and smokeless tobacco. Drug Alcohol
Rev 2010, 29:121–130.
52. Hatsukami DK, Lemmonds C, Zhang Y, et al:Evaluation of carcinogen
exposure in people who used ‘reduced exposure’tobacco products.
J Natl Cancer Inst 2004, 96:844–852.
53. Fagerström K, Eissenberg T: Dependence on tobacco and nicotine
products: a case for product-specific assessment. Nic Tob Res 2012,
14(11):1382–1390.
54. Gilljam H, Galanti MR: Role of snus (oral moist snuff) in smoking cessation
and smoking reduction in Sweden. Addiction 2003, 98(9):1183–1189.
55. Mendoza-Baumgart MI, Tulunay OE, Hecht SS, et al:Pilot study on lower
nitrosamine smokeless tobacco products compared with medicinal
nicotine. Nic Tob Res 2007, 12:1309–1323.
56. Caldwell B, Burgess C, Crane J: Randomized crossover trial of the
acceptability of snus, nicotine gum, and Zonnic therapy for smoking
reduction in heavy smokers. Nic Tob Res 2010, 12:179–183.
57. Carpenter MJ, Gray KM: A pilot randomized study of smokeless tobacco
use among smokers not interested in quitting: changes in smoking
behavior and readiness to quit. Nic Tob Res 2010, 12:136–143.
58. Caponnetto P, Campagna D, Cibella F, Morjaria JB, Caruso M, Russo C,
Polosa R: EffiCiency and Safety of an eLectronic cigAreTte (ECLAT) as
Tobacco Cigarettes Substitute: A Prospective 12-Month Randomized
Control Design Study. PLoS ONE 2013, 8(6):e66317.
59. Food and Drug Administration: Brief in Opposition to Motion for Preliminary
Injunction. Washington DC: United States Food and Drug Administration;
2009. http://www.fda.gov/downloads/NewsEvents/PublicHealthFocus/
UCM173191.pdf.
60. Polosa R, Caponnetto P, Morjaria JB, et al:Effect of an electronic nicotine
delivery device (e-Cigarette) on smoking cessation and reduction: a
prospective pilot study. BMC Public Health 2011, 11:786.
61. Cahn Z, Siegel M: Electronic cigarettes as a harm reduction strategy for
tobacco control: a step forward or a repeat of past mistakes? J Public
Health Policy 2011, 32(1):16–31. Epub 2010 Dec 9.
62. Miura K, Kikukawa Y, Nakao T: Safety assessment of electronic cigarettes
in smokers. SEIKATSU EISEI (Journal of Urban Living and Health Association)
2011, 55(1):59–64.
63. Trehy M, Ye W, Hadwiger M, Moore T, Allgire JF, et al:Analysis of electronic
cigarette cartridges, refill solutions and smoke for nicotine and nicotine
related impurities. Journal of Liquid Chromatography & Related Technologies
2011, 34:1442–1458.
64. Laugesen M: Ruyan e-cigarette bench-top tests. Dublin: Poster: Society for
Research on Nicotine and Tobacco; 2009. http://www.healthnz.co.nz/
DublinEcigBenchtopHandout.pdf.
65. US Food and Drug Administration: FDA News Release, FDA and Public Health
Experts Warn About Electronic Cigarettes. 2009. http://www.fda.gov/
NewsEvents/Newsroom/PressAnnouncements/2009/ucm173222.htm.
66. Chen IL: FDA summary of adverse events on electronic cigarettes.
Nicotine Tob Res 2013, 15(2):615–616.
67. US Food and Drug Administration: Final Report on FDA Analyses. 2009.
http://www.fda.gov/downloads/Drugs/ScienceResearch/UCM173250.pdf.
68. Westenberger B: Evaluation of e-cigarettes. Rockville, MD: US Food and Drug
Administration, Center for Drug Evaluation and Research, Division of
Pharmaceutical Analysis; 2009.
69. Etter J-F, Zäther E, Svensson S: Analysis of refill liquids for electronic
cigarettes. Addiction 2013:. online first - doi:10.1111/add.12235.
70. Kim H-J, Shin H-S: Determination of tobacco-specific nitrosamines in
replacement liquids of electronic cigarettes by liquid chromatography-
tandem mass spectrometry. J Chromatogr A 2013, 1291:48–55.
71. Goniewicz M, Kuma T, Gawron M, Knysak J, Kosmider L: Nicotine levels in
electronic cigarettes. Nicotine Tob Res 2012, 15:158–166.
72. Goniewicz ML, Knysak J, Gawron M, Kosmider L, Sobczak A, Kurek J,
Prokopowicz A, Jablonska-Czapla M, Rosik-Dulewska C, Havel C, Jacob P III,
Benowitz N: Levels of selected carcinogens and toxicants in vapour from
electronic cigarettes. Tob Control 2013. doi:10.1136/tobaccocontrol-2012-
050859.
73. Williams M, Villarreal A, Bozhilov K, Lin S, Talbot P: Metal and silicate
particles including nanoparticles are present in electronic cigarettes
cartomizer fluid and aerosol. PLoS ONE 2013, 8:e57087. doi:10.1371/journal.
pone.0057987.
74. Bullen C, McRobbie H, Thornley S, et al:Effect of an electronic nicotine
delivery device (e cigarette) on desire to smoke and withdrawal, user
preferences and nicotine delivery: randomised cross-over trial.
Tob Control 2010, 19(2):98–103.
75. Eissenberg T: Electronic nicotine delivery devices: ineffective nicotine
delivery and craving suppression after acute administration. Tob Control
2010, 19(1):87–88.
