Skip to main content

Review of epidemiologic data on the debate over smokeless tobacco's role in harm reduction


Some tobacco researchers have argued that the European Union should remove its ban on a form of low-nitrosamine smokeless tobacco referred to as Swedish 'snus'. This argument has developed in to an international debate over the use of smokeless tobacco as a measure of harm reduction for smokers. Leading authorities in the USA have firmly stated that there is no safe tobacco - a message which does not allow for any discussion of comparative tobacco risks. This commentary is intended to review the origin of the controversy over Swedish 'snus', to examine briefly the meta-analysis on cancer risks by Peter Lee and Jan Hamling (published in July in BMC Medicine) and to discuss the anticipated direction of the debate on tobacco-harm reduction in the USA. We anticipate that much of the debate will shift from the discussion of epidemiologic data to the discussion of the marketing, health communication and economics of smokeless tobacco. While the Food and Drug Administration's newly approved authority over tobacco will undoubtedly affect the smokeless products, it may not be the sole determinant of harm reduction's fate in the USA.

See associated research article by Lee and Hamling:

Origin of the controversy

The controversy over smokeless tobacco, considered by some as a potential substitute for cigarettes, originates from epidemiologic studies in Sweden - a country which has one of the lowest rates of daily smoking in Europe in recent years [1]. This achievement in tobacco control was particularly remarkable because of the significant gender difference in the smoking rates, leading one expert to question whether an experiment in harm reduction was underway [2]. The decline in daily smoking over the past two decades was more pronounced in Swedish males than in females [3, 4], resulting in a lower prevalence by 2001 (15% versus 19%, respectively) [5]. This steep decline coincided with Swedish males' increased use of 'snus', a form of moist smokeless tobacco which harbours fewer cancer-causing nitrosamines than its American counterparts [6]. Furthermore, the apparent substitution of tobacco products by the Swedish males coincided with a decrease in the incidence of lung cancer, a trend which has not been observed in Swedish females [7]. It is unlikely that existing tobacco-control policies could account for the difference in the prevalence of both smoking and smoking-related morbidity. Yet it is important to note that virtually all of the Swedish data supporting the cause of harm reduction is based on observational study designs, notably the cross-sectional design [3, 5, 8, 9]. Thus, it is premature to state that the increased use of 'snus' is causally associated with tobacco substitution and the decline in morbidity. Emerging clinical trials are investigating smokeless tobacco as a tool for smoking cessation [10]. In one randomized clinical trial of smokeless-tobacco use in combination with group support (versus group support alone), smoking rates decreased at the end of the 7-week period for the intervention group [11]. This effect, however, was not maintained after 6 months.

The current debate over harm reduction has focused primarily on two epidemiologic issues. The first relates to the cancer risk from the use of smokeless products, the basis for our commentary on the article by Peter Lee and Jan Hamling [12]. The second issue addresses whether use of smokeless tobacco is associated with the initiation or cessation of smoking. These issues have increasingly been investigated in the USA where smokeless tobacco is frequently marketed. Data, based on a single cross-sectional study [13], suggests that smokers in the USA are exchanging their cigarettes for smokeless tobacco. However, a longitudinal study of USA residents [14] reported that only 0.3% of male smokers changed to smokeless tobacco compared to 3.9% of male smokeless-tobacco users who subsequently changed to smoking tobacco.

The issue concerning the transition from smokeless tobacco to smoking raises the specter of the gateway effect. This issue has attracted much attention because of the belief that non-smoking adolescents could be unduly influenced to use a form of smokeless tobacco ('snus') intended for use by established smokers. A gateway effect, which could consequently lead to an adolescent's uptake of smoking, has been reported in some USA reports [1517] but refuted in others [18, 19]. One opposing argument states that the underlying risk factors for smoking, which tend to be greater in users of smokeless tobacco, account for the observed association between the tobacco products. This hypothesis was the basis for our use of the propensity score [20] in matching the users and non-users of smokeless tobacco [19]. Smokeless tobacco was a significant risk factor for smoking in this longitudinal study, but only prior to the matching of individuals on the propensity score. Even if a gateway effect to smoking exists, which is doubtful, only a minority of smokeless-tobacco users would be affected. Analyses of two national surveys indicate that less than 40% of smokeless-tobacco users in the USA had initiated use prior to the onset of smoking [21, 22]. The remainder had either never initiated smoking or had smoked prior to their initial use of smokeless tobacco.

