The smoking rate of combustible cigarettes (CCs) among adults in Korea has been continuously decreasing over the past 20 years. Specifically, the CCs smoking rate among men has decreased from 66.3% in 1998 to 30% in 2022. Among women, the rate initially was 6.5% in 1998, peaked at 7.5% in 2018, and subsequently declined to a record low of 5.0% in 2022 [1]. Additionally, the global prevalence of CC smoking has also declined over the past decades [2].

Conversely, the trend in the usage of heated tobacco products (HTPs) in Korea has diverged from the decreasing trend observed with CCs. Since the introduction of HTPs in 2017, the smoking rate for HTPs stagnated, moving from 6.2% in 2019 to 5.2% in 2020, and dropping further to 4.6% in 2021. However, it rose again to 5.9% in 2022. Specifically, the current usage rate of HTPs among men was 9.2% in 2022, and for women, it was 2.4%, marking increases of 1.9%p and 0.7%p, respectively, from 2021 [1]. Among adolescents, male smoking rates slightly decreased to 2.7% in 2023 from 3.2% the previous year, while female rates have seen a gradual increase from 0.8% in 2021 to 1.4% in 2023 [3]. Sales of HTP sticks in the country have also surged, rising from 78 million packs in 2017 to 444.1 million packs in 2021, and further to 538.6 million packs in 2022 [4]. Furthermore, a market report by Philip Morris International (PMI), a leading HTP producer, noted that Japan and South Korea held the largest HTP market shares in 2021 [5].

HTPs, also known as heat-not-burn tobacco products, involve heating specially treated tobacco leaves and additives to 350°C or less using electronic devices, without directly burning the tobacco. The resulting vapor is then inhaled by the user.

PMI claims that this method of “heating” rather than “burning” tobacco significantly reduces the emission of harmful substances by up to 95% compared to CCs [6]. In 2020, the US Food and Drug Administration approved the IQOS 3 as a modified-risk tobacco product [7].

However, the World Health Organization maintains that there is insufficient research to confirm that HTPs are less harmful than CCs. It contends that smoking HTPs can expose users to a variety of harmful substances not present in CC smoke, and that the health effects of HTPs are not yet adequately studied [8]. HTPs are often recognized for their stylish design, reduced odor, and purported harm reduction features. They are predominantly used by young adults aged 19–39 [8,9]. In short, while HTPs are gaining popularity due to their perception of being less harmful, there is still limited evidence to support this.

Conversely, smoking CCs is well-known as a direct risk factor for cardiovascular diseases (CVD). This is partly due to the effects of nicotine, which alters serum lipid profiles by increasing triglycerides (TGs) and low-density lipoprotein-cholesterol (LDL-C), and decreasing high-density lipoprotein-cholesterol (HDL-C) among smokers [10]. Additionally, harmful and potentially harmful constituents (HPHCs) are produced when tobacco combusts, leading to an increase in free radicals and lipid peroxidation. These substances contribute to several mechanisms associated with CVD, including disturbances in lipid metabolism and endothelial dysfunction. This can result in the formation of atherosclerotic plaques and an increased risk of CVD [11].

It has been demonstrated that smoking HTPs increases both nicotine and biomarkers of carcinogens in the body [12]. The Korea Disease Control and Prevention Agency has conducted studies on behavioral changes among smokers following the introduction of electronic cigarettes (ECs) and HTPs, and investigated how different types of tobacco use affect the biomarkers of smokers [12]. The analysis revealed that concentrations of nicotine, cotinine, and OH-cotinine in HTPs single users were similar to those of CCs single users. Additionally, for dual (CCs+HTPs, CCs+ECs) and triple tobacco users (CCs+HTPs+ECs), levels of nicotine, cotinine, OH-cotinine, and NNAL—an indicator of exposure to nicotine-derived nitrosamine ketone—were comparable to those found in CCs only users.

Harada et al. [13] analyzed the metabolomics of single users of CCs and HTPs. They found that metabolites in HTPs single users were more similar to those of CCs single smokers than to those of non-smokers. Notably, serum glutamate levels, which are associated with future CVD and arteriosclerotic plaques, were significantly higher among HTPs users.

Therefore, this study attempted to examine the basic characteristics of Korean HTPs users using data from the Korea National Health and Nutrition Examination Survey (KNHANES) and to determine whether there are differences in serum lipid levels compared to non-smokers and CCs smokers.

Various findings have been reported on the relationship between LDL-C levels and smoking CCs. In the study by Scherer [14], which analyzed 23 studies on the correlation between CC smoking and LDL-C levels, it was found that the LDL-C levels of CC smokers were about 4% higher than those of non-smokers across a total of 50,000 participants. Moreover, only four out of 17 studies showed significant differences in LDL-C levels between smokers and non-smokers. Studies comparing current smokers with ex-smokers found no significant differences in LDL-C levels. Among the seven studies comparing ex-smokers with never-smokers, only one reported higher LDL-C levels in the ex-smokers. This suggests that it can take a relatively long time—approximately 2 years on average—for LDL-C levels to return to those seen in nonsmokers after quitting smoking. In the present study, the “HTPs only user” group included individuals who had transitioned from smoking CCs to using HTPs. Therefore, it is possible to speculate that current HTP use, combined with a history of CC smoking, may have jointly influenced LDL-C levels.

