Health issues with Snus

Snus has been popular in Sweden since the 1970s, allowing long-term research into its use and harm reduction potential. A long-term study, , published in June 2007 in the British medical journal Lancet, begun in 1978 by Dr. Olof Nyren and his colleagues at the Clinical Epidemiology Unit at Stockholm's Karolinska Institute and involving 280,000 Swedish male construction workers, found no increased risk of lung or oral cancer among snus users compared to people who had never smoked.

ITS- - Institute for Tobacco Studies
Director and Principal Investigator, Lars M. Ramström Ph.D.

The Swedish experience, Smoking cessation
As was pointed out in the background paper for the current reflection process, Europe’s lowest rate of lung cancer, the most typically smoking-related one of all diseases, is found in Sweden. The obvious reason for that is that Sweden has the lowest male smoking rates in Europe as a result of record high quit smoking rates. Therefore, when it comes to the top priority task to encourage and support adults to quit smoking, the Swedish experience may offer points of interest.


The overall development of tobacco use in Sweden since the late 1970s can be seen in the diagram below.



































The decrease of smoking among men and women can be attributed to a combination of several factors. For example, Sweden was the first country in the world to establish governmentally funded public education on smoking and health (in 1963), smoking cessation clinics were established already in the 1950s and the nicotine chewing gum for smoking cessation was developed in Sweden and used there earlier than in other countries. In addition there is one more Sweden-specific factor of importance. The steady decrease of male smoking rates appears to be linked to a likewise steady increase in male use of snus, the Swedish oral tobacco. In females there is a smaller decrease of smoking than among men and a smaller increase of snus use than among men. This pattern suggests that the increasing snus use among men has been an important contributory factor making it possible for males (a group with many snus users) to quit smoking to a larger extent than women (a group with fewer snus users). This suggestion is supported by recent research providing more in depth analysis of the development.

Part of those supportive findings from scientific studies are reported in one of the attached papers (Foulds et al, 2003). There we find for example that cessation rates are much higher among men with a history of snus use than among those without (71% vs 54%) and that, among men, snus is the most commonly used cessation aid, being used at the latest quit attempt by 68% of all male aid users. Later research (Ramström, to be published) has further demonstrated that the success rate is higher among snus users (71%) than among gum or patch users (37%). Other studies that demonstrate the supportive role of snus use in smoking cessation are also reported in the Foulds et al paper. In summary, there is solid evidence to show that male snus use in Sweden has been an important factor contributing to the increase in smoking cessation and thereby to the decrease of smoking prevalence and to the subsequent decrease of smoking-related disease.


Smoking initiation
There is other evidence suggesting that snus has contributed to less smoking also by keeping down smoking initiation rates. In the above mentioned paper a number of such findings are reported, for example data saying that among primary-snus-users (those having started daily snus use without previous daily smoking) just 20% have subsequently started smoking, while 46% of non-primary-snus-users have done so. These findings do also offer an explanation why, among 16 year olds, smoking rates (sum of daily and occasional smoking) are higher (30 %) in girls, with just 6 % snus use, than in boys, 20 % smoking, 24 % snus use (Hvitfeldt et al, 2004).


Snus and health
For smokers the dominating part of he health risks are attributed to various smoke constituents that are formed during the burning process (carbon monoxide, oxidizing chemicals, benzo(a)pyrene and other “tar” ingredients etc). Since the snus user is not exposed to any of those combustion products, the health risks are bound to be much less than those of the smoker. The 2002 report of The Royal College of Physicians estimates (page 5) that “… the consumption of non-combustible tobacco is of the order of 10–1,000 times less hazardous than smoking, depending on the product.” There are reasons to believe that Swedish smokeless tobacco, snus, would be in the lower part of that interval, since it is manufactured by a different kind of process than American snuff (Ramström, 2000) resulting in levels of the carcinogenic nitrosamines being significantly lower than in American snuff (Hatsukami et al, 2004, Rodu et al, 2004). There are epidemiological studies confirming low or non-detectable risk levels for a number of diseases including oral cancer. Details and references to original studies are found in the attached paper by Foulds et al.


Snus and nicotine dependence
Use of snus does certainly give a nicotine exposure capable of causing and maintaining nicotine dependence. In this relation there is, however, a common myth that has to be rejected. It says that the typical snus user suffers from a higher “nicotine load” than the average smoker and that this would entail a higher degree of nicotine dependence. But, studies have shown that daily nicotine intake is just the same. Further, the speed of delivery of nicotine from snus is slower than from cigarettes. Since speed of delivery is even more important than total exposure as a determinant of strength of dependence, theoretical considerations would suggest that snus use is less addictive than smoking. Further details and references are found in another one of the attached papers (Ramström, 2003a).


Policy implications -
meaningful regulation of all smokeless tobacco products instead of ban of the least harmful one
Snus does carry some health risks, but these are small enough to be much closer to no-tobacco risk than to cigarette smoking risk. This low risk level in combination with the potential usefulness as cessation aid and as a means of keeping down smoking initiation means that the Swedish experience must be seen as a favourable one. We do not know how this product could influence tobacco use in other countries. But, the potential benefits and the small risks make it unreasonable to let the current EU ban continue to deprive other European citizens of a potentially beneficial option at their own free choice. The questions around these matters have been extensively discussed in a position paper by six European scientists. I am attaching a copy of this paper as it was published in Tobacco Control (Bates et al, 2003). As argued in that paper there are strong reasons to change the regulations so that, instead of banning a product with very low health risk but important beneficial potential, there should be a regulatory system that can keep out of the market such products that do entail severe health risks, for example some chewing tobacco products that are currently allowed and causing increasing concern, especially among South-East Asian immigrants in the UK.


SNUS: PART OF THE PROBLEM OR PART OF THE SOLUTION?
The recognition of tobacco dependence as a disorder due to use of a psychoactive substance, nicotine, has led to a growing awareness that total eradication of nicotine use may not be a realistic goal. Therefore, reduction of tobacco-related ill health should not rely entirely on total abstinence from nicotine but also include options for nicotine delivery in a less harmful form than smoking. Since the major harmful exposure from cigarettes comes from combustion products, a great deal of interest has been given to non-combustible tobacco products, especially snus, a Sweden-specific kind of moist oral snuff. This is because Swedish men have been combining record high consumption of snus and record low levels of tobacco-related illness. Matters regarding Swedish snus are addressed in this issue of Addiciton in articles by Gilljam & Galanti and Fagerström & Schildt [1,2]. One key question deals with the role of snus in smoking cessation. Gilljam & Galanti found that the proportion of men that had ever used snus was larger among former than among continuing smokers (55% versus 45%). This suggests a beneficial effect of snus use on smoking cessation.

