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141. Dietary supplementation with vitamins C and E inhibits in vitro oxidation of lipoproteins.

J Am Coll Nutr 1993 Dec;12(6):631-7
Rifici VA, Khachadurian AK Department of Medicine, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick.

The oxidative modification of lipoproteins has been implicated in atherogenesis, suggesting a protective role of circulating antioxidants. VITAMIN C (Ascorbic acid, 1 g/day) and vitamin E (dl alpha-tocopheryl acetate, 800 IU/day) were administered to healthy female and male volunteers. Lipoproteins with density < 1.063 g/mL were isolated from serum before and after vitamin supplementation and incubated with copper (Cu) or mononuclear cells (MC) plus Cu. Administration of vitamins C and E together to 4 subjects for 10 days resulted in a 57% (range 40-72%) decrease in Cu-catalyzed production of thiobarbituric acid reactive substances (TBARS) under the following conditions of assay: incubation times of 0-8 hours, Cu concentrations of 0-10 microM lipoprotein protein concentrations of 0.1-0.5 mg/mL. Decreases in other parameters of lipoprotein oxidation, i.e,, electrophoretic mobility, production of conjugated dienes and modification of amino groups, were also observed. Vitamin E administration alone produced a 52% inhibition and VITAMIN C alone a 15% inhibition of TBARS formation. Vitamins C and E supplementation resulted in a 78% decrease in the susceptibility of lipoproteins to MC-mediated oxidation. There was a strong inverse correlation (r = -0.64, p < 0.0007) between vitamin E levels in the lipoproteins and TBARS production in samples from 12 subjects administered vitamins C and E. In 3 individuals vitamin E levels remained low and in 2 of these subjects there was no effect of vitamins C and E administration on TBARS production. These results suggest a protective role of antioxidant vitamins and significant individual variability in response. PMID: 8294717, UI: 94124856

142. Successful treatment of a patient with recurrent furunculosis by VITAMIN C: improvement of clinical course and of impaired neutrophil functions.

Int J Dermatol 1993 Nov;32(11):832-4
Levy R, Schlaeffer F Laboratory of Infectious Diseases, Soroka Medical Center of Kupat Holim, Beer Sheva, Israel.

BACKGROUND. Neutrophils play a critical role in host defense against a variety of microbial pathogens. There is much information to suggest a role for VITAMIN C in the physiology of neutrophils. Thus, the effects of VITAMIN C treatment were studied in a patient with a history of recurrent furunculosis who showed altered neutrophil functions. METHODS. Superoxide generation was measured by cytochrome C reduction. Phagocytosis of opsonized zymosan by neutrophils and chemotaxis on agarose plates were determined. RESULTS. Chemotaxis, phagocytosis, and superoxide generation of the patient's neutrophils were significantly lower than those of the matched control. Treatment with VITAMIN C (500 mg/day) for 30 days caused a dramatic clinical response and a significant improvement of all three neutrophil functions to values similar to those of the controls. CONCLUSIONS. We suggest that the patient described here had a temporary defect in neutrophil functions. The treatment with VITAMIN C probably prevented neutrophil oxidation, thus contributing to recovery of neutrophil function and arrest of furunculosis. PMID: 8270350, UI: 94095303

143. Absence of an effect of high VITAMIN C dosage on the systemic availability of ethinyl estradiol in women using a combination oral contraceptive.

Contraception 1993 Oct;48(4):377-91
Zamah NM, Humpel M, Kuhnz W, Louton T, Rafferty J, Back DJ Truman Medical Center, Kansas City, Missouri 64108.

