Background: A constellation of reactive oxygen species (ROS) capable of damaging cellular constituents generated in excess during the chronic, inflammatory, neurodegenerative disease process of leprosy. The consequences of this leads to enhanced oxidative stress and lower antioxidant status. Enzymatic antioxidants provide first line defense against ROS. We have measured the levels of oxidative stress indices like lipid peroxidation (LPO), protein carbonyls together with enzymatic antioxidants in the blood samples of control and leprosy patients. Nutritional rehabilitation by way of exogenous supplementation of functionally efficient antioxidants like vitamin E reactivates the enzymatic antioxidant system and guards against the insult caused by ROS during the pathogenesis of the disease and antileprosy chemotherapy. Design: Untreated leprosy patients were selected on the basis of clinical examination and skin smear. All diagnosed untreated leprosy patients received multi drug therapy (MDT) consisting of rifampicin, dapsone and clofazimine as recommended by World Health Organization. A small number of untreated cases were selected for co-supplementation of vitamin E along with MDT. Oxidative stress indices, enzymatic and nonenzymatic antioxidant status were assayed in untreated, MDT treated and those supplemented vitamin E along with MDT. Statistical methods: We have compared the significance in the mean±s.d. values of the oxidative stress indices and the levels of antioxidants using one way analysis of variance (ANOVA) between control, untreated, MDT treated and those supplemented vitamin E with MDT and the results were significant at P < 0.05. Statistical analysis of the results suggests that oral administration of vitamin E lowers oxidative stress and augments antioxidant status in affected individuals. Results: Enhanced oxidative stress as evidenced by increased LPO and protein carbonyl in leprosy cases lowers the antioxidant status. Treatment with MDT has a limited impact on increased oxidative stress and decreased antioxidant status. Coadministration of vitamin E along with MDT decreases oxidative stress and activate the antioxidant status. Discussion: The excess production of ROS as seen in leprosy cases could lead to degeneration of tissues and derangement of internal organs. The possible reason for the decreased antioxidant status in leprosy cases may be increased production of ROS, deranged liver function, and the free radical producing ability of drugs used in MDT of leprosy. Intervention with antioxidant supplementation like vitamin E prevents oxidative stress mediated through ROS and activates the net antioxidant status during the chronic course of the disease and antileprosy chemotherapy. © 2005 Nature Publishing Group. All rights reserved. Results:Results are given for the whole group of patients without separate data for patients receiving Lamprene, rifampicin, dapsone, and vitamin E. Increase in the LPO was observed in untreated leprosy cases when compared with healthy controls indicating that oxidative stress is operational in affected individuals. LPO levels did not decline on treatment with MDT. Co-administration of vitamin E with MDT decreased plasma LPO to near normal level with a similar trend in protein carbonyl levels. Treatment with MDT had only a limited impact on the increased LPO and protein carbonyl level. Untreated leprosy patients showed decreased antioxidant enzymes when compared healthy controls. Leprosy patients under MDT also showed decreased antioxidant enzymes when compared with untreated leprosy patients (group II vs. group IIa). Exogenous supplementation of vitamin E lowers oxidative stress and reactivate enzymatic antioxidant and nonenzymatic antioxidant status. Treatment with MDT did not enhance the nonenzymatic antioxidant status while vitamin E augmented the levels of nonenzymatic antioxidants. AdverseEffects:No adverse events were mentioned. Indications:50 patients with leprosy (Hansen's disease). Patients:75 subjects aged 25 to 45 years were studied. Group I (control): 25 clinically normal healthy subjects. Group II (untreated): 50 patients. Group IIa (MDT only): 25 patients. Group IIb (MDT + vitamin E): 25 patients. TypeofStudy:This study analyzed the relationship between oxidative stress indices and enzymatic and nonezymatic antioxidant status in untreated and multiple drug therapy (MDT; Lamprene, rifampicin, and dapsone) treated leprosy (Hansen's disease) cases and patients co-administrated vitamin E along with MDT. This study also examined the recuperative effect of exogenous supplementation of anti-oxidant vitamin E and observed the changes in biochemical markers relating to oxidative stress. DosageDuration:Single dose of 300 mg monthly and 50 mg daily. Duration: 12 months. FreeText:Concomitant drugs were rifampicin or rifamicin (600 mg), dapsone (100 mg), and vitamin E (400 IU). Oxidative stress indices: lipid peroxidation (LPO) and protein carbonyl and enzymatic antioxidant (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase) levels.