Swedish Smokeless Tobacco Research Articles

Incidence of LADA and Type 2 Diabetes in Relation to Tobacco Use and Genetic Susceptibility to Type 2 Diabetes and Related Traits: Findings From a Swedish Case-Control Study and the Norwegian HUNT Study.

Smoking and Swedish smokeless tobacco (snus) are associated with latent autoimmune diabetes in adults (LADA) and type 2 diabetes (T2D). Our aim was to investigate whether genetic susceptibility to T2D, insulin resistance (IR), and insulin secretion (IS) aggravate these associations. We used data from two population-based Scandinavian studies with case subjects with LADA (n = 839) and T2D (n = 5,771), matched control subjects (n = 3,068), and 1,696,503 person-years at risk. Pooled, multivariate relative risks (RR) with 95% CI were estimated for smoking/genetic risk scores (T2D-GRS, IS-GRS, and IR-GRS), and ORs for snus or tobacco/GRS (case-control data). We estimated additive (proportion attributable to interaction [AP]) and multiplicative interaction between tobacco use and GRS. The RR of LADA was elevated in high IR-GRS heavy smokers (≥15 pack-years; RR 2.01 [CI 1.30, 3.10]) and tobacco users (≥15 box/pack-years; RR 2.59 [CI 1.54, 4.35]) compared with low IR-GRS individuals without heavy use, with evidence of additive (AP 0.67 [CI 0.46, 0.89]; AP 0.52 [CI 0.21, 0.83]) and multiplicative (p = 0.003; p = 0.034) interaction. In heavy users, there was additive interaction between T2D-GRS and smoking, snus, and total tobacco use. The excess risk conferred by tobacco use did not differ across GRS categories in T2D. Tobacco use may confer a higher risk of LADA in individuals with genetic susceptibility to T2D and insulin resistance, whereas genetic susceptibility does not seem to influence the increased T2D incidence associated with tobacco use.

Use of Swedish smokeless tobacco during pregnancy: A systematic review of pregnancy and early life health risk.

Smokeless tobacco is a heterogeneous product group with diverse composition and prevalence globally. Tobacco use during pregnancy is concerning due to the risk of adverse pregnancy outcomes and effects on child health. Nicotine may mediate several of these effects. This systematic review measured health outcomes from Swedish smokeless tobacco (snus) use during pregnancy. Literature search was conducted by an information specialist in May 2022. We included human studies of snus use during pregnancy compared with no tobacco use, assessed risk of bias, conducted a meta-analysis and assessed confidence in effect-estimates using Gradingof Recommendations, Assessment, Development and Evaluations (GRADE). We included 18 cohort studies (42 to 1 006 398 participants). Snus use during pregnancy probably (moderate confidence in risk estimates) increase the risk of neonatal apnea, adjusted odds ratio 95% confidence interval [aOR (95% CI)] 1.96 (1.30 to 2.96). Snus use during pregnancy possibly (low confidence in risk estimates) increase the risk of stillbirths aOR 1.43 (1.02 to 1.99), extremely premature births aOR 1.69 (1.17 to 2.45), moderately premature birth aOR 1.26 (1.15 to 1.38), SGA aOR 1.26 (1.09 to 1.46), reduced birth weight mean difference of 72.47 g (110.58 g to 34.35 g reduction) and oral cleft malformations aOR 1.48 (1.00 to 2.21). It is uncertain (low confidence in risk estimates, CI crossing 1) whether snus use during pregnancy affects risk of preeclampsia aOR 1.11 (0.97 to 1.28), antenatal bleeding aOR 1.15 (0.92 to 1.44) and very premature birth aOR 1.26 (0.95 to 1.66). Risk of early neonatal mortality and altered heart rate variability is uncertain, very low confidence. Snus using mothers had increased prevalence of caesarean sections, low confidence. This systematic review reveals that use of smokeless tobacco (snus) during pregnancy may adversely impact the developing child.

The effect of a non-tobacco-based nicotine pouch on mucosal lesions caused by Swedish smokeless tobacco (snus).

