Tobacco harm reduction (THR) products and policies aim to prevent or reduce harm by promoting substitution of combustible tobacco with less hazardous non-combustible sources of nicotine to smokers who are unable or unwilling to quit smoking in response to conventional tobacco control measures [1]. Electronic cigarettes (e-cigarettes)—hand-held devices that use battery power to heat a solution of propylene glycol, glycerol and often flavorings and nicotine, to produce an aerosol that the user inhales—have, in several countries, rapidly grown in popularity among adults as an alternative to smoking conventional cigarettes [2–6]. E-cigarettes are now the most popular assisted method of quitting smoking in the USA, used in 35% of smokers’ most recent quit attempts. [7] By comparison, nicotine patches or gums were used in 25% of most recent quit attempts.

The ability to inhale e-cigarette vapor aerosol in a vast and growing variety of “characterizing flavors”—a distinguishable taste or aroma, other than the taste or aroma of tobacco—is thought to be a major feature accounting for the appeal of e-cigarettes to adult smokers as an alternative to continuing to smoke cigarettes. An estimated 7700 unique e-liquid flavors were available for purchase in 2014, comprising an assortment of fruit, sweet, candy, dessert, food, and drink flavors. [8] Under the Food and Drug Administration’s (FDA) final deeming rule, decisions as to whether authorizing marketing orders for flavored e-cigarette products would be appropriate for the protection of the public health must be based on a weighing of the risks and benefits to both users and non-users of tobacco products. FDA Commissioner, Scott Gottlieb, has stated “it possible for flavors to do both harm and good… On this issue, we see two sides – on the one hand, we need to know the role that flavors, including menthol, play in attracting youth to initiate tobacco use. But on the other hand, we also need to know whether…certain flavors may help adult cigarette smokers switch to potentially less harmful forms of nicotine delivery such as e-cigarettes” [9]. To this end, on March 21, 2018, FDA issued an advance notice of proposed rulemaking (ANPRM) to obtain information related to the role that flavors play in the population’s use of tobacco products. This ANPRM is seeking data, research results, comments, and other information about, among other things, the extent to which certain flavors may attract youth to initiate use of a tobacco product and the extent to which certain flavors may help adult cigarette smokers quit or reduce cigarette use and switch to potentially less harmful products. FDA is seeking this information to inform regulatory actions that FDA might take with respect to flavored tobacco products under the Federal Food, Drug, and Cosmetic Act (“FD&C Act”), as amended by the Tobacco Control Act.

Evidence from cross-sectional surveys of nationally representative samples of US adults and non-probabilistic surveys of dedicated e-cigarette users suggests that smokers tend to initiate e-cigarette use with tobacco-flavored e-cigarettes but transition to exclusive or predominant use of non-tobacco flavored products—particularly fruit, sweet, and dessert flavors—with increased frequency and duration of e-cigarette use [10, 11]. Data from the Population Assessment of Tobacco and Health (PATH) Study shows that the majority of daily e-cigarette users were currently using non-tobacco flavors and were significantly more likely than moderate and infrequent e-cigarette users to have initiated e-cigarette use with a non-tobacco flavor [10]. At the same time, daily e-cigarette use was associated with higher odds of being a former smoker. Another study found that most former smoking e-cigarette users initiated e-cigarette use with non-tobacco flavors, while initiation with tobacco flavors was more common for dual users [11]. These data may indicate that smokers who initiate e-cigarette use with a non-tobacco-flavored e-cigarette are more likely to become daily e-cigarette users, and in turn, more likely to quit smoking.

