ascorbic-acid and Metaplasia

Intestinal metaplasia (IM) of the stomach is a risk factor in developing intestinal-type gastric cancer and hence the question of reversibility is vital. There is emerging epidemiological evidence that with long term follow up, IM may be reversible although a combination of antioxidant agents and eradication of H pylori may be necessary to achieve this. The pathogenesis of IM is currently being elucidated and it is likely that a combination of bacterial, host, and environmental factors will be shown to lead to IM. In assessing gastric cancer risk, histochemical typing of IM will most probably be replaced by molecular markers.

Topics: Alleles; Anti-Bacterial Agents; Ascorbic Acid; CDX2 Transcription Factor; Helicobacter Infections; Helicobacter pylori; Homeodomain Proteins; Humans; Intestines; Metaplasia; Microsatellite Repeats; Precancerous Conditions; Risk; Smoking; Stomach; Stomach Neoplasms; Trans-Activators

In the 1-year double-blind placebo-controlled intervention trial, it was shown that daily supplementation of patients with gastric premalignant lesions (intestinal metaplasia, IM) with a complex, containing Ester-C with antioxidantsand (2100 mg of Ca-ascorbate + 340 mg of bioflavonoids), produced a sharp decrease of abnormally high ornithine decarboxylase activity in IM gastric mucosa that was accom panied by practically total IM regression in 11 of 18 (61%) patients.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; Chronic Disease; Double-Blind Method; Female; Gastric Mucosa; Gastritis, Atrophic; Helicobacter Infections; Humans; Intestines; Male; Metaplasia; Middle Aged; Ornithine Decarboxylase

Intestinal type metaplasia plays a role in intestinal type gastric carcinoma development. Ascorbic acid demonstrates a protective effect against gastric carcinogenesis, due to its ability to inactivate oxygen free-radicals as well as its nitrite-scavenging effects.. To assess whether long-term ascorbic acid administration following Helicobacter pylori eradication could affect intestinal metaplasia regression in the stomach.. Sixty-five patients were included in the study. The inclusion criterion was the presence of intestinal metaplasia on the gastric mucosa after H. pylori eradication. An upper gastrointestinal endoscopy was performed and 3 biopsy specimens were taken in the antrum, 3 in the gastric body, and 2 in the incisura angularis. Patients were randomized to receive 500 mg of ascorbic acid o.d., after lunch (32 patients) for 6 months or no treatment (33 patients). All patients underwent to endoscopic control at the end of the 6 months.. H. pylori infection recurrence was detected in 6 (9.4%) patients (three from each group), and these patients were excluded from further analysis. We were unable to find evidence of intestinal metaplasia in any biopsied site of the gastric mucosa in 9/29 (31%) patients from the ascorbic acid group and in 1/29 (3.4%) of the patients from the control group (P=0.006). Moreover, a further six (20.7%) patients from the ascorbic acid group presenting chronic inactive pangastritis with widespread intestinal metaplasia at entry, showed less extensive antritis with intestinal metaplasia at control, whilst a similar finding was only seen in one patient from the control group (P=0.051).. The administration of ascorbic acid significantly helps to resolve intestinal metaplasia of the gastric mucosa following H. pylori eradication, and its use as a chemoprevention treatment should be considered.

Topics: Adult; Aged; Ascorbic Acid; Female; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Intestinal Diseases; Male; Metaplasia; Middle Aged; Prospective Studies; Recurrence; Stomach Diseases

A randomized chemoprevention trial on precancerous lesions of the stomach is being conducted in Tachira State, Venezuela. The aims of the study are to evaluate the efficacy of vitamin supplementation in preventing the progression rate of precancerous lesions. Here we report on the pilot phase of the study in which two antioxidant preparations were evaluated on their ability to raise antioxidant levels in plasma and in gastric juice. The study aimed also to determine the antibiotic sensitivity profiles of Helicobacter pylori isolates prevalent in the area. Forty-three subjects with precancerous lesions (chronic gastritis, chronic atrophic gastritis, intestinal metaplasia and dysplasia) of the stomach were randomized to one of two antioxidant treatments. Treatment 1 (250 mg of standard vitamin C, 200 mg of vitamin E and 6 mg of beta-carotene three times a day) or treatment 2 (150 mg of standard vitamin C, 500 mg of slow release vitamin C, 75 mg of vitamin E and 15 mg of beta-carotene once a day) for 7 days. Blood levels of total vitamin C, beta-carotene and alpha-tocopherol and gastric juice levels of ascorbic acid and total vitamin C were measured before and after treatment on day 8. Both treatments increased the plasma levels of total vitamin C, beta-carotene and alpha-tocopherol/cholesterol but not those of ascorbic acid or total vitamin C in gastric juice. Treatment 1 was the best choice and resulted in a greater increase in the plasma levels of beta-carotene and alpha-tocopherol. H. pylori was cultured from 90% of the gastric biopsies; 35 isolates were identified which were highly resistant to metronidazole, a front-line antibiotic recommended against H. pylori in other settings.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; beta Carotene; Carotenoids; Chemoprevention; Chronic Disease; Disease Progression; Female; Gastric Juice; Gastritis; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metaplasia; Middle Aged; Pilot Projects; Precancerous Conditions; Stomach Neoplasms; Venezuela; Vitamin E; Vitamins