Furthermore, they found that use of snus at latest quit attempt increased the probability of being abstinent by about 50%. At the same time, they point out that the majority of quitters had not used snus. But they do not report what aid, if any, that had been used by others, although they mention that their study had also collected data regarding use of nicotine replacement therapy (NRT). However, some of those data from the Gilljam & Galanti study are actually reported by Fagerstöm & Schildt using early press release data as source. These data indicate that more Swedish men had used snus than NRT as a cessation aid, as confirmed by other studies and reported by Fagerstöm & Schildt. A recent study has also found a higher success rate among quitters using snus than among those using NRT [3]. Another key question deals with the role of snus in initiation of smoking. As reported by Fagerström & Schildt, there are studies showing evidence that the occurrence of snus has contributed to the decrease of onset rates for smoking among Swedish boys. The Gilljam & Galanti article contains a statement that the snus user ‘typically’ gets nicotine doses equivalent to 35–75 cigarettes per day. This is clearly not correct and it is certainly not supported by the reference given in the text (Holm et al. 1992). That article reports exactly the same average afternoon blood levels of nicotine in snus users as in smokers of 17 cigarettes per day. This is also in good agreement with the data reported by Andersson et al. [4,5]. These investigators measured 24 hour systemic uptake of nicotine in cigarette smokers and snus users. Cigarette smokers with an average consumption of 18 cigarettes per day had an uptake of 25 mg. In a group of heavy snus users, the uptake was 35 mg, corresponding to 25 mg in snus users with average consumption level. The above data illustrate that there is no ground for the widespread myth that snus use would constitute an ‘overload’ of nicotine compared with smoking. Not even dual use of cigarettes and snus represents any overload. First of all, dual daily use is very rare in Sweden, prevalence rate being around 2%; secondly, these smokers have lower than average cigarette consumption, as reported by Gilljam & Galanti.

It is true that some (but not all) of those who have quit smoking using snus as an aid continue to use snus and thus continue to be nicotine-dependent. However, this should not be taken as support for another myth the one that snus users had an even stronger nicotine dependence than smokers. It is true that former smokers who use snus say that it is more difficult to quit snus than it was to quit smoking. But one cannot make a correct comparison between the difficulty of quitting smoking with an efficient aid and the difficulty of quitting snus use without any aid. It is also true that quitting snus use is generally less common than quitting smoking. But this just reflects that snus users feel less strong motives to quit than smokers (as justified by the fact that the health risks of snus use are much lower than those of smoking). Fagerström & Schild give a comprehensive picture of the reasons to believe that the use of snus among Swedish males has been certainly not the only one, but one among other factors contributing to Sweden’s low rates of smoking and of tobacco-related ill health. It is, of course, by principle impossible to make an accurate calculation of what the prevalence of daily smoking in Swedish men would have been if there had been no use of snuff. However, the calculation examples by Fagerstöm & Schildt do seem to be reasonable estimates of order of magnitude.

One more such example could be added. In the period 1976–2002, the prevalence of daily smoking was decreasing by 25 percentage points in Swedish males and by 13 percentage points in Swedish women aged 18–70. Research data indicate that cessation rates are equal for women and for men without snus use, and higher for men with snus use. Consequently, it could be assumed that, if all men had been without snus , the decrease in prevalence of daily smoking among men would have been the same as that among women—i.e. 13 percentage points instead of 25. In that case, the current prevalence of daily smoking among men would have been 27% instead of 15%, as measured in 2002. If, in the fight against tobacco-related ill health, we adopt a puritanical view, rejecting all nicotine use, we shall see snus as part of the problem. But if we adopt a pragmatic view, seeking to exploit all means of possible reduction of these health risks, we might well see snus as part of the solution.
LARS RAMSTRÖM


Snus and pancreatic cancer?
Cancer statistics show no evidence to support a connection between the usage of snus and pancreatic cancer, despite the fact that Swedes consume the most snus in the world. Current epidemiological studies have not provided valid proof for a connection either. Recently, Swedish and Norwegian media have published alarming reports claiming that snus causes pancreatic cancer. But, is the alarm motivated from a scientific perspective?

The most important and well-established risk factor for pancreatic cancer is smoking. There are also studies that support a connection between alcohol, diabetes and pancreatic cancer.


Has the risk of being affected by pancreatic cancer increased in Sweden relative to the increase in the use of snus?
No, the risk has decreased by 50 percent among Swedish men since the middle of the 1980s, despite the increase in snus usage. The reduced risk has been parallel with the decrease in the number of smokers, which illustrates the significance of smoking as cause of this disease. It is also true that Swedish men, compared with men in all 27 EU countries, run a very low risk of being affected by pancreatic cancer.





























[1] The number of new cases of pancreatic cancer among men, age 0 – 85+, per 100,000 inhabitants. Age standardization according to the population in Sweden in 2000. Source: The Swedish Board of Health and Welfare’s statistic database. Portion of daily smokers, users of snus (daily + occasionally). The same scale for smokers and users of snus as a percentage. Source: Sweden’s Central Bureau of Statistics/Swedish Survey of Living Conditions.

Number of new cases of pancreatic cancer per 100,000 men in each EU country

























AGR (Age Standardized Rate), age standardized number of new cases per 100,000 inhabitants, based on a standard for world population (W). Assessments for 2002, based on the most recent available data. Source: WHO/IARC Cancer data GLOBOCAN 2002:  http://www-dep.iarc.fr/


Differing conclusions in studies
The warning in the media about a connection between snus and pancreatic cancer was based on a Norwegian and a Swedish epidemiological study (Bofetta et al, Luo et al). It is generally accepted within epidemiologic science that results from such studies must fulfill a number of criteria in order to draw accurate conclusions on causation. A statistical association alone is not enough. The association found should be strong, the results should be consistent, and there should be a dose-effect relationship, that is, the more snus an individual consumes, the greater the risk.

The two current studies demonstrate none of these criteria: the connection between snus and pancreatic cancer was weak (relative risk <1.5-2), the results were not consistent (the Norwegian study showed an increased risk only among snus users who were also smokers, while the Swedish study observed an increase only among those who did not smoke), and there was no dose-effect relationship. This means that there may well be other explanations for the statistical associations in these studies than that snus causes pancreatic cancer.

There were methodological problems in both studies. For instance, the participants were interviewed several decades ago so it was uncertain whether their tobacco habits had changed during the follow-up period (how many snus users had switched to smoking?) Other problems were the select nature of the participants and the failure to control for other significant life style factors, including alcohol consumption and dietary habits.

The problems with the Norwegian study are such that it was disqualified from a compilation of the scientific literature related to snus and cancer, which was recently published by the equivalent to Swedish Council for Health Care Technology Assessment in New Zealand (Broadstock et al).


Are there studies that do not support a connection?
Yes, there are. In a recently published Swedish epidemiological study by Rosaar et al from 2006, slightly more than 20,000 Swedes were monitored for about 30 years. No association was found between snus usage and smoke-related cancer (including pancreatic cancer).


