<h4>Objective</h4>Nicotine pouch use has been linked to oral health concerns, including oral lesions and gingival irritation. This pilot study examines self-reported oral health outcomes following the use of a novel nicotine pouch (Stingfree Strong Blue Mint), with an impermeable barrier on the interior side designed to reduce mucosal irritation.<h4>Materials and methods</h4>A total of 23 Swedish dentists who were current snus or nicotine pouch users participated in a 5-week observational study. Baseline and follow-up assessments included self-reported oral health status and photographic documentation of mucosal conditions, reviewed by an independent blinded dental expert. Primary outcomes included changes in self-reported snus lesions, gingival recession, gingival irritation, and gingivitis.  Results: The prevalence of self-reported snus lesions decreased from 95.7% (n = 22) to 69.6% (n = 16). Median Axell-scale lesion severity declined from 2 (interquartile range [IQR]: 1-3) to 1 (IQR: 0-2) (z = 3.756, p = 0.0002). Moderate-to-severe lesions (Axell score ≥ 3) dropped from 39.1% (n = 9) to 0% (n = 0). Self-reported gingivitis cases (n = 3) were eliminated, and gingival irritation decreased by 90.0%.<h4>Conclusions</h4>Preliminary findings suggest that the use of the Stingfree Strong Blue Mint nicotine pouch may reduce mucosal irritation. While promising, these findings warrant validation through large randomised controlled trials to establish long-term effectiveness and safety. Despite being marketed as less harmful alternatives to combustible tobacco, research suggests that these products may still contribute to adverse oral health outcomes, including mucosal lesions, gingival recession, and gingival irritation [ 13 – 15 ]. The severity of these effects varies based on factors such as pH levels, nicotine concentration, and frequency of use [ 16 , 17 ]. Both traditional snus and ONPs have been linked to oral mucosal irritation and inflammation, particularly at the placement site [ 17 , 18 ]. To address these concerns, a novel nicotine pouch technology, the Stingfree technology pouches have been developed with an impermeable barrier for protecting the gum to minimise direct gingival irritation [ 19 ]. Designed in a slim format for discreet and easy placement under the lip, these pouches replace tobacco with a blend of tobacco derived nicotine, salt, flavourings, thickeners, fillers, sweeteners, stabilisers, acidity regulators, water, and cellulose fibres. The impermeable barrier, composed of partly (50%) plant-based, renewable materials, is intended to reduce mucosal irritation while preserving sensory experience and nicotine delivery. Materials and methods This pilot study used a pre-post observational design to assess self-reported oral health outcomes among Swedish dentists after switching to Stingfree Strong Blue Mint, a novel nicotine pouch product. Individuals eligible for the study were required to be at least 25 years old, be regular users of snus or nicotine pouches, and interested to switch to a The median consumption of oral pouches among participating dentists was four cans per week, aligning with typical usage patterns in Sweden, with some consuming up to nine cans per week. Baseline assessments indicated that most participants reported oral health concerns related to snus or nicotine pouch use, including mucosal lesions, gingival irritation, and gingival recession. Among the 23 participants who completed the study, baseline lesion severity varied between the two groups. Exclusive snus users had a higher median lesion severity score (median = 2, IQR = 1) compared to exclusive nicotine pouch users (median = 1, IQR = 1). No participants reported worsening mucosal irritation or the development of new lesions during the study. Figure 1 Snus lesion severity before and after a 5-week trial. (A) Severity 3/4 before trial in a 40–45-year-old male dentist using snus and nicotine pouches for 20+ years. (B) Severity reduced to 0/4 after 5 weeks, with a total of 45 cans consumed (9 per week). (C) Severity 4/4 before trial in a 35–40-year-old male dentist using nicotine pouches for 5–10 years. (D) Severity reduced to 1/4 after 5 weeks, with a total of 35 cans consumed (7 per week). Discussion This pilot study provides preliminary insights into the potential effects of Stingfree Strong Blue Mint on self-reported oral health outcomes amongst Swedish dentists who use nicotine pouches or snus. The findings suggest a reduction in the prevalence and severity of snus-induced mucosal lesions, with a 27.3% decrease in lesion occurrence and a significant reduction in lesion severity. In addition, cases of gingivitis were eliminated, and reports of gingival irritation declined by 90% over the 5-week study period. These trends suggest that the impermeable barrier within Stingfree nicotine pouches may reduce mucosal irritation compared to traditional nicotine pouches, aligning with the proposed mechanism of protection [ 19 ]. However, due to the lack of a control group, these findings should be interpreted with caution as external factors, such as changes in user behaviour, cannot be ruled out. Moreover, the available evidence on the regeneration of snus-related lesions in smokers and non-smokers is poor. Further studies are needed to better understand the factors influencing these processes. In addition, while these results suggest that the Stingfree pouch may reduce mucosal irritation, a direct comparison with other nicotine pouches is necessary to determine whether its impermeable barrier provides superior protection against lesion development. Further analysis using ordered logistic regression confirmed that baseline lesion severity was a significant predictor of follow-up lesion severity. This suggests that participants with higher baseline severity scores were more likely to have persistent lesions at follow-up, despite the overall reduction in lesion prevalence and severity.

