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May 9, 2000

National Academy of Sciences References

111. J Am Coll Nutr 1995 Aug;14(4):387-92Metabolic benefits deriving from chronic VITAMIN C supplementation in aged non-insulin dependent diabetics.Paolisso G, Balbi V, Volpe C, Varricchio G, Gambardella A, Saccomanno F, Ammendola S, Varricchio M, D'Onofrio F Department of Geriatric Medicine and Metabolic Diseases, II University of Naples, Italy.

OBJECTIVE: Our study investigated the metabolic benefits deriving from chronic pharmacological VITAMIN C administration in aged non-insulin dependent (Type II) diabetic patients. METHODS: Forty type II diabetic patients (age: 72 +/- 0.5 years) underwent placebo and VITAMIN C (0.5 g twice daily) administration in double-blind, randomized, cross-over fashion. All patients were treated by oral hypoglycaemic agents which continued throughout the study. After baseline observations, treatment periods lasted 4 months and were separated by a 30-day wash-out period. RESULTS: Patients' antropometric data were unchanged throughout the study. Chronic VITAMIN C administration vs placebo was associated with a significant decline in fasting plasma free radicals (0.26 +/- 0.06 vs 0.49 +/- 0.07 p < 0.03) and insulin (90 +/- 4 vs 73 +/- 6 pmol/L p < 0.04), total- (7.3 +/- 0.5 vs 5.8 +/- 0.4 mmol/L p < 0.03), LDL-cholesterol (5.6 +/- 0.6 vs 4.1 +/- 0.3 mmol/L p < 0.05) and triglycerides (2.58 +/- 0.07 vs 2.08 +/- 0.04 mmol/L p < 0.04) levels. In 20 patients, chronic VITAMIN C administration improved whole body glucose disposal and nonoxidative glucose metabolism. Percent increase in plasma VITAMIN C levels correlated with the percent decline in plasma LDL-cholesterol (r = 0.44; p < 0.007) and insulin levels (r = 0.42; p < 0.006). Finally percent increase in plasma VITAMIN C levels was correlated with the percent decline in plasma free radicals and increase in GSH levels. CONCLUSIONS: Chronic VITAMIN C administration has beneficial effects upon glucose and lipid metabolism in aged non-insulin dependent (type II) diabetic patients.

112. Nephrol Dial Transplant 1995;10 Suppl 6:44-7Resistance to erythropoietin in iron-overloaded haemodialysis patients can be overcome by Ascorbic acid administration.Gastaldello K, Vereerstraeten A, Nzame-Nze T, Vanherweghem JL, Tielemans C Department of Nephrology, Dialysis, and Transplantation, Cliniques Universitaires de Bruxelles, Hopital Erasme, Universite Libre de Bruxelles, Belgium.

Haemodialysis patients with iron overload sometimes develop resistance to erythropoietin therapy due to 'functional iron deficiency'. It is known that this resistance may be overcome by iron supplementation; however, the latter could worsen haemosiderosis. Therefore, we treated four iron-overloaded haemodialysis patients who had developed relative resistance to erythropoietin (among whom three had features of 'functional iron deficiency') with Ascorbic acid (500 mg intravenously after haemodialysis, 1-3 times a week). The erythropoietin doses were voluntarily kept unchanged during the study. After a latency of 2-4 weeks, haematocrit and haemoglobin had increased respectively from 26.5 +/- 0.7 to 32.7 +/- 0.4 vol% and from 8.8 +/- 0.3 to 10.8 +/- 0.2 g/dl (means +/- SEM, P < 0.001). While serum ferritin remained unchanged, transferrin saturation increased from 27 +/- 7 to 54 +/- 12% (P < 0.05), suggesting that Ascorbic acid supplementation had allowed mobilization of iron from tissue burdens. In one patient, haematocrit declined after withdrawal of VITAMIN C and increased again after rechallenge. Also, ascorbate supplementation was continued after the study in two patients and allowed the erythropoietin doses to be decreased, 8 and 11 weeks, respectively, after the start of the trial. When a control group of seven patients with normal iron status and without resistance to erythropoietin were challenged in the same manner with ascorbate, no elevation of haematocrit or transferrin saturation was noted. We conclude that ascorbate supplementation may circumvent resistance to erythropoietin that sometimes occurs in iron-overloaded patients, in particular, in the setting of 'functional iron deficiency'.