Commentary on an article by Peter Lee and Jan Hamling

A systematic review by Lee and Hamling provides a comprehensive assessment of the state of evidence on the relationship between smokeless tobacco and cancer in Europe and North America [12]. Carcinogens in smokeless tobacco include high levels of nitrosamines, polycyclic aromatic hydrocarbons and other agents [23], underscoring the biologic relevance of this type of analysis. The primary findings of Lee and Hamling are that oropharyngeal cancers, in addition to prostate cancer (an association that may be spurious as it lacks biologic plausibility and is unsupported by prior research), were the only malignancies significantly associated with smokeless-tobacco use [12].

Researchers in cancer prevention refer to oropharyngeal cancer (along with cancers of the lung, esophagus and stomach) as an aerodigestive malignancy, a heterogeneous group of epithelial tumours affected by 'field carcinogenesis' from a common exposure - inhaled tobacco smoke. Beyond alcohol and tobacco smoking, recent evidence has implicated a new aetiologic factor for a subset of oropharyngeal and laryngeal cancer patients: human papilloma virus (HPV) [24]. In contrast to other oropharyngeal cancers, HPV-associated oropharyngeal cancers occur in younger patients and are characterized by an equal gender distribution, a lower tumour grade of differentiation, less association with alcohol and tobacco use and improved survival outcomes. The relevant oropharyngeal cancer-associated HPV serotypes (HPV 16, 18, others) and mode of transmission (sexual) are common to cervical cancer. Clearly, HPV-status was not reported in the individual studies reviewed in this meta-analysis, but smokeless-tobacco use has been associated with young age [25] and risky behaviour (including youth rebelliousness and pressure to be sexually active) [26]. Although HPV status is a potential confounder for the reported association of smokeless tobacco with oropharyngeal cancer, it is unlikely to explain the excess risk observed in the Lee and Hamling article - an effect that is consistent with other reports [25].

This lack of association of smokeless-tobacco use with cancers of the lung, esophagus, stomach, pancreas, bladder, kidney and haematologic malignancies starkly contrasts with research published over the past six decades on smoking-related cancer risks [2729]. Despite the observational nature of these results, the overwhelmingly null associations with cancer in this high quality analysis are provocative, if not compelling. It is important to note that these results are not entirely congruent with prior reports on smokeless-tobacco use which demonstrate an increased risk of oral, esophageal and pancreas cancers [25]. Potential reasons for the apparent discrepancies are discussed by Lee and Hamling in a separate paper [30].

Future directions

Attention in the coming years is likely to shift from an epidemiologic debate to a debate on the marketing, health communication and economics of the smokeless products. In Europe, researchers and policymakers will continue to debate the European Union's ban on 'snus' [31]. In the USA, attention will most likely be focused on the tobacco industry's marketing of the 'snus'-like products. This, of course, will depend greatly on the Food and Drug Administration's (FDA) newly approved regulation of the tobacco industry [32]. A historical examination of tobacco documents reveals that the Philip Morris company had anticipated smoking restrictions and the benefits of smokeless products as early as 1984 [33]. As a consequence, cigarette manufacturers have invested resources into the smokeless-tobacco market.

A question of primary interest is whether the tobacco companies will market 'snus' (for example, Camel Snus) for harm reduction, given FDA approval, or market the tobacco as a situational substitute for the smokers who frequently encounter smoking restrictions. Carpenter et al.'s examination suggests that the industry is more interested in the dual use of tobacco products, rather than tobacco substitution [33]. A scenario of graver concern is that adolescents will use 'snus' because the tobacco is misperceived as being safe. The low level of nicotine delivery in Marlboro Snus [34], a level insufficient for supplanting cigarettes, elicits memories of the graduation strategy [35] and the related manipulation of the 'free' nicotine content of moist snuff [36]. It is yet to be determined when and if the FDA will regulate the nicotine yields of the smokeless products. The FDA will, however, mandate that tobacco companies provide sufficient evidence of harm reduction before such a claim can be stated publically [37]. This position reflects the sentiment of other state and federal agencies (for example the US Center for Disease Control and Prevention) which are reluctant to disseminate information on comparative tobacco risks. This reluctance may be in response to the wide variation in toxicant levels of smokeless products [38]. Others have argued, however, that such a position is a violation of smokers' rights to be given accurate information [39], and may be a factor which could account for the preponderance of misperceived tobacco risks [4043]. Risk perceptions aside, most smokers are not receptive to using smokeless tobacco as a substitute, a finding reported in the 2005 California Tobacco Survey [44]. Thus, factors other than the FDA's oversight, such as a cultural influence on 'snus' use [45], may ultimately determine the fate of tobacco-harm reduction in the USA.



