C.J. Schorah

Possible prevention of neural-tube defects by periconceptional vitamin supplementation.

Women who had previously given birth to one or more infants with a neural-tube defect (NTD) were recruited into a trial of periconceptional multivitamin supplementation. 1 of 178 infants/fetuses of fully supplemented mothers (0.6%) had an NTD, compared with 13 of 260 infants/fetuses of unsupplemented mothers (5.0%).

Further experience of vitamin supplementation for prevention of neural tube defect recurrences

In accordance with a previous protocol, a second cohort of 254 mothers with a history of previous neural tube defect (NTD) births was before a subsequent conception and continued until the time of the second missed menstrual period. There were 2 NTD recurrences (0.9% of 234 infants/fetuses examined), which is significantly fewer than the 11 NTD recurrences (5.1% of 215 infants/fetuses examined) born to 219 unsupplemented (US) mothers in the same centres over the same period. When the data for the two cohorts were combined, the overall recurrence rates were 0.7% for 454 fully supplemented (FS) mothers and 4.7% for 519 US mothers. The recurrence rates after 1 previous NTD were 0.5% for FS and 4.2% for US mothers: after 2 or more previous NTDs, 2.3% for FS and 9.6% for US. There were no recurrences among the offspring of a further 114 mothers whose duration of supplementation fell short of the full regimen (partially supplemented, PS).

Gastric juice ascorbic acid: effects of disease and implications for gastric carcinogenesis.

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.

The responsiveness of plasma homocysteine to small increases in dietary folic acid : a primary care study

Objectives: To assess the long term effects of small increases in dietary folic acid on the concentration of plasma homocysteine, an independent risk factor for occlusive vascular disease, in a general population.Design: A randomized double-blind placebo-controlled intervention study.Subjects: One hundred and nineteen healthy volunteers, whose intake of fortified or supplemental folic acid was low, were recruited by letter from the patient register of a large inner-city group general practice.Methods: Volunteers were randomized to receive unfortified cereals, or cereals fortified with 200 μg of folic acid per portion, with or without other vitamins. Blood samples were taken presupplement and at 4, 8 and 24 weeks on treatment and analysed for plasma homocysteine, cysteine and vitamin B12 and serum and red cell folate. Ninety-four subjects completed the study providing blood samples on all four occasions.Results: There were no significant changes in any measured parameter in those eating unfortified cereals. Overall, folic acid fortification of cereals led to significant increases (P<0.001) in serum folate (66%), and red cell folate (24%), and a decrease in plasma homocysteine (10%; P<0.001). There were no changes in vitamin B12 or cysteine. The homocysteine decrease persisted until the end of the study and was primarily seen in those who initially had the highest plasma homocysteine or the lowest serum folate.Conclusions: If homocysteine is found to be a causative risk factor in occlusive vascular disease, food fortification with physiological levels of folic acid should have a significant impact on the prevalence of the disease in the general population.Sponsorship: We acknowledge, with thanks, financial support from the Kellogg Company of Great Britain.

Maternal nutrition in early pregnancy.

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.

Determination of Plasma Total Homocysteine and Cysteine Using HPLC with Fluorescence Detection and an Ammonium 7‐fluoro‐2,1,3‐benzoxadiazole‐4‐sulphonate (SBD‐F) Derivatization Protocol Optimized for Antioxidant Concentration, Derivatization Reagent Concentration, Temperature and Matrix pH

