111. Administration of ascorbic acid and an aldose reductase inhibitor (tolrestat) in diabetes: effect on urinary albumin excretion.
Nephron 1998 Nov;80(3):277-84
McAuliffe AV, Brooks BA, Fisher EJ, Molyneaux LM, Yue DK
Department of Life Sciences in Nursing, University of Sydney, Sydney, Australia.
The important role of ascorbic acid (AA) as an anti-oxidant is particularly relevant in diabetes mellitus where plasma concentrations of AA are reduced. This study was conducted to evaluate the effects of treatment with AA or an aldose reductase inhibitor, tolrestat, on AA metabolism and urinary albumin excretion in diabetes. Blood and urine samples were collected at 0, 3, 6, 9, and 12 months from 20 diabetic subjects who were randomized into two groups to receive either oral AA 500 mg twice daily or placebo. Systolic and diastolic blood pressures, HbA1c, plasma lipids, urinary albumin, and total glycosaminoglycan excretion were measured at all time points, and heparan sulphate (glycosaminoglycan) was measured at 0 and 12 months. The same parameters, as well as urinary AA excretion, were determined at 0 and 3 months for 16 diabetes subjects receiving 200 mg tolrestat/day. AA treatment increased plasma AA (ANOVA, F ratio = 12.1, p = 0.004) and reduced albumin excretion rate (AER) after 9 months (ANOVA, F ratio = 3.2, p = 0.03), but did not change the other parameters measured. Tolrestat lowered plasma AA (Wilcoxon's signed-rank test, p < 0.05), but did not change AER or the other parameters measured. The ability of AA treatment to decrease AER may be related to changes in extracellular matrix or improvement in oxidative defence mechanism. Unlike the rat model of diabetes, inhibition of aldose reductase did not normalize plasma AA or AER in humans. In fact, tolrestat reduced the plasma AA concentration, a phenomenon which may be due to increased utilization of AA. Dietary supplementation of AA in diabetic subjects may have long-term benefits in attenuating the progression of diabetic complications.
112. Immune function in aged women is improved by ingestion of vitamins C and E
Can J Physiol Pharmacol 1998 Apr;76(4):373-80
de la Fuente M, Ferrandez MD, Burgos MS, Soler A, Prieto A, Miquel J
Departamento de Biologia Animal II (Fisiologia Animal), Facultad de Ciencias Biologicas, Universidad Complutense, Madrid, Spain.
We have investigated the effects of supplementation of the diet with the antioxidant vitamins C and E on several functions of the immune response of aged women. Ten healthy women and 20 women (72 +/- 6 years old) suffering two diseases often associated with age (10 with major depression disorders, MDD, and 10 with coronary heart disease, CHD) were administered 1 g of vitamin C and 200 mg of vitamin E daily for 16 weeks. Blood samples were collected before and after treatment for measurement of several immunological functions, namely proliferative response of lymphocytes to the mitogen phytohemagglutinin (20 mg/L) and phagocytic functions of polymorphonuclear (PMN) neutrophils, i.e., adherence to vascular endothelium, chemotaxis, phagocytosis of latex beads, and superoxide anion production. In addition, we also determined the levels of serum cortisol and lipid peroxides. Intake of vitamins resulted in a significant increase in the lymphoproliferative capacity and in the phagocytic functions of PMN neutrophils as well as in a significant decrease of serum levels of lipid peroxides and cortisol, both in the healthy aged women and in the aged women with MDD or CHD. These findings suggest an important role of antioxidant supplementation in the improvement of immune function in aged females as well as in the prevention and treatment of specific diseases associated with age that are quite prevalent in the developed countries.
113. Effects of vitamin E and C supplementation on oxidative stress and viral load in HIV-infected subjects.
AIDS 1998 Sep 10;12(13):1653-9
Allard JP, Aghdassi E, Chau J, Tam C, Kovacs CM, Salit IE, Walmsley SL
Department of Medicine, University of Toronto, Ontario, Canada.
