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PubMed1982

Semiautomated system for simultaneous assays of serum vitamin B12 and folic acid in serum evaluated.

We evaluated performance characteristics of a semiautomated radioassay system (ARIA II, Becton Dickinson Immunodiagnostics) for simultaneous measurements of vitamin B12 and folic acid in serum. The system requires off-line boiling of samples, which are then processed on-line. The automated process includes dispensing of boiled samples, tracers, and binders (purified intrinsic factor and milk binder); incubation, separation of bound and free ligands; elution; counting radioactivity of 57Co and 125I; and data reduction. Results were compared with those obtained by a manual method (Diagnostic Products Corp.). Although the nonspecific binding of the ARIA II is more than double that of the manual system, the precision values are comparable (within- and between-assay CVs are less than 8.5%). Values obtained with these two systems correlated well except that folic acid concentrations obtained with ARIA II tended to be lower at high folic acid concentrations. We observed no significant total carryover or drift in the semiautomated system.

Autoanalysis↗
PubMed2002

Folic acid and vitamin B(12) supplementation attenuates isoprenaline-induced myocardial infarction in experimental hyperhomocysteinemic rats.

Hyperhomocysteinemia (Hhcy) is an independent risk factor for cardiovascular disease. Oxidative stress may contribute to the deleterious effects of homocysteine (Hcy). The aim of the present study is to study the effect of folic acid and Vitamin B(12) supplementation on isoprenaline (ISO)-induced myocardial infarction (MI) in hyperhomocysteinemic rats. Hhcy was induced by daily intake of methionine (1 g kg(-1) body weight) in the drinking water for 4 weeks. MI was then produced by a single subcutaneous injection of ISO (300 mg kg(-1), s.c.). Electrocardiographic parameters, heart rate, ST segment, and blood pressure as well as serum marker enzymes, creatine kinase (CK) and lactate dehydrogenase (LDH) were measured. Lipid peroxidation measured as malondialdehyde (MDA) and reduced glutathione (GSH) concentrations in heart tissue were estimated as indices of oxidative stress. Hhcy resulted in significant blood pressure reduction, ST segment elevation and increase in heart rate and serum CK and LDH levels. Cardiac MDA was significantly increased, while GSH was decreased in Hhcy group compared to the normal control group. All the measured parameters were greatly exaggerated in Hhcy rats treated with ISO in comparison with Hhcy rats alone. Administration of folic acid (10 mg kg(-1), orally via gavage) and Vitamin B(12) (500 microg kg(-1), i.m.) concurrently for 4 weeks during the induction of Hhcy markedly reduced the increase in heart rate, ST segment elevation and blood pressure reduction as well as the increase in serum CK and LDH levels. Cardiac MDA content was decreased while cardiac GSH was elevated in the treated group compared to Hhcy + ISO group. Moreover, the severe cardiac histopathological changes observed in Hhcy + ISO group were attenuated by folic acid and Vitamin B(12). These results suggest that Hhcy aggravates MI via oxidative stress mechanisms and that lowering Hcy level with folic acid and Vitamin B(12) can ameliorate the detrimental effects of Hhcy and may reduce the risk of MI.

Animals↗
PubMed2003

[Lactobacillus casei microbiological assay of plasma and RBC concentrations of folic acid with 96-well microtiiter plates].

To investigate the plasma and RBC concentrations of folic acid in normal persons. Microbiological assay was used to determine the plasma and RBC folic acid in 59 normal persons by using of 96-well microtiter plasma. The results showed that the plasma and RBC folio acid concentration were (8.2 +/- 2.9) microgram/L and (337.5 +/- 91.0) microgram/L in male and female normal persons (aged 18 to 32) respectively. The coefficient Variations determined within assay and between assay were 2.2% and 4.7% respectively. This method may reduce reagent costs, shortened the assay time, increase the sensitivity and improve the reproducibility. It can be used for large scale survey.

Adolescent↗
PubMed1989

Folic acid deficiency in intensive care patients: comparison between two regimens of supplementation.