A separate analysis of PATH data found that young adult (aged 18–34) cigarette smokers at wave 1 (2013/14) who were using one non-tobacco/menthol flavor or multiple non-tobacco/menthol flavors in an e-cigarette at wave 2 (2014/15) were 2.5 and 3 times more likely to have quit or reduced smoking in the past year, respectively, compared to non-e-cigarette users [12]. Dedicated e-cigarette users who are also former smokers report that switching between flavors within the same day is common and that regular use of multiple e-liquid flavors was associated with significantly higher odds of having quit smoking [13]. E-cigarette flavor preferences also appear to vary by age and smoking status. In a nationally representative survey, young US adult (18–29 years) and older US adult (≥ 30 years) former smokers who had become exclusive e-cigarette users were significantly more likely than dual users of conventional cigarettes and e-cigarettes to have initiated e-cigarette use with a non-tobacco flavor (65.7 vs. 47.3%) [11]. Both former-smoking exclusive e-cigarette users and dual users reported significantly higher rates of current use of a non-tobacco-flavor—72.5 and 72.9%, respectively—compared to initiation, suggesting adult e-cigarette users gravitate towards the use of non-tobacco flavors as e-cigarette use continues, with only around one in ten adult current e-cigarette users using tobacco flavored e-cigarettes. Younger adults were significantly more likely to be currently using fruit (74%) and candy and dessert (50%) flavors than were older adults (47 and 27%, respectively). Older adults were significantly more likely than younger adults to be using tobacco-flavored e-cigarettes (13 vs. 1%). Additionally, exclusive e-cigarette users were more likely than dual users to endorse “liking of flavors” as a reason for current e-cigarette use (69.8 vs. 48.9%), suggesting the use of non-tobacco flavors may be positively associated with smokers’ likelihood of transitioning to exclusive e-cigarette use.

Despite evidence of a potential role of non-tobacco e-cigarette flavors in helping adults to quit or reduce cigarette smoking, the same concerns that led the US Congress to ban the sale of cigarettes with characterizing flavors in 2009 now exist for e-cigarettes. In particular, concerns have been raised that fruit and sweet e-liquid flavors will attract youth and non-smokers to e-cigarette use, that use of flavored e-cigarettes will habituate youth to the effects of nicotine, and in turn, youth who would otherwise not have smoked in the absence of flavored e-cigarettes will “graduate” to use of more harmful tobacco products, such as cigarettes, that deliver nicotine more efficiently [14]. These concerns are borne from data that show the majority of youth and young adults who have ever tried an e-cigarette started their use with fruit or sweet flavors rather than a tobacco flavor and that rates of use of flavored tobacco products are higher among youth and young adults than among older adults [15–18]. Other research suggests adolescents’ intentions to try using e-cigarettes are linked to the availability of non-tobacco flavors [19, 20]. Concerns have also been raised about the long-term health effects of inhalation of e-cigarette flavorings [13].

While the Tobacco Control Act does not ban the sale of flavored e-cigarette products, it does not pre-empt state and local governments from restricting or banning the sale of these products. The city of Chicago, for example, in 2013 adopted an ordinance that prohibited the sale of flavored tobacco products, including menthol cigarettes and e-cigarettes, within 500 ft of schools [21]. In June 2017, the city of San Francisco became the first US city to sign into law an ordinance prohibiting the sale of all flavored tobacco products, including all flavors of e-liquid except tobacco flavor [22]. This ordinance came into effect in April 2018, though the fate of the ordinance will be decided by San Francisco voters after a petition drive by R.J. Reynolds Tobacco Company gained enough signatures to put the ordinance on a ballot in San Francisco County on June 5, 2018 [23]. Both the Chicago and San Francisco ordinances were adopted as precautionary measures in the absence of an established scientific basis for estimating that restricting the use and availability of e-cigarettes in characterizing flavors would be appropriate for the benefit and protection of the public health. The ANPRM recently announced by FDA represents the first steps to establishing a scientific basis for the regulation of flavors in tobacco products, including e-cigarettes, that weighs the risks and benefits of flavored e-cigarettes to the population as a whole, including their appeal to, use by, and effect of the tobacco use behaviors of current users, former users, and non-users of tobacco products.