Unmotivated cancer scares
It is well-established in biomedical science that several high standard studies must show consistent and unambiguous results before there is reason to issue warnings to the general public. In certain studies, even coffee, sugar and alcohol have been associated with risk increases for cancer that have been statistically significant. But, as with snus, there are other studies showing no association. Consequently, there is no motivation for media alarm or warnings about cancer to the general public - either for these products or for snus.


Is moist snuff use associated with excess risk of IHD or stroke? A longitudinal follow-up of snuff users in Sweden.Haglund B, Eliasson M, Stenbeck M, Rosén M.
Centre for Epidemiology, Swedish National Board of Health and Welfare, Stockholm, Sweden.
Background: The potential risks of Swedish moist snuff (snus) are debated and studies have shown diverging results. Aims: The aim of this study is to investigate whether there is any excess risk of ischaemic heart disease (IHD) and stroke from snuff use. Methods: The Swedish Survey of Living Conditions from 1988-89 was record-linked to the Swedish Cause of Death Register and the Swedish Hospital Discharge Register to investigate excess mortality and hospitalization from IHD and stroke. A Poisson regression model was used and incidence rate ratios (IRRs) for snuff and smoking were calculated controlling for age, physical activity, self-reported health, number of longstanding illnesses, residential area, and socioeconomic position. Results: Among snuff users there were no excess risks of mortality or hospitalization from IHD (IRR 0.8; 0.5-1.2,) or stroke (IRR 1.1; 0.7-1.8), but, as expected, clear excess risks were found for smokers (IRR 1.7; 1.4-2.1 for IHD, and IRR 1.4; 1.0-1.9 for stroke). Conclusions: This study has not shown any excess risk among users of snuff for IHD or stroke. If there is a risk associated with snuff it is evidently much lower than those associated with smoking.


PubMed A service of the U.S. National Library of Medicine
and the National Institutes of Health

Is low-nicotine Marlboro snus really snus?
Foulds J, Furberg H.
ABSTRACT: Swedish snus is a medium/high nicotine delivery, low-nitrosamine moist smokeless tobacco product that has been estimated to be at least 90% less harmful than smoked tobacco. More men use snus than smoke cigarettes in Sweden, and a quarter of male former smokers quit by switching to snus. Leading multinational cigarette manufacturers have begun test-marketing snus-like products in the United States and other countries. The version of Philip Morris Marlboro snus currently being marketed in the United States differs from Swedish snus in many ways; it has lower moisture content and pH, but most puzzling is its very low nicotine delivery. Philip Morris, the market-leader in United States cigarette sales, may have designed the product so that it does not satisfy nicotine cravings and fails to enable smokers to switch. In this paper we compare and contrast Swedish snus and Marlboro snus, and speculate as to why Philip Morris may have intentionally designed a product that delivers very low levels of nicotine. We recommend that Philip Morris cease using the term snus to refer to dry tobacco products with low nicotine delivery, so that the term be reserved for moist, low-toxin, medium/high nicotine delivery smokeless tobacco products that are qualitatively similar to the leading brands in Sweden.


Swedish Match report sent to the WHO (World Health Organisation)
Snus – The Swedish Experience
The purpose of this paper is to present the views of Swedish Match on the WHO Framework Convention on Tobacco Control, and especially in relation to the Swedish snus. This paper summarises the scientific data available regarding snus, as we, to the best of our knowledge,understand them. Swedish Match is a Sweden based international group and one of the world's leading companies in the area of niche tobacco products, collectively known as Other Tobacco
Products – Smokeless Tobacco, Cigars and Pipe Tobacco. Swedish Match has long experience within the OTP area and is among the leaders in terms of technical expertise relating to product development and production processes. Swedish Match's extensive range, comprising well-known brands in the OTP area, has resulted in strong market positions in selected geographic markets.


What is Swedish snus?
Swedish snus, manufactured by Swedish Match, is a moist to semi-moist, ground, oral smokeless tobacco product. It is made from selected, mainly air-cured tobaccos, water, salt and flavourings. Snus is produced in a proprietary heattreatment process that complies with food standards. The moisture content of the product ranges between 30 and 60 %. Packaging forms vary: loose snus, which is sold in 50 g cardboard or plastic cans and portion-packed
snus which is sold in three packaging varieties. The vast majority of Swedish snus users place the snus in the upper vestibular cavity of the mouth. Swedish snus is regulated by the Swedish Food Act. Except for Sweden, snus has been banned since 1992 in the European Union countries. The legislative background for the ban is Art. 2.4 of Directive 92/41/EEC. The Article 2.4 defines those smokeless tobaccos that may not legally be sold in the European Union. Since snus is widely used in Sweden, the Swedish government obtained permanent derogation from the ban on certain smokeless tobacco products as part of the terms under which Sweden joined the European Union.


Snus and harm reduction strategies
Swedish Match has put a lot of effort into improving product quality in order to minimise any possible health risks. This goes all the way from the selection of leaf tobacco to the manufacturing process. Swedish Match selects its raw materials carefully taking into account not only traditional leaf characteristics but also chemical data. The manufacturing involves a proprietary heat treatment process instead of the more commonly used fermentation. As a result of these measures snus contains lower levels of nitrosamines, polycyclic aromatic hydrocarbons and other controversial compounds than similar smokeless tobacco products. As all tobacco products, snus contains nicotine. The blood nicotine levels in snus users do not differ from the levels in cigarette smokers. We wish to stress this point as we are aware of the common misconception that snus contains more nicotine and delivers more nicotine than cigarettes (1-3). The health effects associated with the use of snus have been evaluated in several independent scientific studies. These studies show that the adverse health effects associated with the use of snus are much lower than those associated with cigarette smoking (detailed below). Sweden is the only country to have reached the WHO goal of reducing cigarette smoking to less than 20% of the adult population. Sweden has one of the most effective antismoking policies in Europe, measured by the significant reduction of the numbers of smokers. Snus has played an important role in achieving this goal, since 54% of the snus consumers are ex-smokers. Snus is used by 20% of Swedish males and by 2% of Swedish females and consumption is increasing. If snus was not available these people might still have been cigarette smokers.


The evidence available demonstrates:
- That snus is significantly less harmful to health than was previously thought when it was banned by the European Union in 1991 and
- That snus can play a constructive role in a tobacco related harm reduction strategy. Health risks associated with moist snuff - Swedish snus and scientific evidence As stated above, a significant body of scientific evidence now clearly shows that the health risks associated with snus use are significantly lower than those associated with cigarette smoking (this may be understandable since the snus user is not exposed to the toxic pyrolysis products generated by cigarette smoking). The European Commission has recognised this. The proposed Directive on tobacco labelling, endorsed by both the European Council and the Parliament, clearly distinguishes between the health warnings for cigarettes and for smokeless tobacco. The health warning on smokeless tobacco is proposed to be changed to “This product can damage your health and create addiction” instead of the present requirement “Smokeless tobacco damages health seriously” and ”Causes cancer”. The Commission’s moderation of the health warning reflects the scientific consensus, which has developed over the past 10 years. Several, independent, scientific studies have looked at the health patterns of Swedish users of snus and found that the product is not associated with cancer.


