ascorbic-acid and Neural-Tube-Defects

Benefit of micronutrient supplementation on female fertility.. Reports of randomized trials are rare. Most studies are focused on multivitamin supplementations. For some micronutrients, a positive impact on fertility could be shown. This article reviews the available clinical studies as well as the pathophysiological background of possible effects and summarizes the potential benefits of selected micronutrients on female fertility.. Apart from lowering the malformation risk by periconceptional supplementation of folic acid, substitution with different micronutrients, particularly folic acid, vitamin B6, vitamin C, vitamin D, vitamin E, iodine, selenium, iron, and DHA might have a positive impact on infertility treatment. The multivitamin formulation should take the pathophysiology, clinical studies, and upper limits into account.

Topics: Adult; Ascorbic Acid; Birth Weight; Dietary Supplements; Female; Folic Acid; Humans; Infertility, Female; Micronutrients; Neural Tube Defects; Pregnancy; Pregnancy Complications; Premature Birth; Prenatal Nutritional Physiological Phenomena; Randomized Controlled Trials as Topic; Selenium; Vitamin B Complex

The purpose of the present paper is to review our current understanding of the chemistry and biochemistry of folic acid and related folates, and to discuss their impact on public health beyond that already established in relation to neural-tube defects. Our understanding of the fascinating world of folates and C1 metabolism, and their role in health and disease, has come a long way since the discovery of the B-vitamin folic acid by Wills (1931), and its first isolation by Mitchell et al. (1941). However, there is still much to do in perfecting methods for the measurement of folate bioavailability, and status, with a high extent of precision and accuracy. Currently, examination of the relationships between common gene polymorphisms involved in C1 metabolism and folate bioavailability and folate status, morbidity, mortality and longevity is evaluated as a series of individual associations. However, in the future, examination of the concurrent effects of such common gene polymorphisms may be more beneficial.

Topics: Ascorbic Acid; Biological Availability; Folic Acid; Food, Fortified; Hematinics; Humans; Intestinal Absorption; Neural Tube Defects; Nutritional Status; Polymorphism, Genetic

Although vitamin deficiency is encountered infrequently in developed countries, inadequate intake of several vitamins is associated with chronic disease.. To review the clinically important vitamins with regard to their biological effects, food sources, deficiency syndromes, potential for toxicity, and relationship to chronic disease.. We searched MEDLINE for English-language articles about vitamins in relation to chronic diseases and their references published from 1966 through January 11, 2002.. We reviewed articles jointly for the most clinically important information, emphasizing randomized trials where available.. Our review of 9 vitamins showed that elderly people, vegans, alcohol-dependent individuals, and patients with malabsorption are at higher risk of inadequate intake or absorption of several vitamins. Excessive doses of vitamin A during early pregnancy and fat-soluble vitamins taken anytime may result in adverse outcomes. Inadequate folate status is associated with neural tube defect and some cancers. Folate and vitamins B(6) and B(12) are required for homocysteine metabolism and are associated with coronary heart disease risk. Vitamin E and lycopene may decrease the risk of prostate cancer. Vitamin D is associated with decreased occurrence of fractures when taken with calcium.. Some groups of patients are at higher risk for vitamin deficiency and suboptimal vitamin status. Many physicians may be unaware of common food sources of vitamins or unsure which vitamins they should recommend for their patients. Vitamin excess is possible with supplementation, particularly for fat-soluble vitamins. Inadequate intake of several vitamins has been linked to chronic diseases, including coronary heart disease, cancer, and osteoporosis

Topics: Ascorbic Acid; Avitaminosis; Blood Coagulation; Breast Neoplasms; Carotenoids; Chronic Disease; Colorectal Neoplasms; Coronary Disease; Dietary Supplements; Female; Folic Acid; Fractures, Bone; Humans; Lung Neoplasms; Male; Neoplasms; Neural Tube Defects; Prostatic Neoplasms; Risk Factors; Vitamin A; Vitamin B 12; Vitamin B 6; Vitamin D; Vitamin E; Vitamin K; Vitamins

Recent studies have resolved the debate over the role of vitamins in preventing neural tube defects. The British Medical Research Council trial demonstrated that 4 mg of folate daily, but not other vitamins, prevented 72% of recurrences. The Hungarian trial prevented neural tube defects in women who had not previously had affected children by giving multivitamins containing 0.8 mg of folate. The US Public Health Service currently recommends that women at risk for becoming pregnant take 0.4 mg of folate daily. Unfortunately, most pregnancies are unplanned, and women not planning to become pregnant may not follow this recommendation. Therefore, the US Food and Drug Administration is exploring methods of food fortification. Because large doses of folate have been reported to ameliorate B12 deficiency anemia while allowing neurologic damage to progress, and to cause electroencephalogram abnormalities in epileptics, it is important to plan fortification carefully and to monitor both toxicity and benefits.