Serum folic acid (SFA) and red blood cell folic acid (RbcFA) levels were determined in 40 patients on the day of admission to our intensive care unit (ICU, D0). 65% of the patients had low SFA (< 3,4 ng/ml) and 27.5% had low RbcFA (< 275 ng/ml)L. Twenty-four hours later (Day 1:D1), both SFA and RbcFA had decreased significantly (respectively 0.49 ng/ml and 21 ng/ml, p < 0.01) in the 40 patients; the magnitude of RbcFA decrease was greater in patients with sepsis than in those without sepsis (p < 0.02). SFA and RbcFA levels were significantly lower in patients with sepsis on D0 and D1. Forty-two other patients with documented hypofolatemia were then randomly allocated to two regimens of FA supplementation. Patients on regimen A had an intravenous injection of 0.5 mg folinic acid daily for ten days whereas patients on regimen B received a single 5 mg intravenous injection of FA on day 1. Both regimens increased significantly SFA and RbcFA levels. But regimen A should be recommended because 1) RbcFA levels were significantly higher than with regimen B (p < 0.05) and 2) the mean increase was higher, particularly in patients with initial sepsis (p < 0.01).

Journal Article↗
PubMed1993

[Folic acid and vitamin B12 in children under long-term anticonvulsant therapy].

Folic acid (FA) and vitamin B12 have been measured prospectively in 110 children that were under treatment with anticonvulsants. The control group consisted of 59 healthy children. A statistically significant difference in levels of serum FA and mean corpuscular volume (MCV) was observed between groups. Children under anticonvulsant treatment had lower serum FA levels and higher MCV. No significant difference was observed between the two groups in levels of serum vitamin B12. All children with serum FA levels lower than 3 ng/ml were given folate and no adverse side effects were observed due to treatment. Anticonvulsant drugs decrease serum FA levels; therefore, FA should be determined periodically in children under long-term anticonvulsant treatment.

Adolescent↗
PubMed1979

Histochemical study on the dihydrofolatereductase and folic acid in mammalian brain cortex.

Histochemical and biochemical studies on the folate metabolism (folic acid an its principal enzyme-dihydrofolate-reductase) in bovine cortex - gyrus marginallis in the process of ageing were performed, in parallel with NADH2-cytocrom-C-reductase (diaphorase). Folic acid and folate enzyme, weak positive in neurons in young age, increased in old age in nerve cells and especially in their processes and in capillaries. The diaphorase strongly increased in all cells, glia and vessels, in old age.

Aging↗
PubMed1995

Periconceptional folic acid supplementation as a social intervention.

Periconceptional folic acid supplementation has been shown to decrease the first occurrence of isolated neural tube defects (NTDs) by as much as 50%, and to decrease the recurrence risk for NTDs by more than 70%. The possible mechanisms of vitamin supplementation in the prevention of NTDs are discussed, as are the current recommendations for reproductive-age women. Further, the limitations of dietary and pharmacological recommendations with regard to patient compliance as well as the possibility of grain fortification are reviewed.

Diet↗
PubMed1989

The effect of combined dietary iron, calcium and folic acid supplementation on apparent 65Zn absorption and zinc status in pregnant rats.

In the present study the effect of combined iron, calcium and folic acid supplementation of the diet on 65Zn retention and zinc status was studied in the pregnant rat. Female Wistar rats were fed on a low- (8 micrograms/g) or high- (60 micrograms/g) Zn diet for 14 d and then mated overnight. After mating, half the rats were fed on the low- or high-Zn diet as before, whilst the other half were fed on similar diets supplemented with Fe, Ca and folic acid. The level of supplementation was chosen to reflect proportionately the possible increase in daily intakes of these nutrients by pregnant women. Rats which did not mate successfully were used as non-pregnant controls. On day 18 of pregnancy, each animal was given a meal of the appropriate diet labelled extrinsically with 65Zn, and on day 20 rats were killed. Carcass 65Zn retention was lower in pregnant and non-pregnant rats fed on the supplemented diets compared with those fed on the unsupplemented diets. Rats which consumed the supplemented diets throughout pregnancy had reduced plasma Zn concentrations but femur and fetal Zn concentrations were unaffected. Maternal femur Ca and fetal Fe concentrations were lower in the high-Zn groups compared with rats fed on low-Zn diets. It was concluded that the risk of inducing fetal Zn depletion as a consequence of Fe, Ca and folic acid supplementation during pregnancy appeared to be slight.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗
PubMed2005

[Hyperhomocysteinemia and treatment with antiepileptic drugs. Effects of different doses of folic acid].