Centers for Disease Control and Prevention


US Food and Drug Administration


human papilloma virus.


  1. Fagerstrom KO, Schildt EB: Should the European Union lift the ban on snus? Evidence from the Swedish experience. Addiction (Abingdon, England). 2003, 98 (9): 1191-1195.

    Article  Google Scholar 

  2. Henningfield JE, Fagerstrom KO: Swedish Match Company, Swedish snus and public health: a harm reduction experiment in progress?. Tobacco Control. 2001, 10 (3): 253-257. 10.1136/tc.10.3.253.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Foulds J, Ramstrom L, Burke M, Fagerstrom K: Effect of smokeless tobacco (snus) on smoking and public health in Sweden. Tobacco Control. 2003, 12 (4): 349-359. 10.1136/tc.12.4.349.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Rodu B, Stegmayr B, Nasic S, Asplund K: Impact of smokeless tobacco use on smoking in northern Sweden. Journal of Internal Medicine. 2002, 252 (5): 398-404. 10.1046/j.1365-2796.2002.01057.x.

    Article  CAS  PubMed  Google Scholar 

  5. Ramstrom LM, Foulds J: Role of snus in initiation and cessation of tobacco smoking in Sweden. Tobacco Control. 2006, 15 (3): 210-214. 10.1136/tc.2005.014969.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Hatsukami DK, Henningfield JE, Kotlyar M: Harm reduction approaches to reducing tobacco-related mortality. Annual Review of Public Health. 2004, 25: 377-395. 10.1146/annurev.publhealth.25.102802.124406.

    Article  PubMed  Google Scholar 

  7. Wicklin B: Differences in smoking habits and lung cancer incidence between Sweden and Norway. Third International Conference on Smokeless Tobacco: Stockholm, Sweden. 2002

    Google Scholar 

  8. Furberg H, Lichtenstein P, Pedersen NL, Bulik C, Sullivan PF: Cigarettes and oral snuff use in Sweden: Prevalence and transitions. Addiction (Abingdon, England). 2006, 101 (10): 1509-1515.

    Article  Google Scholar 

  9. Furberg H, Bulik CM, Lerman C, Lichtenstein P, Pedersen NL, Sullivan PF: Is Swedish snus associated with smoking initiation or smoking cessation?. Tobacco Control. 2005, 14 (6): 422-424. 10.1136/tc.2005.012476.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. []

  11. Tonnesen P, Mikkelsen K, Bremann L: Smoking cessation with smokeless tobacco and group therapy: an open, randomized, controlled trial. Nicotine Tobacco Research. 2008, 10 (8): 1365-1372. 10.1080/14622200802238969.

    Article  PubMed  Google Scholar 

  12. Lee PN, Hamling JS: Systematic review of the relation between smokeless tobacco and cancer in Europe and North America. BMC medicine. 2009, 7 (1): 36-10.1186/1741-7015-7-36.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Rodu B, Phillips CV: Switching to smokeless tobacco as a smoking cessation method: evidence from the 2000 National Health Interview Survey. Harm Reduction Journal. 2008, 5: 18-10.1186/1477-7517-5-18.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Zhu SH, Wang JB, Hartman A, Zhuang Y, Gamst A, Gibson JT, Gilljam H, Galanti MR: Quitting cigarettes completely or switching to smokeless tobacco: do US data replicate the Swedish results?. Tobacco Control. 2009, 18 (2): 82-87. 10.1136/tc.2008.028209.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Tomar SL: Is use of smokeless tobacco a risk factor for cigarette smoking? The U.S. experience. Nicotine Tobacco Research. 2003, 5 (4): 561-569. 10.1080/1462220031000118667.

    Article  PubMed  Google Scholar 

  16. Haddock CK, Weg MV, DeBon M, Klesges RC, Talcott GW, Lando H, Peterson A: Evidence that smokeless tobacco use is a gateway for smoking initiation in young adult males. Preventive Medicine. 2001, 32 (3): 262-267. 10.1006/pmed.2000.0802.

