Oxidative stress increases continuously with BMI and age with unfavourable profiles in males.

Oxidative stress is a risk factor for chronic diseases and was previously shown to be independently associated with obesity. The authors investigated the relationship between body mass index (BMI), age and oxidative stress on 2190 subjects undergoing a health care examination. Total antioxidant status (TAS), total peroxides (TOC) and autoantibodies against oxidized LDL (oLAb) were used as oxidative stress biomarkers in addition to serum lipoproteins, bilirubin and uric acid. Gender-specific differences were observed for age, BMI, serum concentrations of bilirubin, low-density lipoprotein (LDL), uric acid and TAS, all of which were higher in males (p < 0.001), while high-density lipoprotein (HDL), HDL/LDL ratio and TOC were higher in females (p < 0.001). Total cholesterol (p < 0.05) and LDL were increased (p < 0.05), while HDL was decreased (p < 0.05) in overweight and obese subjects. This was accompanied by increased uric acid and TAS concentrations. Lowest oLAb titers were detected in obese subjects. In extremely obese subjects, increased TOC and decreased TAS were observed in spite of high uric acid levels. These results demonstrate that oxidative stress increases with increasing BMI and age, as a sequel to an impaired antioxidant status, the consumption of oLAbs, an increase of peroxides and uric acid and a disadvantaged lipid profile.

Antioxidant status of patients on peritoneal dialysis: associations with inflammation and glycoxidative stress.

BACKGROUND: Patients on peritoneal dialysis (PD) frequently exhibit oxidant-antioxidant imbalance, advanced glycation end-product overload, and subclinical inflammation but the interrelations between these pathophysiological changes have not been fully elucidated. SUBJECTS AND METHODS: To study possible associations, a cross-sectional study of antioxidant status, glycoxidative stress, and inflammation, using HPLC and ELISA methods, was undertaken in 37 PD patients and age- and sex-matched healthy controls. RESULTS: Plasma ascorbate concentrations were low in patients not taking at least low-dose vitamin C supplements. In patients taking vitamin C supplements, there was a positive relation between ascorbate and pentosidine concentrations. Vitamin E and carotenoid concentrations were comparable between patients and controls, while lycopene and lutein/zeaxanthin concentrations were lower. Interleukin-6, C-reactive protein (CRP), and pentosidine concentrations were elevated in PD patients. beta-Cryptoxanthin, lycopene, and lutein/zeaxanthin concentrations were inversely related to interleukin-6 concentrations. beta-Cryptoxanthin concentrations were also inversely related to CRP concentrations. Pentosidine showed a low dialysate-to-plasma ratio, indicating low peritoneal clearance. Pentosidine concentrations increased with duration of PD therapy, while alpha- and beta-carotene concentrations decreased. Malondialdehyde concentrations were elevated compared to controls but remained within the normal range. Retinol concentrations decreased with PD therapy and were inversely related to interleukin-6 and CRP concentrations. CONCLUSIONS: Low-dose vitamin C supplements and a carotenoid-rich diet should be recommended for PD patients to maintain normal antioxidant status and efficiently counteract the chronic inflammatory response, rather than high doses of vitamin C, which could play a role as a precursor of pentosidine.

Reference values for plasma concentrations of asymmetrical dimethylarginine (ADMA) and other arginine metabolites in men after validation of a chromatographic method.

