9. Flavours in novel and emerging nicotine and tobacco products

Abstract

Nicotine and tobacco products contain characterizing flavours that mask their harshness, ease their use and increase their acceptability. Recent estimates indicate that flavour use is common, and thousands of flavours are now available for electronic nicotine delivery systems. Non-traditional flavours, like fruit and confectionery, are particularly appealing to young people, and use of these flavours is also increasing among adults, especially among adult smokers who are trying to quit smoking. Flavours in all nicotine and tobacco products have been shown not only to increase the appeal and first use of the products but may also contribute to extent of use, progression from experimental to regular use and dependence. Another concern is that chemicals in flavours may contribute to the toxicity of these products. Flavours are not regulated uniformly in nicotine and tobacco products or among countries. Some countries ban all flavours in all products, others have bans on only some flavours (e.g. excluding menthol), while others include only certain products (e.g. traditional products, such as cigarettes and smokeless tobacco) in regulations. This report on flavours in nicotine and tobacco products calls for adoption of common terminology for flavours in nicotine and tobacco products and consideration of policy for reducing the availability of flavoured nicotine and tobacco products on the market to those for which there is clear evidence of benefit in assisting smokers in quitting use of traditional smoked tobacco products.

9.1. Background and introduction

Addition of flavours to tobacco products dates back to the nineteenth century, when fruity flavours were added to smokeless tobacco products (1). Now, almost all nicotine and tobacco products, including traditional smoked tobacco products such as cigarettes and cigars, newer products such as snuff and snus, heated tobacco products (HTPs) and electronic nicotine delivery systems (ENDS) are available with a variety of flavours, which contributes to their increased appeal, the prevalence of use and the perception of reduced harm (2,3). Flavourings mask the harshness of nicotine and tobacco, ease their use and also reduce secondhand exposure to harsh odours, thus increasing their acceptability and potentially leading to progression and maintenance of dependence on these products. Flavourings also enhance the appeal of nicotine and tobacco products to novice users and vulnerable populations, thus increasing initiation and progression in the use of these products (4). The dual role that flavours play in enticing novice users, especially young people, to initiate nicotine and tobacco product use and in prolonging use by current users should be addressed by health authorities and public health communities to ensure the best regulations to address the inclusion of flavours in nicotine and tobacco products (5-8).

Flavoured nicotine and tobacco products are used all over the world. There is limited systematic evidence about their availability and use globally, and preferences for such products are often specific to countries and regions. For example, traditional cigarettes that contain cloves and oils (kretek) are highly popular in Indonesia, and spiced smokeless tobacco containing tobacco mixed with spices, oils, flavouring, betel nut and other ingredients (pan masala, gutka) is widely used in India. Hookah smoking, which involves heating heavily flavoured, sweetened tobacco, originated in India and the Middle East but has become increasingly popular among young people in Europe and North America.

Restrictions on the use of flavours in nicotine and tobacco products differ by country. Some countries, such as Brazil, Chile, Ethiopia, the Republic of Moldova, and some Canadian provinces restrict all flavours in nicotine and tobacco products, including menthol, although flavours that impart a port, wine, rum or whisky flavour are allowed in Canada (9). In May 2020, the European Union, with 28 Member States, implemented a ban on menthol cigarettes and roll-your-own tobacco (10). Brazil, Canada, Chile and Ethiopia include non-cigarette smoked products, such as little cigars and cigarillos, in flavour restrictions, while others, including those in the European Union, the Republic of Moldova and Turkey, do not extend the restrictions to products other than cigarettes and roll-your-own tobacco (11). There is also variation in whether menthol is included in restrictions; for example, while Brazil has banned all characterizing flavours (defined as flavours with a taste or aroma, apart from tobacco, distinguishable before, during or after tobacco consumption (12)), including menthol, in all tobacco products, in the USA, characterizing flavours except menthol are banned only in cigarettes and roll-your-own tobacco in most jurisdictions (13), although some localities (e.g. San Francisco, California) have banned all characterizing flavours, including menthol (14) in tobacco products. In the European Union, as in the Republic of Moldova, Turkey and the USA, this ruling does not extend to other tobacco products, such as cigars, cigarillos, little cigars and smokeless tobacco products (15).

ENDS may be regulated differently from tobacco products, as they do not contain tobacco. While WHO does not consider them to be tobacco products (16), some countries include these products under existing tobacco product laws, while others consider these products separately from tobacco products.

The sale of these products is banned in 30 countries, and several countries have regulations to restrict the availability of flavours (17) and limit the maximal nicotine concentration. Restrictions on the addition of flavours to pod-based ENDS were instituted in the USA in late 2019, but many states have local restrictions on sales of flavoured nicotine and tobacco products (18). The sale of nicotine-containing e-cigarettes is banned in some countries, including Australia and Japan (19). e-Cigarettes that do not contain nicotine are referred to as electronic non-nicotine delivery systems (ENNDS) and, depending on regulations, are still available with flavours. In countries in which ENDS are available, the rate of ENNDS use is reported to be low (20); as a result, they are often included with ENDS in evaluations of flavoured electronic systems. In this review, we have distinguished the two where possible in descriptions of the patterns of ENDS use.

Since the introduction of ENDS onto the global market in 2003, there has been renewed interest in the role of flavours. The popularity of ENDS has grown globally, but they are arguably most popular in Canada, Europe and the USA (21). ENDS are available in an ever-growing range of customizable e-liquid flavours. A study of the online ENDS marketplace in 2013–2014 found 7764 unique e-liquid flavours (22), and a follow-up in 2018 showed that the figure had doubled, to 15 586 flavours (23). The availability of ENDS has led to debate in the public health field about use of these devices to reduce harm by helping smokers quit use of more harmful traditional smoked tobacco products. The debate has carried over into one on the risk versus benefit of flavours in ENDS. Some researchers and advocates argue that addition of flavours to ENDS products is beneficial, as it may potentially help smokers to quit smoking (24-26), while others argue that the presence of flavours only enhances the appeal of these devices to young people and leads to increased use and dependence (26-29).

ENDS are not the only relatively new product on the market. Heated tobacco products (HTPs), which have unique characteristics but are tobacco products, emerged in their current iteration in 2013. These products do not have the variety of ENDS flavours but are marketed similarly, in that they are advertised as potential alternatives to traditional tobacco products.

