Abstract: This study reports the effect of paraquat (PQ) on concentrations of four elements (Cu, Fe, Mg, Zn) in lung, kidney, spleen, liver, and heart of male osteogenic disorder Shionogi (ODS) rats, a strain not able to synthesize vitamin C. PQ significantly increased the Cu concentrations in lung, liver, and plasma, accompanied by a fall in renal levels. Fe levels were elevated in liver and spleen but lowered in plasma. PQ produced an increase in kidney Mg and a rise in liver Mg and Zn levels. Cardiac elemental levels were not affected by PQ treatment. PQ, a known oxidant, produced changes in tissue elements involved in antioxidant mechanisms.
Notes: Department of Legal Medicine, Hamamatsu University School of Medicine, Japan. kminakat@hama-med.ac.jp.
Abstract: PURPOSE: To examine the relation between serum ascorbic acid (SAA), a marker of dietary intake (including supplements), and cause-specific mortality. SUBJECTS AND METHODS: We analyzed data from a probability sample of 8,453 Americans age > or = 30 years at baseline enrolled in the Second National Health and Nutrition Examination Survey (NHANES II), who were followed for mortality endpoints. We calculated relative hazard ratios as measures of disease association comparing the mortality rates in three biologically relevant SAA categories. RESULTS: Participants with normal to high SAA levels had a marginally significant 21% to 25% decreased risk of fatal cardiovascular disease (CVD) (p for trend = 0.09) and a 25% to 29% decreased risk of all-cause mortality (p for trend <0.001) compared to participants with low levels. Because we determined that gender modified the association between SAA levels and cancer death, we analyzed these associations stratified by gender. Among men, normal to high SAA levels were associated with an approximately 30% decreased risk of cancer deaths, whereas such SAA levels were associated with an approximately two-fold increased risk of cancer deaths among women. This association among women persisted even after adjustment for baseline prevalent cancer and exclusion for early cancer death or exclusion for prevalent cancer. CONCLUSIONS: Low SAA levels were marginally associated with an increased risk of fatal CVD and significantly associated with an increased risk for all-cause mortality. Low SAA levels were also a risk factor for cancer death in men, but unexpectedly were associated with a decreased risk of cancer death in women. If the association between low SAA levels and all-cause mortality is causal, increasing the consumption of ascorbic acid, and thereby SAA levels, could decrease the risk of death among Americans with low ascorbic acid intakes.
Notes: General Internal Medicine Section, Veterans Affairs Medical Center, San Francisco, California 94121, USA. jasimon@itsa.ucsf.edu.
Abstract: Efforts are made to find therapeutic agents capable of minimizing genotoxicity of various natural and man-made compounds. The genotoxicity induced by mercury compounds remains controversial. Therefore we have investigated the genotoxic effect of mercuric chloride (MC; HgCl(2)) at three concentrations (1.052, 5.262 and 10.524 microM) and role of L-ascorbic acid (vitamin C) at a concentration of 9.734 microM on MC-treated short-term human leucocyte cultures. We assessed the proliferative rate index (PRI), sister chromatid exchange (SCE) and chromosomal aberrations (CAS) in control and MC-treated cultures with and without vitamin C supplementation. The results showed that MC has no effect on cell-cycle kinetics, but the frequency of SCE/cell was significantly higher in a dose-dependent manner than control values. HgCl(2) also significantly induced C-anaphases (abnormal mitosis) in blood cultures. These effects were prevented by the addition of vitamin C to MC-treated cultures. The data indicate the mutagenic activity of MC and the protective role of vitamin C on mercury-induced genotoxicity in human blood cultures is probably due to its strong antioxidant and nucleophilic nature.
Notes: Cytogenetics Laboratory, Department of Zoology, University School of Sciences, Gujarat University, 380009, Ahmedabad, India.
Abstract: Scurvy has been known since ancient times, but the discovery of the link between the dietary deficiency of ascorbic acid and scurvy has dramatically reduced its incidence over the past half-century. Sporadic reports of scurvy still occur, primarily in elderly, isolated individuals with alcoholism. The incidence of scurvy in the pediatric population is very uncommon, and it is usually seen in children with severely restricted diets attributable to psychiatric or developmental problems. The condition is characterized by perifollicular petechiae and bruising, gingival inflammation and bleeding, and, in children, bone disease. We describe a case of scurvy in a 9-year-old developmentally delayed girl who had a diet markedly deficient in vitamin C resulting from extremely limited food preferences. She presented with debilitating bone pain, inflammatory gingival disease, perifollicular hyperkeratosis, and purpura. Severe hypertension without another apparent secondary cause was also present, which has been previously undescribed. The signs of scurvy and hypertension resolved after treatment with vitamin C. The diagnosis of scurvy is made on clinical and radiographic grounds, and may be supported by finding reduced levels of vitamin C in serum or buffy-coat leukocytes. The response to vitamin C is dramatic. Clinicians should be aware of this potentially fatal but easily curable condition that is still occasionally encountered among children.