BACKGROUND AND OBJECTIVE: An increase homocysteine values, which is an independent risk factor for atherotrombotic disease, can be produced with antiepileptic treatment. The aims of this study were: 1) to assess the frequency and determinant factors of hyperhomocysteinemia in adult patients receiving antiepileptic drugs, and 2) to know the effect of different doses of folic acid. PATIENTS AND METHOD: Ninety eight patients and 100 healthy controls similar in age and gender were studied. Eighty six patients were treated with hepatic enzyme inductors (diphenylhydantoine and/or phenobarbital and/or primidone and/or carbamazepine), 5 received non inductors (valproate) and 7 were treated with both in combination. Thirty eight patients were randomized to receive in an open and concurrent way folic acid, 0.2 mg (n = 18) or 5.2 mg (n = 20) daily for 3 months. RESULTS: Homocysteine values were increased in patients in relation with controls (mean [SD]12.2 [6.7] 95% confidence interval [CI],10.0-13.5 vs 8.8[2.2] 95% CI, 8.3-9.2 micromol/l; p < 0.001). Hyperhomocysteinemia was found in 28 patients and 4 controls (28.6% vs 4.0%; p < 0.001). In a multivariate analysis hyperhomocysteinemia was positively associated with treatment with antiepileptic inductors and negatively with folate values and female gender. Homocysteine values decreased after treatment with folic acid at high and low doses (p < 0.001 for both groups), and the values observed in the latter group were similar to those in healthy controls. CONCLUSIONS: Hyperhomocysteinemia is frequent in patients treated with antiepileptic drugs. Treatment with hepatic enzyme inductors and low folate values are predictors of hyperhomocysteinemia. Administration of folic acid, even at very low doses, produces a significant decrease of homocysteinemia in these patients.

Adult↗
PubMed1977

Simultaneous radioassay of serum vitamin B12 and folic acid.

The radioassays of vitamin B12 and folic acid can be carried out in a single tube to give the simultaneous assay of both vitamins in 100 microliter of serum. Release of bound vitamins from their endogenous binders and the destruction of these binders are effected by a heating step at pH 9.3. The subsequent binding reactions with hog intrinsic factor and milk binder protein proceed advantageously and simultaneously in the same tube at pH 9.3. A single set of dual reagents replaces two sets of reagents that would normally be used for separate radioassays. Complete separation of bound radioactivities, [57Co]cyanocobalamin and 125I-labeled folate derivative, is obtained in a dual-channel gamma counter with no requirement for any correction for spill-over of counting data. Analytical results are comparable to those found for previously developed individual radioassays. The simultaneous assay has decreased technical time of analysis for these interrelated vitamins by about 50%.

Cobalt Radioisotopes↗
PubMed1991

Coeliac disease, folic acid deficiency and epilepsy with cerebral calcifications.

Two cases of focal occipital epilepsy with cerebral calcifications poorly responsive to antiepileptic treatment are described. In both cases coeliac disease was diagnosed and folic acid deficiency documented. A gluten-free diet and a brief supplementation with folic acid lead to a complete EEG and clinical normalization in one case and to a significant improvement of EEG and seizure control in the other.

Adult↗
PubMed2002

Folic acid fortification, folate status and plasma homocysteine.

Folic acid fortification of enriched cereal-grain products (which became mandatory in the U.S. on January 1, 1998) was intended to increase folate intake among childbearing-aged women to reduce their risk of neural tube birth defect (NTD)-affected pregnancies. Interest now focuses on assessing the effects of fortification on risk of NTDs and on folate intake relative to homocysteine (Hcy) concentrations and risk of vascular disease, although a causal relationship between the latter two has not been demonstrated. Increased serum folate levels were first reported in 1999. Data from the Framingham Offspring Study cohort showed increased mean serum folate in middle-aged and older adults; additionally, the prevalence of high Hcy concentrations had decreased by approximately 50% in subjects examined before (1995-1996) and after (1997-1998) fortification. Another analyses of samples collected between 1994 and 1999 identified a trend of increasing serum folate values from 1996 onward with values in 1998 160% of those measured in 1996. Comparisons between 1988-1994 National Health and Nutrition Examination Survey (NHANES) III data and 1999 NHANES showed increased serum and erythrocyte folate concentrations among childbearing-aged women. While recent data show improved folate status in a short period of time, much about long-term effects of the fortification program remains unknown. Interest in the effects of increased folate intakes on risk of NTDs or vascular disease needs to be balanced against concerns about masking the anemia of vitamin B-12 deficiency and the general lack of data about safety of continuous high intakes. Careful monitoring over time is necessary to determine that the program functions as intended.

