Abbreviations: apo(a1), apolipoprotein A1; apo(b), apolipoprotein B; CHD, coronary heart disease; C-RP, C-reactive protein; ELISA, enzyme-linked immunosorbent assay; ICAM-1, intercellular adhesion molecule 1; IL, interleukin; PBS, phosphate-buffered saline; VCAM-1, vascular cell adhesion molecule 1.A OBJECTIVE -To compare the effects of short-term dietary supplementation with tomato juice, vitamin E, and vitamin C on susceptibility of LDL to oxidation and circulating levels of C-reactive protein (C-RP) and cell adhesion molecules in patients with type 2 diabetes.RESEARCH DESIGN AND METHODS -There were 57 patients with well-controlled type 2 diabetes aged Ͻ75 years treated with placebo for 4 weeks and then randomized to receive tomato juice (500 ml/day), vitamin E (800 U/day), vitamin C (500 mg/day), or continued placebo treatment for 4 weeks. Susceptibility of LDL to oxidation (lag time) and plasma concentrations of lycopene, vitamin E, vitamin C, C-RP, vascular cell adhesion molecule 1, and intercellular adhesion molecule 1 were measured at the beginning of the study, after the placebo phase, and at the end of the study.RESULTS -Plasma lycopene levels increased nearly 3-fold (P = 0.001), and the lag time in isolated LDL oxidation by copper ions increased by 42% (P = 0.001) in patients during supplementation with tomato juice. The magnitude of this increase in lag time was comparable with the corresponding increase during supplementation with vitamin E (54%). Plasma C-RP levels decreased significantly (Ϫ49%, P = 0.004) in patients who received vitamin E. Circulating levels of cell adhesion molecules and plasma glucose did not change significantly during the study.CONCLUSIONS -This study indicates that consumption of commercial tomato juice increases plasma lycopene levels and the intrinsic resistance of LDL to oxidation almost as effectively as supplementation with a high dose of vitamin E, which also decreases plasma levels of C-RP, a risk factor for myocardial infarction, in patients with diabetes. These findings may be relevant to strategies aimed at reducing risk of myocardial infarction in patients with diabetes.

Ingestion of a meal rich in fat previously used for deep frying in a commercial fast food restaurant resulted in impaired arterial endothelial function. These findings suggest that intake of degradation products of heated fat contribute to endothelial dysfunction.

The aim of this study was to compare the acute effect of (i) meals rich in saturated fat, oleic acid, and α-linolenic acid and (ii) meals rich in starch and fiber on markers of inflammation and oxidative stress in obese and lean women. In a crossover study, 15 abdominally obese women (age, 54 ± 9 years; BMI, 37.3 ± 5.5 kg/m 2 ) and 14 lean women (age, 53 ± 10 years; BMI, 22.9 ± 1.9 kg/m 2 ) consumed meals rich in cream (CR), olive oil (OL), canola oil (CAN), potato (POT), and All-Bran (BRAN) in random order. Blood samples were collected before and up to 6 h after the meals and plasma interleukin-6 (IL-6), IL-8, tumor necrosis factor-α (TNF-α), lipid peroxides (LPOs), free-fatty acids (FFAs), insulin, glucose, and cortisol were measured. Plasma IL-6 decreased significantly 1 h after the meals then increased significantly above baseline at 4 h and 6 h in obese women and at 6 h in lean women. The incremental area under the curve (iAUC) for IL-6 was significantly (P = 0.02) higher in obese compared with lean women and was significantly lower following the high fiber BRAN meal compared with a POT meal (P = 0.003). Waist circumference (R = 0.491, P = 0.007) and cortisol AUC (R = −0.415, P = 0.03) were significant determinants of the magnitude of 6 h changes in plasma IL-6 after the meals. These findings suggest that the postprandial response of plasma IL-6 concentrations may be influenced by the type of carbohydrate in the meal, central adiposity, and circulating cortisol concentrations in women.