Polosa et al. Harm Reduction Journal 2013, 10:19 Page 10 of 11
http://www.harmreductionjournal.com/content/10/1/19

76. Keller E: Known fact: electronic cigarettes deliver nicotine more slowly.
Tob Control 2010, 19(1):87–88.
77. Vansickel AR, Cobb CO, Weaver MF: A clinical laboratory model for
evaluating the acute effects of electronic "cigarettes": nicotine delivery
profile and cardiovascular and subjective effects. Cancer Epidemiol
Biomarkers Prev 2010, 19(8):1945–1953. Epub 2010 Jul 20.
78. Vansickel AR, Eissenberg T: Electronic cigarettes: effective nicotine delivery
after acute administration. Nic Tob Res 2013, 15(1):267–270.
79. Darredeau C, Campbell M, Temporale K: Subjective and reinforcing effects of
electronic cigarettes in male and female smokers. Bath, UK: 12th annual
meeting of the Society for Research on Nicotine and Tobacco Europe; 2010.
80. Caponnetto P, Cibella F, Mancuso S: Effect of a nicotine free inhalator as
part of a smoking cessation program. Eur Respir J 2011, 38(5):1005–1011.
81. Polosa R, Morjaria JB, Caponnetto P: Effectiveness and tolerability of
electronic cigarette in real-life: a 24-month prospective observational
study. Intern Emerg Med 2013. in press.
82. Bullen C, Howe C, Laugesen M, McRobbie H, Parag V, Williman J, Walker N:
Electronic cigarettes for smoking cessation: a randomised controlled
trial, in press. Published online. Lancet 2013. September 7, 2013.
http://dx.doi.org/10.1016/S0140-6736(13)61842-5.
83. Bullen C, Williman J, Howe C, Laugesen M, McRobbie H, Parag V, Walker N:
Study protocol for a randomised controlled trial of electronic cigarettes
versus nicotine patch for smoking cessation. BMC Public Health 2013,
13:210.
84. Etter JF: Electronic cigarettes: a survey of users. BMC Public Health 2010,
10:231.
85. Heavner K, Dunworth J, Bergen P: Electronic cigarettes (e-cigarettes) as potential
tobacco harm reduction products: results of an online survey of e-cigarette users.
Tob Harm Reduction [Internet]; working paper 011: [about 15 pp]. Available from:
http://www.tobaccoharmreduction.org/wpapers/011.htm.
86. Etter JF, Bullen C: Electronic cigarette: users profile, utilization, satisfaction
and perceived efficacy. Addiction 2011. doi:10.1111/j.1360-0443.2011.03505.
x. http://onlinelibrary.wiley.com/doi/10.1111/j.1360-0443.2011.03505.x/
abstract.
87. Baker RR: Smoke generation inside a burning cigarette: Modifying
combustion to develop cigarettes that may be less hazardous to health.
Prog Energy Combust Sci 2006, 32(4):373–385.
88. Joksic G, Spasojevic-Tisma V, Antic R, et al:Randomized, placebo-
controlled, double-blind trial of Swedish snus for smoking reduction and
cessation. Harm Reduct J 2011, 8(1):25.
89. Detroit Free Press: Harvard Medical School Adviser: Are e-cigarettes a safe
alternative? 2011. http://www.freep.com/article/20110918/FEATURES08/
109180413/Harvard-Medical-School-Adviser-e-cigarettes-safe-alternative.
90. Foulds J, Veldheer S, Berg A: Electronic cigarettes (e-cigs): views of
aficionados and clinical/public health perspectives. Int J Clin Pract 2011,
65(10):1037–1042.
91. Noel JK, Rees VW, Connolly GN: Electronic cigarettes: a new 'tobacco'
industry? Tob Control 2011, 20(1):81. Epub 2010 Oct 7.
92. Polosa R, Caponnetto P: Regulation of e-cigarettes: the users' perspective.
Lancet Res Medicine 2013, 1(7):e26. doi:10.1016/S2213-2600(13)70175-9.
93. Foulds J, Veldheer S: Commentary on Etter & Bullen (2011): Could E-cigs
become the ultimate nicotine maintenance device? Addiction 2011,
106:2029–2030.
94. Piasecki TM, Fiore MC, Baker TB: Profiles in discouragement: two studies of
variability in the time course of smoking withdrawal symptoms.
J Abnorm Psychol 1998, 107(2):238–251.
95. Rodu B: Tobacco Truth: The Proven Positive Effects of Nicotine and Tobacco.
http://rodutobaccotruth.blogspot.com/2010/05/proven-positive-effects-of-
nicotine-and.html.
96. Electronic nicotine delivery systems: adult use and awareness of the ‘e-cigarette’
in the USA. http://tobaccocontrol.bmj.com/content/early/2011/10/27/
tobaccocontrol-2011-050044.full.
doi:10.1186/1477-7517-10-19
Cite this article as: Polosa et al.:A fresh look at tobacco harm reduction:
the case for the electronic cigarette. Harm Reduction Journal 2013 10:19.
Submit your next manuscript to BioMed Central
and take full advantage of:
• Convenient online submission
• Thorough peer review
• No space constraints or color figure charges
• Immediate publication on acceptance
• Inclusion in PubMed, CAS, Scopus and Google Scholar
• Research which is freely available for redistribution
Submit your manuscript at
www.biomedcentral.com/submit
Polosa et al. Harm Reduction Journal 2013, 10:19 Page 11 of 11
http://www.harmreductionjournal.com/content/10/1/19