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161. Oxidative stress induced by environmental tobacco smoke in the workplace is mitigated by antioxidant supplementation.

Cancer Epidemiol Biomarkers Prev 1998 Nov;7(11):981-8
Howard DJ, Ota RB, Briggs LA, Hampton M, Pritsos CA
Department of Nutrition, Center for Environmental Sciences and Engineering, University of Nevada, Reno 89557, USA.

Environmental tobacco smoke (ETS) is a pervasive contaminant in the workplace. Previous studies by this laboratory have shown that exposure to workplace ETS results in increased oxidative stress and damage, as measured by increased levels of the antioxidant enzymes superoxide dismutase, catalase, glutathione reductase, and glutathione peroxidase. 8-Hydroxy-2-deoxyguanosine, a marker of oxidative DNA damage, was also 63% greater in the exposed group compared with controls. Subjects in the previous study who reported workplace exposure to ETS were given a 60-day supply of an over-the-counter antioxidant formulation consisting of 3000 microg of beta-carotene, 60 mg of vitamin C, 30 I.U. of alpha-tocopherol, 40 mg of zinc, 40 microg of selenium, and 2 mg of copper. After the 60-day supplementation period, blood samples were again drawn, and the results were compared with the presupplementation values. A 62% decrease in 8-hydroxy-2-deoxyguanosine was observed after supplementation. Lipid peroxidation levels were also decreased, as were the antioxidant enzyme activities. The biochemical evidence suggests that exposure to ETS in the workplace increases oxidative stress and that antioxidant supplementation may provide some protection.

162. Biochemical evaluation of oxidative stress in propylthiouracil treated hyperthyroid patients. Effects of vitamin C supplementation.

Clin Chem Lab Med 1998 Oct;36(10):767-70
Seven A, Tasan E, Inci F, Hatemi H, Burcak G
Department of Biochemistry, Cerrahpasa Medical Faculty, Istanbul University, Turkey.

In this study the impact of vitamin C supplementation on oxidative damage as assessed by thiobarbituric acid reactive substances and markers of antioxidant status: namely Cu/Zn superoxide dismutase, glutathione peroxidase, glutathione reductase and glutathione were investigated in 24 hyperthyroid patients under propylthiouracil therapy (3x100 mg/day) for five days and in 15 healthy controls. Ascorbic acid (1000 mg/day) was given as a supplement for 1 month to both the patients and controls during the study period. Heparinised blood samples were taken at the beginning and the end of one month ascorbic acid supplementation. Comparison of the hyperthyroid patients with the controls revealed higher lipid peroxidation (p<0.001), higher Cu/Zn superoxide dismutase activity (p<0.001), higher glutathione level (p<0.001) and lower glutathione reductase activity (p<0.001). Vitamin C supplementation to hyperthyroid patients caused significant increases in glutathione concentration (p<0.001) and glutathione peroxidase activity (p<0.001), whereas there were significant decreases in glutathione reductase (p<0.001) and Cu/Zn superoxide dismutase activities (p<0.01). Thiobarbituric acid reactive substances and thiobarbituric acid reactive substances/glutathione ratio were significantly decreased (p<0.01). Vitamin C supplementation to euthyroid controls caused significant increases in glutathione concentration (p<0.001) and glutathione peroxidase and Cu/Zn superoxide dismutase activities (p<0.001), whereas there was a significant decrease in glutathione reductase (p<0.001). The thiobarbituric acid reactive substances/glutathione ratio was significantly decreased (p<0.05). Our findings reveal the potentiation of antioxidant status and a relief in oxidative stress in both propylthiouracil treated hyperthyroid patients and controls in response to vitamin C supplementation.

163. Effect of a two-year supplementation with low doses of antioxidant vitamins and/or minerals in elderly subjects on levels of nutrients and antioxidant defense parameters.

J Am Coll Nutr 1997 Aug;16(4):357-65
Girodon F, Blache D, Monget AL, Lombart M, Brunet-Lecompte P, Arnaud J, Richard MJ, Galan P Laboratoire de Biochimie des Lipoproteines, Universite de Bourgogne, Digon, France.

