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effect of folic acid and antioxidant vitamins on endothelial dysfunction in patients with coronary artery disease

JOURNAL OF THe AMeRICAN COLLeGe OF CARDIOLOGY 2000年第3期36卷 758-765页

作者： Title, LM Cummings, PM Giddens, K Genest, JJ Nassar, BA Queen Elizabeth 2 Hlth Sci Ctr Div Cardiol Halifax NS B3H 3A7 Canada Queen Elizabeth 2 Hlth Sci Ctr Dept Lab Med & Pathol Halifax NS B3H 3A7 Canada Inst Rech Clin Montreal Montreal PQ H2W 1R7 Canada

OBJeCTIVeS The purpose of this study was to determine whether lowering homocysteine levels with folic acid, with or without antioxidants, will improve endothelial dysfunction in patients with coronary artery disease (CAD). BACKGROUND elevated plasma homocysteine levels are a risk factor for atherosclerosis. Homocysteine may promote atherogenesis through endothelial dysfunction and oxidative stress. MeTHODS In a double-blind, placebo-controlled, randomized trial, we used vascular ultrasound to assess the effect of folic acid alone or with antioxidants on brachial artery endothelium-dependent flow-mediated dilation (FMD). Seventy-five patients with CAD (screening homocysteine level greater than or equal to 9 mu mol/liter) were randomized equally to one of three groups: placebo, folic acid alone or folic acid plus antioxidant vitamins C and e. Patients were treated for four months. ReSULTS Plasma folate, homocysteine, FMD and nitroglycerin-mediated dilation were measured before and after four months of treatment. Plasma folate, homocysteine and FIL LD were unchanged in the placebo group. Compared with placebo, folic acid alone increased plasma folate by 475% (p < 0.001), reduced plasma homocysteine by 11% (p = 0.23) and significantly improved FMD from 3.2 +/- 3.6% to 5.2 +/- 3.9% (p = 0.04). The improvement in FMD correlated with the reduction in homocysteine (r = 0.5, p = 0.01). Folic acid plus antioxidants increased plasma folate by 438% (p < 0.001), reduced plasma homocysteine by 9% (p = 0.56) and insignificantly improved FR ID from 2.6 +/- 2.4% to 4.0 +/- 3.7% (p = 0.45), as compared with placebo. Nitroglycerin-mediated dilation did not change significantly in any group. CONCLUSIONS Folic acid supplementation significantly improved endothelial dysfunction in patients with coronary atherosclerosis. Further clinical trials are required to determine whether folic acid supplementation may reduce cardiovascular events. (C) 2000 by the American College of Cardiology.

关键词：抗氧化剂/副作用抗氧化剂/治疗应用抗坏血酸/副作用抗坏血酸/治疗应用血液循环冠心病/药物疗法冠心病/病理生理学双盲法内皮血管/药物作用内皮血管/病理生理学叶酸/副作用叶酸/治疗应用高半胱氨酸/血液脂类/血液丙二醛/血液硝酸甘油/治疗应用血管舒张血管舒张药/治疗应用维生素B12/血液维生素e/副作用维生素e/治疗应用老年人女(雌)性人类男(雄)性中年人

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Vitamin e is ineffective for symptomatic relief of knee osteoarthritis: a six month double blind, randomised, placebo controlled study

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ANNALS OF THe RHeUMATIC DISeASeS 2001年第10期60卷 946-949页

作者： Brand, C Snaddon, J Bailey, M Cicuttini, FM Alfred Hosp Dept Rheumatol Prahran Vic 3181 Australia Monash Univ Alfred Hosp Sch Med Dept Epidemiol & Prevent Med Prahran Vic Australia