BACKGROUND: Owing to the growing number of reports in the literature on ADMA as a possibly useful marker of endothelial health, its use in the clinical laboratory is of increasing interest. Age dependency and the small, but statistically significant differences between healthy subjects and disease groups are difficult to interpret. Additionally, levels of ADMA in comparable patient groups of different studies vary widely, even when similar methods have been used. METHODS: After analytical evaluation of a chromatographic method according to international guidelines, we analysed asymmetrical (ADMA) and symmetrical dimethyl arginine (SDMA), homo-arginine and arginine in EDTA plasma of 292 healthy males aged 20 to 75 years (y) who had passed strict inclusion/exclusion criteria. For statistical analysis, 4 age groups were formed. Group differences were identified with the non-parametric Kruskal-Wallis test. RESULTS: Calibration curves were linear throughout the selected ranges; the standard deviation for the regression line, recovery, imprecision, and accuracy results were all highly satisfactory. The reference ranges of ADMA for the 4 age groups are presented as age (mean+/-SD of age group, y); number of subjects; median, 2.5th-97.5th percentile: group <35 y: 26.7+/-4.0 y; n=78; 0.58, 0.43-0.69 micromol/L; group 35-49 y: 41.6+/-4.0 y; n=93; 0.59, 0.45-0.73 micromol/L; group 50-65 y: 57.5+/-4.2 y; n=82; 0.61, 0.46-0.78 micromol/L; and group >65 y: 69.6+/-3.3 y; n=39; 0.64, 0.54-0.79 micromol/L. CONCLUSIONS: Only highly precise methods are able to detect small differences between groups. The application of an evaluated method to a well defined group of healthy subjects should provide a basis for comparison of ADMA concentrations in different patient populations of future studies.

Increased concentrations of circulating vitamin E in carriers of the apolipoprotein A5 gene - 1131T>C variant and associations with plasma lipids and lipid peroxidation.

The aim of this study was to investigate the effects of the apolipoprotein A5 (APOA5) 1131T>C gene variant on vitamin E status and lipid profile. The gene variant was determined in 297 healthy nonsmoking men aged 20-75 years and recruited in the VITAGE Project. Effects of the genotype on vitamin E in plasma, LDL, and buccal mucosa cells (BMC) as well as on cholesterol and triglyceride (TG) concentrations in plasma and apolipoprotein A-I (apoA-I), apoB, apoE, apoC-III, and plasma fatty acids were determined. Plasma malondialdehyde concentrations as a marker of in vivo lipid peroxidation were determined. C allele carriers showed significantly higher TG, VLDL, and LDL in plasma, higher cholesterol in VLDL and intermediate density lipoprotein, and higher plasma fatty acids. Plasma alpha-tocopherol (but not gamma-tocopherol, LDL alpha- and gamma-tocopherol, or BMC total vitamin E) was increased significantly in C allele carriers compared with homozygote T allele carriers (P = 0.02), but not after adjustment for cholesterol or TG. Plasma malondialdehyde concentrations did not differ between genotypes. In conclusion, higher plasma lipids in the TC+CC genotype are efficiently protected against lipid peroxidation by higher alpha-tocopherol concentrations. Lipid-standardized vitamin E should be used to reliably assess vitamin E status in genetic association studies.

Vitamin E content of foods: comparison of results obtained from food composition tables and HPLC analysis.

BACKGROUND & AIMS: Data on vitamin E content of foods are essential for nutrition research and its application. The aim of this study was to investigate the precision of calculated vitamin E content of prepared meals. METHODS: The vitamin E content of 69 dishes of a menu cycle sampled at two occasions were calculated using 4 different food composition tables (FCT) and measured by HPLC. RESULTS: Data were complete for 50-69 dishes. The proportion of dishes with differences between FCTs < or = 20% were 17-100%. Differences between HPLC and the Souci-Fachmann-Kraut table were < or = 20% in 8/46 dishes for alpha- and in 14/46 dishes for gamma-tocopherol. Differences fell in the order of baked > raw > fried/roasted > boiled > mixed prepared foods. The 2 samplings taken 6 months apart showed considerable differences. CONCLUSIONS: There are substantial differences in calculated/measured vitamin E content of prepared foods: (i) between different FCTs; (ii) between FCTs and HPLC, and (iii) between different seasons. This can be explained by intrinsic variability (breeding, season, country of origin, ripeness, freshness) and food processing, as well as selection of FCTs and should be taken into account when interpreting data of dietary intervention studies.

Effects of orlistat therapy on plasma concentrations of oxygenated and hydrocarbon carotenoids.