    Article  CAS  PubMed  Google Scholar 

  17. Severson HH, Forrester KK, Biglan A: Use of smokeless tobacco is a risk factor for cigarette smoking. Nicotine Tobacco Research. 2007, 9 (12): 1331-1337. 10.1080/14622200701705209.

    Article  PubMed  Google Scholar 

  18. O'Connor RJ, Flaherty BP, Quinio Edwards B, Kozlowski LT: Regular smokeless tobacco use is not a reliable predictor of smoking onset when psychosocial predictors are included in the model. Nicotine Tobacco Research. 2003, 5 (4): 535-543. 10.1080/1462220031000118676.

    Article  PubMed  Google Scholar 

  19. Timberlake DS, Huh J, Lakon CM: Use of propensity score matching in evaluating smokeless tobacco as a gateway to smoking. Nicotine Tobacco Research. 2009, 11 (4): 455-462. 10.1093/ntr/ntp008.

    Article  PubMed  Google Scholar 

  20. Rubin DB: Estimating causal effects from large data sets using propensity scores. Annals of Internal Medicine. 1997, 127 (8 Pt 2): 757-763.

    Article  CAS  PubMed  Google Scholar 

  21. O'Connor RJ, Kozlowski LT, Flaherty BP, Edwards BQ: Most smokeless tobacco use does not cause cigarette smoking: results from the 2000 National Household Survey on Drug Abuse. Addictive Behaviors. 2005, 30 (2): 325-336. 10.1016/j.addbeh.2004.05.020.

    Article  PubMed  Google Scholar 

  22. Kozlowski LT, O'Connor RJ, Edwards BQ, Flaherty BP: Most smokeless tobacco use is not a causal gateway to cigarettes: using order of product use to evaluate causation in a national US sample. Addiction (Abingdon, England). 2003, 98 (8): 1077-1085.

    Article  Google Scholar 

  23. International Agency for Research on Cancer. Smokeless tobacco products. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. 2008, Lyon: IARC, 89.

  24. Fakhry C, Gillison ML: Clinical implications of human papillomavirus in head and neck cancers. Journal of Clinical Oncology. 2006, 24 (17): 2606-2611. 10.1200/JCO.2006.06.1291.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Boffetta P, Hecht S, Gray N, Gupta P, Straif K: Smokeless tobacco and cancer. Lancet Oncology. 2008, 9 (7): 667-675. 10.1016/S1470-2045(08)70173-6.

    Article  PubMed  Google Scholar 

  26. Coogan PF, Geller A, Adams M: Prevalence and correlates of smokeless tobacco use in a sample of Connecticut students. J Adolesc. 2000, 23 (2): 129-135. 10.1006/jado.2000.0303.

    Article  CAS  PubMed  Google Scholar 

  27. Doll R, Hill AB: Smoking and carcinoma of the lung; preliminary report. Br Med J. 1950, 2 (4682): 739-748. 10.1136/bmj.2.4682.739.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Wynder EL, Graham EA: Tobacco smoking as a possible etiologic factor in bronchiogenic carcinoma; a study of 684 proved cases. J Am Med Assoc. 1950, 143 (4): 329-336.

    Article  CAS  PubMed  Google Scholar 

  29. Doll R, Peto R, Wheatley K, Gray R, Sutherland I: Mortality in relation to smoking: 40 years' observations on male British doctors. BMJ. 1994, 309 (6959): 901-911.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Lee PN, Hamling J: The relation between smokeless tobacco and cancer in Northern Europe and North America. A commentary on differences between the conclusions reached by two recent reviews. BMC Cancer. 2009, 9: 256-10.1186/1471-2407-9-256.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Watson R: European Commission asked to investigate use of snus to reduce smoking. BMJ (Clinical Research ed). 2007, 335 (7626): 907-10.1136/bmj.39381.528507.DB.

    Article  Google Scholar 

  32. Samet JM, Wipfli H: Unfinished business in tobacco control. JAMA. 2009, 302 (6): 681-682. 10.1001/jama.2009.1155.

    Article  CAS  PubMed  Google Scholar 

  33. Carpenter CM, Connolly GN, Ayo-Yusuf OA, Wayne GF: Developing smokeless tobacco products for smokers: an examination of tobacco industry documents. Tobacco Control. 2009, 18 (1): 54-59. 10.1136/tc.2008.026583.