Objective-There is a putative role for antioxidant treatment in osteoarthritis (OA) based on animal, epidemiological, and human clinical studies. Vitamin e, a fat soluble vitamin, is one of the major dietary antioxidants. Short term clinical studies using vitamin e in the form of alpha -tocopherol suggested a benefit over placebo of similar dimension to that of diclofenac for relief of OA pain. Methods-A six month, double blind, randomised, placebo controlled study of vitamin e 500 IU/day was carried out. Primary outcome measures were pain, stiffness, and function. Statistical analysis was performed on an intention to treat basis. Results-77 patients were included in the study. Vitamin e showed no benefit over placebo at one month, three months, or six months for any of the outcome measures. The placebo group had higher pain levels (p=0.15) and body mass index (p=0.03) at baseline, and lower pain levels (p=0.02) at completion of the study. Radiological score, exercise score, age, or antioxidant intake at baseline or six months did not differ between the groups. The reasons for the better performance of the placebo group are uncertain but may relate to the initially higher pain score and subsequent regression to the mean. Conclusions-Vitamin e shows no benefit for the management of symptomatic knee OA. The role of vitamin e in preventing OA progression is currently under investigation.

关键词：双盲法运动(exercise) 最小二乘法分析多元分析骨关节炎膝/并发症骨关节炎膝/诊断显像骨关节炎膝/药物疗法疼痛/诊断显像疼痛/药物疗法疼痛/病因学疼痛测定放射摄影术治疗结果维生素e/治疗应用成年人老年人女(雌)性人类男(雄)性中年人

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effects of vitamin e on chronic and acute endothelial dysfunction in smokers

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JOURNAL OF THe AMeRICAN COLLeGe OF CARDIOLOGY 2000年第2期35卷 277-283页

作者： Neunteufl, T Priglinger, U Heher, S Zehetgruber, M Söregi, G Lehr, S Huber, K Maurer, G Weidinger, F Kostner, K Univ Vienna Sch Med Dept Cardiol A-1090 Vienna Austria Univ Vienna Dept Clin Chem A-1090 Vienna Austria Univ Vienna Inst Med Stat A-1090 Vienna Austria Univ Innsbruck Dept Cardiol A-6020 Innsbruck Austria

OBJeCTIVeS The aims of this study were to determine whether chronic or acute impairment of flow mediated vasodilation (FMD) in the brachial artery of smokers can be restored or preserved by the antioxidant vitamin e. BACKGROUND Transient impairment of endothelial function after heavy cigarette smoking and chronic endothelial dysfunction in smokers result at least in part from increased oxidative stress. MeTHODS We studied 22 healthy male smokers (mean +/- SD, 23 +/- 9 cigarettes per day) randomly assigned to receive either 600 IU vitamin e per day (n = 11, age 28 +/- 6 years) or placebo (n = 11, age 27 +/- 6 years) for four weeks and 11 age-matched healthy male nonsmokers. Flow mediated vasodilation and endothelium-independent, nitroglycerin-induced dilation were assessed in the brachial artery using high resolution ultrasound (7.5 MHz) at baseline and after therapy. Subjects stopped smoking 2 h before the ultrasound examinations. At the end of the treatment period, a third scan was obtained 20 min after smoking a cigarette (0.6 mg nicotine, 7 mg tare) to estimate transient Impairment of FMD. ReSULTS Flow mediated vasodilation at baseline was abnormal in the vitamin e (5.3 +/- 3.8, p < 0.01) and in the placebo group (6.4 +/- 3.5, p < 0.05) Compared with nonsmoking controls (11.6 +/- 4.7). Using a two-way repeated measures analysis of variance (ANOVA) to examine the effects of vitamin e on FMD, we found no effect for the grouping factor (p = 0.5834) in the ANOVA over time but a highly significant difference with respect to time (p = 0.0065). The interaction of the time factor and the grouping factor also proved to be significant (p = 0.0318). Flow mediated vasodilation values remained similar after treatment for four weeks in both groups but declined faster after smoking a cigarette in subjects taking placebo compared with those receiving vitamin e (p values from successive differences for the time/group factor: 0.0001/0.0017). The transient attenuation of FMD (calcu

