European Journal of Cardiovascular Medicine

Evidences show the adverse impact of smokeless tobacco (ST) on heart health. ST consumption has also been shown to considerably raise systolic and diastolic blood pressure (SBP and DBP), contributing to the development of hypertension and a higher susceptibility to heart diseases​​[1]. In a study elsewhere, it was shown that there were higher rates of smoking among ST users​ than in non-users​.[2] Indeed, some studies have noted that ST affects heart rate variability and sympathetic nerve activity, raising the risk of arrhythmias and other cardiac abnormalities​.[2].

Moreover, ST is associated with haematological alterations, a higher count of WBC (white blood cell) being a marker of systemic inflammation​. Modifications in the percentage of lymphocytes and granulocytes have been reported in other studies and may indicate the result of tobacco use's induced effect on the immune system. Nonetheless, Vitamin C supplementation's unique role in improving these health consequences has not been broadly studied. Vitamin C is an antioxidant that improves endothelial function, reduces oxidative stress and may reduce cardiovascular damages from smokeless tobacco use​.[3].

This study aims to evaluate the cardiovascular and haematological effects of  ST use in adults aged between 31-60 years. It will assess the impact on heart rate, blood pressure and haematological parameters like white blood cell count and platelet count. The study also examines whether Vitamin C can mitigate these effects, particularly on blood pressure, heart rate and haematological parameters or not. The hypothesis is that ST users have higher blood pressure, heart rate and altered haematological parameters compared to non-users. Additionally, Vitamin C supplementation is expected to reduce blood pressure and improve haematological parameters in ST users.

An experimental case-control study was conducted in tertiary care centre among 31 to 60 years old participants using ST and non-users. The study participants included 220 control and 180 ST chewers. The participants were chosen randomly from the people attending OPD in tertiary care centre , Index Medical College and Hospital, Indore. The study was approved by the Institutional Ethics Committee (certificate no: MU/Research/EC/Ph.D/2021/180) and written informed consent was obtained from all the participants. Those persons using tobacco chewing for ≥ 1yr were included in this study. The individuals with cardiovascular diseases, diabetes or other significant health problems were excluded in this study. Data were collected on physiological parameters (body mass index, heart rate, and blood pressure) and haematological parameters (white blood cell count, platelet count, and red blood cell indices). All participants from both groups were supplemented with Vitamin C (500 mg, twice a day) for the duration of 45 days. Data were analyzed statistically using unpaired  t -test, one way ANOVA, and Pearson’s correlation to compare the two groups and the rest of the parameters affected by the supplementation of Vitamin C.

Table 1: Demographic and baseline characteristics of participants (Controls vs. ST Users) ​.

The table shows no significant difference in age, height, weight or body mass index (BMI) between both groups . An  asterisk  “ * ” indicates a significant difference between the control and the cases in various cardiovascular parameters.

Table 2: Comparison of haematological parameters (WBC, RBC, haemoglobin, etc.) between the case and control groups​.

The comparisons of haematological  parameters in ST chewers with controls are shown in the table. An asterisk  “ * ” indicates a significant difference  between the control and the cases in various haematological  parameters.

Table 3: Comparison of various physiological parameters before and after Vitamin C supplementation​.

The comparison of BMI , HR, Valsalva  ratio ,systolic blood pressure and sustained Handgrip in ST chewers showed no significant changes before and after supplementation of Vitamin C. An asterisk “*” indicates a significant difference between diastolic blood pressure in ST Chewers before and after supplementation of Vitamin C .                                       

Table 4: Correlations between S. Cotinine , Vitamin C levels and physiological parameters among smokeless tobacco chewers.

An asterisk “*” indicates a significant relation between S. Cotinine, HR and between S.Cotinine and DBP in ST Chewers.

For serum Vitamin C, the positive correlation with the Valsalva Ratio was significant (r = 0.24, p = 0.002), corresponding to higher autonomic activity with higher serum Vitamin C levels. The lack of significant associations between Vitamin C and heart rate,  SBP, DBP, or sustained hand grip on ST Chewers were observed . BP rise may indicate that the impact of Vitamin C on these specific physiological parameters may be minimal.

These results indicate that cotinine levels exert a significant influence on heart rate and autonomic regulation whereas Vitamin C levels have a much greater association with autonomic function ( Valsalva ratio) and the direct effects on blood pressure and heart rate are relatively less impactful.

This study was designed to study the effects of smokeless tobacco (ST) on cardiovascular and haematological parameters to evaluate the role of Vitamin C supplementation. ST use was associated with significant changes in the physiological parameters, including heart rate, systolic and diastolic blood pressure and autonomic function changes.  Additionally, vitamin C supplementation significantly decreased blood pressure among ST chewers, indicating its potential therapeutic relevance in alleviating specific cardiovascular risks from ST usage.

