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Antioxidant Supplementation Effects on Low-Density Lipoprotein Oxidation for Individuals with Type 2 Diabetes Mellitus

Metabolic Research Group, VA Medical Center and Department of Internal Medicine, College of Medicine (J.W.A., M.S.G., J.T., L.N., V.A.D.), University of Kentucky, Lexington, Kentucky
Department of Nutrition and Food Science (C.K.C.), University of Kentucky, Lexington, Kentucky
Department of Pathology (P.R.O.), University of Kentucky, Lexington, Kentucky

Address reprint requests to: James W. Anderson, M.D., Medical Service, 111C, VA Medical Center, 2250 Leestown Road, Lexington, KY 40511

Objective: This study compared susceptibility to oxidation of low-density lipoproteins (LDL) of non-diabetic and diabetic (Type 2) men and examined the response of diabetic men to antioxidant supplementation (-tocopherol, ß-carotene and ascorbate).

Research Design and Methods: Twenty adult non-diabetic and 20 diabetic men were recruited. Oxidation of LDL was assessed by four different assay systems, and the extent of oxidation was assessed by four different measurements. Diabetic men received eight weeks of placebo ("baseline"), twelve weeks of antioxidant supplements ("treated") and eight weeks of placebo ("post-treatment"). Supplements provided 24 mg of ß-carotene, 1000 mg of ascorbate and 800 IU of -tocopherol daily.

Results: With Cu oxidation at 37°C, thiobarbituric reactive substances (TBARS) formation was significantly higher (p=0.032) and loss of free amine groups was significantly greater (p=0.013) in the LDL from diabetic subjects than controls. Antioxidant supplementation of diabetic subjects significantly decreased all parameters of LDL oxidation with Cu at 30°C and 37°C. At 30°C the lag phase increased from 55 to 129 minutes (p<0.0001); conjugated diene formation decreased from 1.23 to 0.62 OD units (p<0.0001); TBARS formation decreased from 78 to 33 nmoles MDA/mg LDL protein (p<0.0001); and free amine loss decreased from 41 to 12% (p<0.0001). With Cu oxidation at 37°C, similar changes occurred.

Conclusions: These studies indicate that the LDL from diabetic subjects are more susceptible to oxidation than LDL from non-diabetic subjects. Supplementation of diabetic subjects with antioxidant vitamins significantly decreases susceptibility of LDL to oxidation by Cu. These studies are consistent with epidemiological and intervention studies suggesting that antioxidant vitamin use significantly decreases risk for coronary heart disease.

Key words: antioxidant, diabetes mellitus, LDL, -tocopherol, ß-carotene, ascorbic acid

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