Oral mucosal lesions are commonly found in Swedish smokeless tobacco (snus) users where the pouch is placed. These lesions are reversible, that is, clinical and histological tissue changes return to normal following cessation. However, the exact mechanisms behind these changes are unknown. The main aim of this study was to investigate how snus‐like non‐tobacco‐based nicotine pouches affect the oral mucosa and the severity of pre‐existing lesions. Sixty regular users of Swedish smokeless tobacco were encouraged to substitute their snus with non‐tobacco‐based nicotine pouch products during a 6‐week period. Meanwhile, oral mucosal lesions were assessed using a four‐degree scale. Over time, a reduction of pre‐existing mucosal lesions was observed between baseline and the final visit. In a second part, the effect of exposure to regular snus on the production of 48 different cytokines in peripheral blood mononuclear cells was compared in vitro with that resulting from exposure to the non‐tobacco‐based nicotine products. Results showed significantly increased production of proinflammatory cytokines in cells exposed to regular snus compared to untreated or cells exposed to the non‐tobacco‐based nicotine products. This may be related to the improved clinical appearance of the oral mucosa in the participants that used the non‐tobacco‐based nicotine test pouches.

Association of snus experimentation in late adolescence with daily cigarette smoking in early adulthood: A longitudinal study among Finnish men.

Aims: Swedish smokeless tobacco (snus) is a lower-risk tobacco product than cigarette smoking for individuals. However, the public health impact of snus use is less well studied. Critically, it is uncertain whether use of snus leads to the onset of smoking. This study aimed to investigate prospectively the association between snus experimentation in late adolescence and daily cigarette smoking in early adulthood among Finnish young men. Methods: Data were obtained from 1090 young men within the population-based FinnTwin12 cohort. At baseline (mean age 17 years), we assessed lifetime use of cigarettes and snus, plus other potential predictors of cigarette smoking. At follow-up (mean age 24 years), participants were categorized according to their current smoking status. The final analyses were conducted among 375 young men who were never smokers at baseline with adequate data on follow-up smoking status and other potential predictors of cigarette smoking. Results: Age-adjusted logistic regressions showed an increased risk of becoming a daily smoker at follow-up among those participants who had at least tried snus but had never smoked cigarettes at baseline (odds ratio (OR) 6.48, 95% confidence interval (CI) 2.02-20.7), compared with those who had never used snus. When additionally adjusted for monthly alcohol intoxication, maternal smoking, and peer drug use, the association between snus experimentation and later daily cigarette smoking was attenuated, but remained significant (OR 3.94, 95% CI 1.22-12.7). Conclusions: Our data support the proposition that snus experimentation during late adolescence is longitudinally associated with daily cigarette smoking in early adulthood. Although a causal association cannot be inferred with certainty, snus experimentation might constitute an indicator of the propensity to proceed to regular snus use and initiation of use of other tobacco or nicotine products.

The composition of contemporary American and Swedish smokeless tobacco products

The major components of 70 brands of smokeless tobacco products (STPs) from Sweden and the US were determined to provide greater understanding of the general chemical composition of these products. Various styles of STPs were examined: loose and portion snus from Sweden, and chewing tobacco, dry snuff, moist snuff, hard pellet, soft pellet and plug from the US. The components analysed were major STP components such as water, nicotine, sugars, humectants, sodium ions, chloride ions and ash. The relative quantities of the components varied significantly between different styles of STP. The major component of moist snuff and Swedish loose snus is water. With Swedish portion snus water and pouch material comprise more than half of the product mass; with chewing tobaccos water and sugars comprise around 60% of the products. With these STPs, tobacco was a minor component (30–35%) of the product mass. By way of contrast, tobacco comprised the majority (around 70–90%) of the product mass with dry snuff, hard pellet and soft pellet products. Additives such as sugars, propylene glycol, glycerol, and sodium chloride comprised up to around 12% of the STPs, except for plug and chewing tobaccos where sugars comprised 15–30% by mass of the STP on average. Significant disagreements were found amongst alternative methods of determining water/moisture content for STPs. In particular the oven method, commonly used to determine moisture in tobacco, gave significantly higher values than the Karl Fischer water method when propylene glycol was present. Smaller but similar differences were found using the Near-Infrared method. Choice of measurement technique has important consequences for accuracy of toxicant levels when reporting on a dry-weight basis, a commonly used parameter in smokeless tobacco research and emerging regulatory standards. Conversion to a DWB was also found to produce a preferential bias between and within different STP categories in favour of drier products. These data provide greater understanding of differences in the compositions of contemporary smokeless tobacco products, and demonstrate challenges associated with conversion of actual product contents to dry weight basis values.

Tobacco and type 2 diabetes: is the association explained by genetic factors?