Notes: Department of Paediatrics, Hospital for Sick Children and University of Toronto, Toronto, Canada. michael.weinstein@sickkids.on.ca.
Abstract: Authors revealed considerable decrease substance of vitamins at patients with chronic tonsillitis in depending on degree of difficulty illness and presence of complication. Content of vitamins B1, B2 and C is decreased more than rest. Results of immune investigations register lowering phagocytic activity of leucocyte and cell immunity at patient with chronic tonsillitis in the presence of the complication.
Notes: Katedra Laryngologii Akademii Medycznej w Grodnie, Bialorus.
Abstract: To investigate the effects of ascorbic acid deficiency on the pathogenesis of hypertension and/or its complications, we established a rat strain with both genetic hypertension and a defect of ascorbic acid biosynthesis. The od gene (L-gulono-gamma-lactone oxidase gene) of the ODS (Osteogenic Disorder Shionogi) rat, which is a rat mutant unable to synthesize ascorbic acid, was introduced into spontaneously hypertensive rats (SHR), and a novel congenic strain, SHR-od, was established. SHR-od showed scurvy when fed an ascorbic acid-free diet. Systolic blood pressure of male SHR-od began to increase at 9 weeks of age and reached 190-200 mmHg at 20 weeks of age. In 25-week-old SHR-od, ascorbic acid deficiency when fed an ascorbic acid-free diet for 6 weeks caused a remarkable reduction of blood pressure to lower than 110 mmHg. The wall to lumen ratio of the testicular artery in ascorbic acid-deficient SHR-od was lower than that of the control rats. When rats were fed a diet supplemented with ascorbic acid (300 mg/kg), ascorbic acid concentration in SHR-od was lower in the serum and liver than that in ODS rats. These results indicate that ascorbic acid could be closely related to the development of hypertension in SHR-od. We believe that SHR-od will be a useful model for experimental studies on hypertension and its complications, since all of them suffer from hypertension spontaneously and the level of ascorbic acid deficiency in these rats could be controlled at will both in concentration and duration.
Notes: Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Japan. horiof@agr.nagoya-u.ac.jp.
Abstract: The effects of ascorbate and alpha-tocopherol as antioxidants and as co-operative factors against NADPH-dependent lipid peroxidation in human placental mitochondria have been studied. The addition of ascorbate at low concentration (up to 50 microM) to the NADPH-generating system resulted in increasing lipid peroxidation and Fe3+ to Fe2+ reduction. High concentration of ascorbate (150 microM), which produced maximal rate of ascorbate-dependent lipid peroxidation, was found to inhibit almost completely NADPH-dependent lipid peroxidation by maintaining too much iron in its reduced form. Either stimulatory or inhibitory effect of ascorbate on NADPH-dependent lipid peroxidation depends on the appropriate Fe3+/Fe2+ ratio. Alpha-tocopherol caused a decrease of NADPH-dependent lipid peroxidation, inhibiting completely this process at 150 microM concentration. The inhibitory effect of alpha-tocopherol increased rapidly with the increasing ascorbate concentration, almost complete inhibition of NADPH-dependent lipid peroxidation being obtained at 25 microM alpha-tocopherol and 50 microM ascorbate. This strong inhibitory combined effect of alpha-tocopherol and ascorbate was independent of the Fe3+/Fe2+ ratio, as alpha-tocopherol is not able to reduce Fe3+ to Fe2+ under the conditions employed. These findings suggest that antioxidant effects of ascorbate in placental mitochondria are mediated by recycling of alpha-tocopherol rather than by strong reduction of Fe3+ to Fe2+. On the basis of the results obtained, we assume that adequate concentrations of alpha-tocopherol and ascorbate in placental tissue may prevent the release of lipid peroxide from placental mitochondria and therefore could be protective against the development of preeclampsia.
Notes: Department of Biochemistry, Medical University of Gdansk, Faculty of Pharmacy, Poland.
