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High dose ascorbic acid in Nigerian asthmatics.

Forty-one asthmatic patients in remission were randomly allocated to two treatment groups in a double-blind trial. One group took 1 g, of ascorbic acid as one effervescent tablet once daily and the second group took a matching placebo. The asthmatics were selected from those attending the Asthma Clinic. One criterion for selection was the increase in exacerbation during the rainy season. These exacerbations were precipitated by respiratory infection. After 14 weeks, an assessment of the severity and rate of attacks showed that those on ascorbic acid suffered less severe and less frequent attacks of asthma during the study period. Plasma ascorbic acid astimations showed a significant rise in the level in those taking ascorbic acid over those on placebo. (P < 0.01). Cessation of ascorbic acid in the group taking it increased attack rates. It is concluded that high dose ascorbic acid is probably a good prophylaxis in some bronchial asthmatics.

Adolescent↗

Cerebrospinal fluid ascorbic acid levels during the neonatal period.

Corresponding plasma and cerebrospinal fluid ascorbic acid levels were determined in 13 term and 17 preterm newborn infants during the neonatal period. On the first day of life preterm C.S.F ascorbate value of 5.2 +/- 0.8 mg/dl (mean +/- S.E.) was higher than the 3.8 +/- 0.3 mg/dl value in term infants (P less than 0.1). Later determinations during the neonatal period did not demonstrate a difference between term and preterm C.S.F ascorbate values and levelled at 2.9 +/- 0.2 mg/dl. There was a significant negative correlation between the C.S.F/plasma ascorbate ratio and the plasma ascorbate levels and the shape of the regression line was suggestive of a saturable active ascorbate transport from the plasma into the cerebrospinal fluid. Ascorbic acid in the C.S.F of additional six neonates with a neurological disorder was lower than expected on the basis of their plasma levels, the C.S.F/plasma ascorbate ratios being 8.3 +/- 0.9 in the apparently normal infants and 3.7 +/- 0.6 in the neurological patients, (P less than 0.025). The possible mechanism of ascorbate loss from the central nervous system is discussed and it is speculated that ascorbic acid administration following a neurological insult may prove beneficial.

Ascorbic Acid↗

Levels of active oxygen species are controlled by ascorbic acid and anthocyanin in Arabidopsis.

Stabilization of the levels of active oxygen species (AOS) is important to the survival of organisms. To clarify the system controlling levels of AOS in plants, this study used an electron spin resonance (ESR) method to directly measure superoxide radical (O(2)(.-)) scavenging activities in the wild-type Arabidopsis thaliana (Col and Ler ecotypes), two anthocyanin mutants (tt3 and ttg1), and an ascorbic acid mutant (vtc1). Under ordinary growth conditions, Arabidopsis contained superoxide-scavenging activity (SOSA) of approximately 300-500 SOD units/g of fresh weight. The ESR pattern indicated that most (40-50%) of this activity was due to ascorbic acid. For the analysis of SOSA under conditions of oxidative stress, synthesis of AOS was induced by gamma-irradiation. The radical scavenging activity in irradiated plants increased approximately 10-fold following an associated increase in the accumulation of ascorbic acid and anthocyanin. The accumulation of ascorbic acid and anthocyanin was suppressed by treatment with an antioxidant before irradiation and was induced by treatment with a radical-generating reagent. The contributions of ascorbic acid and anthocyanin to the total superoxide radical scavenging activity differed among ecotypes. In the Ler ecotype, ascorbic acid accumulated at twice the level of that in the Col ecotype, and induction of anthocyanin was half that in Col. To confirm the activity of ascorbic acid and anthocyanin against AOS stress, the viability of the wild type and mutants (tt2, tt3,tt5, ttg1, and vtc1) was examined after gamma-irradiation. Only the plants in which ascorbic acid and anthocyanin were induced had the ability to grow and flower.

Anthocyanins↗

Experimental and clinical studies on the reduction of erythrocyte sorbitol-glucose ratios by ascorbic acid in diabetes mellitus.

