The SCENIHR has been asked to evaluate the health effects of smokeless tobacco products (STP) with particular attention to tobacco for oral use, moist snuff, which is called “snus” in Sweden. In addition to tobacco for oral use, STP include chewing tobacco, dry snuff and nasal snuff. The EC Tobacco Products Directive (2001/37/EC) defines tobacco for oral use as “…all products for oral use, except those intended to be smoked or chewed, made wholly or partly of tobacco, in powder or in particulate form or in any combination of those forms”. Synonyms for “tobacco for oral use” are moist snuff (snus) and oral tobacco. Marketing of oral tobacco is banned in all EU countries except Sweden, while other STP are allowed in EU.
Marketed STP vary considerably in form and content of toxicants, including nicotine, and thereby in associated health effects.
All STP contain nicotine, a potent addictive substance. The major group of carcinogens in STP includes non-volatile tobacco-specific nitrosamines (TSNA) and N-nitroamino acids. During the last two decades the levels of TSNA in snus have been considerably lowered. Some forms of STP contain polycyclic aromatic hydrocarbons depending on type of curing. Aqueous and organic extracts of American and Swedish moist snuff and Indian chewing tobacco cause mutations and chromosomal damage in bacterial and mammalian cell cultures. Increased micronuclei formation in oral epithelial cells as evidence of chromosomal damage, has been associated with moist snuff use.
Use of American and Swedish moist snuff results in localised lesions in the oral epithelium, where the snuff is placed. These changes are reversible, whereas gingival retractions caused by moist snuff are not reversible. Moist snuff in portion-bag sachets gives less severe epithelial changes than snuff in loose form.
There is sufficient evidence that the use of a wide variety of STP causes cancer in humans. The pancreas has been identified as a main target organ in two Scandinavian cohort studies. Furthermore, several studies from the USA have provided additional support for a causal association between the use of smokeless tobacco and pancreatic cancer. There is inadequate evidence that STP cause lung cancer.
Risks of oral cancer have been found to be strongly associated with the use of American snuff in the USA. Studies in India, Pakistan and Sudan have reported large increases in the risk for oral cancers related to the use of various STP. In Sweden, the evidence for an increased risk of oral cancer in users of oral tobacco is less clear. In one study from Sweden among users of moist snuff, an increased risk of head and neck cancer has been found among never-smokers. A recent cohort study from Sweden reported a statistically significant three-fold increase of oral and pharyngeal cancer, adjusted for tobacco smoking and alcohol drinking.
There are suggestions that nasal snuff use increases the risk for certain cancers, including oral cancer.
It appears that the use of smokeless tobacco increases the risk of death after myocardial infarction, but that it does not increase the risk of myocardial infarction. Animal experiments and human studies indicate that oral tobacco use has short-term effects resulting in an increase of blood pressure and heart rate. Whether long-term use increases the risk of hypertension is uncertain. These data indicate a potential effect on the risk of cardiovascular disease.
The data on reproductive effects in relation to oral tobacco use during pregnancy are too sparse to allow conclusions. Nonetheless, studies in female Swedish users of moist snuff indicated an increased risk for prematurity and pre-eclampsia. Other studies indicate that use of STP during pregnancy is associated with reduced birth weight and reduction in gestational age.
Various studies suggest that diabetes and other components of the metabolic syndrome might be associated with use of moist snuff.
Based on the available evidence it is difficult to identify overall relative risk estimates for the various adverse health effects from oral tobacco products as a whole because the products and conditions of use (e.g. frequency, duration, mode of use, other lifestyle factors) vary widely.
In conclusion, all STP contain nicotine, a potent addictive substance. They also contain carcinogenic tobacco-specific nitrosamines, albeit at differing levels. STP are carcinogenic to humans and the pancreas has been identified as a main target organ in American and Scandinavian studies. All STP cause localised oral lesions and a high risk for development of oral cancer has been shown for various STP but has not been proven for Swedish moist snuff (snus). There is some evidence for an increased risk of fatal myocardial infarction among STP users. Some data indicate reproductive effects of smokeless tobacco use during pregnancy but firm conclusions cannot be drawn.