Given the relatively recent appearance of HTPs on the market and the fact that they may be marketed as a lower-risk product, it is important to understand how flavours contribute to their appeal and use, especially among non-users and young people (30).

This report is an update to that in the seventh report of the WHO Study Group on Tobacco Product Regulation (31). We describe the epidemiology of flavoured products, the impact of flavours on appeal, experimentation and continual use of nicotine and tobacco products, the most commonly used flavours, their health effects and current regulation of flavours in these products.

9.2. Epidemiology of flavoured products (frequency, patterns and reasons for use by sociodemographic variables)

Although flavoured nicotine and tobacco products are used globally, there is limited systematic information on their use. Most of the information is for the USA, where surveys indicate high rates of use. The National Adult Tobacco Survey in 2013–2014 indicates that an estimated 10.2 million ENDS users (68.2%), 6.1 million hookah users (82.3%), 4.1 million cigar smokers (36.2%) and 4.0 million smokeless tobacco users (50.6%) had used flavoured products in the past 30 days (32). In the same survey, among cigarette smokers, the use of cigarettes flavoured with menthol (the only characterizing flavour in cigarettes in the USA at the time of the survey) was relatively high, comprising 39% of cigarettes used (33). Similar results were reported from a population-based survey in 2014–2015, which showed that 41.4% of nicotine and tobacco users reported use of flavoured products, ranging by product from 28.3% of cigar smokers to 87.2% of hookah users (34).

Limited data exist on global use of flavoured nicotine and tobacco products and are sorely needed to evaluate the scope of flavour use worldwide. Information should be generated on use of flavoured nicotine and tobacco products elsewhere in the world. Although data for the USA provide a reasonable estimate, the types of flavoured nicotine and tobacco products used and regulation of these products differ by country, which may affect the use of different flavours. The patterns of use of flavoured tobacco products may differ according to their availability and popularity. Nevertheless, there is a higher prevalence of use among adolescents and young adults than among older adults. Evidence on the epidemiology of flavour use in different tobacco products is described below.

9.2.1. Electronic nicotine and non-nicotine delivery systems

Flavours are increasingly available for use in ENDS, because of both the dynamic growth in the number of flavours available (23) and their popularity among adolescents and young adults (8). The Population Assessment of Tobacco and Health (PATH), a longitudinal national survey conducted in the USA, indicated that use of flavoured ENDS by current vapers was most prevalent among adolescents aged 12–17 (97%), followed by young adults aged 18–24 (97%) and adults aged ≥ 25 years (81%). A similar pattern was observed in initiation of ENDS products, 93% of adolescents, 84% of young adults and 55% of adults reporting initiation of ENDS with a flavoured product (35). These patterns of use of flavoured ENDS are confirmed by other studies (36-38) and recent reviews (39,40), which suggest that use of flavoured ENDS use is more prevalent among adolescents and young adults than among older adults. A report from the National Youth Tobacco Survey in the USA on tobacco product use by middle- and high-school students in 2019 indicated that use of flavours by current ENDS users was most prevalent among non-Hispanic white adolescents (77%) and similar among males (71%) and females (69%) (41).

Use of non-traditional flavours (i.e. other than tobacco or menthol flavours) is more prevalent among adolescents and young adults; however, a shift in flavour preferences towards non-traditional flavours appears to be occurring in all age groups. Wave 2 of the PATH study suggested that fruit flavours were the category most commonly reported by adolescents, and menthol or mint, a flavour traditionally found in tobacco products, was most commonly reported by adults (42). A follow-up study of wave 3 showed that fruit flavours were those most commonly used by both young and adult users and that dessert or confectionery was also highly popular among young and adult users (29). These findings are consistent with other recent work; specifically, evidence that fruit flavours are the most highly endorsed flavour category across age groups, including youth, young adults and adults (36,43,44). A study of long-term use of flavours in ENDS in the USA found that a preference for tobacco and menthol or mint flavours decreased over time, preference for fruit flavours remained stable, and preference for dessert and sweet flavours increased (45).

Research has also been conducted on the flavour preferences of ENDS users who are current or former users of other tobacco products (i.e. cigarettes). This is important because, particularly in Europe and the USA, there is debate about whether and how flavours reduce the appeal of ENDS for young people or enhance their appeal for users of tobacco products, such as cigarette smokers, who wish to switch to ENDS. Fruit flavours appear to be popular regardless of the type of tobacco use. A global Internet survey of former and current adult cigarette smokers found that, while fruit and sweet flavours were the most popular (69% and 61%, respectively), current cigarette smokers were more likely to report use of tobacco flavours and less likely to report use of fruit and sweet flavours than former cigarette smokers (24). In a study in New Zealand, fruit flavour was preferred by exclusive ENDS users, former cigarette smokers and current cigarette smokers (46). Even as flavour preferences appear to be shifting to non-traditional flavours in all age groups, it is important to note that the prevalence of use of non-traditional flavours in ENDS products appears still to be the highest among young people (47).

Many users of flavoured ENDS report that they use several flavours (e.g. fruit, dessert or confectionery, menthol or mint). A study of ENDS users in the USA suggested that multiple flavour use is more prevalent among adolescents (46%) than adults (32%) (29). In India, adult ENDS users reported a relatively high rate (65%) of use of several flavours (48). The global Internet survey of current and former adult cigarette smokers who used ENDS (24) indicated that switching between flavours was common; 68% reported switching at least daily, 16% weekly and 10% less than weekly.

Although there is limited evidence on use of flavoured ENNDS, a study among adolescents and young adults (18–29 years) in Japan, where these products are banned, indicated use by 4.3% of the group. Although flavour use was not directly studied, the main reason reported for using the product use was fruit flavours, suggesting that flavours are a reason for using ENNDS (49).