关键词：动脉硬化/病因学动脉硬化/预防和控制血流速度/药物作用肱动脉/诊断显像肱动脉/药物作用肱动脉/病理生理学胆固醇 LDL/血液双盲法内皮血管/药物作用内皮血管/病理生理学丙二醛/血液硝酸甘油氧化性应激/药物作用吸烟/副作用吸烟/血液吸烟/病理生理学硫巴比妥酸反应物/代谢超声检查血管舒张/药物作用血管舒张药维生素e/血液维生素e/治疗应用成年人人类男(雄)性

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effects of vitamin e and selenium supplementation on esophageal adenocarcinogenesis in a surgical model with rats

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CARCINOGeNeSIS 2000年第8期21卷 1531-1536页

作者： Chen, XX Mikhail, SS Ding, YW Yang, GY Bondoc, F Yang, CS Rutgers State Univ Coll Pharm Canc Res Lab Piscataway NJ 08854 USA

Two well-known antioxidative nutrients, vitamin e and selenium, were used in this study to investigate possible inhibitory action against the formation of esophageal adenocarcinoma (eAC) in rats. In this model, carcinogenesis is believed to be driven by oxidative stress. Male Sprague-Dawley rats (8 weeks old) were divided into four groups and received esophagoduodenal anastomosis (eDA) surgery plus iron supplementation (12 mg/kg/week), Vitamin e and selenium were supplemented in the diet in the forms of alpha-tocopheryl acetate (750 IU/kg) and sodium selenate (1.7 mg Se/kg), which were 10 times the regular amounts in the basic AIN93M diet. At 40 weeks after surgery, all the eDA groups had lower body weights than the non-operated control group. Iron nutrition (hemoglobin, total serum iron and transferrin saturation) was normal as a result of iron supplementation after eDA, Vitamin e supplementation maintained the normal plasma level of alpha-tocopherol in eDA rats, but not those of gamma-tocopherol and retinol, Selenium supplementation increased the serum and liver selenium contents of the eDA rats. Histopathological analysis showed that selenium supplementation increased the incidence of eAC and the tumor volume. The selenium level in the tumor is higher than that in the duodenum of the same animal,Vitamin e supplementation, however, inhibited carcinogenesis, especially in the selenium-supplemented group. We believe that vitamin e exerts its effect through its antioxidative properties, and a high dose of inorganic selenium may promote carcinogenesis by enhancing oxidative stress.

关键词：吸收腺癌/病因学腺癌/预防和控制吻合术外科抗致癌药/治疗应用抗氧化剂/治疗应用营养保健品疾病模型动物十二指肠造口术食管肿瘤/病因学食管肿瘤/预防和控制食管造口术铁右旋糖酐复合物/投药和剂量肝/代谢氧化性应激大鼠 Sprague-Dawley 硒化合物/药代动力学硒化合物/治疗应用维生素e/类似物和衍生物维生素e/治疗应用 α生育酚/类似物和衍生物动物男(雄)性大鼠

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The effects of combined conventional treatment, oral antioxidants and essential fatty acids on sperm biology in subfertile men

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PROSTAGLANDINS LeUKOTRIeNeS AND eSSeNTIAL FATTY ACIDS 2000年第3期63卷 159-165页

作者： Comhaire, FH Christophe, AB Zalata, AA Dhooge, WS Mahmoud, AMA Depuydt, Ce State Univ Ghent Hosp Dept Internal Med Endocrinol Sect B-9000 Ghent Belgium Mansoura Univ Fac Med Dept Biochem Mansoura Egypt Assiut Univ Hosp Dept Dermatol & Androl Assiut Egypt