In order to confirm the effect of ascorbic acid (AA) on human erythrocyte sorbitol accumulation and explore its mechanism of action, the effects of ascorbic acid in vitro on the sorbitol (S) and glucose (EG) content of human erythrocytes and in particular on the S/EG ratio as a marker of aldose reductase (AR) activity were carefully observed. The results showed that both the accumulation of erythrocyte sorbitol and the S/EG ratio were strongly reduced by the addition of AA. The sorbitol content in the erythrocyte and the S/EG ratio were reduced by a maximum of 87.3% and 83.4% and 93.8% and 63.9% when the medium's AA concentration was at its peak with 5.6 mmol/l and 28 mmol/l glucose in the medium, respectively. The contents of erythrocyte glucose measured coincidentally revealed a positive correlation with the ascorbic acid concentration in the medium during incubation in 5.6 mmol/l glucose while at a higher glucose level (28 mmol/l) in the medium the correlation became negative. These results suggested that the polyol pathway could be inhibited effectively by AA through its direct action on AR. The results of a double-blind cross-over trial using AA tablets or inositol tablets in eight diabetic patients showed that the supplementation of 1000 mg AA/day for 2 weeks resulted in reductions of 12.2% and 21.8% in erythrocyte sorbitol and red cell sorbitol/plasma glucose (S/PG) ratio, respectively (P < 0.05), whereas the fasting plasma glucose levels measured coincidentally revealed no changes (P > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Relationships between ascorbic acid and alpha-tocopherol during diquat-induced redox cycling in isolated rat hepatocytes.

The effects of diquat-induced redox cycling on the levels of cellular ascorbic acid and alpha-tocopherol were investigated in isolated rat hepatocytes. In untreated hepatocytes, the metabolism of 1 or 2 mM diquat resulted in the depletion of cellular ascorbic acid and glutathione, but not of alpha-tocopherol, in association with the induction of cell death during the experimental period. In 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) pretreated cells, 1 mM diquat induced cell death accompanied by glutathione was rapid (to 9% of controls by 15 min) and cell ascorbate was completely consumed by 2 hr of incubation. In contrast, cellular alpha-tocopherol levels were stable for the first 30 min, but were depleted in association with the onset of lipid peroxidation. Supplementation of 0.1 or 1.0 mM ascorbic acid in the incubation medium delayed the onset of diquat-induced alpha-tocopherol loss, lipid peroxidation and cytotoxicity. When the concentration of exogenous cellular ascorbic acid was consumed to below that of endogenous ascorbic acid, alpha-tocopherol loss and lipid peroxidation were initiated. The results indicate that untreated hepatocytes have an effective multicomponent antioxidant system against diquat-induced oxidative stress. However, when glutathione is depleted from hepatocytes by treatment with BCNU and diquat, ascorbic acid plays a vital role in maintaining cellular alpha-tocopherol levels and survival of the cell.

Animals↗

Studies on the ameliorating effect of ascorbic acid on mineral toxicities in the chick.

The effect of dietary ascorbic acid on the toxicity of high levels of cobalt, selenium, vanadium, cadmium, copper, and mercury was determined in chicks. The vitamin reduced the growth retardation caused by cobalt, selenium, vanadium, and cadmium administration but had no such effect on copper and mercury toxicity at the levels used. The effect of ascorbic acid on growth could not be mimicked by ferrous iron administration. Ascorbic acid did not alleviate the increased susceptibility of chicks to Salmonella gallinarum caused by feeding high levels of these elements.

Animals↗

Modulation of neurosteroid synthesis/accumulation by L-ascorbic acid in rat brain tissue: inhibition by selected serotonin antagonists.

We have investigated the possibility that the synthesis/accumulation of neurosteroids, i.e., brain-produced steroids putatively endowed with modulatory actions in the CNS, is regulated by monoaminergic receptor-mediated mechanisms. In minces of rat brain cortex, L-ascorbic acid concentration-dependently (0.07-1.0 mM) increases the levels of pregnenolone, allotetrahydrodeoxycorticosterone, and dehydroepiandrosterone. This effect of L-ascorbic acid is region-dependent: in hippocampus, progesterone and allopregnanolone are also increased, whereas dehydroepiandrosterone is unchanged, and in corpus striatum only progesterone is increased significantly. 5-Hydroxytryptamine (10 microM), 1-(3-chlorophenyl)piperazine (1.0 microM), and 5-methoxytryptamine (0.4 microM) mimic the effect of L-ascorbic acid, whereas a pretreatment with p-chlorophenylalanine (400 mg/kg i.p., 2 days) reduces the amplitude of the L-ascorbic acid effect on brain cortical neurosteroids. The effect of L-ascorbic acid is blocked by the nonselective serotonin antagonists methiothepin, clozapine, methysergide, and pizotifen, but not mesulergine, spiperone, MDL 72222, and DL-propranolol, nor by the catecholaminergic receptor antagonists prazosin and S(-)-sulpiride. L-Ascorbic acid is not additive with dibutyryl-cyclic AMP and, furthermore, the inhibition of adenylate cyclase by MDL 12330A, but not of phospholipase C by U-73122, markedly attenuates the L-ascorbic acid-induced increase of pregnenolone in rat brain cortical minces. Together these data suggest that L-ascorbic acid plays a role in the modulation of neurosteroidogenesis, presumably by favoring the activation of the purported serotonin type 6 receptor by endogenous serotonin.