Cancer
Swedish snus does not increase the risk of dysplastic changes and is not a risk factor for oral or gastric cancer.


The key findings of the scientific studies are:
- High daily use of snus gives rise to oral mucosal changes, which are reversible after cessation of snus use (4). The probability of these lesions to transform into cancer appears to be low (5).
- No statistically significant association between oral cancer and snus use was observed in two epidemiological case-control studies. It was also shown that tobacco smoking and alcohol intake had a strong interactive effect on the risk of carcinoma (6,7).
- There is no association between any type of cardiac or gastric cancer and snus use. By contrast, active smokers have a higher risk of gastric or cardiac cancers than neversmokers (8).
- Gastric cardia adenocarcinoma is associated with smoking among heavy smokers but not with alcohol or snus use. Oesophageal squamous-cell carcinoma is strongly associated with smoking, moderately with alcohol, but not with snus use (9).
- No increased cancer mortality was found among snus users in a large co-hort study on Swedish construction workers (10).


Cardiovascular diseases
The use of snus appears to be unrelated to the incidence of myocardial infarction, but there is conflicting evidence on the role of snus on mortality from cardiovascular disease.


The key findings are:
- Snus usage is associated with lower risk of myocardial infarction than cigarette smoking in middle-aged men (11).
- The risk of myocardial infarction is not increased in snus users. Nicotine is probably not an important contributor to ischemic heart disease in smokers (12).
- An excess risk of dying of cardiovascular disease has been observed among snus users in a co-hort study comprising Swedish construction workers (10). However, the survey included no adjustment for alcohol consumption – a positive co-variation has been demonstrated between use of alcohol and snus and it has been contended that this plays an important part in the interpretation of epidemiological studies (13). 
- No significant elevation of diastolic blood pressure, haemoglobin concentrations, white cell count, serum cholesterol or triglyceride levels has been found in snus users. This is in contrast with findings for cigarette smokers. The use of snus by young men appears to have less impact than smoking on cardiovascular risk factors with the possible exception of elevated serum insulin and plasma fibrinogen levels (14).
- The use of snus does not appear to affect potential cardiovascular risk factors measured as plasma fibrinogen levels, fibrinolytic activity, glucose tolerance and serum insulin levels (15).
- An increased cardiovascular risk on use of snus was observed in a large co-hort study (16).
- Snus users do not significantly differ from nonusers with respect to atherogenic risk factors such as increased levels of serum lipids, fibrinogen, blood glucose and blood cell count (17).

These data relate only to Swedish snus. The types of oral tobacco favoured, for example, in the Asian sub-continent, have different health risk profiles probably due to different product composition with high levels of undesired constituents and to different usage patterns. It is noteworthy that the current EU ban on the sale of smokeless tobacco products is based on a definition that does not take into account the widely different health risks that are associated
with different oral tobacco products.


Snus and the Framework Convention on Tobacco Control
On several recent conferences on tobacco related health issues, the differences in health effects of different tobacco products have been recognised. Some scientists have now included snus as one possible “alternative nicotine delivery system” in the reduction of cigarette smoking. They conclude that an efficient smoking cessation strategy must include less harmful substitutes for cigarette smoking (18). Swedish Match would welcome that the FCTC Intergovernmental negotiating body discusses the status of snus and reviews all tobacco products based on independent, scientific evidence of the health risks. We would like to stress once again the role snus can play in harm reduction strategies, as has been demonstrated by Swedish studies. We also believe that snus can play a useful role in WHO’s strategy to reduce cigarette smoking by providing a viable alternative to cigarettes. As stated earlier, Sweden is the first country in the world to have reached the WHO’s target of less than 20 % of the adult population being daily cigarette smokers. The presence of snus in Sweden has clearly played an important role in that context.

Therefore, it is our belief that snus could play a valuable part in encouraging cigarette smokers to switch to a less harmful product also in other countries. This view is shared by, among others, the senior lawyer of the Canadian Smoking and Health Action Foundation, who has reviewed existing law, nicotine delivery systems and current scientific knowledge on nicotine. The review states that support is growing for the proposal that tobacco-related health risks may be reduced by switching existing smokers to less harmful nicotine-containing products. In this review Swedish snus, specifically, is mentioned as much less harmful than cigarettes (19). The WHO Framework Convention on Tobacco Control must recognise that tobacco is not one but several different product categories and each one of them must be judged on its own records. It is our strong belief that when evaluating the available evidence on its own merits, snus will appear more as a solution than as part of the problem. Swedish Match would welcome any further opportunity to discuss the role of snus in a global tobacco harm reduction strategy.


Research on snus
In recent years, a number of Swedish studies have been published on the effects of snus on health, based on Swedish conditions. Previously published research on oral tobacco products has mainly dealt with product types used in other parts of the world, such as India, meaning the results have not been representative. The information given here is a summary of current research on snus of the type used in Sweden and the rest of the Nordic region.


Swedish Match seeks to constantly reduce or minimize presumed health risks in its snus products and to contribute to increased knowledge on the characteristics and use of snus. Consequently, Swedish Match supports independent research, while also conducting its own research and development efforts, which focus on the continuous improvement of products.


200 years of Swedish snus
Snus of the type used in the Nordic region has a history stretching back nearly 200 years. In Sweden, snus has been one of the dominant tobacco products for an entire century. Its health effects have now been well elucidated in a large number of Swedish scientific studies. Overall, the use of tobacco in Sweden is on a level comparable to many other European countries. Despite this fact, the risk of dying of a tobacco-related disease is lower in Sweden than in any other European country. This is true of men. One reason contributing to this is thought to be the fact that Swedish men use snus considerably more than they smoke. The risk for Swedish women is comparable to that for women in other parts of Europe.


Current research findings
According to three Swedish studies (of which, two were conducted within the framework of the World Health Organizations MONICA project), the use of snus does not increase the risk of heart attack. However, there are contradictory results regarding the use of snus and other cardiovascular diseases. But snus does not appear to contribute to hardening of the arteries. The use of snus has a direct effect on heart rate and blood pressure. However, it is unclear whether snus causes chronic high blood pressure. Elevated blood pressure has been observed in some studies but not in others.

"No evidence to support a connection between the usage of snus and pancreatic cancer".

A Swedish study (within the framework of the World Health Organizations MONICA project) showed that the use of snus does not increase the risk of cerebral hemorrhage (stroke).

