OBJECTIVE: Obesity, defined as a body mass index (BMI) greater than 30 kg/m2, is now recognised as a risk factor for diabetes mellitus, hyperlipidaemia, colon cancer, sudden death and other cardiovascular diseases. In this study, it is hypothesized that obesity is an independent risk factor for lipid peroxidation and decreased activities of cytoprotective enzymes in humans. SUBJECTS: Fifty normal healthy subjects with healthy BMI (19-25 kg/m2) and 250 subjects with different grades of obesity (30-50 kg/m2) with no history of smoking or biochemical evidence of diabetes mellitus, hypertension, hyperlipidaemia, renal or liver disease or cancer. MEASUREMENTS: To test this hypothesis, we assessed lipid peroxidation and cytoprotection by measuring the concentrations of plasma malondialdehyde (P-MDA) and the activities of erythrocyte copper zinc-superoxide dismutase (CuZn-SOD) and glutathione peroxidase (GPX). RESULTS: The concentration of P-MDA was significantly lower (P<0.001) in subjects with healthy BMI (2.53±0.04 µmol/l) than in those with BMI above 40 kg/m2 (4.75+0.05 µmol/l). Furthermore, there was a significantly positive association (r=0.342, P=0.013) between BMI and P-MDA. On the other hand, subjects with healthy BMI had significantly higher (P<0.001) erythrocyte CUZn-SOD (1464±23 units/g Hb) and GPX (98.4±3.3 units/g Hb) than those with BMI above 40 kg/m2 (1005±26 units/g Hb) and (84.3±6.7 units/g Hb) respectively. Furthermore, erythrocyte CuZn-SOD and GPX activities were negatively associated with BMI (r=-0.566, P=0.005 and r=-0.436, P=0.018) respectively. CONCLUSION: It is concluded from these results that obesity in the absence of smoking, diabetes mellitus, hyperlipidaemia, renal or liver disease causes lipid peroxidation and decreased activities of cytoprotective enzymes, and should therefore receive the same attention as obesity with complications. International Journal of Obesity (2002) 26, 1159-1164. doi:10.1038/sj.ijo.0802066 | 