Adenylyl Cyclase Inhibitors↗

Effect of dietary ascorbic acid on the incidence of spontaneous mammary tumors in RIII mice.

A study of the effect of different amounts of L-ascorbic acid (vitamin C), between 0.076% and 8.3%, contained in the food has been carried out with ten groups of RIII mice (seven ascorbic acid and three control groups), with 50 mice in each group. With an increase in the amount of ascorbic acid there is a highly significant decrease in the first-order rate constant for appearance of the first spontaneous mammary tumor after the lag time to detection by palpation. There is also an increase in the lag time. The mean body weight and mean food intake were not significantly different for the seven ascorbic acid groups. Striking differences were observed between the 0.076% ascorbic acid and the control groups (which synthesize the vitamin): smaller food intake, decreased lag time, and increased rate constant of appearance of the first mammary tumor. This comparison cannot be made experimentally for guinea pigs and primates because the control groups would develop scurvy.

Animals↗

Effects of seasonings on the stability of ascorbic acid in a cooking model system.

The thermolability of ascorbic acid (AA) in aqueous solution at 100 degrees C was assessed in the presence of various seasonings commonly used in Japanese-style cooking. A model system approximated Japanese cooking with regard to the concentrations of AA and seasonings and the heating time. The decrease of AA in the reaction system of this experiment was a first-order reaction with respect to the concentration of AA loss. Although kinetic constants for AA loss decreased with increasing concentrations of AA (25-400 microg/mL), the absolute amounts degraded were almost the same for all AA concentrations, suggesting that dissolved oxygen is one of main factors affecting the stability of AA solutions during heating at 100 degrees C. When each seasoning was added to AA solution, salt stabilized AA and Japanese alcohol-containing admixtures, such as sake and sweet sake (mirin), did not have a significant effect on the stability. Conversely, soy sauce, miso (fermented soybean paste) and broth powder from skipjack accelerated the decrease of AA in a concentration-dependent manner. The kinetic study suggested that oxygen was rapidly consumed and AA loss accelerated by addition of soy sauce or miso to AA solution. Consequently it is likely that a reaction mechanism shifts from aerobic to anaerobic and the forward reactions proceed. Of the constituents of Japanese seasonings, not only iron but also amino acids are involved in the acceleration of AA degradation. The presence of amino acids should be taken into account when considering the levels of AA in soups.

Amino Acids↗

Interaction of ascorbic acid and glucose on production of collagen and proteoglycan by fibroblasts.

Collagen and proteoglycans are two major constituents of the extracellular matrix, and their abnormalities have been incriminated in the pathogenesis of diabetic complications. A decrease of plasma ascorbic acid has been reported in diabetes and thus may play a role in the collagen and proteoglycan abnormalities in diabetes. Ascorbic acid and glucose share structural similarity, and their metabolism may interact at the level of membrane transport and cellular action. In this study, we used a fibroblast culture system to explore this possibility. Ascorbic acid increased collagen and proteoglycan both in the culture medium and the cell layer. This stimulatory action of ascorbic acid was inhibited by the presence of glucose at a concentration of 25 mM. The effect of high glucose concentration was not mediated by inhibition of ascorbic acid uptake by fibroblasts. Insulin is able to abolish this inhibitory action of glucose on collagen production, but the precise mechanism is unclear. These results show that the high glucose concentration in diabetes can impair the action of ascorbic acid at the cellular level. This may further accentuate the problem of decreased availability of this vitamin as a result of its low plasma concentration.

Amino Acids↗

Influence of oral contraceptives on ascorbic acid and triglyceride status.