Results are contradictory regarding whether snus contributes to an increased risk of age-related diabetes (type-2 diabetes). The largest and most recent Swedish study (Eliason et al, Journal of Internal Medicine 2004) found no verifiably increased risk of age-related diabetes among snus users, although it did find this among smokers.

An expert panel has conducted a risk assessment (published in Cancer Epidemiol Biomarkers 2004) of snus and other products. Choosing snus instead of smoking reduces the risk of death from a tobacco-related disease (defined as lung cancer, oral cancer, coronary diseases and premature death) by 90 percent, according to the assessment.

Professors Brad Rodu and Philip Cole: "With Swedish tobacco habits, 200,000 lives would be saved each year within the EU".


Circulatory disease and smokeless tobacco in Western populations: a review of the evidence.Lee PN.
PN Lee Statistics and Computing Ltd., 17 Cedar Road, Sutton, Surrey, SM2 5DA, UK.
BACKGROUND: Use of oral snuff or 'snus' has risen in Sweden. Sales of snuff in the US have also risen, overtaking sales of chewing tobacco. There is some evidence that nicotine contributes to circulatory disease (CID) from smoking. We therefore reviewed the evidence relating smokeless tobacco (ST) to CID and related risk factors. METHODS: Publications that described relevant cohort, case-control and cross-sectional studies were identified from in-house files, a Medline search in December 2005 and reference lists. Relative risks (RRs) and odds ratios (ORs) for ischaemic heart disease, stroke and all CID for ST use, stratified by smoking habit, were estimated and combined by meta-analysis to provide an overall RR estimate. For diabetes, increased blood pressure, and other risk factors, evidence was qualitatively reviewed, with results from clinical studies also considered. RESULTS: ST use in non-smokers was associated with an increased risk of heart disease (RR 1.12, 95% CI 0.99-1.27, n = 8), stroke (1.42, 1.29-1.57, n = 5) and CID (1.25, 1.14-1.37, n = 3). The increases mainly derived from two large US studies. The Swedish studies provided little evidence of an increase for heart disease (1.06, 0.83-1.37, n = 5) or stroke (1.17, 0.80-1.70, n = 2), although the estimates by country are not notably heterogeneous, even for stroke (P = 0.29). No dose-response was evident. No increase was seen in former users of ST, or in ST users who also smoked. No clear relationship to diabetes was seen. In the US, an acute blood pressure rise following ST use was consistently reported, and isolated reports linked specific risk factors to ST. In Sweden, though one study reported that snuff acutely increased blood pressure, and two linked snuff to Raynaud-type symptoms, the overall evidence for an effect was inconclusive. Swedish studies generally showed no chronic effect of snuff on blood pressure or various risk factors. CONCLUSIONS: Any CID risk from ST appears to be substantially less than from smoking, and no clear risk from Swedish snuff is seen. However, the overall evidence is limited.


Decreased levels of tobacco-specific N-nitrosamines in moist snuff on the Swedish market.Osterdahl BG, Jansson C, Paccou A. Swedish National Food Administration, Box 622, SE-751 26 Uppsala, Sweden.
Moist snuff, or snus, on the Swedish market in 2001 and 2002 was analyzed for tobacco-specific N-nitrosamines (TSNAs) using a recently developed LC-MS/MS method. All samples of moist snuff analyzed were found to contain detectable levels of N'-nitrosonornicotine (NNN), N'-nitrosoanatabine (NAT), N'-nitrosoanabasine (NAB), and 4-(N-methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). In the survey in 2001, all samples except for one were produced by Swedish Match (n = 14), which is the dominating manufacturer on the Swedish snuff market. In the survey in 2002, samples from both Swedish Match (n = 7) and seven smaller manufacturers (n = 20) were analyzed. Total TSNA levels of between 0.15 and 3.0 microg/g wet weight were found. In the survey in 2001 and 2002, the mean level of the total TSNA content in moist snuff was 1.1 microg/g (n = 14) and 1.0 microg/g (n = 27), respectively. The result of the survey shows that the level of TSNAs in moist snuff on the Swedish market has been greatly reduced since the middle of the 1980s. Clearly, efforts have been made by the manufacturers to reduce the level of TSNAs in snuff.


Genotoxicity testing of extracts of a Swedish moist oral snuff.Jansson T, Romert L, Magnusson J, Jenssen D.
Genotox AB, Stockholm, Sweden.
The present study was designed to investigate the potential genotoxicity of aqueous and methylene chloride extracts of Swedish moist oral snuff. The test systems were selected to provide optimal data for the prediction of carcinogenicity in rodents and included assays for the induction of mutation in bacteria, sister-chromatid exchanges (SCE) in human lymphocytes, of chromosome aberrations and gene mutations in V79 Chinese hamster cells and of micronuclei in mouse bone marrow cells. In addition, the methylene chloride extract was tested for the induction of sex-linked recessive lethal mutations in Drosophila melanogaster. The aqueous extract of 'Snus' induced SCE in human lymphocytes and chromosome aberrations in V79 cells, the latter effect being observed both with and without metabolic activation. No induction of point mutations was detected with the Ames test or in V79 cells and the micronucleus test in mice was negative. It was demonstrated that the induction of chromosome aberrations without metabolic activation may be due to a high salt concentration, indicating that the clastogenic agent(s) in this extract required metabolic activation. The methylene chloride extract showed genotoxicity in the Ames test, the SCE test and the chromosome aberration test, whereas no induction of gene mutations in V79 cells was observed. Once again, the results suggested that metabolism is required for genotoxicity. The methylene chloride extract did not cause induction of micronuclei in mice or of sex-linked recessive lethal mutations in Drosophila melanogaster. These combined data on genotoxicity were analyzed using various models for the prediction of carcinogenicity. In a sequential testing model, the probabilities that the aqueous and methylene chloride extracts of 'Snus' are carcinogenic due to a genotoxic mechanism were both predicted to be low. Using carcinogenicity prediction by battery selection (CPBS), the probabilities of the methylene chloride and aqueous extracts being correctly identified as non-carcinogens are 71 and 77%, respectively. Up to date, the CPBS approach has been validated primarily for individual compounds, so some caution should at present be exercised in interpreting the results using this method. Based on these results, the carcinogenic potential of Swedish 'Snus' should be considered to be low, a conclusion in agreement with the low incidence of oral cancer in Sweden compared to other countries.


Research Reports from Gothiatek.com


Several research reports dealing with effects of Swedish Snus use on health have been published in the last 10 -15 years. Previously published reports on oral tobacco use mostly dealt with products from other countries, products which are not used in Sweden.


