Moist Smokeless Tobacco Research Articles

The more smoking the more cataract: A study on smoking, snus use and cataract in a Swedish population.

To examine the prevalence of self-reported cataract and cataract surgery, and the incidence of cataract surgery, in relation to smoking and use of the moist smokeless tobacco product snus. In 2014/2015, individuals born in 1951 (n = 18 055) in the Västra Götaland County, Sweden, were invited to participate. Of these, 9743 (54%) accepted participation and 9316 (52%) remained after exclusion criteria were applied. Participants answered a questionnaire with items about eye conditions, smoking, snus, gender, education, asthma, chronic obstructive pulmonary disease, corticosteroid use, diabetes mellitus, weight and height. Prevalence ratios (PRs) for self-reported cataract and cataract surgery were calculated. The incidence of cataract surgery was assessed, and hazard ratios (HRs) were presented. Having ever smoked was associated with a higher prevalence ratio of self-reported cataract (PR 1.19, 95% confidence interval [CI] 1.04-1.35) and cataract surgery (PR 1.27, 95% CI 1.06-1.53), compared to those who had never been daily smokers. Currently, a smoker was associated with a higher HR of cataract surgery (HR 1.34, 95% CI 1.04-1.74), as well as having been a former smoker (HR 1.27, 95% CI 1.03-1.56). Total years of smoking were associated with an increased risk for cataract surgery (HR 1.05, 95% CI 1.02-1.08 for 5 years of smoking). Snus use was not associated with an increased prevalence of cataract or incidence of cataract surgery, except among women who were current snus users (HR for cataract surgery 2.04, 95% CI 1.16-3.60 n = 108). Smoking is associated with a higher prevalence of cataracts, and a higher incidence of cataract surgery, indicating a dose-response relationship. However, there was no firm association between snus use and cataract.

Evaluation of Dissolution Release Profiles of Nicotine and Three Distinct Flavor Markers in Loose Moist Smokeless Tobacco Products

Summary This study describes the dissolution release profiles of nicotine and flavor markers from three loose moist smoke-less tobacco (MST) products, same brand, each made with a distinct flavor. The US Pharmacopeia flow-through cell dissolution apparatus 4 (USP-4) was employed, following a previously published method that was validated to study the nicotine release from MST products. Herein, we expanded the scope of the analytical method by incorporating three flavor markers including methyl salicylate, ethyl salicylate, and glycyrrhizic acid to provide an understanding of the dissolution release profiles of not only nicotine but also of flavor markers. The dissolution release profiles of nicotine were found to be equivalent across all three tobacco products. In contrast, the release profiles of the studied flavor markers exhibited distinct differences, primarily influenced by their chemical properties, particularly polarity. Notably, glycyrrhizic acid demonstrated the most rapid release rate, while ethyl salicylate exhibited the slowest release rate. This study serves as a valuable resource for researchers, manufacturers, and regulatory bodies involved in the evaluation of MST products attributes and performance.

Salting-Out-Assisted Liquid-Liquid Extraction Method for the Determination of Nicotine from Oral Traditional and Innovative Tobacco Products Using UPLC-MS/MS.

In this study, we developed and validated a novel method that allows for the extraction and quantitation of nicotine from a variety of commercially available oral tobacco products including loose and pouched traditional moist smokeless tobacco products, and oral tobacco-derived nicotine (OTDN) lozenges, gums, and pouches. The method employed an extraction technique consisting of salting-out assisted liquid-liquid extraction using sodium hydroxide and acetonitrile in conjunction with ultra-high pressure liquid chromatography coupled to mass spectrometry. Accurate quantitation was obtained using nicotine methyl-d3 isotopically labeled internal standard. Chromatographic separation of nicotine and nicotine methyl-d3 internal standard was achieved using a Waters Acquity C18 column (50 mm × 2.1 mm i.d., 2.5 μm) with 10 mM ammonium acetate buffer (pH = 10) and acetonitrile as mobile phase A and B, respectively. Using a gradient elution and a flow rate of 0.4 mL/min for 5 min runtime, nicotine eluted at 1.74 min. The method was validated according to ICH guidelines for all the sample types with an accuracy for nicotine within 89-109%. Repeatability and intermediate precision were both estimated to be ≤7% relative standard deviation (% RSD). This method is applicable for a wide range of traditional moist smokeless and OTDN tobacco products.