OBJECTIVE -Markers of oxidative stress and plasma alanine transferase (ALT) levels are increased and circulating antioxidant concentrations are reduced in individuals with insulin resistance. Vitamin E improves glycemic control in people with diabetes. We tested the hypothesis that vitamin E would decrease markers of oxidative stress and plasma ALT levels and improve insulin sensitivity in overweight individuals. RESEARCH DESIGN AND METHODS -Eighty overweight individuals (BMI Ͼ27 kg/m2 ) were randomly allocated to receive either 800 IU vitamin E per day or a matching placebo for 3 months. The dose of vitamin E was increased to 1,200 IU per day for a further 3 months.RESULTS -Plasma peroxides decreased by 27% at 3 months and by 29% at 6 months in the group that received vitamin E and were positively correlated with plasma vitamin E concentrations at the 6-month time point. At 3 months, fasting plasma glucose and insulin concentrations were significantly reduced and homeostasis model assessment increased. These changes were not apparent at 6 months. Plasma ALT concentrations declined significantly throughout the study period.CONCLUSIONS -In conclusion, these findings indicate that vitamin E improves oxidative stress and hepatocellular function. Although insulin resistance also improves, this effect appears transient. Diabetes Care 27:2166 -2171, 2004T he prevalence of diabetes is increasing dramatically in the western world (1). This increase parallels that of obesity, with insulin resistance explaining the link between these two entities (2). Although the precise mechanism responsible for insulin resistance remains unclear, it would appear that a number of adipocyte-derived factors impair insulin activity and that the secretion of these factors is altered in the obese individual (3). Diabetes results when, in addition to insulin resistance, ␤-cell dysfunction occurs, leading to relative insulin deficiency. Interventions shown to be effective at preventing the progression to diabetes include lifestyle modification (4,5) and certain pharmacologic agents (4,6).One of the adipocyte-derived factors implicated in the pathogenesis of insulin resistance is the free fatty acid (FFA) (7). Although the rate of release of FFAs from individual adipocytes may not be raised in obesity, the increased amount of adipose tissue overall leads to an increase in the flux of FFAs to the liver and skeletal muscle, the two tissues most intimately involved in glucose handling (8). Once FFAs enter target tissues, they are either stored as triglycerides or are utilized as a substrate for oxidation by the cell's mitochondria. As a result of the normal process of oxidation, reactive oxygen species (ROS) are produced (9). These ROS are potentially harmful to cellular functions. To prevent these harmful effects, the cell has developed a complex antioxidant system to dispose of ROS. However, antioxidant concentrations are reduced in obese individuals, and the resulting imbalance between the production of ROS and antioxidant defenses results in o...

Endothelium-dependent vasodilation is impaired and predicts the risk of a coronary event in patients with coronary artery disease (CAD). Oxidant stress and increased systemic inflammation may contribute to this endothelial dysfunction. Aged garlic extract (AGE) contains antioxidant compounds and increases nitric oxide production and decreases the output of inflammatory cytokines from cultured cells. The aim of this study was to test the effect of treatment with AGE on brachial artery flow mediated endothelium-dependent dilation (FMD) and circulating markers of oxidative stress and systemic inflammation. The trial included 15 men with angiographically proven CAD in a randomized, placebo-controlled, cross-over design with 2-week treatment and washout periods. During AGE supplementation, FMD increased (44%) significantly (p = 0.04) from the baseline and mainly in men with lower baseline FMD. Levels of FMD at the end of AGE treatment were significantly (p = 0.03) higher compared with the corresponding levels at the end of placebo treatment when the variation in baseline body weight was taken into account. Markers of oxidant stress (plasma oxidized low density lipoprotein and peroxides), systemic inflammation (plasma C-reactive protein ad interleukin-6) and endothelial activation (VCAM-1) did not change significantly during the study. These data suggest that short-term treatment with AGE may improve impaired endothelial function in men with CAD treated with aspirin and a statin. Whether improvement in endothelial function decreases the risk of future cardiovascular events remains to be determined.