The sale, distribution, and indiscriminate use of new tobacco and nicotine products have multiplied. The most relevant products are: electronic cigarettes (ECs), heated tobacco (HT), and nicotine pouches (NPs). From the tobacco industry and its related health sectors, and even from some health institutions with no clear influence from this industry, the use of all these devices is being promoted as an excellent harm reduction strategy for those conventional tobacco smokers who do not want to or cannot quit smoking. This paper reviewed the lack of scientific evidence of this strategy.
La venta, distribución y uso indiscriminado de los nuevos productos de tabaco y nicotina se ha multiplicado. Los productos más relevantes son: cigarrillos electrónicos (CE), tabaco calentado (TC) y bolsas de nicotina (BN). Desde la industria del tabaco y sus sectores sanitarios relacionados, e incluso desde alguna institución sanitaria no claramente influenciada, el uso de todos estos dispositivos está siendo promocionado como una excelente estrategia de reducción del daño para aquellos fumadores de tabaco convencional que no quieren o no pueden dejar de fumar. Este artículo revisa la falta de evidencia científica de este tipo de estrategia.
In recent years, the sale, distribution, and indiscriminate use of new tobacco and nicotine products have multiplied. Although this terminology includes a wide range of products, the most relevant are: electronic cigarettes (ECs), heated tobacco (HT), and nicotine pouches (NPs).1,2
From the tobacco industry and its related health sectors, and even from some health institutions with no clear influence from this industry, the use of all these devices is being promoted as an excellent harm reduction strategy for those conventional tobacco smokers who do not want to or cannot quit smoking. The rationale provided in favor of harm reduction is as follows: (a) the concentration of some tobacco related toxic substances released by these devices is lower than from CCs; (b) the use of new products, especially ECs and NPs, would help to stop smoking CCs and the smoker could gradually cease; and finally, as a logical consequence of the reasons stated, the use of these new products should be recommended to those smokers who do not want to quit or even to those who wish to stop but, after having tried several times with the usual treatments, have not succeed
What is the problem?These sectors, in favor of harm reduction, are developing a well-thought-out communication strategy to the scientific community with the aim of implementing their intentions in daily clinical practice. This strategy fundamentally focuses on the publication, in different medical-scientific journals, of articles, scientific recommendations, or warnings for the correct use of new devices, and even “ad hoc” manuals are disseminated.3–6 It is important to highlight that all these publications have a very similar structure. These are usually their main parts: (a) they begin by stating that the consumption of CCs is the leading cause of death in the world and in developed countries, (b) they extend talking about all the diseases associated with their consumption, (c) they point out that currently new tobacco and nicotine products are available and that their use is accompanied by a significant reduction in the risk of developing the aforementioned diseases and that, in fact, some can be used to help quit smoking, (d) they show scientific data on the effectiveness of psychological and pharmacological treatments for quitting smoking, but they point out that not all smokers want to use them, that the effectiveness of these therapeutic methods is not complete, and that there is a number of smokers who do not want to quit smoking; and (e) they conclude that in these groups of smokers, the use of these new forms of tobacco consumption could be recommended. In the end, they provide a series of recommendations for the proper use of these devices in order to get the best performance from them while running the least risk.
It is important to highlight that the implementation of these harm reduction strategies is aimed at young people. And they are getting many youngers start the consumption of these new tobacco products. According to the data from the latest “”Estudes Survey” in Spain, the percentage of youngers who started using electronic cigarettes increased from 43.3% in 2021 to 49.5% in 2025. In addition, while only 8.1% of them used these devices in 2021, by 2025 this figure had risen to 27.1%.7 Moreover the use of these can be a gateway to consumption of CCs. Moreover, the use of these products can be a gateway to consumption of CCs. Recently a systematic and umbrella review by Golder et al. found a consistent significant association between vaping and smoking initiation, supporting a causal relationship, with pooled ORs of 1.50–26.01 (21 systematic reviews), most of which suggested that young people using e-cigarettes are about three times more likely than those not using them to initiate smoking.8
In order to look for the scientific support of the harm reduction strategy we have performed a bibliographic search in three database: PubMed, Embase and Cochrane Library. As limits we searched only articles in humans, and in English or Spanish, but limiting the same until August 2025. This paper has been promoted by the SEPAR Smoking Group.
What does the scientific evidence support?The evidence does not support that the use of these new tobacco and nicotine products: ECs, HT products, and NPs reduce the harms compared to use of CCs. The evidence to date indicates that such products are ineffective, useless, and may lead to more harm. The following sections review the claims of harm reduction and the data that demonstrate their ineffectiveness and inoperability.