Cohort Studies↗
PubMed2004

Differential effects of fish oil and folic acid supplementation during pregnancy in rats on cognitive performance and serum glucose in their offspring.

OBJECTIVE: We studied the effect of folic acid and polyunsaturated fatty acid supplementation during pregnancy in Wistar albino rats on cognitive performance and serum glucose concentrations in their pups. METHODS: Pregnant female rats from four groups (n = 6/group) were fed casein diets with 18% protein and 2 mg of folic acid/kg of diet (group I), 12% protein and no folic acid (group II), 12% protein and 8 mg of folic acid/kg of diet (group III), or 12% protein and 70 g of cod liver oil/kg of diet (group IV). All pups were weaned on standard control diet with 18% protein. Cognitive performance, brain fatty acid profile, and serum glucose concentrations were studied in offspring at age 6 mo. RESULTS: There was no significant difference in length of gestation or litter size, but the litter weight for group IV was lower (P = 0.047) than that for group I. After weaning, males in group II had lower (P < 0.05) body weights, but those in group III had weights comparable to those in group I for both sexes. In group IV, body weights were lower beyond 15 wk (P < 0.05). Relative brain weight and cognitive performance were significantly higher (P < 0.05) in group IV males and showed higher levels of brain gamma-linolenic acid. Further, these animals had serum glucose levels comparable to those of control animals at age 6 mo, whereas serum glucose levels were higher in males from groups II (P = 0.01) and III (P = 0.01). CONCLUSION: Fish oil supplementation during pregnancy improved cognitive performance and maintained glucose levels into adulthood, unlike folic acid supplementation, which supported only fetal growth and did not maintain glucose levels.

Animals↗
PubMed2005

Betaine concentration as a determinant of fasting total homocysteine concentrations and the effect of folic acid supplementation on betaine concentrations.

BACKGROUND: Remethylation of homocysteine to methionine can occur through either the folate-dependent methionine synthase pathway or the betaine-dependent betaine-homocysteine methyltransferase pathway. The relevance of betaine as a determinant of fasting total homocysteine (tHcy) is not known, nor is it known how the 2 remethylation pathways are interrelated. OBJECTIVE: The objectives of the study were to examine the relation between plasma betaine concentration and fasting plasma tHcy concentrations and to assess the effect of folic acid supplementation on betaine concentrations in healthy subjects. DESIGN: A double-blind randomized trial of 6 incremental daily doses of folic acid (50-800 microg/d) or placebo was carried out in 308 Dutch men and postmenopausal women (aged 50-75 y). Fasted blood concentrations of tHcy, betaine, choline, dimethylglycine, and folate were measured at baseline and after 12 wk of vitamin supplementation. RESULTS: Concentrations of tHcy were inversely related to the betaine concentration (r = -0.17, P < 0.01), and the association was independent of age, sex, and serum concentrations of folate, creatinine, and cobalamin. Folic acid supplementation increased betaine concentration in a dose-dependent manner (P for trend = 0.018); the maximum increase (15%) was obtained at daily doses of 400-800 microg/d. CONCLUSIONS: The plasma betaine concentration is a significant determinant of fasting tHcy concentrations in healthy humans. Folic acid supplementation increases the betaine concentration, which indicates that the 2 remethylation pathways are interrelated.

Administration, Oral↗
PubMed2004

Folic acid improves endothelial function in children and adolescents with type 1 diabetes.

OBJECTIVE: To evaluate the effect of folate supplementation on endothelial function in children and adolescents with type 1 diabetes. STUDY DESIGN: Thirty-six subjects with type 1 diabetes age 13.6+/-2.6 years completed a randomized, double-blind, placebo-controlled crossover trial. Each subject received 8 weeks of oral folic acid (5 mg/d) and 8 weeks of placebo, with an 8-week washout period. Before and after each intervention, we assessed endothelial function by using brachial artery responses to flow (flow-mediated dilatation [FMD]) and glyceryl trinitrate, von Willebrand factor, glucose, hemoglobin A1c, total plasma homocyst(e)ine (tHcy), vitamin B(12), serum folate, and red cell folate (RCF). RESULTS: Folic acid increased FMD by 2.58 (3.1-5.7) % (95% confidence interval, 1.28-3.88), whereas placebo did not change FMD (-0.42%; 95% confidence interval, -1.67 to 0.83; P<.001). Folic acid increased serum folate by 14 nmol/L (6.2 ng/mL, P<.001) and RCF by 467.2 nmol/L (206 ng/mL, P<.001). Change in FMD was related to change in serum folate (r=0.46, P=.005) and RCF (r=0.39, P=.02). Glyceryl trinitrate responses, von Willebrand factor, tHcy, and hemoglobin A1c were not affected by the intervention. CONCLUSIONS: Short-term high-dose folic acid improves endothelial function in children and adolescents with type 1 diabetes and normal folate status independently of tHcy.

