Tobacco has been used by human beings since 600 AD.1 Columbus came to know about tobacco from Caribbean and introduced it in Europe. It was introduced in India in early 1600 AD by Portuguese traders mainly as a barter commodity to trade Indian textiles.2 The harmful effect of tobacco was also known since the Mughal era and the Jahangir, the Mughal emperor of India, had even passed orders to ban it.3 The spiritual leader, Guru Gobind Singh, the 10th Sikh guru, prohibited smoking for the Sikh community. He said, “Wine is bad, Indian hemp (bhang) destroys one generation, but tobacco destroys all generations”.4 Not only in India, the king James I of England and Shah Abbas of Persia were aware of the harmful effect of tobacco. King James described tobacco smoking as “a custom loathsome to the eye, hateful to the nose, harmful to the brain, and dangerous to the lungs”. Initially, it was mainly used by affluent class but gradually penetrated at all socioeconomic strata in various forms.
The term “smokeless tobacco” (SLT) mainly refers to chewing, spitting, sniffing unburned tobacco in one or the other form either alone or mixed with other constituents. The SLT is mainly obtained from Nicotiana rustica which contains more nitrosamines as compared to the tobacco for smoking obtained from Nicotiana tabacum. Mainly, it was consumed with betel quid (pan) for decades and later in the form of bidi (tobacco wrapped in dried leaves of special trees). Some people used for its presumed medicinal value which although has never been proved in any system of medicine being practiced in India.
The various forms and different names of SLT consumed in India are Pan, Gutkha, Zarda, Naswar, and Mishri or Gul (Table 1 and Figs. 1 to 3).
- Pan is a betel leaf containing mixture of tobacco, areca nuts, spices, and lime (to increase the bioavailability of nicotine)
- Gutkha is nothing but powdered form of scented tobacco, areca nut mixed with lime.
- Zarda is Indian chewing tobacco flavored with spices and flavored form of tobacco is also used in pan
- Naswar is a moist, powdered tobacco snuff consumed mostly in India, Pakistan, Afghanistan and neighboring countries.Naswar is snuffed in the floor of mouth, under the lower lip, or inside the cheek for prolong period to get desired effect
- Mishri or Gul is tobacco powder applied to teeth and gums with index fingers and used as dentifrices
- Snuff is a pulverized tobacco either fermented (US type) or nonfermented (Swedish type). The pattern of use of snuff is slightly different in these two countries where in Sweden it is placed under the upper lip and in United States between the lower gum and chin.5 It is usually inhaled or snuffed into the nasal cavity, delivering a swift hit of nicotine. It is usually in the flavored form.
Smokeless tobacco is not only common in middle income and poor countries but is also quite commonly used as snuff in North America and in Europe mainly Sweden. Inhalation of tobacco or snuff is relatively less common in India as compared to western countries
There are more than 350 million populations globally using SLT with the majority living in Southeast Asian region.6 The prevalence of SLT in this region is 1.3–38% in males and 4.6–27.9% in females.7 India is one of the largest consumers of tobacco products both in number and relative share. The prevalence of tobacco use in Indian population more than 15 years age is 34.6% (47.9% males, 20.3% females) and is mainly consumed as SLT (49.3% males, 85.5% females).8 The average age of initiation was 17.9 years similar to that of smoking.9 It is specially increasing in younger children in India. A cross-sectional study in Delhi and Chennai (Project MYTRI) reported higher use of SLT in 6th grade students than 8th grade.10 Tobacco use in any form accounts for 6 million deaths globally every year which is expected to increase 8 million by 2030. According to Tobacco Control Policy (TCP) Indian cohort survey, Gutkha was the most common form of SLT used in India followed by chewing of tobacco (Fig. 4).11
The association of tobacco consumption mainly in form of smoking and cardiovascular disease (CVD) is well established.12 The historical trend of smoking and CVD in Unites states ran parallel in last century. The rate of smoking and CVD increased till first half of 20th century and later decreased gradually because increased awareness and well proven causation of various diseases.13,14 The use of SLT which was common in middle income countries became gradually increased in developed countries as the trends for smoking decreased whereas the smoking and SLT both increased in developing countries especially Southeast Asia.15
FIG. 4: Prevalence of smokeless tobacco used in India.Source: Gravely S, Fong GT, Driezen P, et al. An examination of the effectiveness of health warning labels on smokeless tobacco products in four states in India: findings from the TCP India cohort survey. BMC Public Health. 2016;16:1246.