Harm reduction programs argue that ECs are less toxic to health than CCsScientific reports from relevant medical societies and health institutions indicate that the toxic substances present in the vapor of ECs are causative and contributing factors to the suffering from cardiovascular, pulmonary, tumoral, and infectious diseases.9–13
The main constituents of the liquid contained in ECs cartridges are: propylene glycol, glycerin, nicotine, flavorings (tobacco, mint, fruits, cinnamon, etc.) and other additives. When this liquid is heated, glycerin breaks down and turns into toxic substances such as formaldehyde, acetaldehyde, and acrolein. On the other hand, metals such as nickel, chromium, and lead have been found in the vapor of ECs.14 Likewise, nitrosamines have also been detected.10,11,15 Various studies have shown that these substances can cause inflammation of the vascular wall, platelet activation, thrombosis, endothelial dysfunction, and vasoconstriction, leading to severe peripheral vascular pathology and acute coronary disease.12,16 Additionally, all these substances have also been identified as causing injuries to the airways and the bronchial and alveolar epithelium; decreasing the bronchopulmonary defense mechanisms, thus facilitating the development of bronchial hyperreactivity, hypertrophy of the bronchial mucosa, and the onset of bronchopulmonary infectious diseases.15 Specially harmful have been noted on young asthma patients ECs users presenting severe asthma exacerbations and asthma attacks.17 In these patients, EC have been heavily marketed as healthier alternatives to tobacco smoking, but their use may increase the incidence and severity of bacterial lung infections by both direct effect on human cells of host defense as well as effects on bacterial cells. In high school students in South Korea, EC users have an increased association with asthma and are more likely to have had days absent from school due to severe asthma symptoms.18
A recent study, conducted ‘in vivo’ and ‘in vitro’ models, indicates that the long-term use of ECs leads to increased oxidative stress of bronchial epithelial cells, resulting in an inappropriate and ineffective pathogenic response similar to that detected in the early stages of COPD.19 Other studies have shown that carbonyls, nitrosamines, and polycyclic aromatic hydrocarbons found in the vapor of ECs have the ability to damage cellular DNA and reduce the defense mechanisms for repairing that damage, leading to an increase in DNA adducts and the initiation of the carcinogenesis process.20,21 It is noteworthy that the International Agency for Research on Cancer classifies all those substances as carcinogenic and has not established a safe threshold for exposure.22 Furthermore, we know that the use of ECs has led to the emergence of new unknown pathological processes. We refer to the cases of e-cigarette or vaping product use-associated lung injury (EVALI) reported in North America a few years ago. More than 2700 cases were detected with a mortality rate exceeding 1%, and in more than 60% of cases, patients required admission to the ICU for treatment.23
Considering all this data, it can be concluded that the use of ECs is harmful to health. See Table 1.
Toxic effects from different substances in electronic cigarettes.
| Substance/group | Origin in e-liquid or aerosol | Potential respiratory effects |
|---|---|---|
| Propylene glycol, glycerin | Base solvents | Airway irritation, cough, dryness |
| Nicotine | Present in different concentrations | Addiction, bronchial hyperreactivity, cardiovascular effects |
| Flavorings (tobacco, mint, fruit, etc.) | Added aromas | Cytotoxicity, inflammation, reinforcement of addiction |
| Carbonyls (formaldehyde, acetaldehyde, acrolein) | By-products of heating glycols | Oxidative stress, DNA damage, carcinogenesis |
| Metals (nickel, chromium, lead) | From heating elements | Bronchial and alveolar epithelial injury, systemic toxicity |
| Nitrosamines and PAHs | By-products/contaminants | DNA adduct formation, carcinogenesis |
PAH: polycyclic aromatic hydrocarbons; DNA: deoxyribonucleic acid.