Previous studies in small numbers of women have suggested that the administration of gram quantities of Ascorbic acid interferes with the conversion of ethinyl estradiol (EE2) to its sulfates, leading to higher blood levels of EE2. The possibility of such potentiation has been investigated in 37 women using a combination monophasic oral contraceptive (30 micrograms EE2 and 150 micrograms levonorgestrel) for two consecutive cycles. Concomitant daily administration of 1 g Ascorbic acid taken 1/2 hour before OC intake, was randomly assigned to the first or second cycle of OC use. On the first and 15th day of OC intake, blood samples were drawn 11 times over a 12-hour interval and Cmax and AUC(0-12 h) calculated. On pill days 10 and 21, only 6-hour post-intake samples were obtained. Samples were analyzed for levels of Ascorbic acid, free and sulfated ethinyl estradiol (and a number of other parameters). Cmax and AUC values for EE2 and EE2-sulfate in cycles with and without Ascorbic acid were evaluated statistically by the Grizzle model for days 1 and 15 and the ratios of day 15/day 1 for each of the substances. No effect of Ascorbic acid was observed (alpha = 0.05, 1-beta = 0.9). Only on day 15 was there a significantly lower AUC for EE2-sulfate in the presence of Ascorbic acid intake. Thus, the competition between Ascorbic acid and EE2 for sulfation does not lead to an increased systemic availability of EE2 and is, therefore, unlikely to be of any clinical importance. Ascorbic acid can, therefore, be removed from the list of drugs interfering with the pharmacokinetics of ethinyl estradiol. Publication Types: Clinical trial Randomized controlled trial PMID: 8222665, UI: 94038010

144. Effects of vitamin antioxidant supplementation on cell kinetics of patients with adenomatous polyps.

Gut 1993 Jul;34(7):963-7
Cahill RJ, O'Sullivan KR, Mathias PM, Beattie S, Hamilton H, O'Morain C Department of Gastroenterology, Meath Hospital, Trinity College, Dublin, Ireland.

Colonic crypt cell proliferation is used as an indicator of risk of colorectal carcinoma. Subjects with adenomatous polyps and cancer have an increased cell proliferation and a shift of the proliferative zone towards the apex of the crypt. Epidemiological and in vitro studies have confirmed a link between vitamins A, E, C, beta-carotene, and colorectal cancer. In vitro bromodeoxyuridine immunohistochemical technique was used to assess the effect of daily oral supplementation with vitamin E (160 mg), VITAMIN C (750 mg), or beta-carotene (9 mg) on the colonic crypt cell proliferation in patients with adenomatous polyps (n = 40) compared with normal subjects with no colonic disease (n = 20). The patients were given supplementation for one month and colonic biopsy specimens were taken before and at the end of the trial. Patients with adenomatous polyps had a significantly higher mean labelling index per cent than controls (p < 0.001). VITAMIN C or beta-carotene supplementation, however, significantly reduced the total proliferation (p < 0.005) whereas vitamin E supplementation had no effect on the colonic crypt cell proliferation. beta-carotene reduced cell proliferation at the base of the crypt only. VITAMIN C reduced cell proliferation in all the crypt compartments from the apex to the base to those values seen in age and sex matched controls. These findings indicate that prolonged supplementation with VITAMIN C may reduce the recurrence of adenomatous polyps. PMID: 8344584, UI: 93345888

145. VITAMIN C elevates red blood cell glutathione in healthy adults.

Am J Clin Nutr 1993 Jul;58(1):103-5
Johnston CS, Meyer CG, Srilakshmi JC Department of Family Resources and Human Development, Arizona State University, Tempe 85287.

We examined the effect of supplemental Ascorbic acid on red blood cell glutathione. Subjects consumed self-selected VITAMIN C-restricted diets, and, under double-blind conditions, ingested placebo daily for week 1 (baseline), 500 mg L-ascorbate/d for weeks 2-3, 2000 mg L-ascorbate/d for weeks 4-5, and placebo daily for week 6 (withdraw). Mean red blood cell glutathione rose nearly 50% (P < 0.05) after the 500-mg period compared with baseline, and the changes from baseline for individual subjects ranged from +8% to +84%. However, the increases in plasma VITAMIN C and red blood cell glutathione were not correlated (r = 0.22). At the 2000-mg dosage, mean red blood cell glutathione was not significantly different from the value obtained at the 500-mg dosage. After the placebo-controlled withdraw period, red blood cell glutathione did not differ from baseline. These data indicate that VITAMIN C supplementation (500 mg/d) maintains reduced glutathione concentrations in blood and improves the overall antioxidant protection capacity of blood. Publication Types: Clinical trial PMID: 8317379, UI: 93304290

146. Antioxidant vitamins or lactulose for the prevention of the recurrence of colorectal adenomas. Colorectal Cancer Study Group of the University of Modena and the Health Care District 16.