<h4>Background</h4>Tobacco use is a global issue, and non-combustible nicotine products (NCNPs) like electronic nicotine delivery systems, nicotine pouches, snus, and nicotine replacement therapies offer potential risk/harm reduction for smokers unable or unwilling to quit. Although NCNPs are less harmful than tobacco smoking, their impact on oral health remains unclear. A systematic review and network meta-analysis will be conducted to answer the research question: What are the oral signs and symptoms associated with NCNPs as both monotherapies and combination therapies compared to each other, placebo, standard care, no drug treatment, and combustible cigarette smoking?<h4>Methods</h4>We will search PubMed and Scopus databases, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to August 2024. This review will focus on randomized controlled trials (RCTs) with a minimum follow-up period of 1 month, comparing any NCNPs versus placebo, standard care, no drug treatment, combustible cigarette smoking or to each other in adult smokers. Our primary outcomes will be the number of participants reporting any oral side effect, aphthous ulcers, dry mouth and mouth irritation. Studies will be excluded if they involve: non-smokers, pregnant women, individuals with mental health or neurological disorders, participants consuming alcohol or other substances. Data will be analyzed using a network meta-analysis framework, estimating odds ratios with 95% confidence intervals. Risk of bias will be determined using the Cochrane risk of bias tool-version 2.0 for included RCTs and the Confidence In Network Meta-Analysis tool will be employed to assess the confidence of evidence contributing to each network estimate.<h4>Discussion</h4>Our findings will provide critical insights into the oral health implications of NCNPs, informing clinical and public health decisions. Results are expected by May 2025 and will be disseminated through publications and presentations to guide tobacco harm reduction strategies.<h4>Systematic review registration</h4>PROSPERO CRD42024565118.