Smoking and use of Swedish smokeless tobacco (snus) are associated with increased risk of type 2 diabetes (T2D). Our aim was to estimate the unique and shared genetic components of these traits and to what extent the association is explained by shared genetic factors. We used twins of the Swedish Twin Registry who responded to a questionnaire between 1998 and 2006 (n = 40 247) and were followed until 2015 in the National Prescription and Patient Registries. We estimated hazard ratios (HRs) and odds ratios (ORs) for the association between smoking/snus use and T2D (n = 2130) and used structural equation models to estimate genetic and environmental variance components and genetic correlations. Current smokers [HR 1.69, 95% confidence interval (CI), 1.49-1.92] and snus users (HR 1.19, 95% CI 1.01-1.41) had an increased risk of T2D. In within-pair analyses of monozygotic twins, corresponding ORs were 1.36, 95% CI 0.75-2.46 (smoking) and 1.54, 95% CI 0.80-2.99 (snus). Heritability was 43% (95% CI 36-51)for ever smoking, 58% (95% CI 44- 70) for ever snus use and 66% (95% CI 59-72) for T2D. The genetic correlation with T2D was 18% (95% CI 1-35) for smoking and -6% (95% CI -24 to 4) for snus use, indicating that only a small fraction of the genetic influence is shared. We could confirm that consumers of snus and cigarettes are at increased risk of T2D. Both snus use and smoking have strong genetic components, which appears to be attributable primarily to genes that are distinct from those promoting T2D.

Smokeless tobacco use and circulatory disease risk: a systematic review and meta-analysis

ObjectiveSmokeless tobacco use is a public health issue throughout the world, but reviews and analyses of circulatory disease risks associated with smokeless tobacco use may be outdated or incomplete. This...

Cardiovascular effects of electronic cigarettes.

Cardiovascular safety is an important consideration in the debate on the benefits versus the risks of electronic cigarette (EC) use. EC emissions that might have adverse effects on cardiovascular health include nicotine, oxidants, aldehydes, particulates, and flavourants. To date, most of the cardiovascular effects of ECs demonstrated in humans are consistent with the known effects of nicotine. Pharmacological and toxicological studies support the biological plausibility that nicotine contributes to acute cardiovascular events and accelerated atherogenesis. However, epidemiological studies assessing Swedish smokeless tobacco, which exposes users to nicotine without combustion products, generally have not found an increased risk of myocardial infarction or stroke among users, but suggest that nicotine might contribute to acute cardiovascular events, especially in those with underlying coronary heart disease. The effects of aldehydes, particulates, and flavourants derived from ECs on cardiovascular health have not been determined. Although ECs might pose some cardiovascular risk to users, particularly those with existing cardiovascular disease, the risk is thought to be less than that of cigarette smoking based on qualitative and quantitative comparisons of EC aerosol versus cigarette smoke constituents. The adoption of ECs rather than cigarette smoking might, therefore, result in an overall benefit for public health.

Smokeless tobacco (snus) is associated with an increased risk of type 2 diabetes: results from five pooled cohorts.

Smoking and nicotine exposure increase insulin resistance and the risk of type 2 diabetes. Swedish smokeless tobacco (snus) is high in nicotine, and its use is prevalent in Scandinavian countries, but few studies have investigated snus use in relation to diabetes risk. To explore the association between snus use and risk of type 2 diabetes using pooled data from five cohorts. Analyses were based on prospective studies conducted between 1990 and 2013 including 54 531 never-smoking men and 2441 incident cases of type 2 diabetes identified through screening, self-reporting and hospital and prescription registries. Hazard ratios (HRs) and 95% confidence intervals (CIs) were assessed and adjusted for age, body mass index, educational level, alcohol consumption and physical activity. Compared to never users, the HR of type 2 diabetes was 1.15 (95% CI: 1.00-1.32) in current users of snus. In individuals consuming 5-6 boxes per week, the HR was 1.42 (95% CI: 1.07-1.87); in those consuming ≥7 boxes per week, the HR was 1.68 (95% CI: 1.17-2.41). Each additional box of snus consumed per week yielded an HR of 1.08 (95% CI: 1.01-1.16). Our findings indicate that high consumption of snus is a risk factor for type 2 diabetes. The risk was similar to that in smokers, implying that smokers will not reduce their risk of type 2 diabetes by changing to snus use. The results also support the notion that nicotine increases the risk of type 2 diabetes.

Use of Swedish smokeless tobacco (snus) and the risk of Type 2 diabetes and latent autoimmune diabetes of adulthood (LADA).