Oral lesions associated with daily use of snus, a moist smokeless tobacco product. A cross-sectional study among Norwegian adolescents

Objective Use of snus, a moist, smokeless tobacco product, may lead to local changes in the oral mucous membrane in the area where the snus is placed. It can also cause irreversible gingival retraction. This cross-sectional study aimed to investigate the relationship between use of snus, oral mucosal lesions (snus induced lesions) and gingival retractions among adolescents in Norway. Material and Methods All 18–20 years olds visiting public dental health clinics in the south-eastern region of Norway between October 2015 and December 2016 were invited to participate. All participants (n = 1363) filled in an electronic questionnaire before a clinical examination. Of these, 216 used snus daily. Results Snus induced lesions were observed in 79.2% of daily snus using participants. In adjusted regression analyses, the odds of having a more severe lesion as opposed to a less severe lesion were 1.12 times greater for each additional box of snus used in a month (p < .01). Women were 46% less likely to have a severe lesion than men (p = .03). Gingival retractions were observed in 18.4% of the participants. The odds for dental retraction were significantly higher by 34% for each year of snus use. Conclusions Most of the adolescents using snus had snus induced lesions, whereas approximately one-fifth had gingival retractions. The severity of the lesion and gingival retraction increased with the amount of snus boxes used and the duration of the snus use, respectively.

Tobacco use and risk of COVID-19 infection in the Finnish general population

Empirical evidence, primarily based on hospital-based or voluntary samples, suggests that current smokers have a lower risk of COVID-19 infection than never smokers. In this study, we used nationally representative data to examine the association between tobacco use and the risk of having a confirmed COVID-19 case. We explored several forms of tobacco use, contributing to separate the role of nicotine from smoking. We used data from 44,199 participants from three pooled national health surveys in Finland (FinSote 2018–2020). The primary outcome was a confirmed COVID-19 case. We examined current smoking, moist smokeless tobacco (snus), e-cigarettes with and without nicotine and nicotine replacement therapy products. Current daily smokers had a relative risk of 1.12 of a confirmed COVID-19 case (95% CI 0.65; 1.94) in fully adjusted models compared with never smokers. Current snus use was associated with a 68% higher risk of a confirmed COVID-19 case (RR 1.68, 95% CI 1.02; 2.75) than never users. We did not find conclusive evidence of associations between e-cigarettes with and without nicotine and nicotine replacement therapy products and the risk of confirmed COVID-19 cases. Our findings suggest that nicotine might not have a protective role in the risk of COVID-19 as previously hypothesized.

Nicotine pharmacokinetics and subjective responses after using nicotine pouches with different nicotine levels compared to combustible cigarettes and moist smokeless tobacco in adult tobacco users

RationaleOral tobacco–derived nicotine products include on!® nicotine pouches (NPs) which are tobacco-leaf free and available in multiple flavors and nicotine levels. Switching completely to NPs from cigarettes and moist smokeless tobacco (MST) has the potential to reduce harm for adult tobacco consumers. However, the dependence potential of NPs is not established. Therefore, we characterized the abuse potential of NPs with different nicotine levels compared to cigarettes and MST.ObjectivesTo evaluate nicotine pharmacokinetics (PK) and subjective effects of NPs (ranging from 1.5 to 8 mg nicotine) compared to own brand cigarettes (OBCs) and MST (OBMST).MethodsWe used a randomized, in-clinic, partial single-blind, 7-way crossover design to assess nicotine PK and subjective effects in dual users of cigarettes and MST.ResultsThe mean nicotine Cmax for NPs increased with nicotine level, ranging from 3.5 ng/mL (1.5 mg NP) to 15.4 ng/mL (8 mg NP), compared with 12.2 ng/mL for OBCs and 9.8 ng/mL for OBMST. Nicotine tmax was much longer for all NPs and OBMST (32.5–34.4 min) compared to OBCs (8.5 min). Reductions in urges to smoke after use of the 2 mg, 3.5 mg, and 8 mg NPs were not statistically different (p > 0.05) relative to OBC. Also, NPs resulted in lower ratings of positive subjective effects relative to OBCs and OBMST.ConclusionsOverall, based on the study results and literature reported nicotine PK values for cigarettes and MST, the abuse potential of NPs is not likely to be higher than OBCs and OBMST. NPs may be potentially acceptable switching products for users of cigarettes and MST products.

Assessment of the Exposure to NNN in the Plasma of Smokeless Tobacco Users.