Abstract: OBJECTIVES: To investigate the association between prediagnostic plasma ascorbic acid concentrations and subsequent breast cancer risk in a nested case-control study. METHODS: Female volunteer residents of Washington County, MD, donated 14,625 non-fasting blood samples in 1989. Incident breast cancer cases (n = 115) and controls (n = 115) were matched by age, menopausal status at donation, and date and hour of blood donation. RESULTS: Median ascorbic acid concentrations were similar between cases and controls (1.44 mg/dl vs. 1.39 mg/dl. p = 0.78). There was no evidence for a dose-response relationship between higher plasma ascorbic acid concentrations and breast cancer risk [highest vs. lowest fifths: ORadjusted = 0.90, Ptrend = 0.98). CONCLUSIONS: Findings from this prospective study do not suggest a protective association between prediagnostic plasma ascorbic acid concentrations and breast cancer risk in the subsequent 5 years of follow-up.
Notes: Department of Epidemiology, Johns Hopkins University, School of Hygiene and Public Health, Baltimore, MD 21205, USA.
Abstract: Placebo-controlled trials have shown that vitamin C supplementation decreases the duration and severity of common cold infections. However, the magnitude of the benefit has substantially varied, hampering conclusions about the clinical significance of the vitamin. In this paper, 23 studies with regular vitamin C supplementation (> or = 1 g/day) were analyzed to find out factors that may explain some part of the variation in the results. It was found that on average, vitamin C produces greater benefit for children than for adults. The dose may also affect the magnitude of the benefit, there being on average greater benefit from > or = 2 g/day compared to 1 g/day of the vitamin. In five studies with adults administered 1 g/day of vitamin C, the median decrease in cold duration was only 6%, whereas in two studies with children administered 2 g/day the median decrease was four times higher, 26%. The trials analyzed in this work used regular vitamin C supplementation, but it is conceivable that therapeutic supplementation starting early at the onset of the cold episode could produce comparable benefits. Since few trials have examined the effects of therapeutic supplementation and their results have been variable, further therapeutic trials are required to examine the role of vitamin C in the treatment of colds.
Notes: Department of Public Health, University of Helsinki, Finland.
Abstract: BACKGROUND: An ever increasing demand to evaluate the effect of dietary supplements on specific health conditions by use of a "significant scientific" standard has prompted the publication of this study. OBJECTIVE: To study the effect of megadose Vitamin C in preventing and relieving cold and flu symptoms in a test group compared with a control group. DESIGN: Prospective, controlled study of students in a technical training facility. SUBJECTS: A total of 463 students ranging in age from 18 to 32 years made up the control group. A total of 252 students ranging in age from 18 to 30 years made up the experimental or test group. METHOD: Investigators tracked the number of reports of cold and flu symptoms among the 1991 test population of the facility compared with the reports of like symptoms among the 1990 control population. Those in the control population reporting symptoms were treated with pain relievers and decongestants, whereas those in the test population reporting symptoms were treated with hourly doses of 1000 mg of Vitamin C for the first 6 hours and then 3 times daily thereafter. Those not reporting symptoms in the test group were also administered 1000-mg doses 3 times daily. RESULTS: Overall, reported flu and cold symptoms in the test group decreased 85% compared with the control group after the administration of megadose Vitamin C. CONCLUSION: Vitamin C in megadoses administered before or after the appearance of cold and flu symptoms relieved and prevented the symptoms in the test population compared with the control group.
Abstract: The plasma vitamin levels are discussed in association with human diabetic condition. 1) Plasma vitamin B1 level of diabetic patients is revealed in the state of marginal deficiency. 2) Vitamin B6, as the coenzyme pyridoxal phosphate, plays an important role in the metabolism of carbohydrates, therefore B6 has been associated with impairments in gluconeogenesis and abnormal glucose intolerance. 3) Vascular complications of diabetes mellitus, such as atherosclerosis and retinopathy are considered to be related with glycation of low density lipoprotein which induces oxidative injuries to vascular endothelium. Administration of vitamins to diabetic patients reduces insulin requirement and attracts much attention for improvement of vascular complications. Vitamins play as not only nutritional supplements for deficiency, but pharmacological agents for treatment.
Notes: Department of Pediatrics, Osaka Medical College.
Abstract: Plasma chemistry and haematological studies were conducted on chickens with coccidiosis. Male White Leghorn chickens, of two weeks old, were inoculated with 5 x 10(4) Eimeria tenella sporulated oocysts or with 1 x 10(6) E acervulina sporulated oocysts. Blood samples were taken four, seven and 11 days after inoculation. A wet chemistry system was applied to measure the plasma activities of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma glutamyltransferase, creatine kinase, amylase and lactate dehydrogenase and the concentrations of creatine, total bilirubin, urate, total cholesterol, total protein, albumin, glucose and triglycerides. A dry chemistry system was applied to measure sodium, potassium, chloride and calcium. The number of red blood cells and packed cell volume were determined by a micro cell counter and blood pH was measured with a blood gas analyser. The erythrocyte count, packed cell volume, sodium and chloride levels in the chickens infected with E tenella were significantly (P < 0.05) lower than those of the uninfected controls. The significant decrease in blood pH of the chickens infected with E acervulina suggests malabsorption associated with duodenal lesions induced by the infection.
