Smokeless Tobacco

September 2010

Nicotiana tabacum L. Family: Solanaceae (nightshades)

Smokeless tobacco , chewing tobacco , moist snuff , dry snuff , compressed tobacco lozenges , iq-mik (Alaska) , betel quid (India) , snus (Sweden). The use of “noncombusted oral tobacco products” has been suggested as an alternate generic term for “smokeless tobacco products.” Common commercial preparations used in clinical trials include Ariva and Stonewall (tobacco lozenge), Revel and Skoal Dry (spit-free smokeless tobacco), Commit (nicotine lozenge), Copenhagen (moist snuff).

Uses

The role of smokeless tobacco in smoking cessation is debated. Issues relate to the lack of evidence for efficacy in achieving long-term smoking cessation (greater than 6 months) and the health risks of smokeless tobacco products. Concern has been raised that smokeless tobacco use serves as a gateway to smoking.

Dosing

Users of smokeless tobacco regulate consumption to meet cravings and withdrawal symptoms.

Contraindications

None well documented.

Pregnancy/Lactation

Avoid use. Smokeless tobacco use during pregnancy is associated with decreased birth weight and increased risk of preterm delivery.

Interactions

None well documented.

Adverse Reactions

An increased risk of oropharyngeal cancer exists. Data for other cancers are less consistent. An association between the risk of fatal myocardial infarction and fatal stroke in users of smokeless tobacco has been shown. Other oral pathologies, such as inflammation, leukoplakia, and tooth decay have been described with smokeless tobacco use.

Toxicology

The International Agency for Research on Cancer (IARC) recognizes that smokeless tobacco contains at least 30 cancer-causing agents and is carcinogenic to humans.

Smokeless tobacco products are derived from the same botanical source as smoking tobacco ( Nicotiana tabacum ). The tobacco plant originated in South America more than 7,000 years ago. Smokeless tobacco products often are flavored with sugar or artificial sweeteners. ^1, , ²

American Indians may have been using tobacco throughout North and South America by the time the first European explorers arrived in the late 1400s and early 1500s. Tobacco use spread to Europe, Africa, China, and Japan over the next few centuries. Snuff use (at the time, finely ground tobacco that primarily was sniffed through the nose) was introduced to North American colonists in Jamestown, VA in 1611. Tobacco chewing by colonists probably began in the early 1700s and was widely accepted by the 1850s. Snuff was the most popular form of smokeless tobacco in Europe and America prior to the 1800s. A current practice in the United States and many other parts of the world is “snuff dipping” in which, the small amount of powdered tobacco is placed in the buccal area between the gum and cheek where it is retained for a period of time. The resultant saliva is then usually spit or swallowed. Snuff is taken as loose portions or from small prepackaged bags of tobacco. In many parts of the world, the tobacco is mixed with other stimulants such as betel or areca nut. Some users chew a portion of smokeless tobacco. ^2, , ^3, , ⁴

Tobacco contains more than 2,500 chemical constituents. Some of these constituents are present naturally while others are added during cultivation, harvesting, and processing. For example, chewing tobacco consists of the tobacco leaf with the stem removed, with added sweeteners, and flavorings (eg, honey, licorice, rum). Snuff consists of the entire tobacco leaf (dried and powdered or finely cut) and additives such as menthol, peppermint oil, camphor, attar of roses, and oil of cloves.

Scientific literature lists at least 30 carcinogenic agents in smokeless tobacco forms. Of these agents, N-nitrosamines are considered the major contributors to carcinogenic activity. Volatile and nonvolatile nitrosamines include tobacco-specific N-nitrosamines (TSNAs), polynuclear aromatic hydrocarbons, and polonium-210 (210Po). The most carcinogenic TSNAs, including 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N-nitrosonornicotine (NNN), are found in concentrations that produced cancer in laboratory animals. Despite newer products claiming processing that reduces tobacco-specific nitrosamine content, smokeless tobacco products still contain carcinogenic nitrosamines in concentrations higher than those permitted in food.