Most e-cigarettes contain nicotine, and their use allows users to achieve blood nicotine levels high enough to stimulate the nicotinic receptors of the ventral tegmental area of the midbrain and facilitate the release of dopamine in the Nucleus Accumbens, consequently triggering the neurophysiological mechanisms of addiction.24 Two recent studies of regular vapers found that both the average nicotine level with habitual use (∼9.91ng/ml) and the peak level right after EC initiation (∼12.7ng/ml) were sufficient to stimulate nicotinic receptors.25,26 In addition, it is known that the flavorings and aromatizers that are usually added to the liquid of ECs are capable of stimulating the oropharyngeal nerve endings and thus increase and facilitate the addictive capacity of nicotine.27,28 All these mechanisms are favored because many of the ECs contain specific chemical formulations of nicotine (nicotine pyruvate, nicotine benzoate) that facilitate the drug's absorption more easily and allow a greater amount of it to reach the bloodstream.29–31 To all this, it should be added that the use of ECs is accompanied by a gestural and inhalation mechanism very similar to that of CC, and this mechanism facilitates the maintenance of dependence in the vaper.24 It is worth noting that many of these mechanisms are present even in nicotine-free e-cigarettes.32
There is data in daily clinical practice indicating the association between vaping and addiction. Up to three specific questionnaires have been developed to analyze the degree of physical dependence on nicotine in vapers: Penn State E-Cigarette Dependence Index (PS-ECDI)32; E-Cigarette Dependence Scale (EDS-4)33; and Fagerström Test of Cigarette Dependence (FTCD) adapted for ENDS (e-FTCD).34 The use of these questionnaires, especially the PS-ECDI, is recommended to determine the degree of dependence in vapers in relation to the different treatment recommendations for these individuals.35
Data from a meta-analysis by Butler et al. that analyzed the prevalence of ECs use for more than six months in 19 studies involving 7787 subjects showed that the prevalence ranged from 54% to 70% and there were no significant differences between the use of ECs with and without nicotine, RR: 1.15 (95% CI: 0.94–1.41).36
All these studies support that e-cigarettes, with or without nicotine, cause dependence.
Harm reduction programs declare that ECs help to quit smoking CCFrom 2021 to 2025, four Cochrane meta-analyses have been published concluding that nicotine ECs are more effective than nicotine replacement therapy (NRT) for quitting smoking.37–40 All of them base their conclusions on the results of a group of 5–7 clinical trials, two of which41,42 contribute a very significant weight, greater than 50%, to support this conclusion. It is relevant to point out that both studies have notable methodological limitations.41,42 Among them, the following should be highlighted: (a) neither of the two studies is placebo-controlled nor double-blind41,42; (b) in one study the authors acknowledge that they made a mistake when making the calculation to obtain an adequate sample and detects that the way the medication was distributed between the groups benefited the ECs groups41; (c) both studies show notable problems of adherence to nicotine medication with respect to adherence to ECs. In both studies adherence was always superior in the ECs groups than in the NRT groups.41,42 In both studies adherence to NRT at first month was lower than adherence to ECs.41,42 Nicotine withdrawal syndrome is very intense during the first four weeks and the need for medication to control it is very high. According to adherence data the majority of subjects in the NRT groups were not using adequate medication during this period of time compared with subjects in the ECs groups. All these aspects are important limitations to obtain adequate conclusions.43,44 Another important problem was detected in these studies41,42: the persistence in the use of ECs beyond the established time. In the study by Bullen et al., 38% of those who were abstinent at six months of follow-up were still using ECs, even 29% of those who had relapsed and were smokers of CC, were still using ECs at that time.41 In the study by Hajek et al. the results showed that around 80% of those who used ECs to quit smoking were still using them after a year.42 This is another reason to claim about the high addictive capacity of ECs.36,43,44
Recently Lindson et al. published a metanalyses aims to investigate the comparative benefits, harms and tolerability of different smoking cessation pharmacotherapies and ECs when used to help people stop smoking. Authors conclude that the most effective interventions were nicotine ECs, varenicline, combination NRT and cytisinicline.45 A strange aspect of this metanalyses is that the use of nicotine ECs is rated as similarly effective and safe for smoking cessation as pharmacological treatments such as varenicline or NRT. Taking into account that there are much more randomized control trials (RCTs) of varenicline or NRT than RCT using nicotine ECs. Moreover, there are many RCTs showing efficacy and safety of varenicline and NRT in smokers with severe controlled diseases: cardiovascular, pulmonary and neuropsychiatric disorders. None RCT using ECs has been carried out in smokers with controlled severe disorders.43,44 It is also surprising in this metanalyses that regarding harm and tolerability there are not any conclusions about long term use of nicotine ECs.43–45
All this data indicates that there are no firm conclusions about the effectiveness and safety of using e-cigarettes to help quit smoking.41–45