The overall purpose of this study was to determine the influence of oral contraceptive agents on ascorbic acid and triglyceride status of young women by measurement of plasma and whole blood ascorbate and serum triglycerides on three days during one oral contraceptive or menstrual cycle. The subjects' food intake records were evaluated to determine the relationship between dietary intake and ascorbic acid blood levels. Results indicate that, with adequate intake of ascorbic acid, there in no threat to ascorbic acid status as a result of using oral contraceptives for periods of six months to seven years. Although bordering on being significant, the serum triglycerides did not appear to be alarmingly elevated.

Adult↗

Chronic oral ascorbic acid therapy worsens skeletal muscle metabolism in patients with chronic heart failure.

BACKGROUND: Chronic heart failure (CHF) is associated with abnormalities of skeletal muscle metabolism. This may be due to impaired oxygen delivery as a result of endothelial dysfunction. AIMS: We postulated that ascorbic acid would improve oxygen delivery to exercising muscle and improve skeletal muscle metabolism. METHODS: We studied skeletal muscle metabolism using (31)P magnetic resonance spectroscopy in 39 CHF patients. Endothelial function was assessed by changes in pulse wave velocity. Subjects were randomised to receive 4 g ascorbic acid daily for 4 weeks in a placebo-controlled double-blind study. RESULTS: Ascorbic acid significantly increased phosphocreatine utilization during exercise. In addition, glycolytic ATP synthesis increased in the ascorbic acid group (change in rate of ATP synthesis at 1 min -0.21+/-0.76 with placebo, 2.06+/-0.60 following ascorbic acid; p<0.05). Phosphocreatine and ADP recovery after exercise were not changed. The fall in pulse wave velocity during reactive hyperaemia was increased by ascorbic acid from -6.3+/-2.6% to -12.1+/-2.0% (p<0.05). CONCLUSIONS: These findings suggest that ascorbic acid increased both phosphocreatine utilization and glycolytic ATP synthesis during exercise in patients with CHF implying worsened skeletal muscle metabolism despite improvements in endothelial function.

Adenosine Triphosphate↗

Serum alpha-tocopherol and ascorbic acid concentrations in Type 1 and Type 2 diabetic patients with and without angiopathy.

BACKGROUND: Alpha-tocopherol and ascorbic acid form a part of scavenger system influencing the level of oxidative stress in diabetes mellitus. The aim of this study was to evaluate serum concentrations of alpha-tocopherol and ascorbic acid in Type 1 and Type 2 diabetes mellitus and to compare them with the presence of vascular complications as well as with oxidative stress and endothelial dysfunction. METHODS: A total of 38 Type 1 and 62 Type 2 diabetic patients were subdivided into those with and without angiopathy. Serum alpha-tocopherol and ascorbic acid concentrations were estimated in all patients and in 38 healthy persons. Their results were compared with diabetes control, with oxidative stress measured by plasma malondialdehyde and with endothelial dysfunction estimated by serum N-acetyl-beta-glucosaminidase activity. In addition, the differences in biochemical variables were compared between patients with and without angiopathy. RESULTS: Serum alpha-tocopherol related to the sum of cholesterol and triglyceride concentrations (AT/CHT ratio) was significantly lower in diabetic patients with macroangiopathy than in those without vascular changes (p<0.05). Serum ascorbic acid levels were significantly lower only in Type 2 diabetic patients with macroangiopathy as compared with healthy controls as well as with patients without vascular disease (p<0.01). Positive relationship was observed between serum alpha-tocopherol and cholesterol or triglyceride concentrations in both Type 1 and Type 2 diabetic patients. The presence of oxidative stress together with endothelial dysfunction measured by N-acetyl-beta-glucosaminidase activity was accompanied by lower AT/CHT ratio (p<0.005) in Type 2 diabetic patients. CONCLUSION: Diabetic patients with proven angiopathy or with advanced oxidative stress and endothelial dysfunction have significantly lower AT/CHT ratio and ascorbic acid concentration in serum. Their low concentrations may participate at the increased level of oxidative stress in these individuals.

Acetylglucosamine↗

Ascorbic acid absorption in humans: a comparison among several dosage forms.

There have been few studies conducted to determine the efficiency of ascorbic acid absorption in humans. Differences in the extent of its absorption among individuals may contribute to the outcome of clinical trials. Ascorbic acid absorption in four subjects was investigated from several oral dosage forms containing 1 g of the vitamin (solution, tablet, chewable tablet, and timed-release capsule. Approximately 85% of an intravenous dose was recovered in the urine as ascorbic acid and its major metabolites. In contrast, only approximately 30% of the dose was recovered from the solution and tablet forms. A considerably smaller fraction of the dose (approximately 14%) was recovered from the timed-release capsule. There was considerable intersubject variation in ascorbic acid absorption and there appeared to be good and poor absorbers of the vitamin. Consideration should be given to the influence of the extent of ascorbic acid absorption on the results of clinical trails.