The main reason of increased use of SLT is because of its easy availability, lack of awareness of its harmful effect, aggressive marketing by the companies, presumption of it being medicinal value, as mouth freshener, and dentifrices. Tobacco consumption is the most important preventable risk factor for premature death especially in young middle-aged adults.16
PHARMACOKINETICS OF SMOKELESS TOBACCO
Nicotine is the main constituent in tobacco causing addiction and most of its harmful effect. The level of nicotine in blood depends upon the concentration of tobacco in the product, its pH level, moisture level, and the size of tobacco cutting.17,18 It is water- and lipid-soluble weak base and readily crosses the mucosa in unionized form. If the pH of the SLT is higher, i.e., if it is more alkaline then more nicotine remains in unionized form, hence more absorbed resulting in higher nicotine blood level.19 The maximum level of nicotine is similar in both smoking and SLT but the level of nicotine is more sustained in SLT as compared to smoking where rapid peaks and troughs are seen.20
SMOKELESS TOBACCO AND CARDIOVASCULAR RISK FACTORS
Nicotine increases the blood pressure (BP) and heart rate (HR) by enhancing the release of dopamine, epinephrine, norepinephrine, vasopressin, etc. and activation of sympathetic nervous system. The long-term effect of SLT on BP depends on many factors including the type and amount of SLT used and level of physical activity. Increase in BP is not only because of nicotine but also because of high sodium content of the tobacco product and licorice in SLT. This has been proved by measuring the urinary sodium content in various types of SLT.21 The licorice increases the sodium level by inhibiting the metabolism of mineralocorticoids and thus increases the BP. The acute effects of SLT causes increase in HR and BP which in one of the study shows increase by 19 beats/min of HR and by 21/14 mm Hg of BP.22 In a population-based survey of more than 30,000 participants in Sweden, the chronic SLT users were more likely to have higher BP (>160/90 mm Hg).23 More often it is the diastolic BP which is elevated as shown in a study of 135 middle aged healthy volunteers with ambulatory BP monitoring.24 But in those who are physically active like baseball players, no significant elevation in BP and HR was noted in SLT users.25 Use of tobacco has been shown to be associated with insulin resistance and incident diabetes. Higher serum level of insulin and fibrinogen was noted in SLT users as compared to non-users.26 A prospective population-based study in middle aged Swedish men using snuff found significant risk of developing diabetes at follow-up of 10 years.27 SLT has also been associated with abnormal lipid profile. A study conducted in Asians with regular tobacco chewing habits reported significantly high level of low-density lipoproteins cholesterol (LDL-C) and low level of high-density lipoproteins cholesterol (HDL-C).28 Similarly, Tucker et al. in a population based study reported 2.5 times higher prevalence of hypercholesterolemia in SLT users.29 Gupta et al. studied association between SLT and CV risk factors in a population based case control study in Bikaner region, India.30 They found significant higher prevalence of hypertension, tachycardia, dyslipidemia and diabetes as compared to nontobacco users. All these studies were in isolation and in different regions of the globe where different types of SLT products with different tobacco content and other constituents were being used. The effect of SLT on vascular inflammation, atherosclerosis and thrombosis is still unclear and needs large studies with all types of SLT products.
SMOKELESS TOBACCO AND CARDIOVASCULAR DISEASE
Smokeless tobacco has been associated with various diseases including cancer of the oral cavity, esophagus, and pancreas.31,32 It has also been associated with low birth weight, preterm or stillbirth.30 The association of SLT with CVD is not very well established as it is for smoking.33 Various studies in different regions of the world produced different results depending upon the type of SLT consumed and their level of chemical constituents. Apart from the Southeast Asian countries, the main consumer of SLT although in different forms is in Sweden and United States. The SLT consumed in India have high levels of tobacco-specific nitrosamines as compared to that present in moist snuff available in European market.34,35 Also, the SLT available in India has varied methods of preparation, variable tobacco content and varied methods of using it which causes different effects as compared to SLT available in western countries. The meta-analysis by Boffetta and Straif calculated SLT-attributable fraction of CVD.36 In their analysis, SLT use contributed 5.6% of fatal coronary heart disease (CHD) in Sweden and 0.5% in America. This meta-analysis included eight studies that evaluated the risk of fatal myocardial infarction and five studies that evaluated the risk of fatal stroke but this analysis did not include Asian studies. Three studies showed significant association of SLT and CV death (including stroke and CV death) but other studies did not show that strong association. But the overall cohort has shown positive association between CV death and SLT. The meta-analysis by Vidyasagaran et al. has shown increased risk of fatal ischemic heart disease (IHD) and stroke with SLT.37 Another study by Gupta et al. also known as Mumbai cohort study the results was mixed. At follow-up of 5 years, SLT use was associated with significant fatal CV event in females but not in males.38 The study including patients from India, China, and Taiwan has shown insignificant association of SLT and CV mortality in India but significant association in China and Taiwan.39 The incidence of nonfatal stroke did not show an increased risk in SLT users but most of the studies with this end point have been conducted in Nordic region like Sweden.40 The incidence of nonfatal IHD shows significant heterogeneity depending upon the geographical area of study. The studies conducted in Nordic region did not show an increased risk for nonfatal IHD but those from the Asian region showed a 40% increased risk.41 No data available for this outcome from North American studies. There are limited data on the risk of CHD with different type of SLT products. Gupta et al. first time did a meta-analysis with different SLT products and risk of CHD.42 They found a significant association between snuff use or snus (most commonly consumed in Europe) and fatal CHD. But there was no significant association between chewing tobacco (most commonly consumed in Asia) and fatal CHD which may be due to small studies and significant heterogeneity between the studies. This study also analyzed the fraction of fatal CHD attributable to SLT in different regions where it was found to be highest in Sweden (5%) followed by Southeast Asia (0.77%), and least in United States (0.14%).
