Effects of zinc or citrus flavonoid supplementation on indices of oxidative stress in non-insulin-dependent diabetic women /

Oxidative stress has been implicated in the development of atherosclerosis, a condition which leads to premature death in thousands of people each year. The mechanism by which free radicals increase susceptibility to the development of atherosclerosis is not yet known. However, oxidation of very low-density lipoprotein/lowdensity lipoprotein (VLDL/LDL), a marker of oxidative stress in vivo, may be critical to the pathogenesis of atherosclerosis. Little research has examined the effects of zinc or citrus flavonoids, two potentially important antioxidants, on indices of oxidative stress. Therefore, the purpose of this study was to 1) determine if VLDL/LDL oxidation can be used to assess zinc deficiencyinduced oxidative stress in a rat model, and 2) determine if zinc or citrus flavonoid supplementation can improve indices of oxidative stress, specifically VLDL/LDL oxidation, in women with non-insulin-dependent diabetes mellitus. For the rat study, twenty-four rats were randomly assigned to one of three feeding groups: low zinc diet, adequate zinc diet pair fed to the mean intake of rats fed the low zinc diet, and adequate zinc diet fed ad libitum. Rats were maintained on their respective diet two weeks prior to sacrifice. For the human study, sixty postmenopausal NIDDM women, between the ages of 40 and 60 years, were recruited for participation in this investigation. Subjects were randomly assigned to receive either a zinc supplement (30 mg zinc/d as amino acid chelated zinc), a flavonoid supplement (2000 mg flavonoid complex/d as two tablets, each containing the following complexes: 500 mg citrus bioflavonoids, 200 mg orange bioflavonoids, 200 mg lemon bioflavonoids, 50 mg quercetin, 50 mg rutin), or placebo for three weeks. The lag time for copper-catalyzed VLDL/LDL oxidation was significantly shorter for rats fed a low zinc diet compared to an adequate zinc diet, while the oxidation propagation rate was significantly higher in the deficient rats. Based on body weight and plasma zinc, rats fed low zinc diet were moderately zinc deficient. The rat study demonstrated that VLDL/LDL oxidation is a good indicator of zinc deficiency-induced oxidative stress. Three weeks of zinc supplementation significantly increased indicators of zinc status, including plasma zinc and plasma 5’-nucleotidase activity, in women with NIDDM. In addition, insulin-like growth factor1 (IGF-1), a potential functional indicator of the effects of zinc, significantly increased in subjects with initial values below 165 ng/mL while IGF-1 significantly decreased in subjects with initial values above 165 ng/mL. Despite the fact that zinc status was seemingly improved, zinc supplementation had no significant effect on VLDL/LDL oxidation. Three weeks of citrus flavonoid supplementation did not significantly affect VLDL/LDL oxidation. Initial plasma vitamin C levels, measured as a possible effect of citrus flavonoid supplementation, were very low in the diabetic patients. However, plasma vitamin C was unaffected by supplementation. Plasma IgE, a potential marker of oxidative stress, was elevated drastically above normal in women with NIDDM. IgE levels were unaffected by zinc or citrus flavonoid supplementation. In addition, tumor necrosis factor (TNF) was elevated slightly above normal. TNF levels were also unaffected by zinc or citrus flavonoid supplementation. Myeloperoxidase activity was not elevated in the NIDDM patients. However, values tended to increase following three weeks of zinc supplementation. This study strengthened the contention that patients with NIDDM may be prone to both zinc deficiency and low levels of plasma vitamin C. In addition, plasma IgE was elevated in patients with NIDDM and may be a useful marker of oxidative stress. Finally, because patients with NIDDM have a propensity toward poor antioxidant defense, poor zinc status and high oxidative stress, more rigorous antioxidant supplementation may be necessary to protect against the damaging effects of oxidative stress. Dedicated to my family