This study adds to the existing body of evidence demonstrating the adverse cardiovascular effects of smokeless tobacco use. In particular, ST chewers had markedly increased heart rate and increased SBP and DBP compared to controls. These results indicates that smokeless tobacco products evoke sympathetic nervous system stimulation, leading to increased heart rate and blood pressure​​. The raised heart rate and blood pressure seen in ST users may result from nicotine, a potent sympathomimetic agent that activates catecholamine release, causing vasoconstriction and increasing cardiac output​.[4-6]

Significant blood pressure reduction was also seen with ST chewers after Vitamin C supplementation in our study. Vitamin C acts as an antioxidant and has improved endothelial function and reduced oxidative stress, both of which lead to improved vascular health​. Previous studies have shown that Vitamin C supplementation can lower systolic and diastolic blood pressure by increasing nitric oxide (NO) bioavailability and decreasing vascular resistance ​​.[7] Therein, the current study's findings align with such literature, as Vitamin C can antagonize the endothelial dysfunction and oxidative damage​ caused by smokeless tobacco.[8-10]

ST chewers had significantly altered haematological parameters compared to controls. ST chewers had a higher white blood cell (WBC) count, a well-established marker of inflammation​.[11]  Like other literature, an increase in WBC count in our study indicates that smokeless tobacco condition is an inflammatory response, which is likely to have a connection with increased risk of cardiovascular disease . Chronic inflammation is a major cause of atherosclerosis and other vascular complications​​. In addition, elevation of granulocytes, monocytes and platelets in the blood of ST chewers suggest a possible disturbance of the immune system and a decrease of haemostasis.[12-14]

Interestingly, in this study, Vitamin C supplementation had an insignificant effect on WBC count and platelet levels, which is contrary to studies that suggest antioxidants, including Vitamin C, may modulate immune responses and platelet function​.[15-17] Nonetheless, this result may be due to the short duration of supplementation (45 days), and longer treatments may produce clearer effects on immune and haematological parameters.

ST chewers had significantly lower Valsalva ratios than controls, suggesting impaired autonomic regulation in the ST chewers. This finding is consistent with previous research indicating that tobacco use (smokeless tobacco included) can cause disturbance in autonomic function and may contribute to the risk of arrhythmias and other cardiovascular conditions​​.[20] Our study shows a positive association between serum level of Vitamin C and the Valsalva ratio, which indicates the Vitamin C's role in restoring autonomic balance and possibly enhancing cardiovascular outcomes. This observation confirms the progressively available evidence that Vitamin C has a substantive impact on limiting oxidative stress and maintaining autonomic functions​.

In conclusion, this study demonstrates that smokeless tobacco (ST) use is correlated with significant effects on cardiovascular and haematological parameters leading to increased heart rate, systolic blood pressure,diastolic blood pressure and changes in number of granulocytes and platelets. Our observations also indicate that the intake of Vitamin C may be used as a potential intervention for promoting better cardiovascular health among ST users, which would merit further investigation for its long-term effects.

