- Systematic review finds consistently lower toxicant and inflammatory biomarker levels in heated tobacco users than in smokers
- Studies report comparable or modestly improved respiratory function among heated tobacco users
- Biomarkers tied to cancer risk, oxidative stress and cardiovascular strain were significantly reduced
- No studies showed worse outcomes for heated tobacco users compared with smokers
A new systematic review and meta-analysis has found that heated tobacco products (HTPs) are associated with lower toxicant exposure and improved health markers compared with conventional cigarettes.
The findings, published in the Cureus Journal of Medical Science, add to a growing body of evidence supporting tobacco harm reduction.
The review assessed 20 studies and included a quantitative meta-analysis of nine, drawing on data from clinical trials, cross-sectional studies, case-control research and cellular investigations.
Across the board, the studies compared adults using heated tobacco with those smoking combustible cigarettes, examining outcomes ranging from respiratory function and nicotine exposure to inflammation, oxidative stress and oral health.
HTPs – devices that heat processed tobacco rather than burn it – produce aerosols with markedly fewer combustion-derived toxicants, a factor reflected in the biological profiles tracked in the studies.
Consistently lower biomarkers of exposure
One of the strongest patterns in the analysis was a clear reduction in toxicant exposure among heated tobacco users. Several studies found markedly lower levels of NNAL, a carcinogenic tobacco-specific chemical.
Carbon monoxide levels were also consistently lower, with controlled trials showing drops of more than 10 parts per million.
Inflammatory biomarkers followed the same direction. Measures such as C-reactive protein, IL-6 and TNF-α were notably reduced in heated tobacco users, as were markers of oxidative stress including
8-hydroxy-2′-deoxyguanosine and lactate dehydrogenase. Together, these findings point to lower systemic inflammation and oxidative strain.
Although there was variation between studies, the results were consistently aligned: none reported higher toxicant exposure among heated tobacco users, and many showed statistically significant reductions.
Respiratory and cardiovascular indicators
Respiratory outcomes were generally positive. Three studies reported higher or similar lung function – measured by forced expiratory volume in one second (FEV₁), a standard indicator of how well the lungs work – in heated tobacco users compared with smokers.
The pooled result was not statistically significant, but the overall trend favoured HTPs, reflecting reduced airway irritation when there is no combustion.
Metabolic and cardiovascular markers also moved in a favourable direction. One study reported lower LDL cholesterol – often referred to as “bad” cholesterol – among heated tobacco users. Other research found reduced activity associated with tissue scarring in heart cells exposed to blood samples from HTP users.
Reduced nicotine exposure and dependence
Nicotine biomarkers, including salivary cotinine, were consistently lower in HTP groups. Two population-level studies found reduced nicotine dependence scores and fewer days of monthly use among heated tobacco users compared with cigarette smokers.
These behavioural patterns may reflect differences in delivery, user habits or product design, though the review notes that causality cannot be established.
Oral health improvements
Oral health outcomes showed some of the largest relative differences. Studies reported substantially reduced tooth discoloration and lower oral hygiene index scores among HTP users, attributed in part to the lower temperatures used and the absence of tar.
Evidence base and limitations
Risk-of-bias assessments rated the randomised trials as generally low risk, while observational studies were more variable, with some concerns related to confounding and exposure classification. Despite these limitations, sensitivity analyses suggested that the overall findings were robust.
However, the authors emphasise gaps in long-term evidence. Most studies were short-term or cross-sectional, meaning they could not capture chronic outcomes such as cancer, chronic obstructive pulmonary disease (COPD) progression or cardiovascular events. High heterogeneity in biomarker reporting also limits the precision of pooled estimates.
Implications for harm reduction
While the review stresses that heated tobacco products are not risk-free, the compiled evidence indicates a substantially lower harm profile compared with combustible cigarettes. The reductions in carcinogen exposure, systemic inflammation and oxidative stress – combined with stable or improved respiratory markers – suggest meaningful differences in biological impact.
For policymakers, the findings provide additional detail for harm reduction strategies aimed at adults who smoke but do not quit. The authors note, however, that concerns about dual use, youth uptake and the variability of product designs mean regulation should remain cautious and evidence-based.
The review concludes that HTPs may play a role in reducing smoking-related disease burden, but calls for long-term, independent studies to clarify their full risk profile and public health impact.