It has been suggested that moist snuff (snus), a smokeless tobacco product that is high in nicotine and widespread in Scandinavia, increases the risk of Type 2 diabetes. Previous studies are however few, contradictory and, with regard to autoimmune diabetes, lacking. Our aim was to study the association between snus use and the risk of Type 2 diabetes and latent autoimmune diabetes of adulthood (LADA). Analyses were based on incident cases (Type 2 diabetes, n = 724; LADA, n = 200) and population-based controls (n = 699) from a Swedish case-control study. Additional analyses were performed on cross-sectional data from the Norwegian HUNT study (n = 21 473) with 829 prevalent cases of Type 2 diabetes. Odds ratios (OR) were estimated adjusted for age, BMI family history of diabetes and smoking. Only men were included. No association between snus use and Type 2 diabetes or LADA was seen in the Swedish data. For Type 2 diabetes, the OR for > 10 box-years was 1.00 [95% confidence interval (CI), 0.47 to 2.11] and for LADA 1.01 (95% CI, 0.45 to 2.29). Similarly, in HUNT, the OR for Type 2 diabetes in ever-users was estimated at 0.91 (95% CI, 0.75 to 1.10) and in heavy users at 0.92 (95% CI, 0.46 to 1.83). The risk of Type 2 diabetes and LADA is unrelated to the use of snus, despite its high nicotine content. This opens the possibility of the increased risk of Type 2 diabetes seen in smokers may not be attributed to nicotine, but to other substances in tobacco smoke.

Inhibition by blueberries (bilberries) and extract from milk thistle of rat forestomach hyperplasia induced by oral smokeless tobacco (Swedish snus)

The aim of this study was to identify palatable additives which have a significant protective action against soft tissue changes in the oral cavity caused by Swedish smokeless tobacco (“snus”), and that satisfy existing legal requirements.Although the cancer risk from snus is extremely low, long term use may result in highly undesirable keratotic lesions and associated epithelial abnormalities in the oral cavity.The rat forestomach, which is vulnerable to the irritative action of non-genotoxic compounds like butylated hydroxyanisole, propionic acid as well as snus, was chosen as an experimental model. Studied toxicological endpoints included histopathology and cellular proliferation based on DNA incorporation of bromodeoxyuridine.After 6 weeks' exposure, blueberries (bilberries) and an extract from the common milk thistle were found to exert a highly significant inhibition of cell proliferation induced by snus in the rat forestomach epithelium, indicating a potential protection with respect soft tissue changes in the human oral cavity.

Sources of polycyclic aromatic hydrocarbons in US and Swedish smokeless tobacco products

Sources of polycyclic aromatic hydrocarbons in US and Swedish smokeless tobacco products

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.

Polycyclic aromatic hydrocarbons in US and Swedish smokeless tobacco products

BackgroundDebate about the health implications of using smokeless tobacco products (STPs) has prompted considerable interest in characterising their levels of toxic and carcinogenic components. In the present study seventy smokeless tobacco products from the US and Sweden, categorized as chewing tobacco, dry and moist snuff, hard and soft pellets, plug, and loose and portion snus, were analysed for twenty one polycyclic aromatic hydrocarbons (PAHs). The tested brands represented 80-90% of the 2008 market share for the major STP categories in these two countries.ResultsThere were significant differences in the total and individual PAH concentrations in the different styles of product. Substantially higher levels of total PAHs (10–60 fold) were found in moist and dry snuff and soft pellets than in the other smokeless tobacco styles. The individual PAH concentrations followed the same patterns as total PAHs except for naphthalene, for which the highest concentrations were found in snus and moist snuff. Good correlations were obtained between benzo[a]pyrene (B[a]P) and all the other PAHs except naphthalene, 1-methylnaphthalene and 2-methylnaphthalene, providing evidence for the first time that it can be used as a good marker for PAHs in STPs. Results were generally in good agreement with two previous studies of PAHs in STPs, except for naphthalene for which significantly lower concentrations were found than previously reported. Analysis of the ratios of different PAHs confirmed that the use of fire-cured tobaccos in the snuffs and soft pellet were the major source of PAHs in these product styles, and provided, for the first time, some indications as to the source of PAHs in the other STP styles, including petrogenic and other combustion sources.ConclusionsThis study confirms the presence of PAHs in STPs, and identifies substantial differences between the levels in different STP categories. Since previous studies of naphthalene concentrations in STPs differed so markedly from those found in this study, it is recommended that further work on PAH determination is undertaken to investigate the source of this discrepancy.