N-Nitrosonornicotine (NNN) is a human carcinogen present in cigarette smoke and smokeless tobacco. Urinary NNN is usually measured in order to assess the exposure to this toxicant for tobacco users. NNN excretion in urine can be highly biased due to the formation of NNN by nitrosation of nornicotine under acidic conditions, both endogenously and exogenously. Hence, urinary NNN levels may not necessarily correctly reflect the product-specific exposure. Measurement of plasma NNN may be less prone to endogenous formation due to the stable pH (7.4) of blood. We developed an LC–MS/MS method for the quantification of NNN using 1 mL of human plasma. Validation according to FDA guidelines proved that the method is selective and highly sensitive with an LLOQ of 0.3 pg/mL. Accuracy and precision averaged to 98.7 and 7.5% (CV), respectively. The assay was applied to plasma samples collected from 10 experienced moist smokeless tobacco users during and after a single use of 2 g of the product for 40 min under controlled use conditions. Blood was drawn at 15 time points over a 6 h time course. The maximum NNN concentration (Cmax) ranged from 3.5 to 10 pg/mL (mean: 7.1 pg/mL) at a tmax of 32 min. Plasma NNN and nicotine were found to have similar time courses. In conclusion, the determination of NNN in plasma may be fit-for-purpose to evaluate the product-use-specific exposure to this carcinogen.

Nicotine Content in Swedish-Type Snus Sold in Norway From 2005 to 2020.

IntroductionUse of snus (moist smokeless tobacco) is widespread in Scandinavia and increasingly popular in the U.S. Snus products vary in terms of product design, portion size, and nicotine content. The aim of this study was to examine variations in the nicotine content in snus sold on the Norwegian market from 2005 to 2020.MethodsWe calculated the nicotine content in dry snus in milligram per gram (mg/g) and milligram per serving (mg/s), weighted by the products’ market share from data on nicotine content, water content, and portion size (both for portion and loose snus) for the ten most sold snus products from each of the three largest manufacturers in 2005, 2010, 2015, and 2020.ResultsIn all snus products combined, the nicotine content per gram snus (mg/g) increased from 16.3 to 24.1, while nicotine per serving (mg/s) was stable around 13.0. In portion snus, the nicotine content increased for both mg/g and mg/s, most notably from 2005 to 2010. In loose snus, mg/g decreased marginally, while mg/s was stable throughout the period.ConclusionsIn a period with increasing snus use, the nicotine content in snus increased per gram snus, but not per serving. The stability in nicotine per serving is likely due to a decreasing market share of loose snus which accounted for 54% of the snus products in 2005 and 5% in 2020, and which traditionally has a high content of nicotine per serving.ImplicationsUse of snus is popular in Scandinavia, most notably in Sweden and Norway, but also increasingly common in Finland, especially among young adults. There are no prior market-based studies of variations in the nicotine content in Swedish snus over time. We found that the average amount of nicotine per gram snus sold on the Norwegian market increased in the period 2005 to 2020, most notably from 2005 to 2010, while the amount of nicotine per serving was stable in the same period, primarily due to a decreasing share of loose snus.

Bacteriome of Moist Smokeless Tobacco Products Consumed in India With Emphasis on the Predictive Functional Potential.

Smokeless tobacco products (STPs) carry assorted microbial population that contributes to carcinogens synthesis like tobacco-specific nitrosamines (TSNAs). Extensive exploration of microbiota-harboring STPs is required to understand their full carcinogenic potential. Here, we applied 16S rRNA gene sequencing to investigate bacteriome present in moist STPs immensely consumed in India (Khaini, Moist-snuff, Qiwam, and Snus). Further, the functional metagenome was speculated by PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) to assign the abundance of genes related to nitrogen metabolism, bacterial toxins, antibiotic drug resistance and other pro-inflammatory molecules. Highly diverse bacterial communities were observed in all moist STPs. Taxonomic analysis revealed a total of 549 genera belonging to four major phyla Proteobacteria, Firmicutes, Bacteroidetes and Actinobacteria. Overall, the core bacterial genera Acinetobacter, Bacillus, Prevotella, Acetobacter, Lactobacillus, Paracoccus, Flavobacterium, and Bacteroides were significantly abundant in moist STPs. Elevated moisture-holding products like Moist-snuff and Qiwam harbor rich bacterial species diversity and showed similar bacteriome composition. Furthermore, Qiwam products showed the highest level of genes associated with nitrogen metabolism, antibiotic resistance, toxins, and pro-inflammation (predicted by PICRUSt) which can contribute to the synthesis of TSNAs and induction of oral cancer. The present broad investigation of moist STPs-associated bacteriome prevalence and their detailed metabolic potential will provide novel insight into the oral carcinogenesis induced by STPs.