Ascorbic acid, the reduced form of vitamin C, may protect against gastric cancer and is secreted by the normal stomach. Secretion is impaired in Helicobacter pylori (H pylori) associated chronic gastritis. This study examined if eradication of H pylori improves gastric juice ascorbate values. Fasting gastric juice and plasma samples were collected at endoscopy from patients participating in trials of H pylori eradication for duodenal ulcer disease and intestinal metaplasia before and up to 15 months after attempted eradication. Ascorbic acid and total vitamin C concentrations were determined by high performance liquid chromatography. In 12 patients in whom H pylori was successfully eradicated gastric juice ascorbate and total vitamin C concentrations and the ratio of juice to plasma vitamin C rose after treatment. Analysis after treatment suggested that the rise was greatest in patients with high final plasma vitamin C concentrations, even though these did not change with treatment. By contrast, in 22 patients in whom H pylori eradication was unsuccessful there were no significant changes in juice or plasma concentrations after treatment. It is concluded that successful eradication of H pylori improves secretion of vitamin C into gastric juice. It is speculated that this increases protection against gastric cancer.

Topics: Aged; Ampicillin; Anti-Ulcer Agents; Ascorbic Acid; Drug Therapy, Combination; Duodenal Ulcer; Fasting; Follow-Up Studies; Gastric Juice; Helicobacter Infections; Helicobacter pylori; Humans; Intestines; Male; Metaplasia; Metronidazole; Organometallic Compounds; Oxytetracycline; Treatment Outcome

Studies have suggested that the dietary intake of antioxidant vitamins, such as vitamin C and vitamin E, has a potential role in inhibiting gastric carcinogenesis. The present study investigated the effect of antioxidant vitamins on the incidence of gastric intestinal metaplasia (GIM).. This study included 67,657 Koreans free of GIM who periodically underwent health check-ups. Dietary intake was assessed by a semiquantitative food frequency questionnaire based on the Korean National Health and Nutrition Examination Survey. Participants were categorized into 4 groups by quartiles of dietary vitamin C and vitamin E intake. The Cox proportional hazard assumption was used to determine the multivariable hazard ratio (HR) and 95% confidence interval (95% CI) for GIM.. The third and fourth quartiles of vitamin C intake had a lower risk of GIM than the first quartile (multivariable-adjusted HR, 0.95; 95% CI, 0.88 to 1.03 in the second quartile, HR, 0.88; 95% CI, 0.81 to 0.97 in the third quartile, and HR, 0.85; 95% CI, 0.76 to 0.95 in the fourth quartile). Vitamin E intake greater than the second quartile level was significantly associated with a lower risk of GIM than the first quartile (multivariable-adjusted HR, 0.90; 95% CI, 0.82 to 0.97 in the second quartile, HR, 0.90; 95% CI, 0.82 to 0.99 in the third quartile, and HR, 0.83; 95% CI, 0.74 to 0.94 in the fourth quartile). This association was observed only in the subgroup analysis for men.. Higher dietary intake of vitamin C and vitamin E was associated with a lower risk of GIM.

Topics: Antioxidants; Ascorbic Acid; Diet; Eating; Humans; Male; Metaplasia; Nutrition Surveys; Republic of Korea; Risk Factors; Vitamin A; Vitamin E; Vitamins