Adult↗

High plasma ascorbic acid levels in premature neonates with intraventricular hemorrhage.

The accumulation of ascorbic acid in the brain by active transport establishes a high brain-plasma gradient of the vitamin. An insult to the CNS may result in an efflux of ascorbate into the circulation with a consequent rise of plasma levels. We measured plasma ascorbic acid levels in premature neonates on days 1, 3, and 5 of life, and the infants underwent ultrasonographic examination to detect intracranial hemorrhage. Neonates with intraventricular hemorrhage sustained significantly higher plasma ascorbate levels than their controls. Infants with massive bleeding had higher levels than those with a smaller hemorrhage. These results suggest that an efflux of ascorbic acid into the circulation occurs secondary to intracranial hemorrhage.

Apgar Score↗

Reduced viability of vascular endothelial cells by high concentration of ascorbic acid in vitreous humor.

Normal mammalian vitreous humor maintains its avascularity after regression of hyaloid vessels. Neovascularization in adults is only detected under pathological conditions which suggests that antiangiogenic factors are present in the vitreous humor. To elucidate the mechanism of vitreal angiogenic inhibition, we investigated the effect of vitreous humor on cultured vascular endothelial cells. When bovine aortic endothelial cells were cultured in the presence of bovine vitreous humor in medium, a decrease in cell viability was observed within 24 h. Ascorbic acid from vitreous humor has been identified as a cell death inducing factor with high performance liquid chromatography (HPLC) and molecular mass analysis. Ascorbic acid reduced endothelial cell viability at concentrations normally present in vitreous humor. This effect was completely inhibited by antioxidants, N-acetylcysteine and catalase. Amongst the ascorbic acid derivatives tested, ascorbic acid 2-phosphate did not induce cell death, suggesting that the production of ascorbyl radical is required for induction of cell death. Furthermore, capillary formation in three-dimensional collagen gel cultures characteristic of vascular endothelial cells were disrupted in the presence of ascorbic acid. Since ascorbic acid is highly concentrated in ocular tissues, especially in vitreous humor, it may function as a neovascularization inhibitor.

Acetylcysteine↗

Effect of ascorbic acid on the intragastric environment in patients at increased risk of developing gastric cancer.

Ascorbic acid has been shown to decrease nitrosation in vivo, and epidemiological data suggest that the consumption of foods rich in this vitamin is associated with a reduced risk for gastric cancer. In order to study this suggestion further, fasting gastric juice samples were obtained from 62 high-risk patients (seven with atrophic gastritis, ten with pernicious anaemia, ten with partial gastrectomy, 21 with vagotomy and drainage and 14 with highly selective vagotomy), before, during four weeks' treatment with 1 g ascorbic acid four times daily, and four weeks after treatment. Samples were analysed for pH, total and nitrate-reducing bacterial counts, nitrite and N-nitroso compounds. Treatment with ascorbic acid lowered the median pH only in the vagotomized patients (p less than 0.001) but resulted in a reduction in median nitrate-reducing bacterial counts and in nitrite and N-nitroso compound concentrations in all groups, except for an increase in the nitrate-reducing bacterial count in atrophic gastritis patients and in nitrite in those with pernicious anaemia. These data suggest that treatment with a high dose of ascorbic acid reduces the intragastric formation of nitrite and N-nitroso compounds.

Adult↗

[Catalytic kinetic spectrophotometric determination of trace ascorbic acid].

In this paper, a new catalytic kinetic spectrophotometric method for the determination of trace amounts of ascorbic acid has been studied. The method is based on the activation effect of ascorbic acid on vanadium (V) catalyzed oxidation of deoxidized rhodamine B by potassium bromate in weak acidic medium at pH 4.5. The optimal experimental conditions have been discussed. The absorbance was measured at 555 nm. The linear range of the method was 0-7.0 microg x mL(-1). The detection limit for ascorbic acid was 2.5 x 10(-7) g x L(-1). The method has been applied to the determination of ascorbic acid in vitamin C tablet and tomato with satisfactory results.

Ascorbic Acid↗