The major chemical groups in tobacco include aliphatic and aromatic hydrocarbons, aldehydes, ketones, alcohols, phenols, ethers, alkaloids (including nicotine, nornicotine, anabasine, anatabine, and myosmine), carboxylic acids, esters, anhydrides, lactones, carbohydrates, amines, amides, imides, nitrites, N- and O-heterocyclic compounds, chlorinated organic compounds, and at least 35 metal compounds. Nicotine content varies with commercial brand, but has been measured for some products and ranges from 1.22% for chewing tobacco to 2.58% for moist snuff. Dry snuff contains approximately 1.82% dry weight. ^2, , ^4, , ^5, , ^6, , ^7, , ^8, , ^9, , ¹⁰

Smoking cessation The role of smokeless tobacco in smoking cessation is debated. ^11, , ^12, , ^13, Issues relate to the lack of evidence for efficacy in achieving long-term smoking cessation (greater than 6 months), ^14, , ^15, health risks of the smokeless tobacco products, ^16, and the concern that smokeless tobacco use could serve as a gateway to smoking. ^9, , ^11, , ^13, , ¹⁷

As with smoking tobacco, the pharmacologic effect of smokeless tobacco is related in part to its nicotine content. Blood nicotine levels are achieved rapidly with smokeless tobacco use (within 5 minutes) and can reach 40 ng/mL, comparable with peak levels found in heavy cigarette smokers (who average approximately 35 ng/mL). ^8, , ¹⁸

Use of smokeless tobacco products is anticipated to increase due to antismoking action, and a perception that such products are safer than smoking prevails. A proposal to give the Food and Drug Administration authority over tobacco products has been considered in the US Senate. ^11, , ¹²

Users of smokeless tobacco regulate consumption to meet cravings and withdrawal symptoms. ^9, , ¹⁰

Avoid use. Data from the United States are lacking; however, data from Sweden and India describe an increase in the risk of decreased birth weight, and preterm and stillbirth delivery in pregnant users of smokeless tobacco products. ^19, , ^20, , ^21, , ²²

One case report documents the potential interaction between tobacco (which contains high levels of vitamin K) and warfarin. ^23, , ^24, Candied smokeless tobacco products contain significant glucose (50 to 150 mg/g) and may contribute to hyperglycemia in susceptible people. ^25, Tobacco products may affect blood pressure because of its high sodium content. ^23, , ²⁴

Less data are available regarding the adverse reactions of smokeless tobacco than the adverse effects of smoked tobacco, and generalization from available studies is limited because of the confounding effects of concurrent smoking and geographical diversity. The risks of adverse reactions, however, are greater for smokers than for users of smokeless tobacco, which are in turn greater than for nonusers of tobacco. A relationship exists between the duration of exposure to smokeless tobacco and the risk of adverse reactions. As users increase their consumption of smokeless tobacco to increase effect, exposure to nicotine and carcinogens increases as well. ^10, , ^26, , ^27, , ²⁸

Tobacco dependence An estimated prevalence for smokeless tobacco use in Americans 18 years of age or older is 20%, and in 2005 an estimated 7.7 million Americans 12 years of age and older were reported to be current (past month) users. ^29, , ³⁰

Concerns exist regarding the intrinsic health risks of smokeless tobacco use, as well as its role as a gateway to smoking tobacco. ²⁹

Strategies for smokeless tobacco cessation include behavioral and pharmacologic therapy, with evidence to suggest behavioral interventions may be successful, ^31, , ^32, , ^33, , ^34, whereas neither nicotine replacement nor bupropion have been shown to increase long-term abstinence. ^29, , ^34, , ³⁵

Risk of cancer Data from studies conducted in the United States and Scandinavia have shown an increased risk of oropharyngeal cancer from the use of oral tobacco, as well as nasal tobacco products. The data for other cancers, such as esophageal, larynx, lung, and pancreatic cancer, are less consistent. ^10, , ^16, , ^27, , ^36, , ^37, The clinical appearance of oral lesions in users of smokeless tobacco is reported to be different from those of smokers, with differing morphologies described. ^10, , ³⁸

Risk of cardiovascular events A meta-analysis of 11 studies conducted in the United States and in Sweden found a small but definitive increase (narrow confidence intervals) in the risk of fatal myocardial infarction and fatal stroke in users of smokeless tobacco versus nonusers. The data for nonfatal cardiovascular disease was limited by heterogeneity. ^26, Previous reviews have been unable to find an association. ^37, , ^39, , ^40, , ⁴¹

Other risks Oral pathologies, such as gum recession and inflammation, leukoplakia, tooth erosion and decay, and periodontal alveolar bone loss have been associated with smokeless tobacco use. ^27, , ⁴²

The IARC recognizes that smokeless tobacco contains at least 30 cancer-causing agents and is carcinogenic to humans. ^9, , ¹⁰

1. Nicotiana tabacum L. USDA, NRCS. 2007. The PLANTS Database ( http://plants.usda.gov , February, 2010). National Plant Data Center, Baton Rouge, LA 70874-4490 USA.