Many epidemiological studies show the benefit of fruits and vegetables on reducing risk of lung cancer, the leading cause of cancer death in the United States. Previously, we demonstrated that cigarette smoke exposure (SM)-induced lung lesions in ferrets were prevented by a combination of low dose of β-carotene, α-tocopherol (AT), and ascorbic acid (AA). However, the role of a combination of AT and AA alone in the protective effect on lung carcinogenesis remains to be examined. In the present study, we investigated whether the combined AT (equivalent to ∼100 mg/day in the human) and AA (equivalent to ∼210 mg/day) supplementation prevents against SM (equivalent to 1.5 packs of cigarettes/day) induced lung squamous metaplasia in ferrets. Ferrets were treated for 6 weeks in the following three groups (9 ferrets/group): (i) Control (no SM, no AT+AA), (ii) SM alone, and (iii) SM+AT+AA. Results showed that SM significantly decreased concentrations of retinoic acid, AT, and reduced form of AA, not total AA, retinol and retinyl palmitate, in the lungs of ferrets. Combined AT+AA treatment partially restored the lowered concentrations of AT, reduced AA and retinoic acid in the lungs of SM-exposed ferrets to the levels in the control group. Furthermore, the combined AT+AA supplementation prevented SM-induced squamous metaplasia [0 positive/9 total ferrets (0%) vs. 5/8 (62%); p<0.05] and cyclin D1 expression (p<0.05) in the ferret lungs, in which both were positively correlated with expression of c-Jun expression. Although there were no significant differences in lung microsomal malondialdehyde (MDA) levels among the three groups, we found a positive correlation between MDA levels and cyclin D1, as well as c-Jun expressions in the lungs of ferrets. These data indicate that the combination of antioxidant AT+AA alone exerts protective effects against SM-induced lung lesions through inhibiting cyclin D1 expression and partially restoring retinoic acid levels to normal.

Topics: alpha-Tocopherol; Animals; Antioxidants; Ascorbic Acid; Cyclin D1; Dietary Supplements; Ferrets; Genes, jun; Keratins; Lung; Malondialdehyde; Metaplasia; Microsomes; Proliferating Cell Nuclear Antigen; Respiratory Mucosa; Retinoids; Smoke; Smoking

Antioxidants may protect against the development of esophageal adenocarcinoma. Blood samples and endoscopic biopsies (squamous, Barrett's, and gastric mucosa) were obtained from 48 Barrett's esophagus (BE) patients, while 48 age- and sex-matched controls provided blood samples only. Plasma concentrations of vitamins A, C, and E were measured in all subjects, while vitamin C was measured in relation to the type of mucosa. Plasma total vitamin C level, but not vitamin A or E, was lower in BE patients compared to controls (P = 0.014). Tissue levels of total vitamin C were significantly lower in Barrett's compared with squamous mucosa (P = 0.047). A positive association was observed between plasma vitamin C and dietary intake of vitamin C, while there was an inverse association with alcohol consumption. The lower levels of vitamin C in plasma of BE patients and in Barrett's mucosa compared with squamous mucosa are consistent with oxidative stress being of importance in the pathogenesis and neoplastic progression of BE.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; Barrett Esophagus; Case-Control Studies; Diet; Esophagus; Female; Gastric Mucosa; Humans; Male; Metaplasia; Middle Aged; Vitamin A; Vitamin E

To investigate the effect of vitamin C and E supplementation in the levels of nitrite, nitric oxide (NO) related metabolite, and ocular surface parameters in diabetic patients.. 50 patients with non-insulin dependent diabetes mellitus were given vitamin C (1000 mg/day) and vitamin E (400 IU/day) supplementation for 10 days. Nitrite levels in tears were measured by photometric determination before and after vitamin supplementation. Tear function parameters (Schirmer test I, BUT, ocular ferning test) and brush cytology analysis of the conjunctival epithelium were also evaluated.. Nitrite levels were found to be significantly reduced (p<0.05) after 10 days of vitamin C and E supplementation. Improved values for Schirmer test, BUT test, and ocular ferning test were also found. Goblet cell density and grading of squamous metaplasia showed a significant improvement.. Oxidative stress and free radical production are elevated in diabetes mellitus. Antioxidants, such as vitamin C and vitamin E, probably have an important role in reducing the oxidative damage produced by nitric oxide and other free radicals and improving the ocular surface milieu.

Topics: Administration, Oral; Aged; Ascorbic Acid; Conjunctiva; Diabetes Mellitus, Type 2; Female; Humans; Male; Metaplasia; Middle Aged; Nitric Oxide; Nitrites; Tears; Vitamin E

Topics: Achlorhydria; Ascorbic Acid; beta Carotene; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Metaplasia; Phenotype; Precancerous Conditions; Remission Induction; Stomach Neoplasms; Treatment Outcome

Latent scurvy is characterized by a reversible atherosclerosis that closely resembles the clinical form of this disease. Acute scurvy is characterized by microvascular complications such as widespread capillary hemorrhaging. Vitamin C (ascorbate) is required for the synthesis of collagen, the protein most critical in the maintenance of vascular integrity. We suggest that in latent scurvy, large blood vessels use modified LDL--in particular lipoprotein(a)--in addition to collagen to maintain macrovascular integrity. By this mechanism, collagen is spared for the maintenance of capillaries, the sites of gas and nutrient exchange. The foam-cell phenotype of atherosclerosis is identified as a mesenchymal genetic program, regulated by the availability of ascorbate. When vitamin C is limited, foam cells develop and induce oxidative modification of LDL, thereby stabilizing large blood vessels via the deposition of LDL. The structural similarity between vitamin C and glucose suggests that hyperglycemia will inhibit cellular uptake of ascorbate, inducing local vitamin C deficiency.