Topics: Ascorbic Acid; Dose-Response Relationship, Drug; Female; Folic Acid; Food, Fortified; Humans; Infant, Newborn; Neural Tube Defects; Pregnancy; Vitamin B 12 Deficiency; Vitamins

The main iron chelator used for transfusional iron overload is desferrioxamine, which is expensive, has toxic side effects, and has to be given subcutaneously. An orally active iron chelator is therefore required. The effects of oral 1,2-dimethyl-3-hydroxypyrid-4-one on urinary iron excretion were studied in eight patients who had received multiple transfusions: four had myelodysplasia and four beta thalassaemia major. Different daily doses of the drug up to 100 mg/kg/day, alone or in combination with ascorbic acid, were used. In three patients with thalassaemia the effect of the drug was compared with that of subcutaneous desferrioxamine at the same daily dose. In all eight patients a single dose of oral 1,2-dimethyl-3-hydroxypyrid-4-one resulted in substantial urinary iron excretion, mainly in the first 12 hours. Urinary iron excretion increased with the dose and with the degree of iron loading of the patient. Giving two or three divided doses over 24 hours resulted in higher urinary iron excretion than a single dose of the same amount over the same time. In most patients coadministration of oral ascorbic acid further increased urinary iron excretion. 1,2-Dimethyl-3-hydroxypyrid-4-one caused similar iron excretion to that achieved with subcutaneous desferrioxamine at a comparable dose. In some cases the iron excretion was sufficiently high (maximum 99 mg/day) to suggest that a negative iron balance could be easily achieved with these protocols in patients receiving regular transfusions. No evidence of toxicity was observed on thorough clinical examination or haematological and biochemical testing in any of the patients. None of the patients had any symptoms that could be ascribed to the drug. These results suggest that the oral chelator 1,2-dimethyl-3-hydroxypyrid-4-one is as effective as subcutaneous desferrioxamine in increasing urinary iron excretion in patients loaded with iron. Its cheap synthesis, oral activity, and lack of obvious toxicity at effective doses suggest that it should be developed quickly and thoroughly tested for the management of transfusional iron overload.

Topics: Administration, Oral; Adolescent; Adult; Aged; Ascorbic Acid; Clinical Trials as Topic; Deferiprone; Deferoxamine; Drug Therapy, Combination; Female; Humans; Iron; Iron Chelating Agents; Male; Middle Aged; Neural Tube Defects; Pyridones; Thalassemia

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%).

Topics: Abortion, Spontaneous; Ascorbic Acid; Avitaminosis; Clinical Trials as Topic; Drug Combinations; Female; Folic Acid; Follow-Up Studies; Humans; Infant, Newborn; Neural Tube Defects; Niacinamide; Pregnancy; Prospective Studies; Pyridoxine; Riboflavin; Thiamine; Vitamin A; Vitamin D; Vitamins

Nitrosatable drugs, such as secondary or tertiary amines and amides, form N-nitroso compounds in the presence of nitrite. Various N-nitroso compounds have been associated with neural tube defects in animal models. Using data from the National Birth Defects Prevention Study, the authors examined nitrosatable drug exposure 1 month before and 1 month after conception in 1,223 case mothers with neural tube defect-affected pregnancies and 6,807 control mothers who delivered babies without major congenital anomalies from 1997 to 2005. Nitrite intakes were estimated from mothers' responses to a food frequency questionnaire. After adjustment for maternal race/ethnicity, educational level, and folic acid supplementation, case women were more likely than were control women to have taken tertiary amines (odds ratio = 1.60, 95% confidence interval (CI): 1.31, 1.95). This association was strongest with anencephalic births (odds ratio = 1.96, 95% CI: 1.40, 2.73); odds ratios associated with tertiary amines from the lowest tertile of nitrite intake to the highest tertile were 1.16 (95% CI: 0.59, 2.29), 2.19 (95% CI: 1.25, 3.86), and 2.51 (95% CI: 1.45, 4.37), respectively. Odds ratios for anencephaly with nitrosatable drug exposure were reduced among women who also took daily vitamin supplements that contained vitamin C. Prenatal exposure to nitrosatable drugs may increase the risk of neural tube defects, especially in conjunction with a mother's higher dietary intake of nitrites, but vitamin C might modulate this association.

Topics: Amides; Amines; Ascorbic Acid; Case-Control Studies; Dietary Supplements; Female; Humans; Neural Tube Defects; Nitrites; Nitroso Compounds; Pregnancy; Prenatal Exposure Delayed Effects

The Hungarian participation in the establishment of the new primary prevention of neural-tube defects by periconceptional supplementation with multivitamins including folic acid or with folic acid alone has been significant. Food and supplement consumption during the preconceptional period are hypothesized to closely reflect intakes during the time of neural-tube development, i.e., between the 15th and 28th day postconception. A daily personal diary of food intake during one month of the preconceptional period was evaluated and the data on vitamin supplement use were obtained by interview. In Hungary, folic acid (158.5 micrograms/day) in the normal diet does not seem to be sufficient to reduce the risk of neural-tube defects. The women who used multivitamin supplements routinely in the preconceptional period were not attempting to prevent neural-tube defects as no women took single folic acid supplement in the study.