The Effect of Swedish Snuff (Snus) on Offspring Birthweight: A Sibling Analysis

Current observational evidence indicates that maternal smoking during pregnancy is associated with reduced birthweight in offspring. However, less is known about the effect of smokeless tobacco on birthweight and about the possible mechanisms involved in this relationship. This paper studies the effect of Swedish smokeless tobacco (snus) on offspring birthweight comparing the results obtained from a conventional linear regression analysis and from a quasi-experimental sibling design using a multilevel linear regression analysis. From the Swedish Medical Birth Register, we investigated 604,804 singletons born between 2002 and 2010. From them, we isolated 8,861 siblings from 4,104 mothers with discrepant snus-use habits (i.e., women who had at least one pregnancy during which they used snus and at least one other pregnancy in which they did not). The conventional analysis shows that continuous snus use throughout the pregnancy reduces birthweight in 47 g while quitting or relapsing snus has a minor and statistically non-significant effect (−6 g and −4 g, respectively). However, using a sibling analysis the effect observed for mothers who continue to use snus during pregnancy is less intense than that observed with previous conventional analyses (−20 g), and this effect is not statistically significant. Sibling analysis shows that quitting or relapsing snus use after the first trimester slightly reduces birthweight (14 g).However, this small change is not statistically significant. The sibling analysis provides strong causal evidence indicating that exposure to snus during pregnancy has a minor effect on birthweight reduction. Our findings provide a new piece of causal evidence concerning the effect of tobacco on birthweight and support the hypothesis that the harmful effect of smoking on birthweight is not mainly due to nicotine.

Initial Reactions to Tobacco Use and Risk of Future Regular Use

Studies suggest that initial smoking pleasure influences future smoking behavior. We investigated how initial reactions to cigarettes or Swedish smokeless tobacco (snus) were associated with future use among 10,708 adults from the Swedish Twin Registry. The Early Smoking Experience questionnaire captured physiologic reactions to initial tobacco use. Binary recursive partitioning (BRP) identified combinations of initial reactions predictive of regular tobacco use. Analyses, stratified by sex, were conducted separately among those who experimented with only cigarettes (EC), only snus (ES), and both products (EC+S). Among EC, 39.8% of men and 43.7% of women became smokers, while among ES, 78.6% of men and 53.7% of women became snus users. Among EC+S, 31.3% of men and 20.0% of women became dual users. BRP identified different reactions as predictive of future smoking for men (buzz) and women (dizziness, difficulty inhaling). No initial reaction predicted future snus use among men, but pleasant sensations, later age at first use, and relaxation predicted future snus use for women. Among EC+S, future exclusive use of either product was associated with a favorable initial reaction to that product. Dual users experienced higher prevalence of pleasant reactions and lower prevalence of unpleasant reactions in response to both products. Our findings support that those who progress to regular tobacco use may be sensitive to the rewarding effects of nicotine but suggest that initial reactions differ by tobacco type. A high proportion of men became regular snus users regardless of initial reactions.

Overweight and perception of overweight as predictors of smokeless tobacco use and of cigarette smoking in a cohort of Swedish adolescents

To study the association between measured or perceived overweight in adolescence and subsequent uptake of cigarette smoking and of the Swedish smokeless tobacco 'snus' (oral moist snuff). Population-based prospective cohort study with 7 years' follow-up. Self-administered questionnaires and school nurses' visits. A total of 2922 children of both sexes and mean age 11.6 years at recruitment, resident in the Stockholm region, Sweden. Tobacco use was self-reported at baseline and on six subsequent surveys. Subjects' height and weight were measured by school nurses during the first 4 years, self-reported thereafter. Overweight perception was self-reported at the age of 15 years. Overweight and perception of overweight were not associated with subsequent uptake of either smoking or snus among males. Among females, overweight at baseline was associated with uptake of smoking [adjusted hazard ratio (HR) 1.34, 95% confidence interval (CI) 1.09-1.63], but not of snus. A similar pattern was found with overweight status during follow-up. Among girls with low-educated parents, overweight at baseline predicted the uptake of both snus and smoking. Among 15-year-old females who never used tobacco perceived overweight was associated with subsequent uptake of smoking (adjusted HR 1.71, 95% CI 1.20-2.46), but not of snus. In Sweden, adolescent girls with actual or perceived overweight are at increased risk to start smoking, while indications that this increased risk applies to smokeless tobacco (snus) are limited to girls of low socio-economic status.