The transport of vitamin C and effects of disease.
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Biomedical subjects
Publications and source records attributed to C J Schorah.
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N-nitroso compounds (NOC) are strongly implicated in the causation of cancer of the stomach and it has been suggested that ascorbic acid might reduce the risk of gastric cancer by preventing their formation within gastric juice. However, until recently there have been no measurements of gastric juice ascorbic acid concentrations. We have measured both gastric juice ascorbic and total vitamin C (ascorbic acid and dehydroascorbic acid). Our findings suggest that ascorbic acid is secreted into the gastric lumen so that gastric juice concentrations are often greater than those in plasma. Gastric pathology affects this secretion, leading to values in gastric juice that are lower than plasma levels. Stimulation of gastric secretion does not raise vitamin C concentrations in individuals whose values are initially low. The role of ascorbic acid in preventing formation of NOC and protecting against gastric cancer is discussed in the light of these findings.
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.
The symptomatology of a case of acute infection with Helicobacter pylori is described, together with the accompanying changes in gastric mucosal histology, local and systemic humoral immune response, and gastric ascorbic acid concentration. The patient was an endoscopist, previously negative for the carbon-14 urea breath test, who had a week of epigastric pain and then became asymptomatic. H pylori was detected by culture of antral biopsy specimens and was still present after 74 days. Five days after infection the histological findings showed acute neutrophilic gastritis; by day 74 changes of chronic gastritis were evident. The patient seroconverted by IgG enzyme linked immunosorbent assay by day 74, but a mucosal IgM and IgA response was evident as early as day 14. Infection was accompanied by a transient hypochlorhydria but a sustained fall in gastric juice ascorbic acid concentration.
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Ascorbic acid, the reduced form of vitamin C, may protect against gastric cancer. Accordingly, this study assessed the variability of ascorbic acid and vitamin C in the gastric juice of 77 patients with dyspepsia. There was a vitamin C concentration gradient from gastric juice down to plasma in subjects with normal gastric mucosa, but not in those with chronic gastritis. Patients with chronic gastritis had significantly lower gastric concentrations of vitamin C and ascorbic acid, and ascorbic acid concentrations were especially low in subjects with hypochlorhydria. The presence of the concentration gradient suggests that a mechanism for the secretion of vitamin C into the stomach exists. This is compromised by chronic gastritis. The very low ascorbic acid concentrations in hypochlorhydria may be a consequence of oxidation by bacterial nitrite. Those patients who by the Correa model are at greatest risk for gastric cancer have the lowest gastric levels of ascorbic acid.
Many chronically ill mental patients show rapid and severe weight loss leading to severe nutritional debilitation. Excessive energy requirements secondary to hypermetabolism or hyperactivity have been proposed as the cause. This hypothesis was tested using the new doubly-labelled water (2H218O) technique to obtain accurate estimates of total energy expenditure (TEE) in 14 such patients. Mean TEE was very low (6.1 +/- 1.3 MJ/day). None of the subjects was in significant negative energy balance when studied. Mean resting metabolic rate (RMR) was lower than predicted from standard equations based on healthy elderly subjects. The energy cost of physical activity plus thermogenesis was also low (1.7 +/- 0.9 MJ/day) in all except one subject. The data refute the initial hypothesis and suggest that negative energy balance may be episodic, perhaps during periods of infection and subsequent recovery.
Fasting gastric juice pH and concentrations of vitamin C in gastric aspirate and plasma were measured in 73 patients undergoing endoscopy. Vitamin C concentrations were significantly lower in those with hypochlorhydria (pH greater than 4; n = 23) compared with those with pH less than or equal to 4 (p less than 0.005) and there was a significant correlation between gastric juice and plasma concentrations (p = 0.002). Patients with normal endoscopic findings had significantly higher intragastric concentrations of vitamin C than those with gastric cancer (p less than 0.001), pernicious anaemia (p less than 0.005), gastric ulcer (p less than 0.01), duodenal ulcer (p less than 0.05), or after gastric surgery (p less than 0.01). There was a strong trend (0.05 less than p less than 0.1) towards lower intragastric concentrations of vitamin C in patients with chronic atrophic gastritis. In vitro, vitamin C concentrations remained stable in acidic but fell significantly over 24 hours in alkaline gastric aspirate. Gastric secretory studies in five volunteers showed that vitamin C concentrations increased significantly after intramuscular pentagastrin. These findings suggest that the low fasting levels of vitamin C in hypochlorhydric gastric juice may be caused by chemical instability and that vitamin C may be secreted by the human stomach.