Plasma Cotinine Is Positively Associated with Homocysteine in Smokers but Not in Users of Smokeless Tobacco.

Plasma total homocysteine (tHcy) is a risk marker, and smoking is an established risk factor for cardiovascular disease. It is unclear if the effect of smoked tobacco on homocysteine is mediated by nicotine or other combustion products in smoked tobacco. Snus (moist smokeless tobacco) is high nicotine-containing tobacco, and little is known about the effect of snus on plasma homocysteine. Therefore, we studied, in a cross-section of subjects (n = 1375) from the Northern Sweden Health and Disease Study, with strictly defined current smokers (n = 194) and snus users (n = 47), the impact of tobacco exposure on tHcy, assessed by self-reported tobacco habits and plasma cotinine concentrations. The snus users had higher cotinine concentrations than the smokers. Cotinine, creatinine, methylmalonic acid, and the methylenetetrahydrofolate reductase genotype (MTHFR) T allele were positively associated with tHcy among the smokers, but not among the snus users. No association was observed between tHcy and the number of cigarettes/day. There was a positive association between cotinine and tHcy in the smokers, but not among the snus users. This indicates that substances other than nicotine in tobacco smoke could be responsible for the differential effects on homocysteine status. Self-reported smoking should be complemented by a cotinine assay whenever possible.

Snus and Alcohol: Mutually Rewarding Effects in the Brain? A Matched Controlled Population Study.

Background:The use of moist smokeless tobacco (snus) is increasing in the U.S. and other Western countries, and especially among young people. Snus is associated with several health problems, but the relationship between use of snus and alcohol is scarcely explored. Neuro-cognitive and psychological research suggest an association due to possible mutually rewarding effects in the limbic brain. We investigated this issue in a matched controlled population study.Methods:Matched control group design where drinking habits and alcohol consumption in a group of users of snus (n = 1043, mean age = 35.20; n men = 749, n women = 294) were compared to a control group of non-users matched on age and gender (n = 1043, mean age = 35.65; n men = 749, n women = 294). In addition, we registered background variables such as level of education, income, self-perceived general, dental health, mental health, current depressive symptoms, and BMI. In estimation of alcohol consumption, the background variables were used as covariates in factorial analyses of variance (ANCOVA).Results:Users of snus had lower level of education, lower income, poorer general, dental, and mental health status than non-users, but there were no differences in BMI. Differences in mental health status were related to drinking habits. Users of snus had a higher frequency of drinking, higher frequency of intoxication, and showed more excess drinking. Controlled for background variables users of snus had a 25.2% higher estimated yearly consumption of alcohol in terms of standard units of alcohol on the weekdays, 26.4% higher on weekends and a 60.2% higher yearly excess consumption.Conclusion:Users of snus had an elevated alcohol consumption and another drinking style than non-users. The findings are discussed according to neuro-cognitive and psychopharmacological mechanisms, reward learning and conditioning. The results have implications for prevention, treatment and rehabilitation of alcohol and nicotine dependence.

Variability of TSNA in U.S. Tobacco and Moist Smokeless Tobacco Products

Tobacco-specific nitrosamines (TSNAs) have been of concern to the public health community for decades and their reduction through agricultural practices, plant breeding, and tobacco processing has also been a decades-long industry effort. Despite those efforts, TSNAs, though lower, continue to be constituents of concern in tobacco products. This paper examines the TSNA levels of dark air-cured, dark fire-cured, and burley tobaccos purchased in the United States by U.S. Smokeless Tobacco Company LLC (USSTC) and of nine finished USSTC moist smokeless tobacco products. TSNA values of the incoming purchased tobaccos and the finished products showed considerable variability. For the incoming tobaccos, the coefficient of variation was generally more than 100 % for each tobacco type and for each of the measured TSNAs. The relative TSNA variability of the finished tobacco products was also considerable, averaging approximately 25 %. It was also found that the measured values for the finished products averaged well above the proposed FDA NNN proposed product standard of 1.0 μg/g dry weight. Because of the large variability in NNN values, products would have to average well below FDA’s proposed product standard to be consistently compliant.

