Why public health people are more worried than excited over e-cigarettes

ECs are marketed as safe products delivering pure nicotine and releasing harmless water vapor that vanishes in seconds [3],[4], but is this true? The research field is characterized by severe methodological problems, severe conflicts of interest, relatively few and often small studies, inconsistencies and contradictions in results, and a lack of long-term follow-up. Therefore, no firm conclusions can be drawn on the safety of ECs [5],[6], and much is left to subjective interpretations. Most probably ECs are less harmful than conventional cigarettes, but they can hardly be called safe. An experimental study found that cells exposed to high-nicotine vapor showed a similar pattern of gene expression to those exposed to tobacco smoke [7]. Very short-term experimental exposure to EC vapor showed effects that are reminiscent of the obstructive effects seen with smoking [8]-[10], even though the impact on lung function was smaller than with smoking. An experimental animal study found that EC fluid can exacerbate allergy-induced asthma symptoms [11]. Furthermore, a study found that the vapor induced release of cytokines and pro-inflammatory mediators [12] and many studies have found cytotoxicity [13],[14] and harmful substances in fluid and vapor (e.g., fine or ultrafine particles [15]-[17], harmful metals [13],[18], carcinogenic tobacco-specific nitrosamines [19]-[23], carbonyls [19],[21],[24],[25], volatile organic compounds [19],[26], polycyclic aromatic hydrocarbons [18],[22]) or in urine [18]. It is true that most studies found low or very low concentrations, but values below the threshold-limit do not necessarily protect against a negative health effect of 200 to 300 daily inhalations [27] over decades.

The EC is a radically different product than the CC and, therefore, it seems wrong to base an assessment of the safety of EC on comparisons with CCs only. Of special concern are compounds not found in CCs: the glycols (propylene glycol and sometimes glycerin) are major ingredients of ECs [28]-[32] used to create the visible fume. A report commissioned by vapers and vendors of ECs concluded that “estimated levels of exposure to propylene glycol and glycerin are close enough to threshold-limit values to warrant concern” and that “the threshold-limit value is based on uncertainty rather than knowledge” [33]. Several studies on glycols have raised health concerns [34]-[37]. Other concerns are the flavors, metals, and silicone [13],[14],[38]. Finally, nicotine itself is probably not harmless [39], and it is highly addictive. Studies show that non-smokers passively exposed to ECs absorb nicotine [18],[40],[41].

In the first years, the ECs were bought by smokers only; however, recently, their use has also spread to ex-smokers [42]-[45] and never smokers [45]-[49]. The intensive marketing, the novelty, the use of celebrities as role models, and the candy-like flavors appeal to young people. Experimental use in minors has doubled within one year [45],[48],[50]. A high proportion of adolescents have tried ECs [46],[47],[49], even at age 12 to 14 years [47]. Of special concern is that young never-smokers are experimenting with ECs [45]-[49] and the use of ECs might undermine decades of efforts to de-normalize smoking [51]. A brand new study from Poland finds that almost every third adolescent is current user of ECs and more than every fifth has a dual use of CCs and ECs. However, the most alarming finding is that the prevalence of smoking increased with increasing rates of EC use, from 24% to 38% during a period of only three years, indicating a renormalization of smoking [52].

It would be naïve not to expect that the manufacturers will try hard to spread the use of their product to as many consumers as possible, and history has shown that the tobacco industry has no ethical constraints [53].

Making strong conclusions based on smoking rates and rates of EC-use in different countries is difficult, as smoking rates are influenced by political decisions as price and availability, changes in the social norm, etc. Some prospective studies were very promising [54],[55], and a recent large ‘real-world’ study taking smoker’s addiction into account showed that use of ECs increased cessation rates more than no aid/nicotine replacement products bought over the counter [56]. However, a meta-analysis based on five population-based studies found that EC users were significantly less likely than non-users to have stopped smoking [6], a longitudinal study in cancer patients showed that EC users were twice as likely to be smoking at the time of follow-up as non-users [57], and the only existing randomized smoking cessation study showed that ECs were not significantly more effective than nicotine patch therapy [58]. A survey sponsored by EC manufacturers found that only 1% of EC users achieved permanent abstinence [59], but I have not seen this study cited by harm reduction advocates. Unfortunately, it seems that many smokers use ECs with the intention to quit but switch to long-term use of ECs [58] or end with dual use, supplementing their smoking with the EC [42]-[44],[60] – dream-scenarios for the industry.

When we compare with a CC, the most harmful legal product on the market, everything seems harmless. For a smoker reluctant to stop smoking, the EC will most probably be a less harmful alternative – but we cannot focus on these smokers only! The impact of a product on public health is determined by two factors: i) the degree of toxicity or harm of the substance; and ii) how widespread the exposure is. Even if ECs are significantly less harmful than CCs, the product may have a negative impact on public health if the use is spread to a large part of the population (Figure 1). ECs might achieve popularity as high as that of CCs in the 1960s, before an awareness of harm became widespread in the population. The potential health benefits obtained by some smokers (Figure 2) must outweigh the potential harm by use of ex- and never-smokers, of smokers who intended to quit but switched to ECs, of smokers’ dual use, and of eventual re-normalization of smoking.