Dis Colon Rectum 1993 Mar;36(3):227-34
Roncucci L, Di Donato P, Carati L, Ferrari A, Perini M, Bertoni G, Bedogni G, Paris B, Svanoni F, Girola M, et al Istituto di Patologia Medica, Modena, Italy.

Colonic adenomas represent the natural precursor lesions of most colorectal cancers. The treatment of choice is endoscopic polypectomy. However, after endoscopic removal, polyps recur in a large fraction of cases. Thus, we evaluated the effect of antioxidant vitamins or lactulose on the recurrence rate of adenomatous polyps. After polypectomy, 255 individuals were randomized into three groups. Group 1 was given vitamin A (30,000 IU/day), VITAMIN C (1 g/day), and vitamin E (70 mg/day); Group 2 was given lactulose (20 g/day); Group 3 received no treatment. Forty-six subjects had to be excluded because the histologic diagnosis was not consistent with adenoma. The remaining 209 individuals were included in the analysis according to the "intention to treat" criterion, though 34 did not adhere to the scheduled treatment or were lost during the follow-up. Subjects were followed at regular intervals for an average of 18 months. Polyps recurring before one year from index colonoscopy were considered missed by the endoscopist. In the 209 evaluable subjects, the percentages of recurrence of adenomas were 5.7 percent, 14.7 percent, and 35.9 percent in the vitamins, lactulose, and untreated groups, respectively. The fraction of subjects remaining free of adenomas, estimated by Kaplan-Meier survival curves, was significantly different among the three groups (log-rank chi-squared = 17.138; P < 0.001). Using Cox's regression analysis, treatment was the only variable that significantly contributed to the model (regression coefficient = 0.905; P < 0.001). In conclusion, either antioxidant vitamins or, to a lesser extent, lactulose lower the recurrence rate of adenomas of the large bowel and can be proposed as chemopreventive agents, at least in high-risk individuals. Publication Types: Clinical trial Randomized controlled trial PMID: 8449125, UI: 93193586

147. [Intermittent high-dose VITAMIN C therapy in patients with HTLV-I-associated myelopathy].

Rinsho Shinkeigaku 1993 Mar;33(3):282-8
Kataoka A, Imai H, Inayoshi S, Tsuda T Third Department of Internal Medicine, Oita Medical University.

The aim of this study was to determine the efficacy and safety of intermittent high-dose VITAMIN C therapy in patients with HTLV-I associated myelopathy (HAM). Seven HAM patients (4 men and 3 women, aged 36 to 81 years), who were repeatedly given a daily oral dose of 1.5 to 3.0 g of VITAMIN C (40 mg/kg/day) for 3 to 5 successive days followed by a two-day withdrawal period, were followed for a mean period of 9.7 +/- 5.8 months after the therapy. The therapeutic efficacy was evaluated by a 10-grade disability scoring (DS) system, short somatosensory evoked potentials (SSEP) elicited by tibial nerve stimulation and several immunological parameters before and at 2.0 to 14 months after the therapy. All HAM patients responded well to intermittent high-dose VITAMIN C therapy, 6 being excellent responders (DS improvement > or = 2 grades) and one being a good responder (DS improvement of one grade). The grade of DS was decreased at 9.7 +/- 5.8 months after the therapy from 5.9 +/- 1.6 (baseline) to 3.0 +/- 1.5 (p < 0.01), indicating an excellent clinical outcome. SSEPs were obtained before and after the therapy in 4 of the patients. On SSEP before therapy, all the patients showed abnormally prolonged P37 peak latency. N20 was not recorded in 2 patients. After the therapy, N20 appeared and prolonged P37 peak latency improved in 2 patients. Immunoglobulin concentrations, T-B lymphocyte subsets and HTLV-I antibody titer in serum did not change. Publication Types: Clinical trial PMID: 8334790, UI: 93327524

148. Effect of VITAMIN C administration on the ratio between the pro- and antioxidative factors.

Rom J Endocrinol 1993;31(1-2):81-4
Dumitrescu C, Belgun M, Olinescu R, Lianu L, Bartoc C C.I. Parhon Institute of Endocrinology, Bucharest, Romania.