Notes: Department of Veterinary Medicine, College of Agriculture, Osaka Prefecture University, Japan.
Abstract: BACKGROUND: Many studies describe the protective role of vitamin C (ascorbic acid) against cancer development and in treatment of established cancer. The present study investigated whether ascorbic acid demonstrates a therapeutic benefit for prostate cancer. METHODS: Androgen-independent (DU145) and androgen-dependent (LNCaP) human prostate cancer cell lines were both treated in vitro with vitamin C (0-10 mM). Cell counts, cell viability, and thymidine incorporation into DNA were determined. RESULTS: Treatment of DU145 and LNCaP cells with vitamin C resulted in a dose- and time-dependent decrease in cell viability and thymidine incorporation into DNA. Vitamin C induced these changes through the production of hydrogen peroxide; addition of catalase (100-300 units/ml), an enzyme that degrades hydrogen peroxide, inhibited the effects of ascorbic acid. Superoxide dismutase, an enzyme that dismutates superoxide and generates hydrogen peroxide, did not prevent decreases in cell number and DNA synthesis, suggesting further the involvement of hydrogen peroxide in vitamin C-induced changes. These results clearly indicate that reactive oxygen species (ROS) are involved in vitamin C-induced cell damage. However, that singlet oxygen scavengers such as sodium azide and hydroquinone and hydroxyl radical scavengers such as D-mannitol and DL-alpha-tocopherol did not counteract the effects of ascorbic acid on thymidine incorporation suggests that vitamin C-induced changes do not occur through the generation of these ROS. CONCLUSIONS: Vitamin C inhibits cell division and growth through production of hydrogen peroxide, which damages the cells probably through an as yet unidentified free radical(s) generation/mechanism. Our results also suggest that ascorbic acid is a potent anticancer agent for prostate cancer cells.
Notes: Division of Urologic and Transplantation Surgery, University of Massachusetts Medical Center, Worcester 01655, USA.
Abstract: The high levels of ascorbic acid (vitamin C) which are maintained in the gastric mucosa and in normal gastric juice suggest that the vitamin has a metabolic role within the stomach. Epidemiological associations between foods containing vitamin C and a reduced risk of gastric cancer together with the ability of ascorbate to quench the mutagenic activity of reactive species produced in the gastric environment, indicate a potential role in the prevention of carcinogenesis. This short review assess the balance of the current evidence and indicates that gastric ascorbate could provide some protection against the development of gastric cancer. However, it is only depletion of ascorbate from the gastric lumen that is likely to contribute significantly to increased risk of malignancy.
Abstract: Carcinogenesis by 4-nitroquinoline-1-oxide (NQO) in the oral mucosa is a reliable method of obtaining oral mucosal squamous cell carcinoma (OMSCC) and allows examination of various stages of oral cancer development. In vivo and in vitro studies have indicated that L-ascorbic acid (AA) may have a role in cancer prevention. The Wistar "scurvy-prone" osteogenic disorder Shionogi (ODS) rat of the od/od substrain is unable to synthesize AA and requires supplementation for its survival. This study examined the effects of NQO on the oral mucosa of ODS and outbred Wistar rats. NQO (0.5%) was applied topically to the palatal mucosa of 72 male ODS and 36 outbred Wistar rats three times weekly for 4, 8, 12, 16, 20, and 24 wks. The ODS rats were divided so that 36 rats were given 2.5 g/l AA in the drinking water and 36 rats were given 0.33 g/l AA. Vehicle-treated and untreated control animals were included. The rats were killed two weeks after the final NQO application, and the tissues were examined. Epithelial dysplasia was assessed using a modified Smith and Pindborg (1969) index. The ordered categorical scores were analyzed appropriately. Plasma AA levels were checked in ODS and outbred rats at the start and end of the experiment. The results indicated that the oral mucosa of the ODS and outbred rats were susceptible to NQO but that the rate of dysplasia and OMSCC development differed between them, with more rapid changes being found in the ODS rats (p < or = 0.05). No significant difference was found in the dysplasia scores and in the rate of OMSCC development between ODS rats given 2.5 g/l of AA and ODS rats given 0.33 g/l of AA (p > 0.05). No epithelial changes were observed in the palatal mucosa of vehicle-treated and untreated controls. The plasma AA level mean (+/- SEM) was 56 +/- 6 microM for the outbred rats, 8 +/- 1 microM for the ODS rats given 0.33 g/l AA supplementation, and 29 +/- 2 microM for the ODS rats given 2.5 g/l AA. It was concluded that the chronic AA-deficient state in ODS rats played an insignificant role in oral carcinogenesis and that other factors, for example, genetic differences in susceptibility to NQO, contributed to the present findings.