It is widely accepted that nicotine is the primary addictive constituent of tobacco, and nicotine demonstrates the properties of a drug of abuse. All commercially successful tobacco products deliver psychoactive levels of nicotine to users. Denicotinised tobacco products are typically not widely accepted by chronic tobacco users and are of marginal commercial importance.
Smokeless tobacco delivers quantities of nicotine comparable to those typically absorbed from cigarette smoking, although delivery of nicotine from STP lacks the high initial concentration and speed of delivery that results from inhalation of tobacco smoke, and may therefore have relatively less addiction potential than cigarettes. Nicotine levels obtained from STP are generally higher than those typically obtained from nicotine replacement therapy, which is considered to have a low addiction potential.
The time course and symptoms of withdrawal from smokeless tobacco are generally similar to those of cigarette smokers, although depressive symptoms and negative affect do not appear to be observed among abstinent STP users. It seems also that symptoms of withdrawal are stronger with some brands of smokeless tobacco delivering higher levels of nicotine compared to other brands with lower levels. There is a lack of evidence relating to the effects of additives introduced to tobacco in the manufacturing process on the initiation of use of STP and subsequent dependence.
In conclusion, smokeless tobacco is addictive and withdrawal symptoms are broadly similar to those seen in smokers.
No randomized trial has been conducted on smokeless tobacco as an aid to smoking cessation and no randomized trial has compared smokeless tobacco to pharmaceutical nicotine replacement products in this respect. Some observational studies have looked at the use of smokeless tobacco, and in one study also nicotine replacement products, in relation to change in smoking habits but the results of these studies are inconsistent. On the available evidence it is therefore not possible to draw conclusions as to the relative effectiveness of smokeless tobacco as an aid to smoking cessation in comparison with established therapies.
The association between smokeless tobacco use and cigarette smoking initiation is likely to be confounded by socio-demographic factors. In addition, across countries there are possible differences in risk for which the determinants are not fully understood. The associations observed may be due to an increased likelihood of all substance use (including STP and cigarettes) as part of a broader spectrum of risky and impulsive behaviours in adolescence.
There is some evidence from the USA that smokeless tobacco use may lead to subsequent cigarette smoking. The Swedish data do not support the hypothesis that smokeless tobacco (i.e. Swedish snus) is a gateway to future smoking. The marked social, cultural and product differences between North America and Europe suggest caution in translating findings across countries, also within Europe.
Presently, Sweden is the only EU-country in which it is legal to supply oral tobacco as defined by the EC (see above). All other smokeless tobacco products (chewing tobacco, nasal snuff) can be sold in all EU-countries. Aggregate data on smokeless tobacco product use and cigarette smoking show that particularly in Swedish men, there is a clear trend over recent decades for smoking prevalence to decrease and for use of oral tobacco (snus) to increase. The prevalence of smoking has also decreased markedly in Swedish women during this period, but to a lesser extent than in men, and in conjunction with a lesser increase in snus use. It has been suggested that the greater decline in smoking prevalence in men compared to women in Sweden is explained by the availability of snus, and this interpretation is supported by trends in longitudinal, within-person data from a population cohort in northern Sweden (report partly funded by the tobacco industry). However, these trends could also be due to successful non-smoking programs or other socio-cultural factors, and it is therefore not clear whether or by how much the availability of snus has influenced smoking prevalence. Overall smoking prevalence in Norway, as well as in young Norwegians, has decreased at the same rates in men and women during the last decade, whereas a marked increase in snus use during this time period has only occurred in young men. In California both the prevalence of smoking and smokeless tobacco use have decreased concurrently. These data imply that the association between patterns of smokeless tobacco use and smoking cessation differs between populations and is likely to be affected by cultural, societal and other factors.
In conclusion, it is not possible to extrapolate future patterns of tobacco use across countries. In particular, it is not possible to extrapolate the trends in prevalence of smoking and use of oral tobacco if it were made available in an EU country where it is now unavailable.
STP are addictive and their use is hazardous to health. STP contain various levels of toxic substances. Evidence on the effectiveness of STP as a smoking cessation aid is insufficient, and relative trends in progression from STP into and from smoking differ between countries. It is thus not possible to extrapolate the patterns of tobacco use from one country where oral tobacco is available to other countries due to societal, and cultural differences.