OBJECTIVES: The HIV-infected population is known to be oxidatively stressed and deficient in antioxidant micronutrients. Since in vitro replication of HIV is increased with oxidative stress, this study assessed the effect of antioxidant vitamin supplementation on lipid peroxidation, a measure of oxidative stress, and viral load in humans. DESIGN: A randomized placebo-controlled, double-blind study. METHODS: Forty-nine HIV-positive patients were randomized to receive supplements of both DL-alpha-tocopherol acetate (800 IU daily) and vitamin C (1000 mg daily), or matched placebo, for 3 months. Plasma antioxidant micronutrient status, breath pentane output, plasma lipid peroxides, malondialdehyde and viral load were measured at baseline and at 3 months. New or recurrent infections for the 6-month period after study entry were also recorded. RESULTS: The vitamin group (n = 26) had an increase in plasma concentrations of alpha-tocopherol (P < 0.0005) and vitamin C (P < 0.005) and a reduction in lipid peroxidation measured by breath pentane (P < 0.025), plasma lipid peroxides (P < 0.01) and malondialdehyde (P < 0.0005) when compared with controls (n = 23). There was also a trend towards a reduction in viral load (mean +/- SD changes over 3 months, -0.45 +/- 0.39 versus +0.50 +/- 0.40 log10 copies/ml; P = 0.1; 95% confidence interval, -0.21 to -2.14). The number of infections reported was nine in the vitamin group and seven in the placebo group. CONCLUSION: Supplements of vitamin E and C reduce oxidative stress in HIV and produce a trend towards a reduction in viral load. This is worthy of larger clinical trials, especially in HIV-infected persons who cannot afford new combination therapies.
114. Phototoxic lysis of erythrocytes from humans is reduced after oral intake of Ascorbic acid and d-alpha-tocopherol.
Photodermatol Photoimmunol Photomed 1997 Oct-Dec;13(5-6):173-7
Eberlein-Konig B, Placzek M, Przybilla B
Dermatologische Klinik und Poliklinik, Ludwig-Maximilians-Universitat Munchen, Germany.
Ultraviolet (UV) radiation causes hemolysis of human erythrocytes in the presence of photosensitizers. This can be used as an in vitro model for evaluating photosensitizing properties of substances. Antioxidants such as Ascorbic acid (VITAMIN C) and d-alpha-tocopherol (vitamin E) have been found to be photoprotective in such test systems. We assessed the effect of combined systemic intake of both Ascorbic acid and d-alpha-tocopherol by human volunteers on phototoxic in vitro lysis of their erythrocytes. In a double-blind placebo-controlled study, 10 subjects took daily 2 g Ascorbic acid combined with 1000 IU d-alpha-tocopherol, and 10 took a placebo. Blood was taken before and after 7 days of treatment, erythrocytes were prepared and then incubated with 10(-3) mol/l fenofibrate, a photosensitizer acting in the UVA and UVB region. The suspensions were exposed to radiation rich in UVA (up to 40 J/cm2 UVA) or to radiation rich in UVB (up to 1.6 J/cm2). Photohemolysis of the samples was calculated as a percentage of complete hemolysis. At the end of the treatment phase, in the placebo group photohemolysis was not significantly reduced compared with the initial values at all irradiation doses except for 1.6 J/cm2 UVB (96% vs 79%; P < 0.01). In the group taking vitamins, photohemolysis was
significantly reduced at nearly all UV doses, most impressively after moderate UVA irradiation (20 J/cm2 UVA: 86.5% vs 14.5%; P < 0.01). It is concluded that the results of the photohemolysis test are influenced by the antioxidative status of the cell donor and that Ascorbic acid and d-alpha-tocopherol also may protect against phototoxic damage in vivo.