Harm reduction programs state that ECs help significantly reduce the consumption of CCs and can be used as a preliminary step towards quitting tobacco use completelyOne of the first studies that demonstrated that the use of ECs in smokers was accompanied by continued use of CCs was the Swedish study by Hedman et al.46 It was a cross-sectional, population-based study of random samples of the population, conducted within the Obstructive Lung Disease in Northern Sweden (OLIN) study and West Sweden Asthma Study (WSAS). A total of 30,272 participants were studied. The number of current smokers was 3694 (12.3%), and 7305 (24.4%) were former smokers. The number of ECs was 529 (2.0%). Among current smokers, 350 of 3566 (9.8%; 95% CI, 8.8%–10.8%) used ECs compared with 79 of 6875 (1.1%; 95% CI, 0.9%–1.3%) among former smokers and 96 of 15,832 (0.6%; 95% CI, 0.5%–0.7%) among nonsmokers (P<.001). Among ECs users who answered the survey question about cigarette-smoking habits (n=525), 350 (66.7%; 95% CI, 62.7%–70.7%) were current smokers, 79 (15.0%; 95% CI, 11.9%–18.1%) were former smokers, and 96 (18.3%; 95% CI, 15.0%–21.6%) were nonsmokers (P<.001 for trend).39 In most recent studies, a similar conclusion arises: around 50–70% of smokers who use ECs are using CCs at the same time.36,41,42,46
A recent systematic review by Hamoud et al. has studied whether of both dual use of CCs and ECs can promote smoking cessation.47 Authors conducted a systematic search of all longitudinal studies reporting transitions between dual use, exclusive ECs use and exclusive CCs use were included. 16 original studies were identified and eight of them could be pooled for meta-analysis. The main conclusions were as follows: (a) the majority of ECs users evolve into dual users (of CCs and ECs), (b) the majority of dual users continue smoking for two years or more, either because they remain dual users or because they revert to CCs only smokers. The longer the follow-up, the more they stop being dual users and revert to CCs only smokers. Very few evolve into non-users, (c) the majority of CCs smokers remain smokers. Very few evolve into non-smokers and (d) there were no differences in the evolution of ECs users, dual users, or CCs smokers to non-smokers.47
These findings show that the claim that ECs help reduce the consumption of CCs and that they can be used as a step prior to quitting tobacco permanently is not supported by the available evidence.
Harm reduction programs defend that the aerosol released by the HT contains a lower number of toxic substances than that found in the smoke of CCIn this regard, it is important to note four relevant studies that have highlighted the inaccuracy of what the tobacco industry has stated about the greater safety of HT compared to CCs.48–51
An independent study analyzed the toxic substances present in the aerosol released by HT and concluded that the concentration of at least 20 toxic substances is higher in that aerosol than in the smoke from CCs. Many of these substances were carcinogens.48 Additionally, the levels of nicotine released by HT and the levels of nicotine that the consumer of this product absorbs in their blood are similar to those released and obtained by the consumer of CCs. So it is very relevant to state that both products are addictive.48,49
An independent group of experts verified the results that Philip Morris International (PMI) had published regarding its analysis of the toxic substances present in the aerosol released by IQOS.50 The analyses conducted by PMI presented a list of 58 toxic substances in IQOS smoke, which were at higher concentrations than in cigarette smoke. However, when the analyses were conducted by the independent group of experts, the results were very different: the experts found another 56 toxic substances that had not been declared by PMI, and in addition, 22 of those 56 substances were at concentrations over 200% of those found in cigarettes and 7 of them were at concentrations higher than 1000% of those in cigarettes.50
A study conducted by our group demonstrated that the use of an IQOS cigarette according to the manufacturer's standards was accompanied by pyrolysis and that this cigarette not only did not heat up but burned; and when burned, all the toxic substances similar to those of CCs were produced.51
In conclusion the analysis of independent studies indicates that HT is as addictive and toxic as CCs.
Harm reduction programs state that the use of NPs is not addictive and reduces the harms associated with the consumption of CCsRecently, the tobacco industry has launched an intense campaign in Europe and Spain to promote the use of these devices that contain pure nicotine in a pouch that the users must place under their lower lip.52
Data from independent studies indicate that the use of these NPs releases substances into the user's bloodstream as toxic as nicotine, nitrosamines, methyl eugenol, benzophenone, and β-myrcene, all of which have been classified as possibly carcinogenic by the International Agency for Research on Cancer.22,53 Furthermore, the levels of nicotine obtained from the use of these devices are sufficient to produce addiction.53
Independent studies have shown that at the site of NPs placement, lesions such as gingivitis, periodontal disease, and bone destruction occurred. Even in more advanced cases, precancerous lesions appeared.54,55
Data from independent studies indicate that NPs are as toxic as CCs and can cause addiction.52–55
In addition, recent pediatric data indicate a sharp increase in accidental exposures to nicotine pouches among children, in some cases resulting in severe poisoning and even fatalities, highlighting an emerging public health challenge.56
Harm reduction programs argue that HT and NPs can help quit smokingTo our knowledge there is no clinical study that has assessed the effectiveness of any of these devices as an aid to stop use of CCs.