BACKGROUND: Eighty-one elderly hospitalized subjects (> 65 years) were recruited for a double-blind placebo-controlled study to examine low dose supplementation of antioxidant vitamins and minerals on biological and functional parameters of free radical metabolism. Subjects were randomly assigned to one of the four treatment groups, daily receiving for 2 years: placebo group; mineral group: 20 mg zinc, 100 micrograms selenium; vitamin group: 120 mg VITAMIN C (Vit C), 6 mg beta-carotene (beta CA), 15 mg vitamin E (Vit E); mineral and vitamin group: Zn 20 mg, Se 100 micrograms, Vit C 120 mg, beta CA 6 mg, Vit E 15 mg. RESULTS: Fifty-seven subjects completed the study. A large frequency of Vit C, Zn and Se deficiencies were observed at baseline. As early as 6 months of treatment, a significant increase in vitamin and mineral serum levels was observed in the corresponding groups. The increases ranged from 1.1-4.0 fold depending on the nutrient. Antioxidant defense, studied in vitro with a test using red blood cells in presence of 2,2'-azo-bis (2-amidinopropane) by hydrochloride, showed an increase of cell resistance in patients receiving vitamins (p = 0.002); it was positively correlated with serum Vit C (p < 0.0001), alpha-tocopherol/cholesterol (p = 0.06), beta CA (p = 0.0014), serum Cu and Se (p < 0.05). Moreover, red blood cell antioxidant defense was reduced in elderly compared with young control subjects (50% hemolysis time: 69 +/- 14 mn and 109 +/- 12 mn, respectively). Erythrocyte glutathione peroxidase activity was enhanced in groups receiving minerals, whereas no significant change was observed for other indicators of oxidative stress (erythrocyte superoxide dismutase activity, thiobarbituric acid-reactive substances, total glutathione, reduced and oxidized forms). DISCUSSION: Our results provide experimental evidence that a low dose supplementation with vitamins and minerals was able to normalize biological nutrient status as early as 6 months of treatment. In addition, our data indicate that antioxidant defense in elderly subjects was improved with low doses of Vit C, vit E and beta CA as studied by means of a functional test utilizing red blood cells challenged in vitro with free radicals. Publication Types: Clinical trial Randomized controlled trial PMID: 9263186, UI: 97408667

164.Enhancement of natural killer cell activity and T and B cell function by buffered VITAMIN C in patients exposed to toxic chemicals: the role of protein kinase-C.

Immunopharmacol Immunotoxicol 1997 Aug;19(3):291-312
Heuser G, Vojdani A Neuromed & Neurotox Associates, Thousand Oaks, CA 91361, USA.

After exposure to many toxic chemicals, NK function can be decreased significantly. Weeks or months later, natural killer (NK) function can rebound to normal levels in some and can be suppressed for prolonged periods of time in other patients. In view of this, we decided to study the effect of buffered VITAMIN C on NK, T and B cell function in patients who had been exposed to toxic chemicals. After the first blood draw, 55 patients immediately ingested granulated buffered VITAMIN C in water at a dosage of 60 mg/Kg body weight. Exactly 24 hours later, blood was again drawn for a follow-up study of NK, T and B cell function. VITAMIN C in high oral dose was capable of enhancing NK activity up to ten-fold in 78% of patients. Lymphocyte blastogenic responses to T and B cell mitogens were restored to the normal level after VITAMIN C usage. Signal transduction enzyme protein kinase C (PKC) appeared to be involved in the mechanism of induction of NK activity by VITAMIN C. We conclude that immune functional abnormalities can be restored after toxic chemical exposure by oral usage of VITAMIN C.

165. Effect of micronutrient supplementation on infection in institutionalized elderly subjects: a controlled trial.

Ann Nutr Metab 1997;41(2):98-107
Girodon F, Lombard M, Galan P, Brunet-Lecomte P, Monget AL, Arnaud J, Preziosi P, Hercberg S Institut Scientifique et Technique de la Nutrition et de l'Alimentation, Paris, France.