Notes: Oral Medicine and Surgery Research Unit, School of Dental Science, University of Melbourne, Victoria, Australia.
Abstract: Wistar Shionogi rats of the (od/od) substrain with the osteogenic disorder are unable to synthesize L-ascorbic acid (L-AA) and appear to be an appropriate animal model for studying the effect of L-AA in carcinogenesis. To determine the minimal L-AA requirements of these animals for prolonged survival in a satisfactory physical condition during experimentation, four concentrations of L-AA (0.33 g/l, 0.67 g/l, 1.67 g/l and 3.33 g/l) were administered via drinking water to four groups of animals (n = 2). Their water intake per cage was recorded three times weekly and the plasma L-AA levels were determined at the start, after 2, 4, 8 and 12 weeks and at the termination of the experiment. To simulate the procedures to be undertaken in oral mucosal carcinogenesis experiments, the animals were gently restrained and a designated amount of sterile NaCl was applied to the palatal mucosa three times a week for 26 weeks. The L-AA supplement group with the lowest concentration (0.33 g/l L-AA) achieved mean plasma levels of 7 +/- 1.38 microM, approximately one-eighth that of the normal level (mean plasma L-AA level in outbred Wistar rats was found to be 58 +/- 3 microM) whilst those in the higher supplement group (3.33 g/l L-AA) achieved a mean of 18 +/- 1.25 microM. All of the animals employed in the present study survived for 26 weeks and showed no clinical signs of L-AA deficiency during this period.
Notes: Oral Medicine & Surgery Research Unit, School of Dental Science, University of Melbourne, Australia.
Abstract: In 1971, Linus Pauling carried out a meta-analysis of four placebo-controlled trials and concluded that it was highly unlikely that the decrease in the "integrated morbidity of the common cold" in vitamin C groups was caused by chance alone (P < 0.00003). Studies carried out since then have consistently found that vitamin C (> or = 1 g/d) alleviates common cold symptoms, indicating that the vitamin does indeed have physiologic effects on colds. However, widespread conviction that the vitamin has no proven effects on the common cold still remains. Three of the most influential reviews drawing this conclusion are considered in the present article. Two of them are cited in the current edition of the RDA nutritional recommendations as evidence that vitamin C is ineffective against colds. In this article, these three reviews are shown to contain serious inaccuracies and shortcomings, making them unreliable sources on the topic. The second purpose is to suggest possible conceptual reasons for the persistent resistance to the notion that vitamin C might have effects on colds. Although placebo-controlled trials have shown that vitamin C does alleviate common cold symptoms, important questions still remain.
Notes: Department of Public Health, University of Helsinki, Finland.
Abstract: Rats with hereditary defects in ascorbic acid (AsA) synthesis (ODS rats) subjected to AsA-deficiency for 3 weeks showed reductions of plasma alkaline phosphatase and dry and ash weights of the tibia, but no body weight alteration. In accordance with the chemical changes, bone loss and decrease of bone formation by AsA deficiency but not by malnutrition were observed in contact microradiographs of the tibia and by a tetracycline double labeling technique, respectively. The mechanical properties of femora measured by a three point-bending procedure were also altered by AsA deficiency for 3 weeks and showed decreases of 59% in toughness, 32% in strength, 32% in ductility and 22% in stiffness. The biomechanical changes by AsA deficiency were greater than the chemical changes in bone, indicating the usefulness of measuring mechanical properties as a sensitive method for the evaluation of the bone status. The second moment of the area of the femur was not changed by AsA deficiency. These results suggest that AsA deficiency in ODS rats causes marked bone loss and reduction in bone formation, which is accompanied by a greater reduction in biomechanics of the femur without causing macroarchitectural changes.
Notes: Department of Pharmacology, School of Dentistry, Aichi-Gakuin University, Nagoya, Japan.