The present study sought to obtain information on the flavor preferences of frequent e-cigarette users for two main reasons. First, frequent e-cigarette users should be at greater risk of being harmed by and addicted to e-cigarettes compared to infrequent users and former users. Understanding the extent to which different flavors are used by this sub-group, and the effect that frequent use of different flavors has on cigarette smoking, is therefore of great importance to assessing the likelihood that frequent use of different e-cigarette flavors is likely to add or reduce risk of harm to users. Second, much of what is known about the flavor preferences of e-cigarette users is based on surveys of nationally representative samples that are largely comprised of infrequent e-cigarette users. The extent to which the flavor preferences of infrequent e-cigarette users apply to frequent e-cigarette users is unclear.

Assessing the first use and current use of flavored e-cigarettes and e-liquids among current smokers, former smokers, and never smokers who currently use e-cigarettes on a frequent basis can therefore help inform the potential population health impact of these products. The purpose of the present study was to assess the first e-cigarette flavor and current e-cigarette flavors used by a large non-probabilistic sample of adult frequent users of e-cigarettes in the USA.

This study assessed first and current use of tobacco and non-tobacco e-cigarette flavors by a non-probabilistic sample of 20,836 adults in the USA who were using e-cigarettes on a frequent basis, of whom 15,807 (75.9%) had completely switched from smoking cigarettes to using e-cigarettes. Results indicated that adults who have completely switched from smoking cigarettes to using e-cigarettes in the past 5 years are increasingly likely to have initiated e-cigarette use with vapor products not flavored to taste like tobacco. E-cigarette flavors that are not available through cigarettes—particularly fruit, dessert, and pastry flavors—were found to have increasingly replaced tobacco and menthol as the preferred flavors with which adult smokers, former smokers, and never smokers have initiated e-cigarette use.

Between 2011 and 2016, the proportion of first e-cigarette purchases that were flavored to taste like a fruit had almost doubled, while tobacco-flavored first e-cigarette purchases had almost halved. These data suggest a transition in flavor preference at e-cigarette use initiation over time, from tobacco to non-tobacco flavors, which is consistent with data from a US nationally representative survey that found both former-smoking exclusive e-cigarette users and dual users reported significantly higher rates of current use of a non-tobacco-flavor—72.5 and 72.9%, respectively—compared to initiation [11]. The proportions of switchers and dual users who initiated e-cigarette use with fruit flavors did not significantly differ among those who initiated e-cigarette use after 2011. This finding contrasts with the data from a US nationally representative survey that showed former smokers who had become exclusive e-cigarette users were significantly more likely than dual users of conventional cigarettes and e-cigarettes to have initiated e-cigarette use with a non-tobacco flavor (65.7 vs. 47.3%) [11]. One potential explanation for these contrasting findings is the different frequencies of e-cigarette use in the samples analyzed; the majority of individuals in the US nationally representative sample were likely to have been infrequent e-cigarette users—i.e., used an e-cigarette on less than 20 of the past 30 days—whereas the present study included only frequent users. The present findings therefore indicate that switchers and dual users were equally likely to have initiated e-cigarette use with fruit-flavored e-cigarettes at any time after 2011, but both have been increasingly likely to have initiated e-cigarette use with a fruit-flavored e-cigarette.

Current e-cigarette use among participants was dominated by use of non-tobacco flavors, mainly fruit/fruit beverage, dessert/pastry, and/or candy/chocolate/sweets flavors. Once the most popular first flavors purchased by switchers and dual users, tobacco and menthol/mint currently rank as the 5th and 6th most commonly used flavors. Comparable odds of current use of fruit/fruit beverage flavor were observed in switchers, dual users, and never smoker e-cigarette users. These findings suggest both that non-tobacco flavors are comparably attractive to smokers who may or may not intend to quit smoking as they are to non-smokers and that non-tobacco flavors are not more strongly associated with dual use (i.e., continuing to smoke) than they are with quitting smoking. Given that the taste of increasingly preferred e-cigarette flavors such as fruits, desserts, and pastries are very different from the taste of a conventional cigarette, the increasing likelihood that adults will initiate e-cigarette use and currently use an e-cigarette use with a non-tobacco flavor could have the beneficial effects of discouraging a return to smoking among adults who switch to e-cigarettes and discouraging non-smoking e-cigarette users from initiating cigarette use.

