Maternal folate deficiency and pregnancy wastage. IV. Effects of folic acid supplements, anticonvulsants, and oral contraceptives.
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Abnormalities, Drug-Induced↗
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Results for “Serum Folate Level”
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Influence of folate serum concentration on plasma homocysteine levels in HIV-positive patients exposed to protease inhibitors undergoing HAART.
BACKGROUND: Homocysteinemia (Hcy) increase and risk factors in HIV-positive patients are not clear yet. METHODS: HIV-positive patients on stable highly active antiretroviral therapy (HAART) regimens for at least 6 months were enrolled in this cross-sectional study. Among other factors, vitamin B12, folate and length of exposure to protease inhibitors (PIs) were evaluated for their possible correlation with hyper-Hcy (>13 micromol/l in females; >15 micromol/l in males) by logistic regression analysis. RESULTS: Ninety-eight HIV-positive patients were recruited. Twenty-eight (28.6%) had hyper-Hcy. Length of exposure to antiretroviral therapy and PIs did not result to be significantly associated with hyper-Hcy risk. Normal folate level was the only factor associated with the outcome, resulting protective from hyper-Hcy, either at univariate (OR = 0.22; CI 95% = 0.06-0.86; p = 0.029) and multivariable (OR = 0.24; CI 95% = 0.06-0.94; p = 0.04) logistic regression analysis. Folate predictive value of hyper-Hcy risk was driven by levels in the lowest quartiles of the study population (i.e. <10.9 nmol/l). CONCLUSIONS: No significant correlations were observed between hyper-Hcy and length of exposure to antiretroviral therapy or PIs. Folate could be a confounding factor in the association between hyper-Hcy and PI exposure found by others. The potential value of folate supplementation, in those who are deficient and in those with hyper-Hcy, merits study.
Adult↗
Inter-pregnancy folate and iron status of women in an inner-city population.
The purpose of the present study was to evaluate whether micronutrient supplementation improved the nutritional status of women with poor diets during the inter-pregnancy interval. Fifty-five women who had given birth to a low birth weight baby (<2.5 kg), and who planned to have a further pregnancy, were recruited to a prospective randomised study in East London, UK. Of the fifty-five mothers recruited, forty-four (78 %) met fewer than four of sixteen dietary reference values according to the information provided in a 7 d diet diary, and were categorised as having an 'inadequate' diet. Half of the mothers in the 'inadequate'-diet group were randomly assigned to receive a micronutrient and a single cell oil supplement containing docosahexaenoic acid. All participants received dietary advice based on analysis of their diet diaries, and general lifestyle advice on preparing for pregnancy. Mothers had a blood sample taken at 3 and 9 months post-partum to measure their folate, Fe stores and fatty acid status. Mean serum and erythrocyte folate levels increased significantly between 3 and 9 months post-partum in both the adequate-diet group and the supplemented group. At 9 months post-partum, over half of the unsupplemented, inadequate-diet group remained severely deficient in folate (serum folate <230 nmol/l) and had low serum ferritin levels (<15 microg/l). The high prevalence of inadequate diets in this inner-city population and the low motivation of women to participate in a nutrition programme suggests that consideration should be given to the provision of free folate and Fe supplements to all women in this and similar populations, or at least to women who have delivered a low birth weight baby, who plan further pregnancies.
Adolescent↗
Drugs and folate metabolism.
Folates are a group of compounds which are required in the diet and are important in DNA, amino acids and possibly also amine metabolism. The biologically active folates are in the tetrahydro form. Tetrahydrofolates are produced from unreduced dietary folates by the enzyme dihydrofolate reductase. A number of drugs such as aminopterin, methotrexate (amethopterin), pyrimethamine, trimethoprim and triamterene act as folate antagonists and produce folate deficiency by inhibiting this enzyme. With other drugs which produce low serum and tissue concentrations of folate such as anticonvulsants, antituberculosis drugs, alcohol and oral contraceptives, the mechanism of this effect is uncertain. Possible mechanism include reduced absorption, prevention of release of folate from tissue stores, altered plasma protein binding, or increased folate metabolism in the liver. Treatment with folic acid antagonists such as methotrexate readily causes megaloblastic anaemia; this can be prevented by therapy with folinic acid (5-formyltetrahydrofolate). The role of other drugs in producing megaloblastic anaemia is less certain, e.g. it occurs in less than 0.75% of patients receiving anticonvulsants. The possible neurological and psychiatric effects of folate deficiency are also uncertain. However, in patients with folate deficiency who have neuropsychiatric symptoms, neuropathy or myelopathy, and normal vitamin B12 levels, it may be of value to try therapy with folic or folinic acid.
Amines↗
Effects of sub-50 oral contraceptives on homocysteine metabolism: a preliminary study.
The influence of a monophasic sub-50 oral contraceptive (OC), Marvelon, on fasting total homocysteine levels was investigated in OC users and controls. Homocysteine levels in serum of OC users were significantly higher (P less than .01) than in controls during the low-hormonal phase of the cycles and comparable with levels determined in heterozygotes for homocystinuria. Blood levels of pyridoxal phosphate (PLP) were significantly lower (P less than .05) in OC users both in the low and high hormonal phase. However, there were no significant differences in the levels of homocysteine nor in folate and vitamin B12 between both groups in the high-hormonal phase. In contrast to the control group, the homocysteine levels in OC users in the high-hormonal phase of the cycle were significantly decreased compared with those on a low-hormonal day (P less than .05). These data suggest that cyclically recurrent periods of hyperhomocysteinemia do occur during sub-50 OC use in normal women and might be considered a predisposition to the occurrence of vascular complications.