    Article  CAS  PubMed  Google Scholar 

  34. Foulds J, Furberg H: Is low-nicotine Marlboro snus really snus?. Harm Reduction Journal. 2008, 5: 9-10.1186/1477-7517-5-9.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Connolly GN: The marketing of nicotine addiction by one oral snuff manufacturer. Tobacco Control. 1995, 4: 73-79. 10.1136/tc.4.1.73.

    Article  PubMed Central  Google Scholar 

  36. Alpert HR, Koh H, Connolly GN: Free nicotine content and strategic marketing of moist snuff tobacco products in the United States: 2000-2006. Tobacco Control. 2008, 17 (5): 332-338. 10.1136/tc.2008.025247.

    Article  CAS  PubMed  Google Scholar 

  37. Curfman GD, Morrissey S, Drazen JM: Tobacco, public health, and the FDA. The New England Journal of Medicine. 2009, 361 (4): 402-403. 10.1056/NEJMe0905622.

    Article  CAS  PubMed  Google Scholar 

  38. Hatsukami DK, Ebbert JO, Feuer RM, Stepanov I, Hecht SS: Changing smokeless tobacco products new tobacco-delivery systems. Am J Prev Med. 2007, 33 (6 Suppl): S368-78. 10.1016/j.amepre.2007.09.005.

    Article  PubMed  Google Scholar 

  39. Kozlowski LT: Harm reduction, public health, and human rights: smokers have a right to be informed of significant harm reduction options. Nicotine Tobacco Research. 2002, 4 (Suppl 2): S55-60. 10.1080/1462220021000032843.

    Article  PubMed  Google Scholar 

  40. Smith SY, Curbow B, Stillman FA: Harm perception of nicotine products in college freshmen. Nicotine Tobacco Research. 2007, 9 (9): 977-982. 10.1080/14622200701540796.

    Article  PubMed  Google Scholar 

  41. O'Connor RJ, McNeill A, Borland R, Hammond D, King B, Boudreau C, Cummings KM: Smokers' beliefs about the relative safety of other tobacco products: findings from the ITC collaboration. Nicotine Tobacco Research. 2007, 9 (10): 1033-1042. 10.1080/14622200701591583.

    Article  PubMed  Google Scholar 

  42. O'Connor RJ, Hyland A, Giovino GA, Fong GT, Cummings KM: Smoker awareness of and beliefs about supposedly less-harmful tobacco products. American Journal of Preventive Medicine. 2005, 29 (2): 85-90. 10.1016/j.amepre.2005.04.013.

    Article  PubMed  Google Scholar 

  43. Haddock CK, Lando H, Klesges RC, Peterson AL, Scarinci IC: Modified tobacco use and lifestyle change in risk-reducing beliefs about smoking. American Journal of Preventive Medicine. 2004, 27 (1): 35-41. 10.1016/j.amepre.2004.03.010.

    Article  PubMed  Google Scholar 

  44. Timberlake DS: Are smokers receptive to using smokeless tobacco as a substitute?. Preventive Medicine. 2009, 49 (2-3): 229-32. 10.1016/j.ypmed.2009.07.012.

    Article  PubMed  Google Scholar 

  45. Gartner C, Hall W, Chapman S, Freeman B: Should the health community promote smokeless tobacco (Snus) as a harm reduction measure?. PLOS Medicine. 2007, 4 (7): 1138-1141. 10.1371/journal.pmed.0040185.

    Article  Google Scholar 

Pre-publication history

Download references

Author information

Authors and Affiliations


Corresponding author

Correspondence to David S Timberlake.

Additional information

Competing interests

The authors declare that they have no competing interests.

Authors' contributions

DT reviewed articles on harm reduction and authored the sections of the manuscript entitled 'Origin of the controversy' and 'Future directions'. JZ reviewed articles on cancer risks and authored the section entitled 'Commentary on article by Peter Lee and Jan Hamling'.

Rights and permissions

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Reprints and Permissions

About this article

Cite this article

Timberlake, D.S., Zell, J.A. Review of epidemiologic data on the debate over smokeless tobacco's role in harm reduction. BMC Med 7, 61 (2009).

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI:


  • Propensity Score
  • Human Papilloma Virus
  • Harm Reduction
  • Smokeless Tobacco
  • Oropharyngeal Cancer