The positive association observed between the use of fruit flavor and time of first e-cigarette purchase suggests it is likely that future frequent e-cigarette use will be increasingly initiated with the use of non-tobacco flavors, regardless of the individual’s smoking history. Judgements on whether authorizing marketing of flavored e-cigarettes would be appropriate for the benefit and protection of the public health should account for the possibility that adults who have switched completely from smoking cigarettes to using e-cigarettes in non-tobacco flavors may not have attempted to switch to e-cigarettes, or perceived themselves as able to switch, had e-cigarettes only been available in the flavors that are available through conventional cigarettes. A tobacco regulatory policy that maintains adult smokers’ access to the existing market of non-tobacco flavors, and enables manufacturers to innovate existing flavors, could increase the popularity and effectiveness of e-cigarettes as a substitute for cigarette smoking.

A low rate of first use of an e-cigarette that was tobacco-flavored by those who had quit smoking completely prior to their first use of an e-cigarette was observed. A possible explanation for this is that these individuals, having already quit smoking completely, wished to resume using nicotine by inhalation but did not wish to taste a tobacco flavor that has, for them, historically functioned as a conditioned stimulus for smoking thoughts and memories, and in turn, cravings. To the extent that this explains part of these former smokers’ reasons for initiating e-cigarette use with non-tobacco flavored e-cigarettes/e-liquids, then restricting access to non-tobacco flavors may remove a method that many former smokers have found effective for attenuating nicotine cravings and preventing relapse to smoking, and so in turn, increase the likelihood that former smokers will resume cigarette smoking to satisfy nicotine cravings.

This study also identified rapid changes in patterns of e-cigarette use over time that highlight the need for policymakers and researchers to continually update their understanding of smokers’ changing preferences for using e-cigarettes of different styles, formats, and performance capabilities. There is also a need for research to better understand smokers’ objections and barriers to switching to e-cigarettes and other proven and potentially less harmful sources of nicotine, and to respond with policies that are more likely to rationalize a switch away from conventional cigarettes, both among those who are open to giving up smoking if offered an appealing alternative to cigarettes and to those who appear to be hardened against ever stopping smoking.

Above all, there is a need to continually study the effect on adult and youth smoking rates of legislation and regulatory frameworks that either maintain or restrict access to a diverse variety of e-cigarette products that reflect users’ heterogeneity of preferences in terms of esthetic appeal (the look and feel of the device), sensory appeal (the taste and smell of vapor), and pharmacological appeal (the speed and efficiency of nicotine delivery).

This study identified an increasing popularity of non-tobacco flavors and declining popularity of tobacco flavors by over 15,000 adult frequent e-cigarette users who formerly smoked cigarettes. The findings suggest that access to a variety of non-tobacco flavored e-liquid may be important for encouraging and assisting adults to use e-cigarettes in place of conventional cigarettes. Restricting the availability of non-tobacco flavors could reduce adult smokers’ interest in switching to e-cigarettes or rationalize a return to cigarette smoking among frequent e-cigarette users whose journey towards smoking abstinence started with, progressed to, and is being sustained by frequent use of e-cigarettes containing non-tobacco flavors. A tobacco products regulatory framework that balances adult smokers’ increasingly common preference to try to quit smoking by using e-cigarettes that do not taste like cigarettes, with measures that reduce the appeal and use of e-cigarettes by non-smokers and youth, may accelerate the US progress towards the end of the tobacco smoking epidemic that causes the premature death of approximately 480,000 Americans each year [27].