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Introduction: Tobacco consumption is a serious health hazard and most important avoidable cause of death worldwide. Tobacco is recognized as lethal toxin, ripping off 7-11 minutes of human life with each cigarette through harmful compounds and inducing free radical synthesis and a high rate of lipid peroxidation. These free radicals are scavenged by the endogenous antioxidants viz. S. Glutathione (S.GSH) and S.a- Lipoic acid (S. a-LA), thus preventing the endothelial damage. Aim: The present study was designed with an aim to find out the lipid peroxidative stress through S. Malondialdehyde (S.MDA) and its correlation with antioxidant levels like S. Glutathione (S. GSH) and S. a- Lipoic acid (S. a- LA) among tobacco users (in both smokers and chewers). Materials and Methods: A case control cross-sectional study was carried out in the Department of Physiology among 200 subjects; aged 18-50 years of both sexes which were chosen randomly from institutional campus and healthy volunteers. The subjects were broadly divided into two groups (A & B); group A comprised of tobacco users (n=150) with history of smoking cigarette/biddies and chewing tobacco daily, for at least one year and group B had controls (non tobacco users) (n=50). S. MDA, S.GSH and S. a-LA levels were estimated by standardized methods. The data was analysed by unpaired student t-test and Pearson's correlation coefficient (r) for finding the correlation between antioxidants and S.MDA in group-A and group-B. Results: The present study reports the significantly higher (p<0.0001) levels of S.MDA and lower (p<0.0001) levels of S.GSH and S. a-LA in tobacco users as compared to nontobacco users. The observed value of S.MDA was (2.72±0.87, 1.39±0.47) nmol/ ml, S. a-LA was (9.94±5.96, 14.24 ± 4.34) µg/ml and S.GSH was (23.24±7.04, 32.82±2.95) mg/dl respectively in group-A and group-B. A significant (p<0.01) strong negative correlation was observed between S. MDA and antioxidants (S.GSH and S. a-LA) with a Pearson co-efficient of r=-0.619, r= -0.625 respectively, in group A. Conclusion: The decreased level of S. a-LA and S. GSH, in our study clearly indicates potential risk of cellular damage in tobacco users due to lipid peroxidation. Hence, the present study recommends supplementation of S. a-LA and Vitamin C in tobacco users to prevent this damage whereas quitting this evil habit will be the best available option. [ABSTRACT FROM AUTHOR]