Smoking is associated with risk for developing inflammatory bowel disease including late onset ulcerative colitis: a prospective study

Objectives: Life style factors have been associated with inflammatory bowel disease (IBD) but there is a lack of data on the exposure of life styles factors before the onset of IBD. Our aim was to study the association between lifestyle factors and the development of IBD in a prospective setting.Materials and methods: We performed a case control study of 72 patients who later developed ulcerative colitis (UC), 26 patients who developed Crohn’s disease (CD) and 427 healthy controls from the Västerbotten intervention project matched for gender, age, year of health survey and area of residence. At recruitment, participants completed validated lifestyle questionnaires including data on alcohol intake. Information from this was used to assess the connection between lifestyle factors and later developing IBD.Results: For CD and UC, the median age at diagnosis was 53 and 52 years and median time of survey was 4 and 6 years before diagnosis, respectively. Multivariate odds ratio (OR) showed an association between never smoking and not developing IBD, including both UC and CD, OR (95% CI) 0.341 (0.136–0.853) and 0.473 (0.259–0.864), respectively. Marital status, educational level, alcohol consumption, reported physical activity and use of moist smokeless tobacco (snus) did not differ between patients and controls.Conclusions: Smoking proves to be a risk factor for both CD and UC in this prospective case-control study. No association was seen for snus users, implying a non-nicotine pathogenic mechanism from combusted tobacco.

Moist smokeless tobacco (Snus) use and risk of Parkinson's disease.

Cigarette smoking is associated with a lower risk of Parkinson's disease. It is unclear what constituent of tobacco smoke may lower the risk. Use of Swedish moist smokeless tobacco (snus) can serve as a model to disentangle what constituent of tobacco smoke may lower the risk. The aim of this study was to determine whether snus use was associated with a lower risk of Parkinson's disease. Individual participant data were collected from seven prospective cohort studies, including 348 601 men. We used survival analysis with multivariable Cox regression to estimate study-specific relative risk of Parkinson's disease due to snus use, and random-effects models to pool estimates in a meta-analysis. The primary analyses were restricted to never-smokers to eliminate the potential confounding effect of tobacco smoking. During a mean follow-up time of 16.1 years, 1199 incident Parkinson's disease cases were identified. Among men who never smoked, ever-snus users had about 60% lower Parkinson's disease risk compared with never-snus users [pooled hazard ratio (HR) 0.41, 95% confidence interval (CI) 0.28-0.61]. The inverse association between snus use and Parkinson's disease risk was more pronounced in current (pooled HR 0.38, 95% CI 0.23-0.63), moderate-heavy amount (pooled HR 0.41, 95% CI 0.19-0.90) and long-term snus users (pooled HR 0.44, 95% CI 0.24-0.83). Non-smoking men who used snus had a substantially lower risk of Parkinson's disease. Results also indicated an inverse dose-response relationship between snus use and Parkinson's disease risk. Our findings suggest that nicotine or other components of tobacco leaves may influence the development of Parkinson's disease.

Alternative Tobacco Products as a Second Front in the War on Tobacco

Alternative Tobacco Products as a Second Front in the War on Tobacco

Use of moist smokeless tobacco (snus) and the risk of development of alcohol dependence: A cohort study in a middle-aged population in Sweden

BackgroundConvincing evidence shows that smoking is associated with alcohol dependence (AD) and a positive correlation between snus and alcohol consumption was previously shown in cross-sectional studies. We performed a longitudinal evaluation of the risk of snus users to develop AD. MethodsA cohort study in Västerbotten County, Sweden, linked individual data on socioeconomic situation and health survey data from 21,037 men and women (46.5% men). AD was defined by the CAGE questionnaire and evaluated at baseline 1991–1997 and again after 10 years. The risk of developing AD was assessed using logistic regression analysis and propensity score matching. Results2370 men and 430 women used snus and were without AD at baseline. Over the 10-year period, 499 men and 257 women developed AD, among whom 191 and 26, respectively, were baseline snus users. The crude relative risks of AD for male and female snus users compared to non-users were 1.8 with 95% CI (1.5, 2.2) and 2.9 (2.0, 4.3), respectively. Adjusted logistic regression showed a positive dose–response relationship between snus use and risk of AD. Analyses involving propensity score matching revealed 33 and 17 new cases of AD in men and women, respectively, after 10 years given 1000 men and 1000 women without AD had been baseline snus users rather than non-users. Results for current, previous and never smokers were similar. ConclusionsThe use of snus is prospectively associated with an increased risk of AD with a dose–response relationship that is independent of smoking status.