Administration, Oral↗
PubMed2001

Effect of folic acid treatment on endothelium-dependent vasodilation and nitric oxide-derived end products in hyperhomocysteinemic subjects.

PURPOSE: An elevated plasma homocysteine concentration is an independent risk factor for cardiovascular diseases. In this study, we tested the hypothesis that hyperhomocysteinemia induces endothelial dysfunction mediated, at least in part, through nitric oxide-dependent mechanisms and that folic acid supplementation improves endothelial function in hyperhomocysteinemic subjects. SUBJECTS AND METHODS: Endothelial function was evaluated in healthy controls and hyperhomocysteinemic subjects by measuring plasma levels of the nitric oxide-derived end products nitrite and nitrate and by assessing vasodilatory responses in the skin microcirculation and forearm vasculature. In the subjects with hyperhomocysteinemia, these measurements were repeated after 6 weeks and 12 months of folic acid supplementation. RESULTS: Compared with healthy controls, hyperhomocysteinemic subjects had significantly lower median plasma levels of nitric oxide-derived end products (12.1 microM [range 4.4 to 41.8] versus 24.6 microM [13.6 to 53.2]; P <0.001), a significantly lower endothelium-dependent vasodilatory response to acetylcholine (P <0.01), hyperemic response in the microcirculation (P <0.01), and total forearm blood flow during reactive hyperemia (P = 0.01). There was no significant difference in the endothelium-independent response. Folic acid treatment for 12 months increased the plasma level of nitric oxide-derived end products by 121% (95% confidence interval [CI], 72% to 170%), the vasodilatory response to acetylcholine by 124% (95% CI, 36% to 212%), and the ischemia-mediated hyperemic responses in the microcirculation by 60% (95% CI, 25% to 96%) and in the forearm vasculature by 47% (95% CI, 21% to 73%). CONCLUSIONS: Homocysteine appears to induce its atherogenic effect, at least in part, by depressing endothelial function, possibly through nitric oxide-dependent mechanisms. This effect can be reversed by folic acid supplementation.

Adult↗
PubMed1997

Folic acid deficiency enhances oral contraceptive-induced platelet hyperactivity.

In previous studies conducted in female rats and in women, oral contraceptives (OC) were found to induce a platelet hyperactivity that was related to an oxidative stress. Because cases of megaloblastic anemia have been reported to occur in women taking OC, these treatments are suspected of depleting folate stores. In the study presented herein, which was conducted in rats, we sought to determine the influence of dietary folic acid deficiency (FD) on the thrombogenicity of OC. Animals were fed for 6 weeks with either a folic acid-deficient diet (250 micrograms/kg folic acid) or a control diet (750 micrograms/kg). One-half of the animals in each group were treated with OC (ethinyl estradiol plus lynestrenol). FD and OC individually potentiated platelet aggregation in response to thrombin and ADP and the release and metabolism of arachidonic acid, in particular, the biosynthesis of thromboxane. These platelet activities were further enhanced in animals given both the folic acid-deficient diet and the OC treatment. In addition, FD enhanced the pro-oxidant state in OC-treated rats characterized by (1) a fall in platelet and plasma n-3 fatty acids, (2) an increase in plasma lipid peroxidation products such as conjugated dienes, lipid peroxides, and thiobarbituric reactive substances, (3) a rise in ex vivo erythrocyte susceptibility to free radicals. Moreover, we found that OC treatment led to a reduction of plasma and erythrocyte folate concentrations associated with a moderate hyperhomocysteinemia. Under our experimental conditions, we did not find significant synergistic effects between OC and FD. We propose that, although the untoward effects associated with the OC treatment may not primarily be dependent on FD, the folic acid deficiency magnified OC-induced oxidative stress, which resulted in platelet hyperactivity by elevating the pro-oxidant homocysteine plasma concentration. Despite the limitations of this animal model, the data of the present study suggest that in addition to cigarette smoking, inadequate folic acid intake might predispose those taking OC to vascular thrombosis.

Animals↗