A sensitive HPLC-fluorescence method for determining total endogenous plasma homocysteine (Hcy), cysteine (Cys) and cysteinylglycine (Cys-Gly) following derivatization with ammonium 7-fluoro 2,1,3-benzoxadiazole-4-sulphonate (SBD-F) is described. Quantitation utilizes an internal standard, 2-mercaptoethylamine. The derivatization procedure has been optimized for concentration of SBD-F, reducing agent (tributylphosphine) and temperature. Findings indicate that values for plasma determinations vary according to the nature of the matrix in which calibration standards are made up. If quantitation is based on a peak height ratio, then standards should be made up in either pH 7.4 phosphate buffered saline or plasma taking into account the endogenous thiol concentration. These findings are based on calibration data, and 30 plasma samples quantified using thiol standards made up in plasma, pH 7.4 and pH 9.5 buffers. By defining how this matrix/pH effect influences thiol quantitation, it should be possible to make a more meaningful comparison of Hcy measurements between laboratories. The chromatographic separation was investigated at several mobile-phase pH values with the following conditions ascertained to be optimal: a mobile phase consisting of 5% (v/v) acetonitrile in 0.1 M KH2PO4, pH 2.15 was run at a flow rate of 0.5 mL/min. It was used in conjunction with a Supelco LC-18 base deactivated analytical column (150 x 4.6 cm i.d. 3 microM bonded silica). The internal standard and thiols were measured by fluorescence detection at 385 nm excitation and 515 nm emmission. Plasma levels are easily measured in a 100 microL volume. Storage for 2 months at -20 degrees C resulted in no deterioration of thiols. Furthermore, no difference in thiol levels was observed between bloods collected in lithium heparin and EDTA. Collected blood should, however, be separated as soon as possible to avoid red cell metabolism of Hcy which was observed in a case of hyperhomocysteinemia. Once derivatized, thiols are stable for at least one week at +4 degrees C.

The effect of periconceptional supplementation on blood vitamin concentrations in women at recurrence risk for neural tube defect.

1. We measured erythrocyte folic acid and riboflavin, serum folic acid and leucocyte vitamin C in women at high risk for neural tube defect (NTD) recurrence who were receiving periconceptional vitamin supplementation, before they received extra vitamins, after 28 d of supplementation and at the 8th week of pregnancy. Blood vitamin concentrations in unsupplemented high-risk women were also compared with the values found in unsupplemented low-risk women. 2. Vitamin supplementation with Pregnavite Forte F (Bencard) raised the mean values for all vitamins measured by the 8th week of pregnancy. Mean erythrocyte folic acid rose from 250 to 478 ng/ml; plasma folic acid from 8.4 to 26.1 ng/ml; leucocyte vitamin C from 1.82 to 3.21 micrograms/ml blood; erythrocyte riboflavin (glutathione reductase (EC 1.6.4.2) activation ratio) from 1.08 to 1.04. All women receiving supplements had increased their serum and erythrocyte folic acid levels above the highest values found in women in an earlier study, who subsequently gave birth to children with NTD. Not all women, however, increased their leucocyte ascorbic acid or erythrocyte riboflavin levels above the highest values. 3. When vitamin concentrations in unsupplemented high-risk women compared with levels in unsupplemented women at low risk for NTD, no significant differences were found in the mean values. However, a significantly higher proportion of high-risk compared with low-risk women had erythrocyte folic acid and leucocyte vitamin C values on or below the 5th percentile of the adult normal range. 4. The effectiveness of Pregnavite Forte E (Bencard) for increasing maternal vitamin reserves is discussed with a view to preventing NTD and the possibility of identifying groups at risk for NTD because of low blood vitamin levels is considered.

Investigation of folate intake and metabolism in women who have had two pregnancies complicated by neural tube defects

Object To investigate folate intake and blood levels of folic acid and vitamin C in women with and without a history of two NTD‐affected pregnancies and to measure the increase in serum folate following ingestion of orange juice.

Investigation of factors influencing folate status in women who have had a neural tube defect‐affected infant

Objective To investigate folate intake and blood levels of vitamins in women with and without a history of neural tube defect (NTD)‐affected infant and to explore the relation between red cell and serum folate in those women.

Antioxidant-micronutrients and HIV infection

We measured plasma levels of all the antioxidant-micronutrients in subjects with HIV infection and controls. Plasma levels of all the carotenoids, including lutein, cryptoxanthin, lycopene, alpha-carotene and beta-carotene as well as vitamins A, C and E and cholesterol were assayed in 35 subjects with HIV infection and 38 controls. We found a significant depletion of all the carotenoids (P < 0.001) and vitamin C (P < 0.01) and cholesterol (P < 0.001) but not vitamins A or E in HIV-infected subjects. Further analysis of the HIV-infected subjects revealed that plasma levels of 4 of the groups of carotenoids and cholesterol were correlated with CD4 count but that beta-carotene and vitamins A, C and E were not. These results are reviewed in the light of the published literature and we conclude that these abnormalities of antioxidant-micronutrients are likely to reflect a metabolic phenomenon associated with HIV infection. However, an additional contribution to these deficiencies from malabsorption later in HIV disease cannot be ruled out.