Nicotine uptake from snus
Summary
Nicotine, which is present in concentrations of 0.5-1 % in Swedish snus, has well-documented pharmacological effects on the central nervous system. There is, however, no evidence of nicotine per se or any of its metabolites being carcinogenic (Adlkofer et al., 1995). Nicotine is not a risk factor for pulmonary disease as emphysema and is not a risk factor for cardiovascular disease (McNeill et al. 2004). Both the dose and the uptake rate are of importance for understanding the biological effects of nicotine in humans. The amount of nicotine that is absorbed during snus use (nicotine dose) can be quantified by measuring the concentration of nicotine or its metabolites in different body fluids, i.e. blood, saliva and urine. The uptake rate can be estimated by monitoring the increase of the blood nicotine concentration over time. The nicotine uptake from Swedish snus has been described in six scientific publications of different objectives and design.

Important research results on Swedish snus:
• Less than half the amount of nicotine present in a pinch of snus is extracted during snus use.
• Only 10-20 % of the nicotine present in a pinch of snus is absorbed via the mucous membrane and reaches the systemic circulation. This means that only 1-2 mg of nicotine is absorbed into the blood from a one gram pinch containing ca 10 mg of nicotine.
• Nicotine is absorbed quite rapidly from Swedish snus.
• Studies on Swedish snus users have shown that the plasma steady-state levels of nicotine and its main metabolite, cotinine, are similar in Swedish snus users and cigarette smokers.
• Snus users and cigarette smokers, who have similar blood nicotine levels, have reported similar levels of subjective dependence on tobacco.
• The total nicotine uptake (dose) measured as the excretion of nicotine and its metabolites per 24 hours is similar in habitual snus users and cigarette smokers, i.e. 25 mg.
• In contrast to cigarette smokers, snus users do not compensate their nicotine uptake when switching to a low nicotine product. A decrease of the nicotine content of snus by 50 % results in a decrease of the nicotine uptake by about 50 %.
• An experimental cross-over study of blood plasma levels obtained after controlled snus use of four different portion-packed snus products of various weight and format, different nicotine content and different pH values showed that the nicotine intake varies between 0.4 and 1.2 mg per pinch.


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Nicotine absorption
The nicotine uptake from one pinch of snus is determined both by the amount of nicotine that is released from the pinch during snus use and by the amount of nicotine that passes the buccal mucosa and reaches the systemic circulation. Andersson et al. (1994) examined consumption patterns, nicotine uptake and oral lesions in a group consisting of users of portion-packed snus, loose snus and chewing tobacco, respectively. They found that almost half of the nicotine present in the pinch was extracted during snus use (37 % from portion-packed snus and 49 % from loose snus).  By comparison of the total amount of excreted nicotine with the total amount of nicotine in the pinch per time unit, it has been concluded that only 10-20 % of the nicotine originally present in the pinch is absorbed via the buccal mucosa and reaches the systemic circulation (Andersson et al., 1994; Andersson et al., 1995).


Nicotine uptake rate
During snus use nicotine is absorbed via the buccal mucosa. The uptake via the mucous membrane is slower than the the uptake via the lungs during smoking. Holm et al. (1992) measured the absorption of nicotine from a pinch of snus (2 g) during 30 minutes in a group of snus users, who had been abstinent for ca 12 hours prior to the study. They found that the nicotine uptake from Swedish snus was initially quite fast, since the nicotine concentration in the blood increased by ca 10 ng/ml during the first 10 minutes. After that, the uptake rate was somewhat slower and the plasma concentration reached a maximal level after the pinch had been taken out. After the fast increase in blood nicotine concentration during smoking, the nicotine is eliminated quite rapidly after having finished the cigarette. During snus use, however, the nicotine concentration plateaus after the pinch has been taken out. The prolonged elimination of nicotine in snus users has been attributed to continued absorption of nicotine released from the mucous membrane or to absorption of nicotine that has been swallowed (Benowitz et al., 1989).


Steady-state levels of nicotine and cotinine
A comparison of blood nicotine and cotinine levels in a group of snus users and a group of cigarette smokers on a day of normal snus use and smoking, showed that the snus users and cigarette smokers had roughly the same levels of nicotine (37 ng/ml) by the end of the day. The concentration of cotinine was, however, slightly higher in the snus users than in the cigarette smokers (Holm et al., 1992). The same steady-state levels of nicotine and cotinine in blood as those reported by Holm et al. (1992) were found in another study describing the nicotine uptake from Swedish snus (Larsson et al., 1987).In Holm’s study the participants also answered questions about tobacco habits and different measures of subjective nicotine dependence. There was no difference in self-assessed addiction, craving for tobacco or difficulty in giving up between snus users and cigarette smokers (Holm et al., 1992). These results have recently been confirmed in a quit snus use study (Gilljam et al., 2003).

The nicotine uptake has often been estimated by measurement of cotinine in various body fluids. Cotinine, which is the major metabolite (degradation product) of nicotine, is often used as a biomarker for nicotine, since it is more stable, has a longer half-life and is easier to quantify. Wennmalm et al. (1991) used the excretion of cotinine as a measure of nicotine uptake in a study dealing with the association between the risk of cardiovascular disease and tobacco habits in a group of young men. They concluded that snus users and cigarette smokers had roughly the same nicotine uptake since the level of urinary cotinine was similar. There is a tendency towards higher cotinine levels in snus users compared to smokers in some studies. This is most likely due to the fact that some nicotine is swallowed and therefore undergoes first pass metabolism to cotinine before reaching the systemic circulation (Holm et al., 1992; Benowitz et al., 1989).


Total daily nicotine uptake
Since humans differ widely with respect to the metabolism of nicotine to cotinine and subsequent elimination of cotinine, the use of cotinine as a marker of nicotine uptake has been questioned. A more reliable estimate of the daily uptake of nicotine from tobacco is obtained if the total amount of nicotine and its metabolites excreted into urine during 24 hours is measured. Pharmacokinetic studies have shown that some 90 % of the nicotine dose is excreted into urine as nicotine and seven of its largest metabolites. The total amount of nicotine excreted in the urine during 24 hours was measured in a group of snus users who were habitual users of a portion-packed snus containing 0.8-0.9 % of nicotine. The daily nicotine uptake was ca 25 mg in this group of snus users, who consumed 16 one-gram pinches of portion-packed snus per day. The same level was found in a group of habitual cigarette smokers, who smoked 18 cigarettes per day (Andersson et al., 1997). When this group of snus users switched to a snus containing only half the amount of nicotine, the daily nicotine uptake was reduced by about 50 %. The daily nicotine uptake decreased to 14 mg. The same level was obtained in another group of snus users, who had been using the low nicotine snus for more than one year (Andersson et al., 1997). These results show that snus users do not compensate their nicotine uptake upon switching to a snus with lower nicotine content.