Topics: Adult; Ascorbic Acid; Diet; Dietary Carbohydrates; Dietary Fats; Dietary Proteins; Energy Intake; Female; Folic Acid; Humans; Hungary; Neural Tube Defects; Preconception Care; Vitamins

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.. Sixteen women with a history of two NTD-affected infants and 16 controls with no such history, none of whom were either pregnant or taking vitamin supplements. The orange juice loading test was carried out on eight matched pairs.. Dietary intake of folate was assessed by questionnaire and blood levels of folate and vitamin C were measured.. There was no evidence of decreased intake of folate in subjects who had had two NTD-affected pregnancies. In controls, both serum and red cell folate showed significant correlation with dietary folate, while in subjects there was no such correlation. Subjects also had smaller increases in serum folate following an oral load than controls, although the differences were not significant.. Women who have had two NTD-affected pregnancies may have defective folate metabolism. Further investigations on short term utilisation of ingested food folates in these women are required.

Topics: Adult; Ascorbic Acid; Beverages; Citrus; Diet; Erythrocytes; Female; Folic Acid; Folic Acid Deficiency; Humans; Infant, Newborn; Neural Tube Defects; Risk Factors

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.. Twenty-nine women with a history of NTD-affected infant, who had taken periconceptional vitamin supplements one year or more prior to the study and twenty-nine controls with no such history.. Dietary intake of folate was assessed by questionnaire and blood levels of folate, vitamin B12 and vitamin C were measured.. Neither dietary intake of folate nor any of the blood vitamins measured were lower in the women with a history of NTD infant. The majority of women who had received periconceptional vitamin supplementation subsequently had adequate folate intakes and red blood cell folates greater than 160 micrograms/l. Smokers had lower plasma Vitamin C levels than nonsmokers. Multiple regression analysis suggested that the relation between red blood cell (RBC) and serum folate may differ between women with and without a history of NTD.. Women with a history of NTD-affected infants may have different folate metabolism from those who have not.

Topics: Adult; Ascorbic Acid; Diet; Erythrocytes; Female; Folic Acid; Humans; Neural Tube Defects; Preconception Care; Smoking; Time Factors; Vitamin B 12

Folic acid and other vitamin deficiencies may play a role in the etiology of neural tube defects. The Medical Research Council Vitamin Study confirmed the beneficial effect of folic acid supplementation on the prevention of neural tube defects. However, the concentrations of vitamins other than folate were not a common feature of any of the former studies. We measured the concentrations of vitamin A, riboflavin, riboflavine-5'-monophosphate, flavine-adenine-dinucleotide, vitamin B-6, vitamin B-12, vitamin C, vitamin E, folate and ferritin in the serum of women who had previously had a child with a neural tube defect and were planning a further pregnancy. Vitamin and folic acid supplements were supplied before conception to 44 high risk women before conception. Eighteen other high risk women not given supplements were the control group. We concluded that vitamin profiles do not form a suitable means for identifying women at risk for neural tube defects before pregnancy. This endorses the hypothesis that the beneficial effect of folic acid supplementation on the prevention of neural tube defects is possibly at least partly due to the fact that it overrides a relative folic acid shortage caused by a metabolic disorder.

Topics: Ascorbic Acid; Female; Ferritins; Flavin Mononucleotide; Folic Acid; Gestational Age; Humans; Neural Tube Defects; Pregnancy; Pregnancy Outcome; Pyridoxine; Riboflavin; Risk Factors; Vitamin A; Vitamin B 12; Vitamin E; Vitamins

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.

Topics: Ascorbic Acid; Drug Administration Schedule; Drug Combinations; Female; Humans; Neural Tube Defects; Pregnancy; Pregnancy Outcome; Recurrence; Vitamin B Complex

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.

Topics: Ascorbic Acid; Erythrocytes; Female; Folic Acid; Humans; Leukocytes; Neural Tube Defects; Pregnancy; Prenatal Care; Recurrence; Risk; Vitamins

The curly-tail mouse is an animal model for human neural tube defects (NTD). Around 60% have either overt lesions of the neural tube or a curly tail. They were used to examine the gene/environment interaction which is implicated in the aetiology of human NTD. Both a fetal and a maternal genotype contribution to the cause, together with a triggering effect of an environmental component, could be demonstrated in the mice. The environmental limb of the cause appears to be relatively specific. Under certain conditions, administration of an environmental agent to the pregnant curly-tail mouse markedly reduced the incidence of NTD in her offspring. Primary prevention of NTD was thus shown to be possible. The apparent primary prevention of NTD in humans is also described. A multicentre collaborative project which supplemented women "at risk" for NTD with a standard multivitamin tablet with folic acid before they conceived again and in the early stages of pregnancy was associated with a recurrence of only 0.5% compared with 4.3% in unsupplemented controls at a comparable risk. The difference is statistically significant (p = less than 0.01).

Topics: Animals; Ascorbic Acid; Disease Models, Animal; Female; Folic Acid; Genotype; Gestational Age; Humans; Mice; Mice, Neurologic Mutants; Neural Tube Defects; Pregnancy; Sex Factors; Spina Bifida Occulta; Vitamin A