A total of 227 mothers enrolled for periconceptional multivitamin supplementation because of previous neural tube defect (NTD) births took vitamins for less than the recommended minimum period (at least 28 days before conception until two menstrual periods have been missed). Of 213 examined infants/fetuses born to these partially supplemented mothers, two had NTD, one of whom followed four previous NTDs. The observed NTD recurrence rate is similar to that observed in fully supplemented mothers. A further 14 mothers started supplements before the second missed period but after the normal time of neural tube closure. Three of their offspring had NTD. The significance of this apparently high recurrence rate is discussed.
The effect of oral vitamin C has been examined in elderly long-stay inpatients known to have low levels of vitamin C in their plasma and leucocytes. 1 g of vitamin C given daily for 28 days was shown to be associated with slight, but significant, clinical improvement and weight-gain when compared with placebo therapy.
Red cell B vitamins, folate and white cell vitamin C were measured in a group of critically ill surgical patients before and following a course of intravenous nutrition. Patients received a widely used vitamin supplementation regimen in the form of one ampoule of water-soluble vitamins daily and recommended doses of intramuscular folate, vitamin B12 and vitamin K weekly. This regimen was adequate to maintain tissue levels of the water-soluble vitamins and folate. Patients with initially low values had normal values at the end of the treatment period.
1. Leucocyte ascorbic acid concentrations have been measured in 1147 females during early pregnancy and in smaller numbers of women before conception, throughout pregnancy and at 6 months post partum. 2. The leucocyte concentration in the 1st trimester was found to be affected by season, social class and smoking. Selecting individuals by extremes of social class, season and smoking produced two small populations with almost separate ascorbic acid distributions and mean concentrations of 21.7 and 45.1 microgram/10(8) leucocytes. 3. Early pregnancy had little effect on leucocyte ascorbic acid concentrations but values decreased in the second trimester. However, this was associated with a leucocytosis so that the total leucocyte ascorbic acid content of blood was unchanged. 4. Low ascorbic acid concentrations during the 1st trimester were not associated with subsequent spontaneous abortions, still-births or neonatal deaths, but there was an increased frequency of low values in women who gave birth to infants smaller than 3250 g. 5. The adequacy of ascorbic acid reserves in early pregnancy is discussed.
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Indices of nutritional state were measured in 105 surgical patients. The indices were chosen to give information on protein-calorie malnutrition, anaemia, vitamin deficiency. Abnormal values for the various indices were common in the group as a whole and most frequent (50%) in patients who were still in hospital more than a week after major surgery. These patients had a high frequency of anaemia, vitamin deficiency, weight-loss, loss of arm-muscle bulk, and low plasma levels of transferrin and albumin. These abnormalities had gone almost entirely unrecognised, even in patients with sepsis after major surgery, who would benefit from improvement in nutritional state.
1. Mean daily nutrient intakes of 195 women in the first trimester of pregnancy were assessed by weighed dietary records. 2. In comparsion with recommended intakes for non-pregnant women aged 18-55 years (Department of Health and Social Security, 1969), more than two-thirds of the subjects were having insufficient energy, iron and cholecalciferol. Unsatisfactory intakes of other nutrients were not uncommon. In relation to recommended intakes for the second trimester (Department of Health and Social Security, 1969), all mothers were having insufficient cholecalciferol and more than 80% of mothers had unsatisfactory intakes of energy and Fe. 3. Intakes appreciably lower than those recommended were associated with the following factors: social classes III, IV and V; maternal age under 20 years; smoking ten or more cigarettes daily; vomiting on more than 3 d/week.
Serum folate, red cell folate, white blood cell vitamin C, riboflavin saturation index, and serum vitamin A were determined during the first trimester of pregnancy in over 900 cases. For each of these there was a social classes I + II showed the highest levels which differed significantly from other classes, except for serum folate. In 6 mothers who gave birth to infants with neural tube defects, first trimester serum folate, red cell folate, white blood cell vitamin C, and riboflavin values were lower than in controls. In spite of small numbers the differences were significant for red cell folate (P less than 0-001) and white blood cell vitamin C (P less than 0-05). These findings are compatible with the hypothesis that nutritional deficiencies are significant in the causation of congenital defects of the neural tube in man.
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