9.2.2. Traditional smoked and smokeless tobacco products

Although ENDS offer by far the most flavours of all nicotine and tobacco products, flavours are also used in other nicotine and tobacco products, both smokeless and smoked. As for ENDS, use of flavoured tobacco products is more prevalent among adolescents and young adults than adults. In a nationally representative sample of Canadian young people who used tobacco products (cigarettes, pipes, cigars, cigarillos, bidis, smokeless tobacco, hookah, blunts, roll-your-own cigarettes), 52% reported using flavoured products (50). Similarly, a national survey in Poland showed that younger smokers were more likely to use flavoured cigarettes (51). In the PATH study in the USA, about half of users of all ages who reported current use of cigarillos and filtered cigars said that they used a flavoured product, while relatively low proportions of current cigar smokers reported use of flavoured products, from 24% of adults, 27% of adolescents to 36% of young adults. In the same study, the proportions of those who reported that their first tobacco product had been flavoured were 68% of adolescents, 63% of young adults and 42% of adults for cigarillos; and 56% of adolescents, 54% of young adults and 40% of adults for filtered cigars. Among traditional cigar users, the overall prevalence was lower, but the graded effect of age was still evident, with 39% of adolescents, 35% of young adults and 22% adults reporting that their first product had been flavoured (35).

The types of flavours used in more traditional tobacco products were shown in 2013–2014 in the National Adult Tobacco Survey in the USA to be menthol or mint in smokeless tobacco (77%), fruit in hookah tobacco (74%); fruit (52%), confectionery, chocolate and other sweet flavours (22%) and alcohol (14%) in cigars, cigarillos and filtered little cigars; and fruit (57%), confectionery, chocolate and other sweet flavours (26%) and menthol or mint (25%) in pipe tobacco (32).

Capsules have been inserted in cigarettes to incorporate flavours other than traditional tobacco and menthol, and capsule cigarettes appear to be capturing a growing portion of the global market (52). The flavours range from menthol to green tea and whisky and others. Capsule cigarettes are popular among adolescents and young adult smokers. Over half of adolescent cigarette smokers in Australia reported capsule use (53), and young adults in the United Kingdom and the USA expressed a preference for these products (53,54). This may change, as flavour capsules have been banned in Brazil and the European Union since spring 2020 (55).

9.2.3. Heated tobacco products

HTPs have been developed since the 1960s in the USA and globally since the 1980s; however, the early products were unsuccessful. A new generation of HTPs has been marketed since 2013 (30), and they are currently available in about 50 countries, including Canada, Israel, Italy, Japan, the Republic of Korea and, most recently, the USA (56,57). HTPs contain flavours, which may increase their appeal and use (58). These devices produce aerosols containing nicotine and toxic chemicals when tobacco is heated or when a device containing tobacco is activated, and users inhale the aerosol by sucking or smoking. The products have been marketed as a safer alternative to combustible cigarettes (59). They have fewer flavour options than ENDS, the main choices being either tobacco or menthol; other flavour options include “mentholated-fruity” and coffee.

Japan has been a recent test markets for these products. Data from wave 1 of the International Tobacco Control Japan Survey, collected in 2018, indicated that the prevalence of HTP use was only 2.7%. The popularity of flavours appeared to be similar among exclusive HTP users and HTP users who used other products, menthol flavour being the most popular, followed by tobacco and mentholated-fruity flavour (60). Given the evidence that flavours increase the appeal of other nicotine and tobacco products, particularly for adolescents and young adults who do not use tobacco, the alarm has been sounded that these products might appeal as a function of their flavours (58). Comprehensive research should be conducted on the use of flavours in these products as the market for HTPs is extended to other countries.

9.3. Effects of flavours on appeal, experimentation, uptake and sustained use (See also section 3.)

9.3.1. Adolescents and young adults

Appeal

As adolescent and young adult tobacco product users appear to use flavoured products and ENDS at greater rates than adults (36,51), it is important to understand the appeal of these products to adolescents and how it may differ from that to adult users. Comparisons of smoked product use by age show that flavoured cigars, cigarettes and hookahs are more appealing to young than to adult users (61,62). Young people have reported that flavours are the main reason for both initiation and continued use of ENDS (63,64), and sweet and fruit-flavoured e-liquid solutions were more appealing to adolescents and young adults than non-sweet (e.g. tobacco-flavoured) e-liquids (65,66). Similarly, young people reported that flavours were the main reason for cigarillo use (67).

Notably, appeal for flavoured tobacco products may begin even before using the flavour. ENDS. Flavours in both smoked tobacco products and ENDS may appeal not only because of a positive experience associated with flavours (68-70) but also because they reduce the perceived risk of the harm of these products (71-75). ENDS are not only provided in non-traditional tobacco flavours but are also advertised with colourful images and appealing descriptions of the flavours. Functional magnetic resonance imaging showed that, in young adults susceptible to using ENDS, just viewing advertisements showing fruit, mint and sweet flavours for ENDS products increased activity in the nucleus acumens to a greater extent than advertisements for tobacco flavours. Heightened activity was also seen when participants viewed advertisements for non-ENDS fruit, mint and sweet flavours, indicating that the appeal of non-traditional flavours may begin before an ENDS is sampled and the advertisements may lead to initiation (76).

Experimentation, uptake and sustained use

Flavours may play an important role in initiation of ENDS use and progression by adolescents and young adults. Thus, initial use of flavoured ENDS was associated not only with continued use but also with more days of use, suggesting heavier use with time (77). In another study, preference for specific flavours and the total number of flavours used were associated with more days of ENDS use by young people and not by adult users (28), indicating that flavour preferences play a different role in adolescent use from that of adults. Sweet non-traditional flavours, in particular, appeal to young people and may contribute to the uptake and use of ENDS (28,37,63,78,79). In a study in young people, use of flavoured ENDS was associated with non-traditional flavours (i.e. not tobacco, mint or menthol) and continuation but not with the number of days of ENDS use over time, suggesting that use of non-traditional flavours may sustain use (37). This may be due in part to perceived sensory effects of non-traditional flavours. In a laboratory study of ENDS with six commercially available flavours, fruit flavours were considered the sweetest and tobacco flavour the most bitter. When flavours were rated for coolness and harshness, sweetness and coolness were positively correlated and harshness and bitterness negatively correlated with liking (80).

