Assessing the Health Impacts of Heated Tobacco Products Compared to Traditional Tobacco Use: A Systematic Review of Current Evidence.

Heated tobacco products (HTPs) have emerged as alternatives to conventional cigarettes, promoted for their potential harm reduction by heating instead of burning tobacco. While HTPs are increasingly used worldwide, their comparative health impact relative to traditional smoking remains unclear. This systematic review and meta-analysis aimed to assess and compare the health effects of HTPs and conventional combustible tobacco products, focusing on clinical outcomes, biomarkers of exposure and harm, respiratory and oral health, and usage patterns. A comprehensive literature search was conducted across PubMed, Cochrane Library, Scopus, ScienceDirect, and DelNet, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. Eligible studies included adult human participants comparing HTPs and conventional cigarette use, reporting at least one health-related outcome. Data extraction and quality assessment were performed independently by two reviewers. Risk of bias was evaluated using the RoB 2.0 tool for randomized controlled trials and the Risk of Bias in Non-randomized studies of Interventions tool for non-randomized studies. A random-effects meta-analysis was performed wherever appropriate. In total, 20 studies met the inclusion criteria. A meta-analysis of nine outcome measures revealed consistently lower levels of harm among HTP users compared to smokers. Improvements were observed in pulmonary function (mean forced expiratory volume in one second differences: 0.13-0.21 L), and significantly reduced levels of biomarkers including 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (-0.42 ng/mL), interleukin-6 (-24.6 pg/mL), tumor necrosis factor-alpha (-15.2 pg/mL), C-reactive protein (-1.3 mg/L), 8-hydroxy-2'-deoxyguanosine (-1.6 ng/mL), and lactate dehydrogenase (-30 U/L), all with p-values <0.001. Cotinine levels and nicotine dependence scores were also significantly lower in HTP users. Additionally, oral health outcomes such as tooth discoloration and Simplified Oral Hygiene Index scores favored HTP users. Behavioral indicators suggested fewer tobacco use days per month and lower dependence among HTP users. No included study reported worse health outcomes in HTP users relative to smokers. While not risk-free, HTPs appear to be associated with significantly lower exposure to toxicants, reduced inflammation, and improved health indicators compared to traditional smoking. Due to study heterogeneity and limited long-term data, the meta-analytic findings should be interpreted with caution. Further independent, long-term research is needed to fully establish the risk profile of HTPs.