A different method to measure the nicotine dose is to monitor the blood plasma levels during one day of controlled tobacco consumption (snus use or smoking) and then compare the nicotine uptake curves with the corresponding curve for a reference product with a known nicotine dose. Using this method, the nicotine dose from four different portion-packed snus products of various weight and format, different nicotine content and different pH levels was compared in a controlled cross-over study with the dose from a 2 mg nicotine chewing gum (Lunell et al., 2005). The results showed that the dose from a 0.3 g porton-packed snus agreed well with the dose from a 2 mg nicotine chewing gum and corresponded to ca. 0.4 mg. The dose from a 0.5 g portion-packed snus was estimated in a similar manner to be 0.8 mg nicotine, and the dose from the two 1 gram portion-packed snus products to be 0.9 and 1.2 mg of nicotine, respectively.


Effects on the oral mucosa
Summary
The use of Swedish snus and the incidence of dental caries and periodontal disease and various non-carcinogenic oral conditions have been investigated in multiple studies. It is evident that Swedish snus possesses multiple physio-chemical properties, such as pH, chemical composition, particle size and moisture content, that can affect the oral mucosa and in certain cases cause snus lesions. Whether these lesions will result in cancer has attracted scientific attention for a long time.

Important research results on Swedish snus:
• It is unclear whether use of Swedish snus causes dental caries.
• Use of Swedish snus causes reversible inflammation in the gingival mucosa (gingivitis) in some individuals at the site where the pinch is placed. There seems not to be any association between the use of snus and periodontitis (loosened teeth).
• Gingival recessions are more common in users of loose snus than in users of portion-packed snus and are irreversible.
• Snus use causes benign changes in the oral mucosa (snus dipper’s lesions). These changes arise at the site where the pinch is placed.
• There is an association between the degree of oral mucosal lesion and consumption factors such as daily duration, daily consumption and number of years.
• When snus users reduce their daily consumption or when users of loose snus switch to portion-packed snus the degree of oral mucosal lesions decrease both from a clinical and a histological perspective.
• The degree of oral mucosal lesion increases both with increasing pH and nicotine content.
• Snus lesions are reversible, i.e. the oral mucosa reverses to normal condition after cessation of snus use.
• Users of portion-packed snus have less pronounced snus lesions than users of loose snus.
• Epidemiological data do not indicate any association between snus use and serious dysplastic oral mucosal changes or pre-carcinogenic effects in the oral cavity. These results agree well with the fact that no tumours or dysplasia have been found in the oral cavity among 500 snus users who have been examined annually for several years.


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Dental caries and periodontal disease
The association between use of Swedish snus and dental health, i.e. dental caries, tooth wear and tooth loss (parodontitis) has been described in three descriptive studies. Even if the results indicate that there is an association between snus use and these damages, caution should be exercised in interpreting the data since the effects of diet and mouth hygien have not been controlled for (Hirsch et al., 1991, Ekfeldt et al., 1990, Johansson et al., 1994). In a recently published cross-sectional study, the relationship between tobacco use and prevalence of periodontal disease was investigated. There was a significant association between smoking and periodontal disease compared to never-smoking, but there was no significant association between current snus use and periodontal disease compared to never use (Wickholm et al., 2004). Use of snus may cause inflammation of the buccal mucosa in certain individuals. This disease is reversible at an early stage. Use of snus can also cause gum recession (gingivitis), damages that are irreversible and occur more commonly in users of loose snus than in users of portion-packed snus (Andersson and Axéll, 1989a; Frithiof et al., 1983; Modéer et al., 1980).


Mucosal lesions
The association between the use of snus and the prevalence and severity of snus lesions is described in a large number of descriptive studies. Five of these studies describe the type of oral lesions occurring in a group consisting of 252 construction workers (Andersson, 1991a). Several articles deal with the association between the prevalence of snus use and oral lesions in a large population study comprising 30000 individuals (Axéll, 1976). A mucosal change, snus lesion, is found in almost all snus users at the site of the gum where the pinch is placed. The degree of oral lesion is positively correlated with daily duration, daily consumption and number of years of active snus use (Hirsch et al., 1982; Mörnstad et al., 1989; Andersson et al., 1991b). Andersson et al. (1989b) found that portion packed snus results in less pronounced changes of the mucosa than loose snus. In addition, the degree of lesions seems to increase with increasing pH as well as increasing nicotine content (Mörnstad et al., 1989; Andersson et al., 1995). Oral lesions caused by snus are reversible, i.e. the oral mucosa reverses to its original condition in individuals, who have quit the use of snus (Larsson et al., 1991). Frithiof et al. (1983) reported that these lesions were almost entirely reversed 14 days after quitting the use of snus even in individuals, who had used snus for decades. Larsson et al. (1991) examined histological oral mucosal changes in a group consisting of 252 Swedish snus users. They found that 29 of these individuals, who were all users of loose snus, had dysplastic changes in the epithelium. In a follow-up 3-6 months later normal tissues were found in those 20 individuals, who had quit the use of snus and no dysplastic changes were found in those individuals, who had switched to portion-packed snus or reduced their consumption. These results agree well with the fact that no tumours or dysplastic changes have been found in the oral mucosa of those 500 snus users, who have annually been examined for several years (Ahlbom et al., 1997).


Gastrointestinal diseases
Summary
Because saliva produced during the use of snus is often swallowed, it has been of importance to study the association between snus use and gastrointestinal diseases. The scientific literature comprises a descriptive study on the use of snus and general health, including heartburn and peptic ulcer, and a case-control study on the use of snus and risk of two different inflammatory gastrointestinal diseases, Crohn’s disease and ulcerative colitis.

Important research results on Swedish snus:
• Use of Swedish snus does not increase the risk of peptic ulcer.
• Snus users have a significantly lower risk of heartburn than non-tobacco users.
• There is no increased risk of Crohn's disease or of ulcerative colitis for snus users, who have never smoked.


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Peptic ulcer
In a descriptive study comprising a large number of construction workers, who received health examinations during 1971-1974, Bolinder et al. (1992) found that snus users did not have any excess risk of peptic ulcer. They also noted that snus users seem to have somewhat lower risk of heartburn than non-tobacco users.


Inflammatory gastrointestinal diseases
Persson et al. (1993) studied the relationship between the use of tobacco and the risk of inflammatory gastrointestinal diseases. The study base comprised selected male patients from Stockholm, who had been diagnosed with Crohn’s disease or ulcerative colitis in 1980-1984 and matched controls. The results showed that snus use did not increase the risk of these two diseases. The authors found, however, a synergistic interaction between snus use and cigarette smoking in the sense that the risk of Crohn’s disease or ulcerative colitis increase for those who used both snus and cigarettes.



Cardiovascular diseases
Summary
The relationship between the use of Swedish snus and cardiovascular disease has been examined in several studies. Due to the presence of nicotine, which is known to cause acute increase in heart rate and blood pressure, some scientists have assumed that the use of snus can affect the cardiovascular system. The body of published literature examining the relationship between the use of Swedish snus and various measures of cardiovascular disease includes several descriptive studies, two case-control studies, a prospective cohort study and an experimental study. The outcomes studied include general health status, clinical risk factors for cardiovascular disease, development of atherosclerosis, hypertension, the risk of myocardial infarction and mortality from cardiovascular disease.