115. Exercise-induced oxidative stress before and after VITAMIN C supplementation.
Int J Sport Nutr 1997 Mar;7(1):1-9
Alessio HM, Goldfarb AH, Cao G PHS Department, Miami University, Oxford, OH 45056, USA.
VITAMIN C (Ascorbic acid) was supplemented (1 g/day) for 1 day and 2 weeks in the same subjects. Plasma thiobarbituric acid reacting substances (TBARS) and oxygen radical absorbance capacity (ORAC) before and after 30 min submaximal exercise were measured. Different VITAMIN C supplementations did not affect resting TBARS or ORAC. Following 30 min exercise, values for TBARS were 12.6 and 33% above rest with 1 day and 2 weeks of VITAMIN C supplementation, respectively, compared to 46% higher with placebo. ORAC did not significantly change (11%) after exercise with a placebo, nor when subjects were given VITAMIN C supplements for 1 day or 2 days (4.9% and 5.73%, respectively). TBARS:ORAC, a ratio representing oxidative stress, increased 32% (p < .05) with placebo compared to 5.8 and 25.8% with VITAMIN C supplements for 1 day and 2 weeks, respectively. It was concluded that exercise-induced oxidative stress was highest when subjects did not supplement with VITAMIN C compared to either 1 day or 2 weeks of VITAMIN C supplementation.
116. Postprandial hyperinsulinaemia, insulin resistance and inappropriately high phosphaturia are features of younger males with idiopathic calcium urolithiasis: attenuation by Ascorbic acid supplementation of a test meal.
Urol Res 1997;25(1):49-58
Schwille PO, Schmiedl A, Herrmann U, Wipplinger J Department of Surgery, University of Erlangen, Germany.
In idiopathic recurrent calcium urolithiasis (RCU) the state of insulin and carbohydrate metabolism, and relationships to minerals such as phosphate, are insufficiently understood. Therefore, in two groups of males with RCU (n = 30) and healthy controls (n = 8) the response to an oral carbohydrate- and calcium-rich test meal was studied with respect to glucose, insulin, and C-peptide in peripheral venous blood (taken before and up to 180 min post-load), and phosphate and glucose in fasting and post-load urine. In one RCU group (n = 16) the meal was supplemented with Ascorbic acid (ASC; 5 mg/kg body weight). The mean age (RCU 29, RCU + ASC 30, controls 27 years) and mean body mass index [RCU 24.4, RCU + ASC 25.0, controls 24.0 kg/m2] were similar. Insulin resistance (synonymous sensitivity of peripheral organs to insulin) was calculated from insulin serum concentration, as was also integrated insulin, C-peptide, and glucose. Untreated stone patients (RCU) developed hyperinsulinaemia between 60 and 120 min post-load, increased integrated insulin, and insulin resistance (P < or = 0.05 vs controls), whereas the rise of C-peptide and glycaemia (absolute and integrated values) was only of borderline significance. Fasting phosphaturia was low in both RCU subgroups vs controls; however, phosphaturia in untreated RCU rose in response to the meal, contrasting sharply with a decrease in controls. ASC supplementation of the meal (in the RCU + ASC subgroup) normalized insulin, failed to normalize post-load phosphaturia, but reduced post-load glucosuria and urinary pH significantly (mean pH values 5.55 vs 5.93 in untreated RCU, controls 5.50). Postprandial urinary oxalate, calcium, protein, and supersaturation products were not changed. The postprandial changes in phosphaturia and insulin sensitivity were inversely correlated (n = 38, r = -0.44, P = 0.007). It was concluded that in younger RCU males: (1) postprandial hyperinsulinaemia, the failure to reduce phosphaturia and - within limits - glucosuria, appropriately, as well as poor urine acidification are important features of the metabolism; (2) these phenomena are probably caused by insulin resistance of organs, the kidney included; and (3) the addition of a supraphysiological dose of ASC to a meal, the subsequent abolition of hyperinsulinaemia, and the restoration of normal urine acidification suggest that this antioxidant is capable of counteracting some pre-existing basic abnormality of cell metabolism in RCU.