To determine the impact of a trace element and vitamin supplementation on infectious morbidity, a double-blind controlled trial was performed on 81 elderly subjects in a geriatric center during a 2-year period. Subjects were randomly assigned to one of four treatment groups, and received daily: placebo; trace elements/zinc 20 mg; selenium 100 micrograms); vitamins (VITAMIN C 120 mg; beta-carotene 6 mg; alpha-tocopherol 15 mg); or a combination of trace elements and vitamins at equal doses. (1) Before supplementation, low serum values in VITAMIN C, folate, zinc and selenium were observed in more than two thirds of the patients. (2) After 6 months of supplementation, a significant increase in vitamin and trace element serum levels was obtained in the corresponding treatment groups: a plateau was then observed for the whole study. (3) Subjects who received trace elements (zinc and selenium) alone or associated with vitamins had significantly less infectious events during the 2 years of supplementation. These results indicate that supplementation with low doses of vitamins and trace elements is able to rapidly correct corresponding deficiencies in the institutionalized elderly. Moreover, zinc and selenium reduced infectious events. Publication Types: Clinical trial Randomized controlled trial PMID: 9267584, UI: 97412941

166. Iron absorption from a traditional Sri Lankan weaning food and the enhancing effect of Ascorbic acid in adult male volunteers.

Ceylon Med J 1996 Dec;41(4):135-40
Liyanage C, Goonaratna C, Thabrew I Department of Community Medicine, Faculty of Medicine, University of Ruhuna, Galle, Sri Lanka.

OBJECTIVE: To study absorption of iron from Centella gruel and the enhancing effect of Ascorbic acid in young adult males. DESIGN: An in vivo absorption study. SETTING: Faculty of Medicine, Galle. METHODS: The percentage of iron absorbed from the Centella gruel was measured using a double isotope technique with 55Fe and 59Fe on 10 healthy male volunteers. OUTCOME MEASURE: Percentage of iron absorption from the gruel with and without Ascorbic acid. RESULTS: The mean iron absorption from each meal of Centella gruel was 2.2% (SEM 0.8). This increased to 5% (SEM 1.6) by addition of 50 mg Ascorbic acid. When ingested with Ascorbic acid, the bioavailable nutrient density (BND) of the weaning food was increased from 0.23 to 0.53 mg iron/1,000 kcal. To satisfy the daily physiological requirements of iron in infants and toddlers, it was calculated that apart from Ascorbic acid supplementation, the total iron content also needs to be increased from 2.05 mg to 4.0 mg/meal. CONCLUSION: Centella gruel cannot provide the amount of iron to meet the BND for iron required by infants and toddlers, unless supplemented with an enhancer of iron absorption such as Ascorbic acid and its total iron content is increased. PMID: 9141756, UI: 97286609

167. Antioxidant supplementation decreases oxidative DNA damage in human lymphocytes.

Cancer Res 1996 Mar 15;56(6):1291-5
Duthie SJ, Ma A, Ross MA, Collins AR Rowett Research Institute, Bucksburn, Aberdeen, Scotland, United Kingdom.

The association between high intake of fruit and vegetables and low incidence of certain cancers is well established. Dietary antioxidants present in these foods are thought to decrease free radical attack on DNA and hence to protect against mutations that cause cancer, but this causal mechanism remains conjectural. We have adopted a molecular epidemiological approach to this question, based on a modified alkaline single-cell gel electrophoresis assay ("comet assay") which specifically detects oxidation of pyrimidines in the DNA of human lymphocytes. In a survey of men 50-59 years of age living in the northeast of Scotland, smokers initially showed significantly more base damage than nonsmokers. Correlations between oxidative base damage and plasma concentrations of various antioxidants were generally negative but not statistically significant. Supplementation of the diet for 20 weeks with VITAMIN C (100 mg/day), vitamin E (280 mg/day), and beta-carotene (25 mg/day) resulted in a highly significant (P < 0.002) decrease in endogenous oxidative base damage in the lymphocyte DNA of both smokers and nonsmokers. In addition, lymphocytes of antioxidant-supplemented subjects showed an increased resistance to oxidative damage when challenged in vitro with H2O2. These findings strongly support the hypothesis that fruit and vegetables exert a cancer-protective effect via a decrease in oxidative damage to DNA. Publication Types: Clinical trial Controlled clinical trial PMID: 8640816, UI: 96189305

168. Dietary VITAMIN C and beta-carotene and risk of death in middle-aged men. The Western Electric Study.

Am J Epidemiol 1995 Dec 15;142(12):1269-78
Pandey DK, Shekelle R, Selwyn BJ, Tangney C, Stamler J University of Texas School of Public Health, Houston 77030, USA.