Ongoing research has investigated how CC smoking induces dyslipidemia [10,15,16]. Nicotine from cigarettes acts on the adrenal cortex, increasing the secretion of catecholamines, which leads to the breakdown of fat cells and an elevation of free fatty acids in the blood. This process promotes the production of very LDL-C (VLDL-C) and TGs in the liver. HDL-C levels change inversely with VLDL-C concentrations and are known to decrease rapidly after smoking begins. These changes are believed to influence the lipid profile of smokers, including LDL-C levels.

Previous studies on the serum lipid levels of users of HTPs are still limited, particularly those examining the impact of HTP smoking on LDL-C levels. Notably, many of these studies have been led by HTP manufacturers. In a study by Haziza et al. [17], conducted by “IQOS” manufacturer PMI, biomarkers were analyzed for three groups: those who switched from smoking CCs to HTPs, those who continued smoking CCs, and those who quit smoking altogether. Although the P-value was greater than 0.05, LDL-C, HDL-C, apolipoprotein A1, apolipoprotein B, and TC all showed a trend of improvement in the group that switched from CCs to HTPs. In the study of Sakaguchi et al. [18], funded by Japan Tobacco Inc., a cross-sectional analysis of HTP users was performed, and no significant differences in LDL-C levels were found when compared to CC users and non-smokers. However, exclusive HTP users had higher HDL-C concentrations than CC smokers. Additionally, a randomized trial sponsored by PMI showed that CC smokers who switched to HTPs had higher HDL-C concentrations at 6 months compared to those who continued smoking CCs [19]. In an independent, large population-based study in Japan, exclusive HTP users had lower HDL-C concentrations than never-smokers, though their HDL-C levels were still higher than those of exclusive CC smokers [20].

Since the introduction of HTPs, several studies have reported on their harmful components. A study by Uchiyama et al. [21] concluded that the total gaseous particulate matter emitted per cigarette did not differ significantly between CCs and HTPs. Nicotine emissions were measured at 1,900 μg per CC, 1,200 μg per IQOS, and 510 μg per glo. In a study by Bekki et al. [22], the amount of nicotine emitted from the filler and mainstream smoke of IQOS was found to be almost equivalent to that of CCs. However, tobacco-specific nitrosamines (TSNAs) were emitted at one-fifth the level of CCs, and carbon monoxide emissions were one-hundredth of those produced by CCs.

Upadhyay et al. [23] compared various studies that analyzed the harmful components of HTPs. Based on emissions from CCs, they found that nicotine and tar from HTPs amounted to approximately 70% of that from CCs, ammonia and formaldehyde were around 30%, reactive oxygen species were about 25%, TSNAs and acrolein were around 10%, and carbon monoxide was less than 5%. Aromatic amines, known carcinogens, were not detected in HTP smoke. PMI has also submitted data indicating that fewer harmful substances are emitted from IQOS compared to CCs.

However, according to a study by St. Helen et al. [24], pointed out that the data on IQOS provided by PMI included only 40 of the 93 HPHCs identified by the US Food and Drug Administration. They argued that 15 of the HPHCs not analyzed by the manufacturer are produced at more than double the levels in CCs, and seven of these are generated at more than 10 times the amount.

One consideration when comparing harmful emissions from HTPs is that HTP sticks are about half the size of CC sticks [23]. Therefore, even if the amount of nicotine and other harmful substances per HTP stick is slightly lower than that of CCs, smokers might increase their consumption of HTPs per session to meet their usual nicotine intake. Additionally, it cannot be completely ruled out that nicotine and other harmful substances in HTPs, which are not present in CCs, may have influenced smokers’ LDL-C levels.

This study has several limitations. First, as a cross-sectional study using raw data from the National Health and Nutrition Examination Survey, it cannot establish a causal relationship between HTP smoking and increased serum LDL-C concentration. Future research should focus on larger-scale, long-term epidemiological and mechanistic studies. Second, the study did not quantitatively assess the dose-response relationship or cumulative effect of HTP smoking on serum LDL-C levels, as detailed surveys on smoking behavior were not conducted for HTP users. Thus, the amount and duration of HTP use were not considered. Reports suggest that increased smoking among CC smokers exacerbates dyslipidemia, including high LDL-C [15]. Therefore, future studies should take into account various factors in smoking behavior, such as the amount smoked and the total duration of smoking, for HTP users. Third, recall bias may have occurred since smoking habits were self-reported through questionnaires. Using biological markers, such as salivary or urinary cotinine, to verify smoking type could yield more objective results regarding the effects of smoking in HTP users. Finally, the statistical significance of the results may be limited by the relatively small number of HTP users in the study. However, as mentioned in the introduction, the number of HTP users in Korea is steadily increasing, and the market is rapidly expanding. Therefore, research on the health effects of HTPs is essential for public health promotion and disease prevention.

In conclusion, current exclusive HTP smoking is associated with both borderline and high serum LDL-C levels. To our knowledge, no previous studies have addressed this issue. Further research should explore whether long-term HTP use has harmful effects on users’ serum lipid profiles. Additionally, the health risks associated with dual and triple tobacco use should be investigated in larger populations.