Flavours in nicotine and tobacco products may increase their addictive potential, which will sustain their use (81). It has been reported that green apple tobacco flavour in ENDS alters smoking behaviour, which may be associated with upregulation of nicotinic acetylcholine receptors (82), as suggested by a study of the biological mechanisms by which menthol alters tobacco smoking behaviour, including reinforcing sensory cues associated with nicotine, upregulating nicotinic acetylcholine receptors and altering nicotine metabolism to increase its bioavailability (83).

Initiation with flavoured ENDS results in continued, heavier use by young people, and this pattern may also occur with other tobacco products and in older age groups. Longitudinal results from the PATH study indicated that first use of a flavoured (i.e. menthol) cigarette was associated with continued cigarette use in adolescents, young adults and adult smokers, and, in young adults and adults, this pattern extended to other tobacco products. Thus, first use of a flavoured ENDS, cigar, cigarillo, filtered cigar, hookah or any smokeless tobacco was associated with continued use of the product (38).

9.3.2. Adults

Appeal

In adults, flavours also appear to contribute to the appeal of tobacco products. As in young people, flavoured ENDS products in particular appear to be highly appealing. In studies of ENDS users in the Netherlands, New Zealand and the USA, ENDS were rated as appealing as a function of the availability of flavours (46,84). A study of university students (from undergraduates to doctoral candidates) in the Asian–Pacific rim found that 34% of e-cigarettes users used the products because of the flavours offered (85). Flavours may contribute to the appeal in adults by raising positive expectancy about the product (86) and an overall positive perception among both users and non-users (87).

Experimentation, uptake and sustained use

Flavours play a role in uptake not only among adolescents and young adults but also among older adults. In a sample of adults (≥ 25 years), regular current use of flavoured cigarettes, cigars, cigarillos, filtered cigars, hookah, smokeless tobacco and e-cigarettes was associated with flavoured products but not with first use of a non-flavoured product, as among adolescents and younger adults (38). Smokeless tobacco users had a similar pattern of flavour use, whereby those who started with an unflavoured product were likely to switch to a flavoured product, while those who started with a flavoured product were likely to continue using it (88).

There is evidence in adults that the use of flavoured tobacco products leads to greater dependence, which contributes to sustained use. Two markers of dependence on tobacco products, daily use and time to first use in the morning, were associated with use of flavoured products in a survey in the USA in 2014–2015. The same study indicated that use of flavoured ENDS was more likely to be daily than use of unflavoured products. More users of flavoured cigars (large cigars, cigarillos and little cigars) than of unflavoured cigars reported first use in the morning within 30 min of waking (89).

Flavoured products may sustain use because they influence the reward and reduce the aversiveness of nicotine, the dependence-producing constituent in these products (90). There is extensive literature on the interaction of nicotine and menthol in combustible cigarettes, which suggests that menthol serves as a cue for the sensory effects of nicotine (91) and enhances both the reward from nicotine (92) and the withdrawal symptoms (93). This finding may indicate why menthol cigarette use is growing among smokers of combustible cigarettes even as overall use decreases (94) and why smokers of menthol cigarettes have more difficulty in quitting smoking (95). Fruit flavours in ENDS have been shown to enhance the reward and reinforcing effects of nicotine (78,96) and to suppress its aversive effects (97). Menthol flavours improve the taste of e-liquids in ENDS and make higher nicotine concentrations less aversive and more rewarding (96-98). Similar patterns have been observed for combustible products. Tobacco industry documents suggest that flavoured cigar products increase their appeal to naïve users by reducing throat irritation and making emissions easier to inhale (99).

Another mechanism that may sustain use is the perception that, in general, flavoured tobacco products, including ENDS, are less harmful than unflavoured tobacco products. Flavours in ENDS give a false perception of safety not only to users but also to bystanders (100). This attitude is, however, changing, as more voices rise for the inclusion of use of ENDS in designated smoke-free indoor areas, as second-hand aerosols from flavoured ENDS can leave pungent odours (101). Chemical and toxicological assessment of second-hand aerosols from flavoured ENDS is lagging behind their excessive use indoors and in public spaces (102,103).

Questions remain about the role of flavours in switching from conventional smoked products to other products, such as ENDS or HTPs. No studies have yet been reported on the relation between HTPs, flavours and switching behaviour. The flavours in ENDS may appeal to users of smoked products, and use of flavoured ENDS may be associated with a greater likelihood of short and longer attempts to quit use of smoked tobacco products (104,105). There have been no experimental investigations of the specific role ENDS flavours play in switching from traditional smoked products, although many describe the abuse liability of ENDS in adolescents and young adults and in users of noncombustible products. Proof is required to determine the role flavours in ENDS play in product switching.

9.4. Common flavours, properties, health effects and implications for public health

9.4.1. Common flavours in electronic nicotine delivery systems and tobacco products

The National Institute for Public Health and the Environment in The Netherlands has published a “flavour library” of flavours added to tobacco cigarettes and roll-your-own products (106). The flavours are listed in eight main categories: fruit, spice, herb, alcohol, menthol, sweet, floral and miscellaneous. A year later, a similar report was issued in which the authors classified flavours in ENDS into 13 categories: tobacco, menthol, fruit, dessert, alcohol, nut, spices, confectionery, coffee/tea, beverages, sweet-like flavours, unspecified and unflavoured (107). As noted above, the number of unique ENDS flavours on the market has increased dramatically in recent years, from 7764 in 2013–2014 to 15 586 in 2016–2017 (22,23). Unique to ENDS products, users commonly mix and match flavours in refillable ENDS (108), and “do-it-yourself” is common practice, sometimes with the addition of illicit substances (109), and researchers should also consider the impact of such additives on ENDS use.

9.4.2. Chemical and physical properties of common flavours in flavoured products

Flavour ingredients in tobacco cigarettes

The above-mentioned flavour library (106) includes chemical analyses of flavours in tobacco cigarettes and roll-your-own products. This complements analyses of the total tobacco matrix in cigarette filler. Identification of flavour ingredients in tobacco cigarettes and studies to assess their fate after pyrolysis have been reported (110).