Abstract: Non-transferrin-bound iron (NTBI) uptake occurs in a variety of cells by a saturable, specific and temperature-sensitive process. Our previous studies indicated that NTBI uptake by cardiac myocytes and Hep G2 cells was reversibly up-regulated by iron deposition. In the present work we have characterized this up-regulation and examined its mechanism by comparing the uptake of oxidized (Fe3+) and ascorbate-reduced (Fe2+) forms of iron. Iron loading markedly enhanced the uptake of iron both in the presence and absence of ascorbate, but the increment was greater when ascorbate was absent. This up-regulation is partially inhibited by actinomycin D and cycloheximide, indicating a requirement for protein synthesis. Uptake by the iron-loaded cells was less sensitive to thiol-alkylating agents and competing metal ions, but was more sensitive to proteolysis. Iron loading causes an increase in both Km and Vmax for uptake of both Fe2+ and Fe3+, although the values differ, suggesting distinct rate-limiting steps for uptake of Fe2+ and Fe3+. Consistent with this idea, uptake of the two ions showed differential sensitivity to thiol reagents, competing metal ions and monensin. The Fe(2+)-specific chelators bathophenanthroline disulfonate and ferrozine markedly inhibited iron uptake whether ascorbate was present or not, indicating that Fe3+ uptake is dependent on reduction to the ferrous state. This requirement for reduction was independent of the iron status of the cells, demonstrating that the process of up-regulation is not due to the appearance of a new mechanism for translocation of Fe3+ without reduction. Taken together, the evidence favors a model of NTBI transport where an obligate and rate-determining reduction of Fe3+ occurs prior to or during uptake, followed by translocation through an Fe2+ carrier. The distinct translocation mechanisms of uptake in the presence and absence of ascorbate suggest that exogenous Fe2+ does not access the carrier available to the nascent ferrous ion derived from the reductase and is consistent with close coupling between the reduction and the translocation processes. In iron-loaded cells with increased rates of NTBI transport, a similar mechanism prevails.
Notes: Department of Clinical Biochemistry, University of Toronto, Ontario, Canada.
Abstract: We compared the intake and functional levels of vitamins B6, C and B1 in 15 pairs of Alzheimer's disease and normal subjects. These were similar in both groups, except that B1 had lower functional values for the subjects with Alzheimer's disease. This suggests that it is unlikely that B6 or C could be used in the treatment of Alzheimer's disease. The role of B1 needs further exploration.
Notes: Department of Psychiatry, University Hospital, University of British Columbia, Vancouver.
Abstract: Epidemiological studies have shown that diets rich in one or more antioxidant nutrients may reduce the risk of cancers of the lung, uterine cervix, mouth, and gastrointestinal tract. Study of premalignant lesions offers a comparatively expedient approach to identifying and evaluating the efficacy of the cancer chemopreventive components of foods. Some recent findings suggest roles for beta-carotene and/or vitamin C in reversing or reducing the risk of cervical dysplasia and oral leukoplakia. There are some indications that vitamin C and beta-carotene may reduce the risk of atrophic gastritis and gastric cancer. Additional epidemiological and molecular biology studies and clinical intervention trials using premalignant lesions as the marker of specific cancer risks should become an important component of future research in the area of cancer chemoprevention.
Notes: Department of Clinical Nutrition, Hoffmann-La Roche, Inc., Nutley, NJ 07110-1199.
Abstract: Supplementation with 1 g of vitamin C (ascorbic acid) per day decreased the amount of chromosome damage induced in lymphocytes by an exposure to bleomycin during the last 5 h of cell culture. We did not see such changes in lymphocytes from control individuals samples at the same time but not taking vitamin C supplements. This bleomycin assay has been proposed as a test for cancer susceptibility. A similar assay for genetic instability may be useful in detecting heterozygotes for chromosome-breakage syndromes (for example, Fanconi anemia or ataxia telangiectasia). Even though our sample size is small and our results should be interpreted cautiously, statistically significant effects were found with vitamin C supplementation. It would, therefore, be prudent to consider dietary and perhaps other lifestyle factors when interpreting of results from this bleomycin assay and related assays for genetic instability.
Notes: Genetics Branch, Centers for Disease Control, Atlanta, GA 30333.
Abstract: Colostrum-fed, colostrum-deprived, and colostrum-fed and colostrum-deprived calves fed ascorbic acid (1.75 g/d) in whole, raw milk to 6 wk of age were sampled from 0 to 8 wk of age in order to determine whether ascorbate supplementation would increase plasma Ig concentrations, antibody response to immunization, and disease resistance. Plasma IgG concentrations were lower at 14 and 28 d of age in calves fed ascorbate compared with plasma concentrations in calves not receiving ascorbate supplementation, irrespective of colostrum feeding. Colostrum feeding had no effect on antibody titer to keyhole limpet hemocyanin at any age, but ascorbate-supplemented calves had lower plasma antibody titers to keyhole limpet hemocyanin at 35 and 56 d of age. Calves fed ascorbate had lower clinical scores for diarrhea. Dietary ascorbate does not appear to be immunostimulatory in dairy calves to 56 d of age and appeared to inhibit antibody synthesis. However, at 14 d of age there was an interaction of ascorbate supplementation and colostrum feeding; plasma IgG concentrations were higher in colostrum-deprived calves fed ascorbate then in colostrum-deprived calves not fed ascorbate.