We evaluated the effects of combined conventional treatment, oral antioxidants (N-acetyl-cysteine or vitamins A plus e) and essential fatty acids (FA) on sperm biology in an open prospective study including 27 infertile men. The evaluation included sperm characteristics, seminal reactive oxygen species (ROS), FA of sperm membrane phospholipids, sperm oxidized DNA (8-OH-dG), and induced acrosome reaction (AR). Treatment did not improve sperm motility and morphology, nor decrease the concentration of round cells and white blood cells in semen. Sperm concentration increased in oligozoospermic men (7.4 +/- 1.3 to 12.5 +/- 1.9 million/ml). Treatment significantily reduced ROS (mean +/- SeM) (775.3 +/- 372.2 to 150.3 +/- 105.2 x 10(3) counts/10 second) and 8-OH-dG (45.3 +/- 10.4 to 16.8 +/- 3.3 fmol/mug DNA). Treatment increased the AR (551 +/- 2.2 to 71.6 +/- 2.2 %), the proportion of polyunsaturated FA of the phospholipids, and sperm membrane fluidity. The overall pregnancy rate was 4.5% in 134 months. The per month pregnancy rate tended to be higher in partners of (ex)smokers (7.15%, n = 14, 70 months) than in never-smokers (1.6%, n = 13, 64 months) (OR:4.57, 95% Cl:0.55-38.1). (C) 2000 Harcourt Publishers Ltd.

关键词：乙酰半胱氨酸/投药和剂量乙酰半胱氨酸/治疗应用顶体反应抗氧化剂/投药和剂量抗氧化剂/治疗应用细胞膜/代谢 DNA/代谢脂肪酸类必需/治疗应用脂肪酸类不饱和/代谢自由基清除剂/投药和剂量自由基清除剂/治疗应用不育男(雄)性/治疗磷脂类/代谢试点项目妊娠率前瞻性研究活性氧吸烟精子计数精子/药物作用时间因素维生素A/投药和剂量维生素A/治疗应用维生素e/投药和剂量维生素e/治疗应用成年人女(雌)性人类男(雄)性妊娠

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SeLeNIUM AND VITAMIN-e AND INCIDeNCe OF ReTAINeD PLACeNTA IN PARTURIeNT DAIRY-COWS

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JOURNAL OF DAIRY SCIeNCe 1976年第11期59卷 1954-1959页

作者： JULIeN, We CONRAD, HR JONeS, Je MOXON, AL OHIO AGR RES & DEV CTR DEPT DAIRY SCI WOOSTER OH 44691 USA OHIO AGR RES & DEV CTR DEPT VET SCI WOOSTER OH 44691 USA OHIO AGR RES & DEV CTR DEPT ANIM SCI WOOSTER OH 44691 USA

In a 2 .times. 2 .times. 2 factorial experiment, protein intake, Se supplementation, and intake of P were related to the incidence of retained placenta in cows fed varying concentrations of these nutrients during the dry period. The population incidence of 38% retained placenta in 26 control cows was independent of P intake which ranged between 39-95 g/day. When a protein supplement was included in the concentrate as soybean meal, the incidence of retained placenta was reduced to 20% for supplemented animals from 50% for the animals that received no soybean meal. This increased protein in the ration was reflective of a mean increase from .02 ppm of Se to .06 ppm of Se in the ration. By increasing the mean daily intake of Se at least 3 wk prepartum from .23 mg to .92 mg daily, overall incidence of retained placenta was reduced from 38% to 0%. A positive prophylactic effect was achieved regardless of whether .alpha.-tocopherol was supplemented as well. These mature dairy cows were deficient in Se, and supplementation of Se reduced the incidence of retained placenta.

关键词：牛/生理学膳食蛋白质类分娩过程胎盘疾病/病因学胎盘疾病/预防和控制硒/缺乏硒/代谢硒/治疗应用青贮饲料黄豆维生素e/代谢维生素e/治疗应用动物女(雌)性妊娠

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The results of the GISSI-Prevenzione trial in the general framework of secondary prevention

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eUROPeAN HeART JOURNAL 2000年第12期21卷 949-952页

作者： Marchioli, R Valagussa, F Ist Ric Farmacol Mario Negri Consorzio Mario Negri Sud GISSI Prevenz Coordinating Secretariat I-66030 Santa Maria Imbaro Italy Osped San Gerardo Monza Italy

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维生素e抑制脑血管痉挛的实验性研究