113. Eur Surg Res 1995;27(3):158-66Effect of pantothenic acid and Ascorbic acid supplementation on human skin wound healing process. A double-blind, prospective and randomized trial.Vaxman F, Olender S, Lambert A, Nisand G, Aprahamian M, Bruch JF, Didier E, Volkmar P, Grenier JF INSERM U 61, Hospices Civils, Strasbourg, France.

This study aimed at testing human skin wound healing improvement by a 21-day supplementation of 1.0 g Ascorbic acid (AA) and 0.2 g pantothenic acid (PA). 49 patients undergoing surgery for tattoos, by the successive resections procedure, entered a double-blind, prospective and randomized study. Tests performed on both skin and scars determined: hydroxyproline concentrations, number of fibroblasts, trace element contents and mechanical properties. In the 18 supplemented patients, it was shown that in skin (day 8) Fe increased (p < 0.05) and Mn decreased (p < 0.05); in scars (day 21), Cu (p = 0.07) and Mn (p < 0.01) decreased, and Mg (p < 0.05) increased; the mechanical properties of scars in group A were significantly correlated to their contents in Fe, Cu and Zn, whereas no correlation was shown in group B. In blood, AA increased after surgery with supplementation, whereas it decreased in controls. Although no major improvement of the would healing process could be documented in this study, our results suggest that the benefit of AA and PA supplementation could be due to the variations of the trace elements, as they are correlated to mechanical properties of the scars. Publication Types: Clinical trial Randomized controlled trial PMID: 7781653, UI: 95300835

114. Chung Hua I Hsueh Tsa Chih 1994 Sep;74(9):548-51, 583[Reduction of erythrocyte sorbitol by Ascorbic acid in patients with diabetes mellitus].

Wang H, Zhang ZB, Wen RR Department of Endocrinology, First Affiliated Hospital, Nanjing Medical University.

The content of erythrocyte sorbitol could be reduced by Ascorbic acid (AA). To confirm the effect of AA on human erythrocyte sorbitol accumulation and explore its mechanism of the action, we studied in vitro the effects of Ascorbic acid on the contents of both sorbitol and glucose in human erythrocytes. The effect of AA on the ratio of sorbitol to glucose in erythrocyte (S/EG) which was referred to as a marker of aldose reductase (AR) activity was observed. Both the accumulation of erythrocyte sorbitol and S/EG were reduced by the addition of Ascorbic acid (AA) during in vitro incubations. The sorbitol content in the erythrocyte and S/EG were reduced by a maximum of 87.3%, 83.4% and 93.8%, 63.9% when the medium's AA concentration was at its peak in the 5.6 mmol/L and 28 mmol/L glucose concentration of medium respectively. These suggested that the activity of polyol pathway could be inhibited effectively by AA which might directly act on the activity of AR. The results of a double-blind cross-over trial using AA tablets or inert inositol tablets in 8 diabetic patients showed that the supplementation of 1,000 mg AA/day continued for 2 weeks resulted in reductions of 12.2% and 21.8% in both erythrocyte sorbitol and red cell sorbitol: plasma glucose (S/PG) ratio, respectively (P < 0.05). The fasting plasma glucose levels measured coincidently revealed no changes (P > 0.05). This suggests that the supplementation of moderate AA (1,000 mg/day) might provide a simple, safe and effective means of preventing and ameliorating chronic complications of diabetes.

