ascorbic-acid and Achlorhydria

Free radicals and reactive species produced in vivo can trigger cell damage and DNA modifications resulting in carcinogenesis. Dietary antioxidants trap these species limiting their damage. The present study evaluated the role of vitamins C and E in the prevention of potentially premalignant modifications to DNA in the human stomach by supplementing patients who, because of hypochlorhydria and possible depletion of gastric antioxidants, could be at increased risk of gastric cancer. Patients undergoing surveillance for Barrett's oesophagus (n 100), on long-term proton pump inhibitors were randomized into two groups: vitamin C (500 mg twice/d) and vitamin E (100 mg twice/d) for 12 weeks (the supplemented group) or placebo. Those attending for subsequent endoscopy had gastric juice, plasma and mucosal measurements of vitamin levels and markers of DNA damage. Seventy-two patients completed the study. Plasma ascorbic acid, total vitamin C and vitamin E were elevated in the supplemented group consistent with compliance. Gastric juice ascorbic acid and total vitamin C levels were raised significantly in the supplemented group (P=0.01) but supplementation had no effect on the mucosal level of this vitamin. However, gastric juice ascorbic acid and total vitamin C were within normal ranges in the unsupplemented group. Mucosal malondialdehyde, chemiluminescence and DNA damage levels in the comet assay were unaffected by vitamin supplementation. In conclusion, supplementation does not affect DNA damage in this group of patients. This is probably because long-term inhibition of the gastric proton pump alone does not affect gastric juice ascorbate and therefore does not increase the theoretical risk of gastric cancer because of antioxidant depletion.

Topics: Achlorhydria; Adult; Aged; Antacids; Antioxidants; Ascorbic Acid; Barrett Esophagus; Cell Transformation, Neoplastic; Dietary Supplements; DNA Damage; Female; Gastric Acidity Determination; Gastric Juice; Gastric Mucosa; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Precancerous Conditions; Proton Pump Inhibitors; Stomach Neoplasms; Vitamin E

Topics: Achlorhydria; Anemia, Hypochromic; Anemia, Pernicious; Ascorbic Acid; Chemical Precipitation; Gastric Juice; Humans; Intestinal Absorption; Iron; Iron Chelating Agents; Iron Isotopes; Radiometry

pH-dependent drug-drug interactions (DDIs) with poorly soluble, weakly basic drugs may lead to clinical implications. Dasatinib is a tyrosine kinase inhibitor with reduced absorption in patients on acid-reducing agents (ARAs). The objective of this study is to investigate the influence of gastric pH on dasatinib supersaturation and determine if vitamin C (L-ascorbic acid) can improve dasatinib concentrations under simulated hypochlorhydric gastric conditions.. A dynamic, in vitro, multi-compartment, simulated stomach duodenum (SSD) model mimicking fluid volumes and transfer rates was used to investigate the concentration of BCS class IIb drugs versus time curves. Dasatinib and lamotrigine were explored under normal, fasted, simulated gastric fluids (pH 2) (FaSGF), hypochlorhydric simulated gastric fluids (pH 4.5) (FaSGF. Significant supersaturation of dasatinib was observed in the duodenum compartment of the SSD model in FaSGF. A 90% reduction in dasatinib AUC. The SSD model serves as a good in vitro tool for assessing the effect of pH-dependent DDIs on bioavailability of weakly basic drugs with solubility/ dissolution limited absorption. Vitamin C provides a promising approach for improving bioavailability of poorly soluble, weakly basic drugs in hypochlorhydric patients.

Topics: Achlorhydria; Administration, Oral; Ascorbic Acid; Dasatinib; Duodenum; Humans; Hydrogen-Ion Concentration; Lamotrigine; Protein Kinase Inhibitors; Reducing Agents; Solubility

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

Topics: Achlorhydria; Adult; Aged; Ascorbic Acid; Blood Coagulation Tests; Extremities; Glomerular Filtration Rate; Hematoma; Hemorrhage; Humans; Male; Middle Aged; Oral Hemorrhage; Scurvy

Topics: Achlorhydria; Anemia; Ascorbic Acid; Blood Transfusion; Folic Acid; Geriatrics; Humans; Scurvy; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Achlorhydria; Alcoholism; Ascorbic Acid; Blood Chemical Analysis; Ethanol; Hemoglobins; Humans; Hydrochloric Acid; Intestinal Absorption; Iron; Iron Isotopes; Statistics as Topic

Topics: Achlorhydria; Ascorbic Acid; Blood Chemical Analysis; Humans; Hydrochloric Acid; Intestinal Absorption; Intestine, Small; Intestines; Liver Cirrhosis; Metabolism; Vitamins

Topics: Achlorhydria; Ascorbic Acid; Body Fluids; Gastrectomy; Gastric Juice; Humans; Peptic Ulcer; Vitamins

Topics: Achlorhydria; Anemia; Anemia, Hypochromic; Ascorbic Acid; Gastrectomy; Humans; Iron; Vitamins

Topics: Achlorhydria; Ascorbic Acid; Gastrectomy; Humans; Peptic Ulcer; Vitamins

Topics: Achlorhydria; Aged; Anemia; Ascorbic Acid; Hematologic Diseases; Humans; Iron; Polycythemia Vera; Vitamin B 12