Much evidence gathered in the last years involve the free radicals (FR) in the mechanisms of initiation, development of neoplastic transformations in vivo and in vitro, as well as in the activity of specific oncogenes. Most of it comes from the fact that the agents that remove the FR or interfere in the chain of events induced by FR can inhibit the neoplastic process both at cellular and molecular level. The antioxidant and free-radical scavenging activities of VITAMIN C have been intensely investigated, VITAMIN C being considered the most important antioxidant protective agent in the plasma. Our study is focused on the changes in lipid peroxides (MDA), free SH groups and the total antioxidative capacity in the plasma of 22 patients with differentiated thyroid cancer operated and treated with 131I, and then given 1 g VITAMIN C/day along one month. Blood samples were collected before 131I and then 4 days following 131I administration, and after 1 month of VITAMIN C administration per os. The following results were noted: (1) an increase of MDA concentration after 131I; (2) a decrease in the MDA level after one month of VITAMIN C administration; (3) an increase in the concentration of free SH groups after 131I; (4) a decrease in the level of free SH after VITAMIN C, and (5) a non-significant decrease in TAC after 131I and VITAMIN C. The results confirm the change in the balance between the oxidative and antioxidative factors under the effect of ionizing radiations and suggest the involvement of VITAMIN C as a protective and/or potentiating factor for the other antioxidative systems. PMID: 8173577, UI: 94227829

149. [Results of the treatment of chronic idiopathic thrombocytopenic purpura with Ascorbic acid].

Gac Med Mex 1993 Jan-Feb;129(1):23-5
[Article in Spanish] Karduss Urueta A, Morales Polanco MR, Pizzuto Chavez J, Meillon Garcia LA Servicio de Hematologia, Hospital de Especialidades CMN Siglo XXI, IMSS, Mexico D.F.

The main objective of the present work is to describe the results of the treatment with Ascorbic acid in thirteen patients with refractory chronic idiopathic thrombocytopenic purpura (CITP) and to compare its results with those informed in the literature. The patients received Ascorbic acid 2 g/day, orally, in the morning during at least eight weeks. At the end of the period of control there were only four partial responses (30%); the remaining patients did not experience any kind of favorable reaction. Previous publications informed mean partial and complete responses of 11 and 19% respectively. According to such results and those of the present work, and taking into account the generally transitory duration of the response it is concluded that Ascorbic acid is of no use in the treatment of CITP. Publication Types: Review Review literature PMID: 8063073, UI: 94341537 367: Ann Fr Anesth Reanim 1993;12(6):598-600 [VITAMIN C deficiency: a rare cause of poorly tolerated severe anemia]. [Article in French] Pateron D, Benkel J, Tchanjou LE, Blaise M, Pourriat JL Department d'Anesthesie-Reanimation, CHU Jean-Verdier, Bondy. We report the case of a 82-year-old man, living in institution, hospitalized for a severe anaemia due to scurvy. Scurvy is rare in Occident. A multifactorial anaemia is usually associated with scurvy, but is rarely symptomatic. Alcoholism favours scurvy and anaemia. Treatment consisted of parenteral VITAMIN C supplementation associated with blood transfusion. PMID: 8017677, UI: 94288326

150. Effect of Ascorbic acid supplementation on the sperm quality of smokers.

Fertil Steril 1992 Nov;58(5):1034-9
Dawson EB, Harris WA, Teter MC, Powell LC Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston 77555.

OBJECTIVE: To determine the effect of Ascorbic acid supplementation on the sperm quality of heavy smokers. DESIGN: Microscopic examination of semen for 1 month during supplementation with placebo or Ascorbic acid at dose levels of 200 or 1,000 mg/d. SETTING: Department of Obstetrics and Gynecology, The University of Texas Medical Branch. PARTICIPANTS: Seventy-five men (20 to 35 years old) randomly divided into one of three supplementation groups: placebo, 200 mg and 1,000 mg of Ascorbic acid. MAIN OUTCOME: Improvement in sperm quality as compared with presupplementation levels and between the three treatment groups. RESULTS: The placebo group showed no improvement in sperm quality. The groups receiving Ascorbic acid showed improvement in sperm quality with most improvement in the 1,000-mg group. Pearson's correlation showed statistically significant relationships between the weekly group means of serum and seminal plasma Ascorbic acid levels and sperm qualities. CONCLUSIONS: Ascorbic acid supplementation of heavy smokers in excess of 200 mg/d results in improved sperm quality. Publication Types: Clinical trial Randomized controlled trial PMID: 1426355, UI: 93050324.