Tobacco product prices before and after a statewide tobacco tax increase

BackgroundIn 2013, the State of Minnesota Legislature passed a tobacco tax increase that increased the combined cigarette excise and sales tax by US$1.75 (from US$1.60 to US$3.35) and increased the...

Discontinuation of smokeless tobacco and mortality risk after myocardial infarction.

Given the indications of increased risk for fatal myocardial infarction (MI) in people who use snus, a moist smokeless tobacco product, we hypothesized that discontinuation of snus use after an MI would reduce mortality risk. All patients who were admitted to coronary care units for an MI in Sweden between 2005 and 2009 and were <75 years of age underwent a structured examination 2 months after discharge (the baseline of the present study). We investigated the risk of mortality in post-MI snus quitters (n=675) relative to post-MI continuing snus users (n=1799) using Cox proportional hazards analyses. During follow-up (mean 2.1 years), 83 participants died. The mortality rate was 9.7 (95% confidence interval, 5.7-16.3) per 1000 person-years at risk in post-MI snus quitters and 18.7 (14.8-23.6) per 1000 person-years at risk in post-MI continuing snus users. After adjustment for age and sex, post-MI snus quitters had half the mortality risk of post-MI continuing snus users (hazard ratio, 0.51; 95% confidence interval, 0.29-0.91). In a multivariable-adjusted model, the hazard ratio was 0.57 (95% confidence interval, 0.32-1.02). The corresponding estimate for people who quit smoking after MI versus post-MI continuing smokers was 0.54 (95% confidence interval, 0.42-0.69). In this study, discontinuation of snus use after an MI was associated with a nearly halved mortality risk, similar to the benefit associated with smoking cessation. These observations suggest that the use of snus after MI should be discouraged.

In-utero exposure to maternal smoking is not linked to tobacco use in adulthood after controlling for genetic and family influences: a Swedish sibling study.

Previous studies have linked maternal smoking during pregnancy with regular tobacco use in offspring, but findings are not consistent and confounding from genetic and environmental factors have not fully been taken into account. A comparison between siblings discordant for prenatal smoking exposure adjusts for confounding by shared familial (i.e., genetic and environmental) factors. We investigated the association between prenatal exposure to maternal smoking during pregnancy and the risk of regular smoking or snus (Swedish moist smokeless tobacco) use in young adult offspring, using a population based matched cohort study. The cohort consisted of 1,538 randomly sampled same-sex sibling pairs, discordant for maternal smoking during pregnancy, 19-27 years old, participating in a survey conducted in Sweden 2010-2011. Lifetime and current history of tobacco use was self-reported in the survey, and information about maternal smoking during pregnancy was retrieved from the Medical Birth Register. Conditional logistic regression and stratified Cox proportional hazards regression were used to calculate odds ratios, hazard ratios, and corresponding 95% confidence intervals. Analyses of exposure-discordant siblings did not reveal significant associations between prenatal exposure to maternal smoking and lifetime or current daily tobacco use, intensity of use, or time to onset of daily tobacco use. These findings suggest that the previously reported higher risks of tobacco use in offspring of mothers who smoked during pregnancy, compared with offspring of non-smoking mothers, were likely due to confounding from genetic or environmental factors.

Snus (Swedish smokeless tobacco) use and risk of stroke: pooled analyses of incidence and survival

Snus is a moist smokeless tobacco product with high nicotine content. Its use has a short-term effect on the cardiovascular system, but the relationship between snus use and stroke is unclear. The aim of this study was to assess the associations between use of snus and incidence of and survival after stroke, both overall and according to subtypes. Pooled analyses of eight Swedish prospective cohort studies were conducted, including 130485 men who never smoked. We estimated hazard ratios (HRs) with 95% confidence intervals (CIs) of incidence and death after diagnosis using Cox proportional hazard regression models and case fatality and survival using logistic regression and Kaplan-Meier methods, respectively. No associations were observed between the use of snus and the risk of overall stroke (HR 1.04, 95% CI 0.92-1.17) or of any of the stroke subtypes. The odds ratio (OR) of 28-day case fatality was 1.42 (95% CI 0.99-2.04) amongst users of snus who had experienced a stroke, and the HR of death during the follow-up period was 1.32 (95% CI 1.08-1.61). Use of snus was not associated with the risk of stroke. Hence, nicotine is unlikely to contribute importantly to the pathophysiology of stroke. However, case fatality was increased in snus users, compared with nonusers, but further studies are needed to determine any possible causal mechanisms.