Topics: Animals; Arteriosclerosis; Ascorbic Acid; Collagen; Diabetes Complications; Diabetes Mellitus; Foam Cells; Humans; Hyperglycemia; Lipoprotein(a); Metaplasia; Models, Biological; Scurvy

This study aimed to identify the factors associated with the development of gastric precancerous changes, in a prospective series of patients undergoing endoscopy. Risk factors and associated mucosal changes were evaluated in 134 endoscoped patients affected by chronic non-atrophic (n = 76) or atrophic gastritis (CAG) (n = 32), with or without intestinal metaplasia (IM), or lacking any major histological changes (n = 26). The following variables were taken into account: age, alcohol consumption, smoking habit, vitamin C intake (using a questionnaire), gastric juice vitamin C (HPLC on gastric juice samples obtained at endoscopy), H. pylori infection, gastric mucosa malondialdehyde (MDA; a measure of free radical production) and extent of CAG in gastric biopsies (only for IM). Tissue MDA levels were significantly higher, and vitamin C levels significantly lower in CAG and IM patients (P = 0.01). Multiple regression analysis showed significant correlations for: CAG vs age (P < 0.02), MDA (< 0.02) and gastric vitamin C (< 0.05); IM vs age (P < 0.0005), CAG (< 0.0005) and MDA (< 0.001). Using stepwise discrimination analysis, the independent variables included in the model were: for CAG, age (P < 0.003), MDA (< 0.05), gastric juice vitamin C (< 0.05); for IM, CAG (P < 0.0005), age (< 0.001), MDA (< 0.03) and vitamin C intake (< 0.05). H. pylori was not included. The major determinants for CAG and IM were age, free radical production (as measured by MDA), vitamin C (for CAG) and vitamin C intake and CAG (for IM).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Ascorbic Acid; Chronic Disease; Female; Gastric Juice; Gastric Mucosa; Gastritis, Atrophic; Humans; Intestines; Male; Malondialdehyde; Metaplasia; Middle Aged; Prospective Studies

The effects of four fruit juices, processed vegetable juice, orange peel, green tea and low dose vitamin C on endogenous N-nitrosation in 86 subjects from a high-risk area for gastric cancer in Moping County, China were studied using urinary excretion of N-nitrosoproline (NPRO) as an indicator. After ingestion of 300 mg L-proline, urinary excretion of NPRO was significantly increased from a baseline of 2.5 +/- 1.6 micrograms/day to 8.7 +/- 6.2 micrograms/day. (P < 0.001). Vitamin C (75 mg) administration significantly reduced NPRO formation (62.3%, P < 0.002) although NPRO excretion remained higher than the baseline level (4.2 +/- 1.3 vs 2.2 +/- 1.2 micrograms/day, P < 0.001). Intake of fruit juices and green tea extracts (containing 75 mg vitamin C) or of orange peel powder (containing 3 mg vitamin C) together with 300 mg L-proline inhibited NPRO formation effectively to the baseline level or to levels significantly lower than the baseline level (P < 0.05-0.005). A processed juice of a number of vegetables (300 ml) significantly catalysed endogenous nitrosation (14.7 +/- 11.8 vs 9.4 +/- 4.7 micrograms/day, P < 0.05). Endogenous N-nitrosation was unaffected by the presence of intragastric lesions. The present study shows that endogenous nitrosation in this population is profoundly affected by environmental factors and that inhibitors, such as vitamin C, alpha-tocopherol and other non-nutritive compounds in the foods do inhibit endogenous nitrosation either synergistically or in an additive manner. The significance of fruits and vegetables in prevention of human cancers is discussed.