Notes: Department of Animal and Dairy Sciences, College of Agriculture, Auburn University 36849.
Abstract: The effect of exogenous ascorbic acid intake on biosynthesis of ascorbic acid in mice has been studied. After the mice were on diets containing added ascorbic acid for two months, the activities of ascorbic acid synthesizing enzymes in the mouse liver homogenates were measured using L-gulono-gamma-lactone as a substrate. Exogenous ascorbic acid intake (0.5, 1 or 5% in the diet) was able to increase the concentration of ascorbic acid in the blood and to decrease the activities of ascorbic acid synthesizing enzymes in mouse liver. The results suggest that ascorbic acid synthesis was controlled by local regulatory mechanism or by the concentration of ascorbic acid in the hepatic portal blood. Ingestion of dietary erythorbic acid, a stereoisomer of ascorbic acid, had no effect on the activities of ascorbic acid synthesizing enzymes.
Notes: Linus Pauling Institute of Science and Medicine, Palo Alto, California 94306.
Abstract: L-Gulono-gamma-lactone oxidase, one of the microsomal flavin enzymes, catalyzes the last step of L-ascorbic acid biosynthesis in many animals; however, it is missing in scurvy-prone animals such as humans, primates, and guinea pigs. A cDNA clone for this enzyme was isolated by screening a rat liver cDNA expression library in lambda gt11 using antibody directed against the enzyme. The cDNA clone contained 2120 nucleotides and an open reading frame of 1320 nucleotides encoding 440 amino acids of the protein with a molecular weight of 50,605. The amino-terminal sequence (residues 1-33) of the enzyme isolated from rat liver completely coincided with the corresponding part of the deduced amino acid sequence. The identity of the cDNA clone was further confirmed by the agreement of the composition of the deduced amino acids with that determined by amino acid analysis of the enzyme. Hydropathy analysis of the deduced amino acid sequence revealed several hydrophobic regions, suggesting that they anchor the protein into the microsomal membrane. The deduced amino acid sequence showed no obvious homology with the flavin-binding regions of other eight flavoenzymes.
Notes: Institute of Applied Biochemistry, Yagi Memorial Park, Gifu, Japan.
Abstract: A group of 30 coal-tar workers was treated with 1 g of ascorbic acid (AA) orally five times a week for 3 months. The effect of this treatment was assessed on serum IgG, IgM, IgA, alpha 1-antitrypsin, prealbumin, orosomucoid, transferrin, alpha 2-macroglobulin, C-reactive protein, ceruloplasmin, the latex fixation test and cancer serum index (CSI). After 3 months treatment the concentration of AA in the blood increased from 9.52 to 60.75 mumol l-1 (i.e. from 0.15 to 1.07 mg 100 ml-1), prealbumin increased from 0.37 +/- 0.08 g l-1 to 0.48 +/- 0.08 g l-1 (P less than 0.01), CSI decreased from 2.28 +/- 0.88 to 1.76 +/- 0.50 (P less than 0.01) and alpha 2-macro-globulin decreased from 3.40 +/- 0.95 to 2.06 +/- 0.39 g l-1 (P less than 0.01). These findings, together with reports that AA is a strong stimulator of xenobiotics biotransformation in the liver, support the use of AA as a prophylactic agent for coal-tar exposed workers.
Abstract: The regulatory role of ascorbic acid in norepinephrine biosynthesis was studied using digitonin-permeabilized chromaffin cells. When permeabilized chromaffin cells were incubated with [3H]3,4-dihydroxyphenylethylamine ([3H]dopamine) in calcium-free medium, the amounts of radioactive dopamine and norepinephrine measured in the cell fraction were increased as a function of incubation time and dopamine concentration. Both the accumulation of dopamine and the formation of norepinephrine were shown to require the presence of Mg-ATP in the medium. These results indicate that the permeabilization of chromaffin cells by digitonin treatment does not disrupt the functions of chromaffin granules, including dopamine uptake, norepinephrine formation, and storage of these amines. Using this permeabilized cell system, the effect of ascorbic acid on the rates of dopamine uptake and hydroxylation was investigated. The formation of norepinephrine was stimulated by ascorbic acid at concentrations of 0.5-2 mM in the presence of Mg-ATP. By contrast, dopamine uptake was not affected by the presence or absence of ascorbic acid in the medium. These findings provide evidence that ascorbic acid may stimulate the conversion of dopamine to norepinephrine by increasing dopamine beta monooxygenase activity rather than by increasing the substrate supply of dopamine. These observations also suggest that the rate of norepinephrine biosynthesis in adrenal medullary cells may be regulated by the concentration of ascorbic acid within the cell cytoplasm.