Flavour additives in ENDS

Several studies have reported chemical profiling of flavoured ENDS liquids (111,112), indicating the complexity that flavours add to the ENDS matrix (113). Although no comprehensive study is available of the thousands of possible flavours, analysis of commercial flavours showed that some chemicals are commonly used in more than one flavour (114). A meta-analysis of the reported literature (115-117) was recently published by one of the authors of this report of the recurrence of certain chemicals, which indicates the frequency of chemicals such as ethyl maltol (47%), vanillin (37%), menthol (29%), ethyl vanillin (23%), linalool (23%), benzaldehyde (22%), benzyl alcohol (21%), maltol (20%), cinnamaldehyde (20%), ethyl butanoate (19%) and hydroxyacetone (16%). The work also describes the possible contributions of these flavouring additives to the toxicity of the aerosols generated by ENDS activation (115). Flavours are either distilled intact into the aerosol (their contribution to toxicity depends on their properties and emission levels) (118), react with ENDS carriers (propylene glycol and glycerol) to form acetal compounds with unique toxicological properties (119) or undergo thermal degradation to toxicants such as carbonyls (120), reactive oxygen species (121) and volatile organic compounds (122). The gas–particle-phase partitioning coefficients of several flavour ingredients have been determined; they are relevant to assessment of toxicity as they may determine the site of absorption of these chemicals into the body (123).

Flavours added to ENDS not only impart a specific flavour but also increase sweetness (e.g. sucrose) (124), as observed in other products, including smokeless products (125) and cigars (126). Sweeteners, including artificial ones (e.g. sucralose), can increase the appeal of nicotine and tobacco products (65), although there is limited evidence for direct effects of sweeteners (127).

Flavours in other tobacco products

Flavour additives in smokeless tobacco products have been addressed in two studies (128,129). Flavour compounds have also been identified and quantified in bidis (130), clove cigarettes (131) and flavoured waterpipe tobacco (132).

9.4.3. Toxicity of flavours

Flavours in ENDS can strongly increase the general toxicity of the aerosols (133). Several targeted analyses of ENDS liquids included quantification of diacetyl in nutty-flavoured ENDS liquids (134) and found that emission of this chemical and its inhalation by ENDS users increased their risk of bronchiolitis obliterans or “popcorn lung” disease (135). Some cherry-flavoured ENDS liquids expose users to benzaldehyde, albeit at low levels (136). To assess disease risk, the levels of these toxicants in ENDS aerosols are usually compared with workspace exposure limits. Toxicological assessment of flavours in ENDS liquids and aerosols, in cell lines and in animals, showed that flavours increase the toxicity of ENDS aerosols in various ways (121,137). One report showed that adducts of flavours with ENDS carriers are more cytotoxic than their parent flavour compounds (119).

Flavours may also increase the toxicity of ENDS aerosols by adding to toxicant emissions. For example, flavours in liquids increase emissions of carbonyl compounds and other compounds that are known or possible human carcinogens (120). Flavours also increase toxicity by disturbing the oxidative balance in the body, as they increase the presence of radicals and reactive oxygen species in ENDS aerosols over that produced by plain liquids composed only of carriers (138). This type of contribution to the toxicity of aerosols depends on the device operating parameters, such as power input and liquid composition (139), as higher power increases the temperature of the heating coil, resulting in greater degradation of flavour compounds.

At present, the net effect of flavours on the toxicity of emissions from tobacco and nicotine products cannot be determined for products other than ENDS.

9.5. Regulation of flavoured products

9.5.1. Global regulation of flavoured ENDS

The contentious issue of the impact of flavours on the acceptability of ENDS and satisfaction among smokers who are seeking cessation and on the appeal of ENDS for experimentation and continued use by young people is highly polarized and intense (81,140,141). This controversy is reflected in the different approaches used to tackle the ENDS use epidemic by public health authorities in different countries: flavours are banned, restricted or allowed (Table 9.1), depending on the authorities’ assessment of the available information and view of the arguments on both sides of the debate (142,143). Currently, about 100 countries regulate use of ENDS with new regulations or, mainly, by adapting regulations for other tobacco products (144). About 30 countries ban the marketing and sale of ENDS (145,146). A search in June 2020 on the website of the Institute for Global Tobacco Control at the Johns Hopkins Bloomberg School of Public Health in Baltimore (USA) indicated that the policies of 35 countries on ENDS referred to ingredients or flavours (147). Most focus on labelling and ensuring that high-quality ingredients are used, and only five, Canada, Finland, Luxembourg, Saudi Arabia and the USA, had specific regulations on flavours in ENDS (142). Finland bans characterizing flavours (e.g. fruity, confectionery) in all ENDS; Luxembourg’s policy prohibits additives that influence the perceptions of ENDS users with regard to health; Saudi Arabia allows fruit flavours and menthol but prohibits other characterizing flavours (e.g. cocoa, vanilla, coffee, tea, spices, confectionery, chewing-gum, cola and alcohol) (149), while the US Food and Drug Administration (FDA) has issued a policy banning all flavoured cartridge ENDS (except tobacco- and menthol-flavoured products) on the basis of evidence that flavours strongly influence young people’s use of ENDS, especially the extremely popular cartridge products (e.g. JUUL) (150). It also exempts the flavoured liquids used in open-system ENDS (150,151). Canada restricts marketing flavours that may appeal to young people, and, recently, the province of Nova Scotia banned flavoured ENDS; other provinces are considering doing the same (152,153).

Table 9.1.

Country regulatory approaches to flavoured e-cigarettes (as of June 2020)