In the Western Electric Company Study, carried out in Chicago, Illinois, data on diet and other factors were obtained in 1958 and 1959 for a cohort of 1,556 employed, middle-aged men. Nutrients included VITAMIN C and beta-carotene. An index that summarized combined intake of both nutrients was constructed. Mean intakes of VITAMIN C in the lowest and highest tertiles of the index were 66 and 138 mg/day; corresponding values for beta-carotene were 2.3 and 5.3 mg/day. A total of 522 of 1,556 men died during 32,935 person-years of follow-up, 231 from coronary heart disease and 155 from cancer. After adjustment for potentially confounding factors, relative risks (95% confidence intervals) associated with an increment of 19 points in the index (difference between means of the lowest and highest tertiles) were 0.60 (0.39-0.93) for cancer mortality, 0.70 (0.49-0.98) for coronary disease mortality, and 0.69 (0.55-0.87) for all-cause mortality. These results support the hypothesis that consumption of foods rich in VITAMIN C and beta-carotene reduces risk of death in middle-aged men. Publication Types: Clinical trial Randomized controlled trial PMID: 7503047, UI: 96108947

169. The clinical effects of VITAMIN C supplementation in elderly hospitalised patients with acute respiratory infections.

Int J Vitam Nutr Res 1994;64(3):212-9
Hunt C, Chakravorty NK, Annan G, Habibzadeh N, Schorah CJ Food & Nutrition Department, Huddersfield University.

A randomised double-blind trial involving VITAMIN C/placebo supplementation was conducted on 57 elderly patients admitted to hospital with acute respiratory infections (bronchitis and bronchopneumonia). Patients were assessed clinically and biochemically on admission and again at 2 and 4 weeks after admission having received either 200 mg VITAMIN C per day, or placebo. This relatively modest oral dose led to a significant increase in plasma and white cell VITAMIN C concentration even in the presence of acute respiratory infection. Using a clinical scoring system based on major symptoms of the respiratory condition, patients supplemented with the vitamin fared significantly better than those on placebo. This was particularly the case for those commencing the trial most severely ill, many of whom had very low plasma and white cell VITAMIN C concentrations on admission. Various mechanisms by which VITAMIN C could assist this type of patient are discussed. Publication Types: Clinical trial Randomized controlled trial

170. Megadose of VITAMIN C delays insulin response to a glucose challenge in normoglycemic adults.

Am J Clin Nutr 1994 Nov;60(5):735-8
Johnston CS, Yen MF Department of Family Resources and Human Development, Arizona State University, Tempe 85287-2502.

The effect of a megadose of Ascorbic acid (AA) on glucose and insulin responses after an oral-glucose-tolerance test (OGTT) is unknown. With a double-blind, placebo-controlled design, nine normoglycemic subjects (22 +/- 1 y, mean +/- SEM) consumed AA (2 g/d) or placebo for 2 wk after a 2-wk washout period with placebo, and an OGTT was performed after an overnight fast. This 4-wk protocol was repeated in a crossover fashion. Plasma glucose was significantly elevated 1-h postprandial in VITAMIN C-saturated subjects vs those taking a placebo. The plasma insulin response curve was shifted rightward in VITAMIN C-saturated subjects relative to baseline: plasma insulin was significantly depressed at 0.5 h postprandial but significantly elevated at 2 h postprandial. These data indicate that elevated plasma AA delays the insulin response to a glucose challenge in normoglycemic adults, thereby prolonging the postprandial hyperglycemia. These effects might be partially explained by the competitive inhibition of glucose transfer into pancreatic beta cells by high concentrations of circulating AA. Publication Types: Clinical trial Randomized controlled trial PMID: 7942581, UI: 95029077.