2. Hatsukami DK, Ebbert JO, Feuer RM, Stepanov I, Hecht SS. Changing smokeless tobacco products new tobacco-delivery systems. Am J Prev Med . 2007;33(suppl 6):S368-S378. PubMed

3. Grasso P, Mann AH. Smokeless tobacco and oral cancer: an assessment of evidence derived from laboratory animals. Food Chem Toxicol . 1998;36(11):1015-1029. PubMed

4. National Toxicology Program. Smokeless tobacco. Rep Carcinog . 2002;10:236-238. PubMed

5. Brunnemann KD, Qi J, Hoffmann D. Chemical profile of two types of oral snuff tobacco. Food Chem Toxicol . 2002;40(11):1699-1703. PubMed

6. Nilsson R. A qualitative and quantitative risk assessment of snuff dipping. [published correction appears in Regul Toxicol Pharmacol . 1999;29(1):97]. Regul Toxicol Pharmacol . 1998;28(1):1-16. PubMed

7. Djordjevic MV, Doran KA. Nicotine content and delivery across tobacco products. Handb Exp Pharmacol . 2009;(192):61-82. PubMed

8. Kotlyar M, Mendoza-Baumgart MI, Li ZZ, et al. Nicotine pharmacokinetics and subjective effects of three potential reduced exposure products, moist snuff and nicotine lozenge. Tob Control . 2007;16(2):138-142. PubMed

9. Melikian AA, Hoffmann D. Smokeless tobacco: a gateway to smoking or a way away from smoking. Biomarkers . 2009;14(suppl 1):85-89. PubMed

10. Boffetta P, Hecht S, Gray N, Gupta P, Straif K. Smokeless tobacco and cancer. Lancet Oncol . 2008;9(7):667-675. PubMed

11. Timberlake DS, Zell JA. Review of epidemiologic data on the debate over smokeless tobacco's role in harm reduction. BMC Med . 2009;7:61. PubMed

12. Tomar SL, Fox BJ, Severson HH. Is smokeless tobacco use an appropriate public health strategy for reducing societal harm from cigarette smoking? Int J Environ Res Public Health . 2009;6(1):10-24. PubMed

13. NIH State-of-the-Science Panel. National Institutes of Health State-of-the-Science conference statement: tobacco use: prevention, cessation, and control. Ann Intern Med . 2006;145(11):839-844. PubMed

14. Tilashalski K, Rodu B, Cole P. Seven year follow-up of smoking cessation with smokeless tobacco. J Psychoactive Drugs . 2005;37(1):105-108. PubMed

15. T⊘nnesen P, Mikkelsen K, Bremann L. Smoking cessation with smokeless tobacco and group therapy: an open, randomized, controlled trial. Nicotine Tob Res . 2008;10(8):1365-1372. PubMed

16. Lee PN, Hamling J. Systematic review of the relation between smokeless tobacco and cancer in Europe and North America. BMC Med . 2009;7:36. PubMed

17. Stellman SD, Djordjevic MV. Monitoring the tobacco use epidemic II: The agent: Current and emerging tobacco products. Prev Med . 2009;48(suppl 1):S11-S15. PubMed

18. Russell MA, Jarvis MJ, Feyerabend C. A new age for snuff? Lancet . 1980;1(8166):474-475. PubMed

19. England LJ, Levine RJ, Mills JL, Klebanoff MA, Yu KF, Cnattingius S. Adverse pregnancy outcomes in snuff users. Am J Obstet Gynecol . 2003;189(4):939-943. PubMed

20. Gupta PC, Subramoney S. Smokeless tobacco use, birth weight, and gestational age: population based, prospective cohort study of 1217 women in Mumbai, India. [published correction appears in BMJ . 2010;340:c2191]. BMJ . 2004;328(7455):1538. PubMed