117. VITAMIN C intake and susceptibility to the common cold.
Br J Nutr 1997 Jan;77(1):59-72
Hemila H Department of Public Health, University of Helsinki, Finland.
Although the role of VITAMIN C in common cold incidence had been studied extensively, the level of VITAMIN C intake has not been unequivocally shown to affect the incidence of colds. In the present study the six largest VITAMIN C supplementation (> or = 1 g/d) studies, including over 5000 episodes in all, have been analysed, and it is shown that common cold incidence is not reduced in the VITAMIN C-supplemented groups compared with the placebo groups (pooled rate ratio (RR) 0.99; 95% CI 0.93, 1.04). Consequently these six major studies give no evidence that high-dose VITAMIN C supplementation decreases common cold incidence in ordinary people. Nevertheless, the analysis was continued with the hypothesis that VITAMIN C intake may affect common cold susceptibility in specific groups of people. It was assumed that the potential effect of supplementation might be most conspicuous in subjects with low dietary VITAMIN C intake. The average VITAMIN C intake has been rather low in the UK and plasma VITAMIN C concentrations are in general lower in males than in females. In four studies with British females VITAMIN C supplementation had no marked effect on common cold incidence (pooled RR 0.95; 95% CI 0.86, 1.04). However, in four studies with British male schoolchildren and students a statistically highly significant reduction in common cold incidence was found in groups supplemented with VITAMIN C (pooled RR 0.70; 95% CI 0.60, 0.81). Thus, these studies with British males indicate that VITAMIN C intake has physiological effects on susceptibility to common cold infections, although the effect seems quantitatively meaningful only in limited groups of people and is not very large. Publication Types: Meta-analysis Comments: Comment in: Br J Nutr 1997 Nov;78(5):857-9; discussion 861-6 Comment in: Br J Nutr 1997 Nov;78(5):859-61; discussion 861-6 PMID: 9059230, UI: 97212374
118. The effect of VITAMIN C in high doses on plasma and biliary lipid composition in patients with cholesterol gallstones: prolongation of the nucleation time.
Eur J Clin Invest 1997 May;27(5):387-91
Gustafsson U, Wang FH, Axelson M, Kallner A, Sahlin S, Einarsson K Department of Surgery, Danderyd Hospital, Sweden.
VITAMIN C deficiency in guinea pigs leads to cholesterol supersaturation of bile and formation of cholesterol gallstones. It has been suggested that there may also exist an association between VITAMIN C and cholesterol gallstones in man, but such a relationship has not been studied in gallstone patients. In order to study the possible effects of VITAMIN C on gallstone disease in humans, plasma lipid levels, hepatic cholesterol metabolism, biliary lipid composition, cholesterol saturation and nucleation time of gallbladder bile were analysed in 16 consecutive gallstone patients, who were planned for laparoscopic cholecystectomy and were treated with VITAMIN C (500 mg, four times a day) for 2 weeks before surgery. The plasma concentration of VITAMIN C increased by 42% in the treatment group. The concentrations of plasma lipids did not differ before and after VITAMIN C treatment; nor did the plasma levels of lathosterol and 7 alpha-hydroxy-4-cholesten-3-one, reflecting cholesterol and bile acid synthesis respectively. The relative concentrations of cholesterol, bile acids and cholesterol concentration of bile did not differ significantly between the two groups, but the relative concentration of phospholipids was slightly higher in the treated group. The bile acid composition was changed; the percentage of cholic acid being lower and those of deoxycholic acid, ursodeoxycholic acid and lithocholic acid higher in the VITAMIN C-treated patients compared with the untreated group. The nucleation time was significantly longer in the treatment group (7 days) compared with the untreated group (2 days). Our findings indicate that VITAMIN C supplementation may also influence the conditions for cholesterol gallstone formation in humans. PMID: 9179545, UI: 97323055
119. Blocking effect of VITAMIN C in exercise-induced asthma.
Arch Pediatr Adolesc Med 1997 Apr;151(4):367-70
Cohen HA, Neuman I, Nahum H Pediatric Ambulatory Clinic, Rabin Medical Center, Petach Tiqva, Israel.