Country	Regulation
Argentina, Australia, Azerbaijan, Bahrain, Barbados, Brazil, Brunei Darussalam, Cambodia, Chile, Colombia, Costa Rica, Ecuador, Egypt, El Salvador, Fiji, Gambia, Georgia, Honduras, Hungary, Iceland, India, Indonesia, Iran (Islamic Republic of), Israel, Jamaica, Japan, Jordan, Kuwait, Lao People’s Democratic Republic, Lebanon, Malaysia, Maldives, Mauritius, Mexico, Nepal, New Zealand, Nicaragua, Norway, Oman, Palau, Panama, Paraguay, Philippines, Qatar, Republic of Korea, Republic of Moldova, Seychelles, Singapore, South Africa, Sri Lanka, Suriname, Switzerland, Syrian Arab Republic, Tajikistan, Thailand, Timor-Leste, Togo, Turkey, Turkmenistan, Uganda, Ukraine, United Arab Emirates, Uruguay, Venezuela (Bolivarian Republic of), Viet Nam	No specific regulation
Austria, Belgium, Bulgaria, Croatia, Cyprus, Czechia, Denmark, Estonia, France, Germany, Greece, Ireland, Italy, Latvia, Lithuania, Malta, Netherlands, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, United Kingdom (England, Northern Ireland, Wales)	e-Liquid should not contain certain additives (not specified). High-quality ingredients should be used in e-cigarette manufacture. Only ingredients that do not pose a risk to human health in heated or unheated form can be used.
Canada	Marketing and sale of e-cigarettes that contain certain additives is prohibited (not specified). Restrictions on the marketing of flavours that may appeal to young people (including flavour suggestions, confectionery, dessert, cannabis, soft drink and energy drink).
Finland	e-Liquid should not contain certain additives and characterizing flavours (such as confectionery or fruit flavours). High-quality ingredients should be used in e-cigarette manufacture. Only ingredients that do not pose a risk to human health in heated or unheated form can be used.
Saudi Arabia	Flavours in e-cigarette liquids are partially prohibited. Fruit flavours and menthol are allowed, but cocoa, vanilla, coffee, tea, spices, confectionery, chewing-gum, cola and alcohol flavours are banned.
USA	All flavoured cartridge-based ENDS except tobacco- and menthol-flavoured products are banned. Flavoured liquids used in open-system ENDS are exempted.
Luxembourg	Additives that may create the impression that an e-cigarette product has a health benefit or presents a reduced health risk are prohibited (e.g. vitamins). Caffeine, taurine and other stimulants associated with energy or vitality are prohibited. Any additives that add colour, alter the properties of emissions or facilitate inhalation or nicotine uptake are prohibited. Only ingredients that do not pose a risk to human health in heated or unheated form can be used. Additives that have carcinogenic, mutagenic or reproductive toxic properties in their unburnt form are also prohibited. High-quality ingredients should be used in e-cigarette manufacture.

9.5.2. Global regulation of flavoured tobacco products

As for ENDS, regulation of other flavoured tobacco products also differs among countries. Table 9.2 lists countries and territories with different regulatory approaches from an analysis of regulations by the Campaign for Tobacco-Free Kids (154). These can be summarized as no regulations, partial bans on specific categories of flavours (with or without menthol) and full bans on all characterizing flavours (the definition may differ by jurisdiction), which may include menthol. In 2009, the FDA banned all characterizing flavours in cigarettes except for menthol (13). In 2014, the European Union followed suit, with a series of policies banning flavours other than menthol in cigarettes and roll-your-own tobacco (28,155), and the Tobacco Products Directive banned menthol in cigarettes and roll-your-own tobacco in May 2020 (156,157), although the regulations do not apply to other tobacco products (28). Other countries have banned flavours in tobacco products (158), including cigarettes; however, the regulations are either still at legislative level, as in Brazil (159) and Uganda (160), or were recently implemented, as in Turkey (161). In 2014, Singapore prohibited fruit flavours in waterpipe tobacco (63). In 2010, Canada prohibited the sale of all flavoured cigarettes and little cigars but exempted menthol cigarettes, and banned all flavours in other tobacco products, including waterpipe, smokeless tobacco and bidis. In 2017, the provinces of Alberta and Ontario banned the sale of menthol cigarettes (161).

Table 9.2.

Countries and territories approaches to regulation of the contents of tobacco products, including flavours (As of June 2020)

Countries and Territories	Regulation
Afghanistan, Argentina, Azerbaijan, Bangladesh, Belarus, Benin, Bhutan, Botswana, Burkina Faso, Burundi, Cambodia, Cameroon, Cabo Verde, Chad, China, Colombia, Comoros, Congo, Côte d’Ivoire, Djibouti, Egypt, El Salvador, Eritrea, Eswatini, Fiji, France, Gabon, Germany, Ghana, Guinea, Iceland, India, Iran (Islamic Republic of), Israel, Jamaica, Japan, Jordan, Kazakhstan, Lao People’s Democratic Republic, Latvia, Lebanon, Liberia, Madagascar, Malawi, Malaysia, Maldives, Mali, Mauritius, Mexico, Myanmar, Namibia, Nepal, New Zealand, Norway, Oman, Pakistan, Panama, Peru, Philippines, Poland, Qatar, Saudi Arabia, Seychelles, Singapore, Solomon Islands, South Africa, Spain, Suriname, Sweden, Syrian Arab Republic, Timor-Leste, Togo, Turkmenistan, United Arab Emirates, Venezuela (Bolivarian Republic of), Viet Nam, occupied Palestinian territory, including east Jerusalem	The law does not grant authority to regulate the contents of cigarettes.
Algeria, Brunei Darussalam, Chile, Costa Rica, Democratic Republic of the Congo, Ecuador, Gambia, Georgia, Guatemala, Guyana, Honduras, Indonesia, Iraq, Kenya, Rwanda, Thailand, Ukraine, United Republic of Tanzania, Uruguay	The law grants authority to regulate the contents of cigarettes; however, no regulations have been issued.
Australia	The contents and ingredients of cigarettes are not regulated at national level; however, fruit- and confectionery-flavoured cigarettes are banned in all states and territories. Mint is banned in at least one state.
Armenia, Russian Federation	The law regulates specified contents of cigarettes, including banning mint and some herbs, and other, unspecified flavourings.
Brazil, Canada,a Ireland,a Italy, Mauritania, Republic of Moldova, Niger,b Romania,a Senegal, Slovenia,a Sri Lanka, Turkey, Uganda, United Kingdom (England, Northern Ireland, Wales) a	The law regulates specified contents of cigarettes, including banning of sugars and sweeteners, characterizing flavours, menthol, mint and spearmint, spices and herbs, ingredients that facilitate nicotine uptake, ingredients that create the impression of health benefits, other flavourings, ingredients associated with energy and vitality and colouring agents.
Ethiopia, Nigeria	The law regulates specified contents of cigarettes, including banning characterizing flavours, ingredients that create the impression of health benefits and ingredients associated with energy and vitality.

^aMenthol as a characterizing flavour was banned as of 20 May 2020.

^bMenthol is not prohibited.