Orlistat is a lipase inhibitor that is applied for treating obesity. Lipases are required for digestion and absorption of dietary lipids and fat-soluble vitamins and carotenoids. The aim of this study was to compare the effects of orlistat therapy on plasma concentrations of oxygenated (beta-cryptoxanthin, lutein/zeaxanthin) and hydrocarbon (alpha-, beta-carotene, lycopene) carotenoids. Six patients with a body mass index (BMI) > or = 30 kg/m2 received 360 mg/d orlistat over 4.5 mon. Plasma carotenoid concentrations were determined at baseline (T0) and after 3 (T3) and 4.5 mon (T4.5) along with anthropometric, dietary, and biochemical indices, including plasma lipids, retinol, (alpha- and gamma-tocopherols, and FA. Baseline BMI was 32.7 +/- 1.97 kg/m2. Five of six patients lost weight; the average weight loss was 3.6 +/- 2.4% (P = 0.47). There were no significant changes in dietary carotenoid intakes. In contrast, plasma alpha- and beta-carotene concentrations decreased significantly from T0 to T4.5 by 45% (P = 0.006) and 32% (P = 0.013), respectively. Plasma lycopene decreased from T0 to T3 but increased again from T3 to T4.5, while beta-cryptoxanthin and lutein/zeaxanthin concentrations did not change. There were no significant alterations in tocopherol, retinol, and FA concentrations. In conclusion, even though weight loss was not significant, orlistat therapy was associated with significant decreases in plasma concentrations of the highly lipophilic hydrocarbon carotenoids, alpha- and beta-carotene.

Effects of vitamin E depletion/repletion on biomarkers of oxidative stress in healthy aging.

The effects on ex vivo LDL resistance to oxidation and biomarkers of in vivo oxidative stress in response to 3-month dietary vitamin E restriction to 25% of recommended intake and 2-month unrestricted dietary intake and supplementation with 800 IU/d were studied in 100 healthy, nonsmoking 20-75-year-old volunteers. Significant changes in vitamin E status were associated with decreases and increases, respectively, in LDL resistance to oxidation in the depletion and supplementation period and with decreases in lipid peroxidation and oxidative DNA modification in the supplementation period. Healthy aging was not associated with enhanced susceptibility to oxidation in the depletion period.

The decrease in gamma-tocopherol in plasma and lipoprotein fractions levels off within two days of vitamin E supplementation.

The effects of vitamin E supplementation on alpha- and gamma-tocopherol concentrations were studied in plasma and lipoprotein fractions of five healthy volunteers taking 1000 IU/day of RRR alpha-tocopherol for 4 days. Although plasma alpha-tocopherol increased, gamma-tocopherol decreased. Compared with baseline, gamma-/alpha-tocopherol ratios decreased from 48 h onward (P < 0.001). They all leveled off within 48 h. From 12 h onward, gamma-/alpha-tocopherol ratios were higher in VLDL and IDL than in LDL and HDL, indicating that gamma-tocopherol is better maintained in triglyceride-rich lipoprotein fractions. These data suggest that vitamin E supplementation exceeding 2 days does not further decrease gamma-tocopherol concentrations.

Does aging affect the response of vitamin E status to vitamin E depletion and supplementation?

A vitamin E depletion/supplementation study was conducted in 100 healthy 20-75-year-old volunteers. The responses of vitamin E status to 3-week dietary vitamin E restriction to approximately 25% of recommended intake and 2-month unrestricted dietary intake plus 800 IU/d of RRR-alpha-tocopherol were studied as a function of age. Plasma alpha-tocopherol concentrations were closely related to cholesterol concentrations, which increased with age (P < 0.001). Upon dietary restriction, plasma alpha-tocopherol concentrations decreased significantly (P < 0.001) but independently of age. Plasma alpha-tocopherol responses to supplementation increased significantly with age, but this effect disappeared after standardization for cholesterol. gamma-Tocopherol concentrations decreased to less than 30% of baseline.