OBJECTIVE: To determine if VITAMIN C (Ascorbic acid) has a protective effect on the hyperreactive airways of patients with exercise-induced asthma (EIA). DESIGN: All the patients underwent pulmonary function tests at rest, before and 1 hour after receiving 2 g of oral Ascorbic acid. They were then randomly assigned in a double-blind manner to receive 2 g of Ascorbic acid or a placebo 1 hour before a 7-minute exercise session on a treadmill. Pulmonary function tests were performed after an 8-minute rest. This procedure was repeated 1 week later, with each patient receiving the alternative medication. SETTING: A university hospital. PARTICIPANTS: Twenty patients with asthma (13 males and 7 females), with ages ranging from 7 to 28 years (mean, 13.8 years). All patients who had a decline of at least 15% in their forced expiratory volume in 1 second after a standard exercise test on a motorized treadmill received a diagnosis of EIA. MAIN-OUTCOME MEASURES: All patients were advised to stop using their regular asthma medication or bronchodilator 12 hours before the test. Pulmonary function tests were performed in the same ambient conditions on all patients. RESULTS: All patients received a diagnosis of EIA. Ascorbic acid administration did not change the results of pulmonary functions at rest after 1 hour. In 9 patients, a protective effect on exercise-induced hyperreactive airways was documented. Four of 5 patients who received Ascorbic acid and documented a protective effect on EIA continued to receive Ascorbic acid, 0.5 g/d, for 2 more weeks with the same protective effect. CONCLUSIONS: The efficacy of VITAMIN C in preventing EIA cannot be predicted. However, VITAMIN C may have a protective effect on airway hyperreactivity in some patients with EIA. Publication Types: Clinical trial Randomized controlled trial PMID: 9111435, UI: 97265520
120. Supplementation with vitamins C and E enhances cytokine production by peripheral blood mononuclear cells in healthy adults.
Am J Clin Nutr 1996 Dec;64(6):960-5
Jeng KC, Yang CS, Siu WY, Tsai YS, Liao WJ, Kuo JS Department of Medical Research, Taichung Veteran's General Hospital, Taiwan, Republic of China.
The effect of supplementation with vitamins C and E on cytokine production of healthy adult volunteers was studied in a single-blind trial. Ten subjects in each group received daily VITAMIN C (1 g Ascorbic acid), vitamin E (400 mg dl-alpha-tocopheryl acetate), or vitamins C and E for 28 d. Plasma concentrations of alpha-tocopherol, ascorbate, and lipid peroxides as well as the production of cytokines by peripheral blood mononuclear cells (PBMCs) were measured before, during, and at the end of the supplementation and 1 wk later. PBMCs were cultured in the presence of absence of lipopolysaccharide for 24 h. The interleukin 1 (IL-1), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-alpha) in the culture supernates were assayed by enzyme-linked immunosorbent assay methods. Production of IL-1 beta and TNF-alpha in the group supplemented with vitamins C and E was significantly higher (P < 0.05) than that of the groups given vitamin E or VITAMIN C alone. The enhancing effect of supplementation with a combination of vitamins E and C coincided with peak plasma alpha-tocopherol and ascorbate concentrations and the lowest plasma lipid peroxide concentrations (P < 0.05) on day 14. In addition, an in vitro experiment with PBMCs showed that vitamins E and C reduced lipopolysaccharide-induced prostaglandin E2 production and enhanced TNF-alpha production. These results indicate that combined supplementation with vitamins C and E is more immunopotentiating than supplementation with either vitamin alone in healthy adults.