1. Asplund K. Smokeless tobacco and cardiovascular disease. Prog Cardiovasc Dis. 2003 Mar-Apr;45(5):383-94. doi: 10.1053/pcad.2003.00102.
2. Begum A, Itagi H, Arora D, Patil NA, Bailwad SA, Yunus GY, Goel A. Short-term acute effects of gutkha chewing on heart rate variability among young adults: A cross-sectional study. Int J Appl Basic Med Res. 2016 Jan-Mar;6(1):45-49. doi: 10.4103/2229-516X.174008. PMCID: PMC4765274. PMID: 26958522.
3. Higuchi T, Omata F, Tsuchihashi K, Higashioka K, Koyamada R, Okada S. Current cigarette smoking is a reversible cause of elevated white blood cell count: Cross-sectional and longitudinal studies. Prev Med Rep. 2016 Aug 9;4:417-422. doi: 10.1016/j.pmedr.2016.08.009. PMCID: PMC4995538. PMID: 27583199.
4. Conklin DJ, Schick S, Blaha MJ, Carll A, DeFilippis A, et al. Cardiovascular injury induced by tobacco products: assessment of risk factors and biomarkers of harm. A Tobacco Centers of Regulatory Science compilation. ReviewIntegrative Cardiovascular Physiology and Pathophysiology. 25 Mar 2019; https://doi.org/10.1152/ajpheart.00591.2018.
5. Pandey A, Patni N, Sarangi S, Singh M, Sharma K, Vellimana AK, Patra S. Association of exclusive smokeless tobacco consumption with hypertension in an adult male rural population of India. TobInduc Dis. 2009 Nov 24;5(1):15. doi: 10.1186/1617-9625-5-15. PMCID: PMC2789706. PMID: 19930693.
6. Rani M, Bonu S, Jha P, Nguyen SN, Jamjoum L. Tobacco use in India: prevalence and predictors of smoking and chewing in a national cross sectional household survey. Tob Control. 2003;12(4):e4. doi: 10.1136/tc.12.4.e4. [DOI] [PMC free article] [PubMed] [Google Scholar]
7. Hergens MP, Alfredsson PL, Bolinder G. Long-term use of Swedish moist snuff and the risk of myocardial infarction amongst men. J Intern Med. 2007;262:351–9. doi: 10.1111/j.1365-2796.2007.01816.x. [DOI] [PubMed] [Google Scholar]
8. Henley SJ, Thun MJ, Connell C. Two large prospective studies of mortality among men who use snuff or chewing tobacco (United States) Cancer Causes Control. 2005;16:347–58. doi: 10.1007/s10552-004-5519-6. [DOI] [PubMed] [Google Scholar]
9. Bolinder G, Alfredsson L, Englund A, de Faire U. Smokeless tobacco use and increased cardiovascular mortality among Swedish construction workers. Am J Public Health. 1994;84:399–404. doi: 10.2105/AJPH.84.3.399. [DOI] [PMC free article] [PubMed] [Google Scholar]
10. Huhtasaari F, Asplund K, Lundberg V, Stegmayr B, Wester PO. Tobacco and myocardial infarction: is snuff less dangerous than cigarettes? BMJ. 1992;305:1252–56. doi: 10.1136/bmj.305.6864.1252. [DOI] [PMC free article] [PubMed] [Google Scholar]
11. Johansson SE, Sundquist K, Qvist J, Sundquist J. Smokeless tobacco and coronary heart disease a 12-year follow-up study. Eur J CardiovascPrev Rehabil. 2005;12:387–92. doi: 10.1097/01.hjr.0000169189.22302.99. [DOI] [PubMed] [Google Scholar]
12. Ernster VL, Grady DS, Greene JC. Smokeless tobacco use and health effects among baseball players. JAMA. 1990;264:218–24. doi: 10.1001/jama.264.2.218. [DOI] [PubMed] [Google Scholar]
13. Siegel D, Benowitz N, Ernster VL, Grady DG, Hauck WW. Smokeless tobacco, cardiovascular risk factors, and nicotine and cotininelevels in professional baseball players. Am J Public Health. 1992;82:417–21. doi: 10.2105/AJPH.82.3.417. [DOI] [PMC free article] [PubMed] [Google Scholar]
14. Tucker LA. Use of smokeless tobacco, cigarette smoking, and hypercholesterolemia. Am J Public Health. 1989;79:1048–50. doi: 10.2105/AJPH.79.8.1048. [DOI] [PMC free article] [PubMed] [
15. Calzada C, Bruckdorfer KR, Rice-Evans CA. The influence of antioxidant nutrients on platelet function in healthy volunteers. Clin Trial Atherosclerosis. 1997 Jan 3;128(1):97-105. doi: 10.1016/s0021-9150(96)05974-6. PMID: 9051202.
16. Salonen JT, Salonen R, Seppänen K, Rinta-Kiikka S, Kuukka M, Korpela H, Alfthan G, Kantola M, Schalch W. Effects of antioxidant supplementation on platelet function: a randomized pair-matched, placebo-controlled, double-blind trial in men with low antioxidant status. Am J Clin Nutr. 1991 May;53(5):1222-9. doi: 10.1093/ajcn/53.5.1222. PMID: 1826987.
17. Mabile L, Bruckdorfer KR, Rice-Evans C. Moderate supplementation with natural alpha-tocopherol decreases platelet aggregation and low-density lipoprotein oxidation. Atherosclerosis. 1999 Nov 1;147(1):177-85. doi: 10.1016/s0021-9150(99)00169-0. PMID: 10525139.
18. Tayade M, Kulkarni NB. The effect of smoking on the cardiovascular autonomic functions: A cross-sectional study. J Clin Diagn Res. 2013 Jul;7(7):1307-10. doi: 10.7860/JCDR/2013/5526.3133.
19. Shiveta Bansal, Aman Bansal. Effect of Age and Sex on the R-Rinterval in ECG of Healthy Individuals. Indian Journal of Basic andApplied Medical Research; June 2012; 1( 3): 178-84
20. MrunalShenwai, NV Aundhakar. Effect of cigarette smoking on varioushaematological parameters in young male smokers. Indian Journal ofBasic and Applied Medical Research; December 2012; 2(5): 386-92.
21. G Grassi, Mechanisms responsible for sympathetic activation bycigarette smoking in humans, Circulation,1994;90;248-53
22. Singh DK, Sharma S. A cross sectional comparative study –Prevalence of tobacco consumption in school going adolescent boys in urban and rural area: Global J of Research Analysis.2017; 6(10)1-3
23. Singh DK, Kesarwani P, Sinha S, Singh VK. Assessment of prevalence and knowledge, attitude and practice of tobacco consumption among school going adolescent boys in urban field practice area of medical college: a cross sectional study. Int J Community Med Public Health 2019;6(5)