In a study of the response to regulations, quitting behaviour was observed in Canadians who reported daily, some or “never” (i.e. users of non-menthol cigarettes) use of menthol cigarettes after the menthol product ban and found that more daily and occasional users than non-menthol product users had attempted to or had quit cigarette use (162). In a study of residents of San Francisco, USA, menthol product and e-cigarette use decreased among young (18–24 years) and older adults (25–34 years) after a ban on menthol flavour, but cigarette smoking increased among young adults, and 65% of participants did not believe that the ban was enforced uniformly across the city (14). Ethiopia provides an ideal example of a strict tobacco control strategy, with a ban on the sale and distribution of all flavoured tobacco products, including those with menthol, and all ENDS are banned in a comprehensive approach to protect public health (163). Use of tobacco products in the country is lower than in other countries with a low human development index (164).

9.5.3. Pros and cons of common approaches

Flavours in tobacco products increase their appeal and the perceptions of users and bystanders of their safety (100,165-166). National regulatory offices have therefore attempted to reduce the effect of use of these products on public health. As noted above, only a few countries ban characterizing flavours in nicotine and tobacco products, either to respond to their obligations under the WHO Framework Convention on Tobacco Control or to protect young people and public health (158).

The different approaches to regulating flavours globally present a mosaic of policies that could be weighed according to their estimated benefit to public health. Some do not mention flavours, tobacco ingredients or content in general. Such lack of specificity could leave loopholes through which the tobacco industry could address young people. Partial banning of some flavours or banning of flavours in some nicotine and tobacco products also leaves a wide margin for the tobacco industry to advertise other flavours or alternative flavoured nicotine and tobacco products and thus challenge the work of regulators. A full ban on all flavours in all nicotine and tobacco products would appear to be a strong approach to curbing young people’s use of tobacco products, although regulators should consider the potential argument that flavours might be tools to accommodate switching from use of traditional smoked products to other products which could be substitutes. Regulators should make sure that customizable products that can be used to deliver nicotine in products such as open-system ENDS are removed from the market; otherwise, users will add unorthodox and illicit additives to their products (167). There have also been several calls for the removal of flavours from ENDS, as the associated risks outweigh their potential public health benefit (168,169). Both the supply and demand should be addressed in all regulations through widespread advocacy and awareness campaigns to seek support from the public to enforce implementation (170-172).

9.5.4. Impact of regulation of specific flavoured nicotine products

As most regulations on flavoured tobacco products were introduced recently, limited information about their impact is available (173-175). Lessons can nevertheless be learnt of the effects of policies to restrict flavours in tobacco products on their consumption (176-178). For example, assessment of the effect of restrictions of the sale of flavoured cigars (< 1.4 g) in Canada on the sale of other cigars showed an overall decrease. Furthermore, after the ban on mentholated combustible products, more menthol cigarette smokers quit and made quit attempts than smokers of non-mentholated products (162), although the authors noted that the exemption of certain flavours and product types might have reduced the effectiveness of the policy (179). Similarly, evaluation of the effect of the ban on flavoured tobacco products (e.g. cigars, little cigars, roll-your-own) in New York City, USA, showed a significant decrease (28%) in the odds of adolescents using any tobacco product (180), although evaluation of the effect of the ban on menthol in San Francisco, USA, indicated a decrease in e-cigarette use but not cigarette use among younger people (14). Another report suggested that making flavoured tobacco products less accessible and less affordable could help reduce the use of all tobacco products (181).

As there are no or only relatively new regulations on flavouring in ENDS, there are no longitudinal data on their use in ENDS or other tobacco products (182). Impact analysis and modelling have been used to estimate the possible effect of a regulation on use of flavours in ENDS (143,183,184), including the net effect on use of all tobacco products (185). One report showed that restrictive regulations on ENDS flavours could increase the intention of young adults to use cigarettes and both ENDS and combustible cigarettes (183), although reevaluation of the data showed that the net effect of regulation of both products is favourable to public health (185). Estimation of the impact of a ban on all flavours in ENDS, menthol in cigarettes or all flavours in cigarettes showed that the measure that would reduce both smoking and vaping rates would be a ban on all flavours in both products, although use of cigarettes would still be 2.7% higher than the status quo (169). As HTPs are considered to be tobacco products and are included with ENDS in some policies, there are no specific regulations on flavours in these products (186). We have demonstrated that flavours in ENDS increase the abuse liability of these products, specifically among adolescents and young adults, and we have no evidence that specific flavours in ENDS would help cigarette smokers to quit. In considering regulatory measures, it might be important to consider whether unflavoured ENDS have an effect similar to flavoured ENDS in supporting attempts to quit combustible cigarette use and reducing the abuse liability of these products.

9.5.5. Future regulation of flavours

Flavours increase the appeal, continued use, extent of use, dependence and toxicity of nicotine and tobacco products and increase the risk of new generations of nicotine and tobacco addicts. Addiction to nicotine and exposure to the other toxicants emitted place a significant burden on public health (187). The only way in which flavours could benefit public health would be in tobacco products proven to be less toxic, less risky and that support reduced use of combustible tobacco (81). Even so, users of such alternative flavoured tobacco products should be encouraged to stop using them in order to withdraw from nicotine addiction and to avoid any lapse or relapse to use of tobacco or nicotine products.

The section in the seventh report of the WHO Study Group on Tobacco Product Regulation (31) on flavours in tobacco and nicotine products noted that the research priorities were systematic monitoring of the global epidemiology of flavoured conventional, traditional, new and emerging tobacco products, identification of how flavours contribute to the appeal of these products and identification of flavour chemicals, their toxicity and their health effects. This report confirms that flavours are still widely prevalent in all nicotine and tobacco products, that the popularity of ENDS products has increased, that, while there are regulations on the availability of flavours in nicotine and tobacco products, they vary widely by country and that the global epidemiology of flavoured nicotine and tobacco product use should be monitored systematically.

This report also raises concern about the appeal of flavoured products to adolescents and young adults. ENDS are the most commonly used nicotine and tobacco products in these groups, and they have the highest use of flavours of all age groups. Flavours in ENDS may therefore be uniquely appealing to adolescents and young adults. One explanation may be the wide availability of non-traditional flavours (23), which are more popular in these groups than among older adults (47). It has been shown that fruit flavours in ENDS enhance the reward and reinforcing effects of nicotine delivered to the user (24,91).