Important research results on Swedish snus:
• There exists a relationship between the use of snus and the acute effects on the cardiovascular system such as acute increase in blood pressure and heart rate.
• There exists a relationship between the use of snus and impaired flow-mediated dilation of the brachial artery.
• It remains unclear whether the use of snus is a risk factor for hypertension.
• There is no association between the use of snus and atherosclerosis or risk factors for atherosclerosis.
• There is no evidence of an increased risk of myocardial infarction in snus users.
• There are conflicting results whether the use of snus causes an increased mortality from cardiovascular disease.
In a recently published review article Asplund (2003) concludes that the use of smokeless tobacco (mainly snus) is associated with a much lower risk for negative cardiovascular effects than smoking.


Stroke
Summery
Stroke (brain infarction and cerebral haemorrhage) is another form of vascular disease. The relationship between the risk of stroke and snus use has been explored in two epidemiologic studies, one cohort study and one case-control study.


Important research results on Swedish snus:
¨• Whereas regular smoking doubles the risk of stroke in men, snuff use is not associated with any apparent excess risk.
In a cohort study comprising Swedish construction workers the relationship between snus use and a number of different cardiovascular diseases including stroke was investigated (Bolinder et al., 1994). The results showed that snus use did not increase the risk of stroke in men in either of the age groups 35-45 years or 55-65 years.

In a recently published case-control study Asplund et al. (2003) used prospective data from two cohort studies. This study comprised 276 men aged 25-74 years, who had had their first stroke and 551 matched controls, who did not suffer from any cardiovascular disease. There was no excess risk of stoke among snus users, who were never smokers. By contrast, smokers had higher risk than non-tobacco users. One conclusion was that snus use is associated with considerably lower risk of cardiovascular disease than smoking. The increased risk among cigarette smokers can be explained by exposure to the combustion products generated on smoking.


Diabetes
Summery
There are scientific reports in the literature that smokers are at increased risk of developing type 2 diabetes as well as developing the conditions underlying diabetes, i.e. insulin resistance and impaired glucose tolerance. Recent studies have begun to examine the specific relationship between snus use and type 2 diabetes. Diabetes occurs when there is an imbalance in the levels of glucose and insulin in the body. Two precursor conditions underlie this disease and are frequently studied in conjunction with diabetes. Impaired glucose tolerance refers to a condition in which blood glucose levels are higher than normal but not high enough to qualify the individual as diabetic. Insulin resistance is a condition in which target tissues in the body gradually become insensitive to the natural actions of insulin. Type 2 diabetes is the most common form of diabetes, and occurs when a patient’s tissues become resistant to insulin.

Important research results on Swedish snus:
• One cross-sectional study of the relationship of snus use to risk factors for heart disease suggests that it is linked to an increase in insulin levels. Three other studies do not support this finding.
• One cross-sectional study suggests that snus use is linked to an increased prevalence to type 2 diabetes. The results from this study are uncertain and the association has not been confirmed in analytic studies
• In a prospective analytic cohort study that generated both prevalence and incidence data, snus use was not associated with an increased risk of type 2 diabetes.
• In an experimental study acute use of snus had no effect on the insulin function.


Insulin resistance - a risk factor of cardiovascular disease
The relationship of snus use and insulin resistance has been described in four descriptive studies on risk factors for cardiovascular disease. Three of the studies found no statistically significant associations between snus use and insulin reactivity or plasma insulin levels (Bolinder, 1997; Eliasson et al., 1995; Wallenfeldt et al., 2001). The fourth study suggested that serum insulin levels may be significantly higher in snus users compared to non-tobacco users (Eliasson et al., 1991).


Type 2 diabetes
Three studies describe the relationship between snus use and insulin resistance or impaired glucose tolerance as it underlies diabetes. The strongest of these studies (Eliasson et al., 2004) Examined the effect of snus use and smoking on the risk of developing type 2 diabetes among 3384 men in a population based cross-sectional and prospective follow-up study (the Northern Sweden MONICA Study). At the onset of the study the prevalence of clinically diagnosed diabetes was significantly higher among current and ex-smokers compared to non-tobacco users. On the other hand the prevalence was not increased among snus users. The prevalence of pathologic glucose tolerance was not significantly elevated among snus users or smokers at the onset of the study. The risk of developing diabetes under the follow-up time period was increased among smokers and ex-smokers but not among those who used snus exclusively. The authors concluded that snus users do not have an increased risk of developing diabetes. This study is the first study in which prospective data show that snus use is not associated with the same increased risk of diabetes as smoking.

In contrast to the results from the study above, the results from a descriptive study by Persson et al. (2000) suggested that an association exists between snus use and type 2 diabetes. This cross-sectional study examined a cohort of Swedish men, half of whom had a strong family history of diabetes. The results showed that exclusive users of snus had approximately a 4-fold increased prevalence of type 2 diabetes compared to never users of tobacco. However, this finding must be viewed with caution because the risk estimate was based on only four cases of diabetes among snus users. Additional results also indicated that exclusive snus users did not experience impaired glucose tolerance and that snus users did not experience increased insulin resistance, conditions which are recognised precursors to diabetes. An important limitation of cross-sectional studies is that they can’t address causal relationships, i.e. if snus use causes diabetes. Analytic studies such as the study by Eliasson et al. (2004) do not suffer from this limitation.   Attvall et al. (1993) studied acute effects of smoking and snus use on the insulin resistance in a group of healthy habitual smokers. They found that smoking but not snus use causes insulin resistance.


Pregnancy outcomes
Summery
The association between tobacco use and pregnancy outcomes has been investigated in a recently publish cohort study comprising women who used snus or smoked daily and a control who didn’t use tobacco.

Important research results on Swedish snus:
• Daily use of snus during pregnancy is associated with a modest reduction in average birth weight.
• Daily use of snus during pregnancy is associated with a significant increase in risk of preterm delivery and preeclampsia.
• Daily use of snus during pregnancy is not associated with risk of small-for-gestational-age birth.
England et al. (2003) used data from the Swedish Medical Birth Register to compare the birth outcomes of 789 women who used snus daily, 11240 women who smoked cigarettes daily and 11495 women who used no tobacco products. Four health points were evaluated: birth weight, small-for-gestational-age birth, preterm delivery and preeclampsia.

The results showed that compared to non-users of tobacco, the average birth weight of babies born to snus users was reduced by 39 grams, whereas that of cigarette smokers was reduced by 190 grams. The risk of having a small-for-gestational-age baby among snus users was similar to that of non-users of tobacco, but it was significantly increased among cigarette smokers. The results also showed that the risk of preterm delivery was significantly elevated both in snus users and cigarette smokers compared to non-users of tobacco. In addition snus users are at significantly increased risk of preeclampsia.