Abstract: More research is needed to draw definitive conclusions on the relationship between vitamin C intake and cancer, but the following general statements can be made. The effectiveness of megadoses (greater than 1 gm/day) of vitamin C for the cure or prevention of cancer is still unproven; in fact, the safety of megadoses is still in question. Therefore, they are not recommended for the general public at present and, if used at all, should be used under medical supervision. Epidemiologic evidence suggests that vitamin C-rich foods may be beneficial in preventing cancer, and their consumption should be encouraged as a measure to reduce the incidence of cancer. Well-controlled studies should be undertaken to elucidate the relationship between vitamin C and cancer, using both vitamin-containing foods and vitamin C supplements at different intake levels.
Abstract: The ascorbic acid plays an important part by activation of hydroxylation reactions in various biosyntheses, such as in that of tropocollagen, bile acids and carnitine. It also considerably participates in the detoxication of compounds by hydroxylation and in the maintenance of the cytochrome P 450 contents in the liver. A sufficient supply is of importance for the absorption and accumulation of iron as well as for the efficiency of the immune system. After application of 14C-labelled ascorbic acid the compound is retained mainly in the brain, the salivary glands, the adrenal glands, the testes and in the eye lens. The largest contents of ascorbic acid lies in the pituitary gland, in the adrenal glands and in the eye lens. The need of ascorbic acid varies in man in dependence upon the state of development and the loads between 30 and 60 mg/die. In great smokers, after operations and traumas as well as when infections are present the intake of 100 to 200 mg a day are recommended. When more 1 g a day are taken the utilization decreases, the decomposition and the excretion, respectively, increase. A dose of more than 2 g a day inhibits the phagocytosis activity of leucocytes.
Abstract: Levels of certain metabolites of peroxidation of lipids such as diene conjugates malonic dialdehyde, ascorbic acid, dehydroascorbic acid and diketogulonic acid were compared in 39 cases of gastric ulcer, 25 patients with gastric cancer and 14 healthy subjects. Diene conjugates and malonic dialdehyde levels appeared to be increased in cases of gastric ulcer and cancer. This was matched by a decrease in ascorbic acid and dehydroascorbic acid levels. Ulcer patients revealed enhanced diketogulonic acid concentration.
Abstract: Immunological studies are reported showing that ascorbic acid, like selected sulfhydryl inhibitors, can induce immunity against some cancers in mice. Accompanying this immunizing action are changes in the surface structure of the cancer cells, as revealed by scanning electron microscopy. Electron spin resonance measurements show that the ascorbate anion free radical is readily produced in oxygenated cancer tissue and that this radical can react with sulfhydryl groups which are free radical scavengers. It is proposed that ascorbate acts as an effective thiolprive in oxygenated cancer tissues. This action is thought to lead to the observed changes in the cancer cell surface structure and to the concomitant immunological response.
Abstract: Purified commercial hyaluronic acid contains significant amounts of iron. Addition of Fe2+ to solutions of it causes depolymerization, which is inhibited by catalase and scavengers of the hydroxyl radical (. OH) but not by superoxide dismutase. Fe3+ is ineffective. Ascorbic acid also depolymerizes hyaluronic acid, apparently because it can reduce Fe3+ in the reaction mixtures to Fe2+. Ascorbate-induced depolymerization is inhibited by the specific iron chelator desferrioxamine, by catalase, and by scavengers of the hydroxyl radical. The relevance of these observations to rheumatoid arthritis and inflammatory joint diseases is discussed.
Abstract: In view of recent evidence that activation of prostaglandin endoperoxide synthetase by lipid peroxides may relate to the ability of such peroxides to reduce heme, we tested other activators of this enzyme. Epinephrine, norepinephrine, ascorbic acid and tryptophan were all found to reduce Fe3+-heme to Fe2+-heme, though tryptophan was considerably weaker than the others. We suggest that reduction of heme by these compounds might account for their ability to reduce the lag phase on addition of substrate to the enzyme. Epinephrine was assessed for its effects on the lag phase in activation of soybean lipoxygenase and was found to cause a similar reduction of the lag phase of this related enzyme. These findings support the concept that reduction of Fe3+-heme to Fe2+-heme is critical to activation of both the prostaglandin endoperoxide synthetase and soybean lipoxygenase enzymes, and that mechanisms involved in regulation of the valence of iron are important for regulating enzyme activity.
Abstract: 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.
Notes: Lady Sobell Gastrointestinal Unit, Wexham Park Hospital, Slough, Berks, UK.