21. Rogers JM. Tobacco and pregnancy. Reprod Toxicol . 2009;28(2):152-160. PubMed

22. Rogers JM. Tobacco and pregnancy: overview of exposures and effects. Birth Defects Res C Embryo Today . 2008;84(1):1-15. PubMed

23. Kuykendall JR, Houle MD, Rhodes RS. Possible warfarin failure due to interaction with smokeless tobacco. Ann Pharmacother . 2004;38(4):595-597. PubMed

24. Asplund K. Smokeless tobacco and cardiovascular disease. Prog Cardiovasc Dis . 2003;45(5):383-394. PubMed

25. Pyles ST, Van Voris LP, Lotspeich FJ, McCarty SA. Sugar in chewing tobacco. N Engl J Med . 1981;304(6):365. PubMed

26. Boffetta P, Straif K. Use of smokeless tobacco and risk of myocardial infarction and stroke: systematic review with meta-analysis. BMJ . 2009;339:b3060. PubMed

27. Critchley JA, Unal B. Health effects associated with smokeless tobacco: a systematic review. Thorax . 2003;58(5):435-443. PubMed

28. Hecht SS, Carmella SG, Edmonds A, et al. Exposure to nicotine and a tobacco-specific carcinogen increase with duration of use of smokeless tobacco. Tob Control . 2008;17(2):128-131. PubMed

29. Ebbert JO, Montori V, Vickers KS, Erwin PC, Dale LC, Stead LF. Interventions for smokeless tobacco use cessation. Cochrane Database Syst Rev . 2007;(4):CD004306. PubMed

30. Severson HH, Peterson AL, Andrews JA, et al. Smokeless tobacco cessation in military personnel: a randomized controlled trial. Nicotine Tob Res . 2009;11(6):730-738. PubMed

31. Boyle RG, Enstad C, Asche SE, et al. A randomized controlled trial of Telephone Counseling with smokeless tobacco users: the ChewFree Minnesota study. Nicotine Tob Res . 2008;10(9):1433-1440. PubMed

32. Danaher BG, Smolkowski K, Seeley JR, Severson HH. Mediators of a successful web-based smokeless tobacco cessation program. Addiction . 2008;103(10):1706-1712. PubMed

33. Severson HH, Gordon JS, Danaher BG, Akers L. ChewFree.com: evaluation of a Web-based cessation program for smokeless tobacco users. Nicotine Tob Res . 2008;10(2):381-391. PubMed

34. Ebbert JO, Dale LC, Severson H, et al. Nicotine lozenges for the treatment of smokeless tobacco use. Nicotine Tob Res . 2007;9(2):233-240. PubMed

35. Dale LC, Ebbert JO, Glover ED, et al. Bupropion SR for the treatment of smokeless tobacco use. Drug Alcohol Depend . 2007;90(1):56-63. PubMed

36. Accortt NA, Waterbor JW, Beall C, Howard G. Chronic disease mortality in a cohort of smokeless tobacco users. Am J Epidemiol . 2002;156(8):730-737. PubMed

37. Hatsukami DK, Lemmonds C, Tomar SL. Smokeless tobacco use: harm reduction or induction approach? Prev Med . 2004;38(3):309-317. PubMed

38. Warnakulasuriya KA, Ralhan R. Clinical, pathological, cellular and molecular lesions caused by oral smokeless tobacco--a review. J Oral Pathol Med . 2007;36(2):63-77. PubMed

39. Critchley JA, Unal B. Is smokeless tobacco a risk factor for coronary heart disease? A systematic review of epidemiological studies. Eur J Cardiovasc Prev Rehabil . 2004;11(2):101-112. PubMed

40. Huhtasaari F, Lundberg V, Eliasson M, Janlert U, Asplund K. Smokeless tobacco as a possible risk factor for myocardial infarction: a population-based study in middle-aged men. J Am Coll Cardiol . 1999;34(6):1784-1790. PubMed

41. Asplund K, Nasic S, Janlert U, Stegmayr B. Smokeless tobacco as a possible risk factor for stroke in men: a nested case-control study. Stroke . 2003;34(7):1754-1759. PubMed

42. Taybos G. Oral changes associated with tobacco use. Am J Med Sci . 2003;326(4):179-182. PubMed