To better understand the impact of ENDS flavours on use, they have been grouped into categories, similar to those for combustible tobacco (107). For example, flavours such as blueberry and green apple are considered fruit flavours, while muffin and cupcake flavours are categorized as “dessert”. This grouping is useful for interpreting results for products with a wide, growing variety of flavour options.

Use of flavoured products is associated with a greater likelihood of use of other tobacco products (188), especially among young people (189). Policies to reduce all tobacco use must therefore be based on actual use patterns (190). The effect of flavours on the appeal and use of ENDS is controversial from a regulatory perspective, as there is hot debate about whether the availability of many flavours assists in switching from combustible products to ENDS or increases the uptake of ENDS by naïve young people. It has been shown that the availability of flavours in ENDS is an important consideration for acceptance of these products by cigarette smokers (24,191,192).

Flavours in nicotine and tobacco products, especially ENDS, are marketed by vivid descriptions of the taste and sensory experiences associated with them (193). Perhaps not surprisingly, the overwhelming majority of ENDS users – adolescents, young adults and adults – endorsed “Come in flavours I like” as a reason for using ENDS (35), and ENDS users ranked a choice of flavours and unique flavours as two of the most important factors in choosing between competing vape shops (157). The availability of many flavours may make it more likely that users will find a product that appeals to them and may explain why flavours are used to a greater extent in ENDS products than in other tobacco and nicotine products. Flavours are still prevalent in other products with demonstrated appeal and sustained use, such as smokeless and combustible products and newer tobacco products such as HTPs. As tobacco regulations globally increasingly focus on ENDS, regulatory agencies should continue to monitor use of other nicotine and tobacco products in order to reduce their use.

Regulation of ENDS began some time after the major tobacco companies began their production (194). Some advocacy groups have criticized the FDA for not acting fast enough to prevent young people from using ENDS, which may have contributed to the high rates of use by young people in the USA, and health organizations won a lawsuit that obliged the FDA to bring forward the deadline for submission of studies on the safety of ingredients in premarketing applications for ENDS products from 2022 to 12 May 2020 (196-198). Regulation of flavours in other tobacco products, including cigarettes, also lagged behind their spread in the population (37). Flavours were introduced in smokeless tobacco in the nineteenth century, while flavouring of cigarettes flourished only a few decades ago (1,4,199). Flavours are used extensively in other tobacco products such as waterpipes and bidis (2,32), and the wide choice of flavours contributes to their popularity, especially among young people (27,61). Flavours not only increase the addictiveness of tobacco products but also increase their toxic emissions exponentially. Regulation of flavours is therefore at the intersection of harm reduction and a precautionary approach in tobacco regulation (200). The best regulatory approach to stop the tobacco epidemic is to develop complementary policies on all flavoured tobacco products that will eventually bring this epidemic to an end (201,202).

9.6. Discussion

The use of flavours in nicotine and tobacco products is controversial, as they have been clearly shown to contribute to the use and appeal of these products, particularly among young people. ENDS products continue to be a major concern, as their popularity is growing. A major feature of their appeal is the wide variety of flavours, which promote experimentation and prolonged use. Additionally, emerging evidence suggests that flavours may contribute to the toxicity of newer products such as ENDS in unique ways. Increased use of tobacco and nicotine due to flavours increases the burden on public health; however, flavours might be used to reduce the burden, as some adult smokers have reported that the flavours in products like ENDS contribute to their efforts to stop or reduce cigarette use. Policy-makers should consider this aspect when regulating flavours in tobacco products. Regulation of flavouring in tobacco products should be a priority in all regulatory approaches to limit the spread and progression of nicotine and tobacco use and to reduce use of combustible tobacco products.

9.7. Research gaps, priorities and questions

Research is necessary on the following aspects of flavoured nicotine and tobacco products, especially ENDS:

• surveillance studies on the global epidemiology of use of flavoured nicotine and tobacco products;

• longitudinal studies of ENDS use characteristics, reasons for uptake, flavour use over time and continued use;

• scientific classification to provide a means to categorize flavoured tobacco products and their chemical constituents;

• consensus on a current definition of a “characterizing flavour”;

• impact analyses of regulations, restrictions and bans on flavours in new and emerging nicotine and tobacco products, especially ENDS, including modelling of responses to flavour-related policies in hypothetical scenarios and tasks;

• biomedical and behavioural studies on the impact of flavour on the experience of reward with use of nicotine and tobacco products, by age group and tobacco use status; and

• the toxicity of individual flavour ingredients and of chemicals in nicotine and tobacco products and of newly formed combined moieties.

Global priorities are to:

• build evidence of the impact of flavours on use of nicotine and tobacco products by age group and on use of different products in different countries;

• determine the impact of flavours in nicotine and tobacco products on the decades-long effort to reduce nicotine and tobacco use in the population; and

• exchange experience among countries in the regulation of flavours in tobacco products.

Questions to policy-makers and international organizations such as WHO include:

• How can concerns about the use of flavours in nicotine and tobacco products be addressed rapidly to prevent a new generation of users from becoming dependent on nicotine and tobacco?

• What can be done to outpace industry manoeuvres to use flavours to enhance the appeal and use of their products?

• Can a robust, self-developing, sustainable regulatory model be built to address similar concerns for any new or modified risk tobacco product?

9.8. Policy recommendations

A piecemeal approach to regulating flavoured nicotine and tobacco products will not turn the tide of the tobacco epidemic. A multi-pronged combination of various policy tools with a panoramic view of all nicotine and tobacco product use will help health agencies to address the issue of flavoured products (203,204). ENDS could be used as an opportunity to increase the regulation of all tobacco products (205) to achieve the ultimate objective of nicotine- and tobacco-free future generations (206). Policies on flavours in novel and emerging nicotine and tobacco products should include the following.

• Where flavours are not banned, their regulation in nicotine and tobacco products should be consistent globally; i.e. the availability of flavours should be regulated similarly for all nicotine and tobacco products rather than for each product.

• Research should be conducted on the possible role of characterizing flavours in products like ENDS or HTPs in helping smokers to quit.