Increase in nicotine pouch (NP) users, particularly among the young, is a matter of concern requiring a comprehensive understanding of its short- and long-term oral health implications. The objective of this research was to systematically review potential oral side-effects associated with NP usage. This systematic review was conducted following the PRISMA guidelines. Databases (Medline via PubMed, Scopus, Cochrane Trial, and Google Scholar) were searched for relevant studies up to February 2024. Modified Newcastle-Ottawa Scale (NOS) and the Risk Of Bias In Non-randomized Studies - of Exposure (ROBINS-E) tool were used to assess the quality and bias of the included studies. Three studies were included for this review, two from Europe and one from USA, and considered of a total of 190 participants. All studies were deemed to have a high risk of bias. Participants used NP for periods ranging from 1 month to 10 years. Among these studies, only one study provided information on the usage pattern between 1 and 5 units for an average of 11 ± 7 min per session. Oral mucosal changes at the site of placement were common among NP users. Oral lesions varied from slight wrinkling to various white lesions, seemingly related to the NP units consumed per day and their duration of usage. Other oral side effects included dry mouth, soreness, gingival blisters, and a strange jaw sensation. Research on the use of NP and its effect on oral health are currently limited. The use of NP should take into consideration the short-and-long-term effects, especially on oral health. Further studies are crucial to understand oral health implications associated with NP usage. PROSPERO Registration number CRD 42,024,500,711. NP is generally placed between the lips and gums similar to Swedish snus for 30–60 min, which allows nicotine to be absorbed systemically via the oral mucosa. Unlike snus, it is devoid of tobacco leaf and constitutes a nicotine-containing cellulose matrix inside a fiber pouch, and added nicotine can be either naturally or synthetically sourced. Moreover, in many countries there is an absence of proper regulation regarding NP, and most consumers may be unaware of the composition, concentration, and purity of nicotine. 1 PRISMA flowchart for systematic review Table 1 Characteristics of the included studies and outcome of nicotine pouch usage Authors (year) Type of Study Country Number of participants Sex Age (years) Mean ± SD Range Frequency Mean ± SD Range & duration of usage Outcome Note Oral mucosal changes Dental & gingival status Adverse effects Salivary biomarkers Dowd et al. (2022) Cross-sectional Latvia 12 M = 10 F = 2 25.08 Snus and/or NP user = 12 For 2–10 years 9/12 with oral lesions at upper anterior and premolar areas - White, localized and leathery - White grainy lesion - White linear or round lesions - - -Increased levels of IL-1, IL-6, IL-8, TNF-alpha and LRG1 -IL-6 correlated with mucosal change Swedish snus and NP group SD standard deviation, NP Nicotine pouch, M Male, F Female, DMFT Decayed, Missing, filled Teeth, IL Interleukin, TNF tumor necrosis factor, LRG1 leucine-rich alpha-2-glycoprotein 1 Participants All the included studies did not report sample size calculation. Therefore, none of the included studies could definitively determine the impact of NP on oral health conditions. Nicotine-containing pouches raise concerns and potential risks for affecting the oral mucosa due to two primary reasons: first, their placement between the lips and gum allows continuous contact with the mucosa, enabling users to use them longer and more frequently than other tobacco or nicotine products, and second, their high nicotine content, which is primarily absorbed via the oral mucosa. One of the studies included in the analysis showed a significant percentage of mucosal changes in the group of users who used NP and snus, particularly among those with longer years of use and frequent consumption of 5 to 10 pouches per day [ 15 ]. The presence of mucosal white lesions associated with elevated levels of inflammatory biomarkers such as IL-6, IL-8, IL-1 beta, and TNF-alpha suggests a heightened risk of oral cancer [ 15 , 18 , 19 ]. Specifically, individuals in the NP and snus group exhibited the highest levels of these inflammatory markers. In addition, the highest level of LRG1 was found in the NP and snus users [ 15 ]. These findings further emphasized the potential risk for oral cancer development in these populations [ 20 ]. Although the study could not distinguish between users of snus and tobacco-free NP, its results suggested that individuals using NP might have a higher tendency to develop oral mucosal white lesions in the areas where these products are placed compared to other forms of tobacco or nicotine delivery systems. While the toxicant levels in NP appear lower than those in snus and other tobacco products [ 21 , 22 ], numerous NPs contain nicotine levels higher than what is stated on the labels, Previous studies suggest that concentrations exceeding 1 mM are more likely to cause inflammation in the oral cavity [ 34 ], and the increase of nicotine level significantly associated with higher S.mutans and caries severity in rats [ 35 ]. These findings highlight the potential influence of nicotine on periodontal tissue and the oral adverse effects on NP users. Marketing campaigns promoting non-tobacco NP or “novel” nicotine may attract tobacco users [ 36 ] and also appeal to experimental users [ 3 , 37 ], potentially leading to nicotine addiction. Several limitations of this study include data availability, study quality, and participant and outcome heterogeneity. Additionally, individual usage patterns, such as nicotine concentration, percentage of unprotonated nicotine, number of pouches used, duration, and frequency, also influence nicotine release in NP. Therefore, assessing these variables is necessary to compare oral health outcomes and accurately measure the effects of NP.