HEALTH POLICY IMPLICATIONS
Smokeless tobacco has not received much focus among policy makers and researchers because it is presumed to be less harmful than smoked tobacco. It is also thought to be a regional rather than global problem although the most population in developing countries consumes SLT rather than cigarettes. The problem in policy making is lack of concrete evidence against SLT because of its various types and composition. Moreover, the pattern of consumption of the various types of SLT differs in these countries therefore all studies have not shown consistent results. SLT is found to be equally detrimental as compared to smoking at least in Indian subcontinent with little data available with us. The tobacco specific nitrosamine available in the Indian SLT is much higher and varied as compared to that available in Sweden and hence more injurious to health.43 Therefore, the policy needs to be as strict as that for smoking tobacco. Cigarettes and Other Tobacco Products Act (COTPA) 2003 prohibits all type of advertisement of any type of tobacco products. India is a signatory of WHO Framework Convention on Tobacco control (FCTC) and MPOWER package and has implemented tobacco control awareness programs.44 The impact of the FCTC is that the prevalence of smoking has declined in the countries who have strictly implemented it.45 But it is difficult to assess the effect of these measures in controlling the SLT use because of the little available quality data.46 Continuous government efforts, effective advocacy by NGOs, and inclusion of harmful effect of tobacco in all forms in school curriculum are some of the ways in dealing with this problem.
In India, SLT is the dominant form of tobacco used and is equally dangerous to health as smoked tobacco. It causes more sustained raised nicotine level in blood as compared to smoked tobacco and hence is more addictive. It causes raised BP, impaired blood sugar level and dyslipidemia and hence is prone to cause CVD. The available literature from the Indian subcontinent shows an association of SLT and increased risk of fatal IHD and stroke. A multipronged approach is needed for the control of all types of tobacco use so that the younger and productive population of the country remains healthy.
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- Chattopadhayya A. Jahangir's interest in public health and medicine. Bull Inst Hist Med. Hyderabad. 1995;25:170–82.
- Chattopadhayya A. Harmful effects of tobacco noticed in history. Bull Inst Hist Med, Hyderabad. 1993;23:53–8.
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- Sinha DN, Palipudi KM, Rolle I, et al. Tobacco use among youth and adults in member countries of South- East Asia region: Review of findings from surveys under the Global Tobacco Surveillance System. Indian J Public Health. 2011;55:169–76.
- International Institute for Population Sciences (IIPS), Ministry of Health and Family Welfare (MoHFW), Government of India (2010) Global Adult Tobacco Survey India report (GATS India), 2009–10. New Delhi: MoHFW, Government of India; Mumbai: IIPS.
- Reddy KS, Perry CL, Stigler MH, et al. Differences in tobacco use among young people in urban India by sex, socioeconomic status, age, and school grade: assessment of baseline survey data. Lancet. 2006;367:589–94.
- Gravely S, Fong GT, Driezen P, et al. An examination of the effectiveness of health warning labels on smokeless tobacco products in four states in India: findings from the TCP India cohort survey. BMC Public Health. 2016;16:1246.
- Ezzati M, Lopez AD. Measuring the accumulated hazards of smoking: Global and regional estimates for 2000. Tob Control. 2003;12:79–85.
- Nabel EG, Braunwald E. A tale of coronary artery disease and myocardial infarction. N Engl J Med. 2012;366:54–63.
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- Gaziano TA, Bitton A, Anand S, et al. Growing epidemic of coronary heart disease in low- and middle-income countries. Curr Probl Cardiol. 2010;35:7–115.
- World Health Organization. WHO Report on Global Tobacco Epidemic: Warning about Dangers of Tobacco. Geneva: World Health Organization; 2011.
- Fant RV, Henningfield JE, Nelson RA et al. Pharmacokinetics and pharmacodynamics of moist snuff in humans. Tob Control. 1999;8:387–92.
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- Vidyasagaran AL, Siddiqi K, Kanaan M. Use of smokeless tobacco and risk of cardiovascular disease: A systematic review and meta-analysis. Eur J Prev Cardiol. 2016;23:1970–81.
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