Topics: Ascorbic Acid; Beverages; China; Citrus; Female; Fruit; Gastric Mucosa; Gastritis; Humans; Male; Metaplasia; Middle Aged; Nitrosamines; Precancerous Conditions; Proline; Risk Factors; Stomach Neoplasms; Tea; Vegetables

A case-control study has been carried out on 129 patients with newly diagnosed intestinal metaplasia (IM) recruited in four UK centres (London, Slough, Stoke and Glasgow). Serum assays of a range of vitamins demonstrated that 38% of IM patients had serum ascorbic acid levels below the detection levels compared with only 16% of controls free of chronic gastric lesions; this difference was also seen in the patients from the individual centres. There were no major differences between cases and controls in any other serum vitamin levels measured (carotene, tocopherol or the ratio of tocopherol to cholesterol). Comparison of the healthy asymptomatic controls suggested that the intakes of ascorbic acid and of beta-carotene were much higher in southern England than in Stoke or Glasgow. The tocopherol status in the four centres tended to be more similar.

Topics: Adult; Ascorbic Acid; Carotenoids; Case-Control Studies; Cholesterol; England; Female; Gastroscopy; Humans; London; Male; Metaplasia; Middle Aged; Scotland; Stomach; Vitamin A; Vitamin E

To determine the relevance of gastric juice factors to gastric carcinogenesis, 56 patients with unoperated stomachs undergoing endoscopy for dyspepsia had gastric juice aspirated and analysed for pH, ascorbic acid, total bile acids, nitrite, nitrate and total nitroso compounds (NOCs). Plasma was obtained for vitamin C estimation. Antral and body biopsies were assessed for gastritis, Helicobacter pylori, atrophy and intestinal metaplasia (IM). Patients with chronic atrophic gastritis (n = 17) had lower gastric juice ascorbic acid concentrations (P less than 0.001), higher pH (P less than 0.05) and higher incidence of H. pylori infection (P less than 0.001) than normal subjects (n = 12). Patients with reflux gastritis (n = 9) had higher total bile acids (P less than 0.01). Patients with chronic gastritis and IM (n = 11) had higher gastric juice pH (P less than 0.01) and total bile acid concentrations (P less than 0.05), and lower gastric ascorbic acid concentrations (P less than 0.01) than those with chronic gastritis and no IM (n = 24). In chronic gastritis, high nitrite concentrations were associated with high pH (P less than 0.01). However, there were no significant differences in plasma vitamin C or gastric nitrite, nitrate or total NOC concentrations in relation to gastric histology. We conclude that the premalignant condition IM is associated with H. pylori infection, low gastric ascorbic acid levels and elevated total bile acids, but not to elevation in nitrite or total NOCs in fasting gastric juice.

Topics: Adult; Aged; Aged, 80 and over; Ascorbic Acid; Atrophy; Bile Acids and Salts; Gastric Juice; Gastric Mucosa; Humans; Intestines; Metaplasia; Middle Aged; Nitrates; Nitrites; Nitroso Compounds; Precancerous Conditions; Stomach; Stomach Neoplasms

As part of an ongoing cohort study of gastric cancer precursors in Nariño, Colombia, blood levels of ascorbic acid, vitamin E, retinol, pre-albumin, retinol binding protein and carotenoids were measured and correlated with histopathologic findings of gastric biopsies. Carotene levels in both sexes and vitamin E levels in males were significantly lower in subjects with gastric dysplasia than in subjects with normal mucosa and subjects with less advanced gastric lesions (chronic atrophic gastritis and intestinal metaplasia). No other significant correlations were found.

Topics: Adolescent; Adult; Age Factors; Aged; Ascorbic Acid; Carotenoids; Female; Gastric Mucosa; Gastritis; Humans; Male; Metaplasia; Middle Aged; Prealbumin; Retinol-Binding Proteins; Sex Factors; Stomach Diseases; Stomach Neoplasms; Vitamin A; Vitamin E; Vitamins

L-ascorbic acid has been shown to reduce the elevated level of urinary chemiluminescence found in patients with bladder cancer. Thus, it has been suggested that vitamin C might be efficacious in bladder tumor prophylaxis. However, there is no clinical evidence to support this thesis. We evaluated whether L-ascorbic acid given concomitantly with the urinary carcinogen FANFT was capable of reducing the incidence of subsequent bladder tumors. No inhibitory effect was observed. Unless evidence is obtained demonstrating bladder tumor prevention by L-ascorbic acid its routine administration to patients with bladder cancer is not indicated.

Topics: Animals; Ascorbic Acid; Carcinogens; Carcinoma, Transitional Cell; Drug Evaluation; Formamides; Metaplasia; Mice; Mice, Inbred C3H; Nitrofurans; Precancerous Conditions; Thiazoles; Urinary Bladder; Urinary Bladder Neoplasms

Topics: Ascorbic Acid; Bone Diseases; Child; Humans; Male; Metaplasia; Radiography