115. Eur J Clin Invest 1994 May;24(5):316-9Inhibitory effect of vitamins C and E on the oxygen free radical production in human polymorphonuclear leucocytes.Herbaczynska-Cedro K, Wartanowicz M, Panczenko-Kresowska B, Cedro K, Klosiewicz-Wasek B, Wasek W Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.

Beneficial effects of dietary supplementation with antioxidant vitamins are attributed mainly to the influence upon lipid metabolism, endothelial and vascular functions. Their effect upon leucocyte oxygen free radical producing capacity has not been investigated. In 13 healthy volunteers we examined the influence of oral supplementation with vitamins C and E (AA 600 mg per day for 14 days) upon leucocyte oxygen free radical production estimated by lucigenin-amplified chemiluminescence in isolated leucocytes stimulated with arachidonic acid. After supplementation with vitamins, significant increase in serum content of Ascorbic acid and tocopherol was concomitant with significant (P < 0.001) decrease of leucocyte chemiluminescent response (mean 63.2 + 23.0 SD, % of initial values) and lowering of serum lipid peroxides (P < 0.05). These findings suggest that suppression of leucocyte capacity to produce oxygen free radicals as shown in this study, may contribute to vasoprotective action of vitamins C and E.

116. J Am Coll Nutr 1994 Aug;13(4):344-50VITAMIN C: an aldose reductase inhibitor that normalizes erythrocyte sorbitol in insulin-dependent diabetes mellitus.Cunningham JJ, Mearkle PL, Brown RG Department of Nutrition, University of Massachusetts, Amherst 01003-1420.

OBJECTIVE: Diabetic hyperglycemia promotes sorbitol production from glucose via aldose reductase. Since the intracellular accumulation of sorbitol, or its sequelae, are postulated to contribute to the progression of chronic diabetic complications, aldose reductase inhibitors (ARI) offer therapeutic promise. Others have shown that VITAMIN C at pharmacologic doses decreases erythrocyte (RBC) sorbitol. We examined whether smaller, physiologic doses of VITAMIN C were also effective in individuals with insulin-dependent diabetes mellitus (IDDM) and whether VITAMIN C was an ARI in vitro. METHODS: VITAMIN C supplements (100 or 600 mg) were taken daily for 58 days by young adults with IDDM and nondiabetic adults in an otherwise free-living design. Diabetic control was monitored by fasting plasma glucose, glycosylated hemoglobin, and glycosuria and was moderate to poor throughout the study. RBC sorbitol was measured at baseline and again at 30 and 58 days. Three-day dietary records and 24-hour urine collections were performed for each sampling day. RESULTS: RBC sorbitol levels were significantly elevated in IDDMs, on average doubled, despite their more than adequate dietary intakes of VITAMIN C and normal plasma concentrations. VITAMIN C supplementation at either dose normalized the RBC sorbitol in IDDMs within 30 days. This correction of sorbitol accumulation was independent of changes in diabetic control. Furthermore, our in vitro studies show that Ascorbic acid inhibited aldose reductase activity. CONCLUSIONS: VITAMIN C supplementation is effective in reducing sorbitol accumulation in the erythrocytes of diabetics. Given its tissue distribution and low toxicity, we suggest a superiority for VITAMIN C over pharmaceutic ARIs.

117. Rinsho Shinkeigaku 1993 Mar;33(3):282-8[Intermittent high-dose VITAMIN C therapy in patients with HTLV-I-associated myelopathy].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.

118. Rom J Endocrinol 1993;31(1-2):81-4Effect of VITAMIN C administration on the ratio between the pro- and antioxidative factors.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.

119. Gac Med Mex 1993 Jan-Feb;129(1):23-5[Results of the treatment of chronic idiopathic thrombocytopenic purpura with Ascorbic acid].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.

120. Fertil Steril 1992 Nov;58(5):1034-9Effect of Ascorbic acid supplementation on the sperm quality of smokers.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.