Harm reduction programs defend that “Hardcore smokers” can take advantages from their proposalsThe tobacco industry presents the idea of a growing population of “heavy smokers” who supposedly cannot or will not quit, thereby justifying the promotion of alternative nicotine products. Population data from Europe and Asia show a contrary trend: smokers are increasingly reducing their daily consumption, expressing a greater intention to quit, and are doing so without relying on electronic nicotine delivery systems (ENDS). For example, Eurobarometer data indicate that more than half of European smokers have attempted to quit smoking, and the majority have done so without the aid of new nicotine products. These findings suggest a “thinning” rather than a “hardening” of the smoking population.57,58
This mischaracterization serves as a strategic narrative to legitimize the expansion of heated tobacco products, nicotine pouches, and e-cigarettes under the guise of harm reduction. It also risks diverting public health attention and resources away from evidence-based cessation interventions. Reinforcing comprehensive tobacco control measures – including behavioral support, pharmacotherapy, and regulatory enforcement – remains the most effective approach to reducing smoking prevalence and associated morbidity. The perpetuation of the “hardcore smoker” myth should be recognized as a form of policy interference rather than a legitimate public health concern.58
ConclusionsThe data presented shows the following conclusions: (a) all these new forms of tobacco consumption (ECs, HT, and NPs) constitute a new strategy by the tobacco industry to avoid the progress that health authorities and scientific societies have made in favor of tobacco control and smoking cessation, and to create new nicotine addicts, thereby continuing to maintain their deadly business, (b) all these forms are addictive and produce disorders similar to those produced by CCs, in addition to increasing the risk of dual consumption, (c) none of these forms are effective in helping smokers to quit and their use should never be recommended in smoking cessation programs and (d) Fig. 1 illustrates different injuries caused by toxic substances from ECs in various organs of the human body.15,59,60
Effects of electronic cigarettes on different organ system.15,59,60
The paper has been produced without involvement of AI.
FundingNot applicable.
Authors’ contributionsCAJ-R and MC-F wrote the paper and it was sent to the rest of the authors. The contributions of these authors were discussed, approved and added to the paper.
Conflicts of interestCAJ-R has received honoraria for presentations, participation in clinical studies and consultancy from: Adamed, Aflofarm, Bial, Chiesi, GSK, Gebro Pharma, Kenvue, Neuraxpharm and Pfizer.
JIG-O has received honoraria for lecturing, scientific advice, participation in clinical studies or writing for publications for the following (alphabetical order): Aflofarm, Adamed, Boehringer, Esteve, Neuroxpharm and Pfizer.
CRC has received honoraria for speaking engagements, sponsored courses, and participation in clinical studies from Adamed, Aflofarm, GSK, Menarini, Mundipharma, Chiesi, Novartis, J&J, Pfizer, and Teva.
JSC has served as a consultant and received speaking fees at advisory boards for Aflofarm, AZ, BI, and received institutional funding for trials and research from BI, GSK and received support for attending meetings and/or travel from Aflofarm, BI, Faes, Menarini, Teva.
JAR reports grants and personal fees from Aflofarm, Adamed, GSK, grants, personal fees and non-financial support from Pfizer, Novartis AG, Menarini, personal fees and non-financial support from Boehringer Ingelheim, personal fees and non-financial from Astra-Zeneca, Grants and personal fees from, Gebro Pharma, personal fees from Sanofi-Regeneron, outside the submitted work.
EBH-M has received honoraria for lecturing, scientific advice, participation in clinical studies or writing for publications for the following (alphabetical order): Aflofarm, AstraZeneca, Bial, Boehringer Ingelheim, Chiesi, Esteve, FAES, Gebro, GSK, Menarini, Neuraxpharm, Novartis, Pfizer, Rovi, TEVA and Zambon. I have no relationship with the tobacco or electronic or heated cigarette industry.
The other authors declare that they have no conflict of interest with respect to this document.