Adult↗
The effects of ascorbic acid, vitamin B6, vitamin B12, and folic acid supplementation on the breast milk and maternal nutritional status of low socioeconomic lactating women.
In this double-blind study, the effects of ascorbic acid, vitamin B6, vitamin B12, and folate supplementation on the maternal nutritional status and vitamin content of breast milk in 16 low socioeconomic lactating women were studied. Nine subjects were administered a commercial multivitamin-multimineral supplement and seven were given placebos. Milk samples were collected four times per day at 4-h intervals from 5 to 7 and 43 to 45 days postpartum. Fasting blood samples were taken from all mothers at the end of each milk collection period. Dietary records of all foods consumed were kept from 4 to 7 and 42 to 45 days postpartum. There were no significant differences in milk or plasma levels of ascorbic acid between the unsupplemented and supplemented groups. Both the EGPT index and milk concentration of vitamin B6 were significantly different (p less than 0.01) between the unsupplemented and supplemented groups. The milk concentrations of vitamin B12 increased significantly (p less than 0.05) in the supplemented group, as did the milk concentrations of folate (p less than 0.01). Because of consistently low levels of dietary vitamin B6 and folic acid in this group of low socioeconomic lactating women, either dietary changes or supplements could be necessary to maintain recommended levels of these vitamins in the womens' breast milk.
Ascorbic Acid↗
Serum homocysteine concentrations and their relation to serum folate and vitamin B12 concentrations and coronary artery disease prevalence in an urban, bi-ethnic community.
OBJECTIVE: To compare fasting serum total homocysteine (tHcy) concentrations in a randomly selected sample of elderly (> or = 65 years of age) Hispanic and non-Hispanic White (NHW) men and women, to examine associations of tHcy with folate and vitamin B12, and then to correlate these with the prevalence of coronary heart disease (CHD) in these 4 ethnic/ gender groups. DESIGN AND PARTICIPANTS: Equal numbers of Hispanic and NHW men and women were randomly selected from the Healthcare Financing Administration (Medicare) registrant list for Bernalillo County (Albuquerque), New Mexico, and asked to volunteer for a paid home interview, to be followed by a paid, comprehensive interview/examination covering health and health-related issues. INTERVENTIONS AND MAIN OUTCOME MEASURES: Serum concentrations of tHcy, folate, and vitamin B12 were determined and correlated with the prevalence of CHD, after adjusting for other CHD risk factors (age, diabetes, hypertension, smoking, dyslipidemia, adiposity). RESULTS: Men and Hispanics had higher serum tHcy concentrations compared to women and non-Hispanic Whites (NHWs), respectively. After adjusting for lower concentrations of serum folate and vitamin B12 in Hispanics, the differences between Hispanics and NHWs were no longer significant. There was a direct association between serum tHcy concentrations and the prevalence of CHD after adjusting for other known risk factors that was most significant in Hispanic women. CONCLUSIONS: The higher serum tHcy concentrations observed in Hispanics compared to NHWs can be explained by lower levels of serum folate and vitamin B12. A direct association between serum tHcy concentrations and prevalence of CHD was observed primarily in women, and was most significant in Hispanic women.
Aged↗
Iron deficiency in the tropics.
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Absorption↗
Folate status in women of childbearing age, by race/ethnicity--United States, 1999-2000.
In September 1992, the U.S. Public Health Service (PHS) recommended that women of childbearing age (i.e., aged 15-44 years) who are capable of becoming pregnant should consume 400 microg of the B-vitamin folic acid to reduce the number of cases of spina bifida and anencephaly (neural tube defects [NTDs]). Since then, an ongoing national effort has encouraged women to consume dietary supplements containing folic acid. In 1998, the Food and Drug Administration (FDA) required the fortification of enriched cereal grain products with folic acid, and manufacturers have voluntarily added more folic acid to many ready-to-eat breakfast cereals (CDC, unpublished data, 2002). To assess temporal changes in serum and red blood cell (RBC) folate concentrations among childbearing-aged women, CDC compared folate concentrations for childbearing-aged women who participated during 1988-1994 and 1999-2000 in the National Health and Nutrition Examination Survey (NHANES). This report outlines the results of this comparison and describes serum and RBC folate levels by race/ethnicity. The results indicate that over the period studied, the median serum folate concentration for women aged 15-44 years increased approximately threefold, and the median RBC folate concentration increased approximately twofold. These findings indicate that the national health objective for 2010 to increase the median RBC folate level among women of childbearing age to 220 ng/mL RBC (objective 16.16b) has been met for Mexican-American and non-Hispanic white women but not for non-Hispanic black women. To reduce the number of pregnancies affected by NTDs further, all women of childbearing age capable of becoming pregnant should consume the PHS-recommended level of folic acid daily.
Adolescent↗
[Intraerythrocyte folates and leukocytic neutrophil segmentation in macrocytosis in patients with liver disease].
The problem of macrocytosis above all concerns deficiences and the study of these aspects is particularly important in hepatopathic patients for therapeutic purposes. A state of deficiency can also be revealed in morphological terms by the assessment of the hypersegmentation of polymorphonucleate neutrophil leucocytes. In the group of hepatopathic patients included in the study there was no significant differences in vitamin B12 concentrations in comparison to normal values, whereas mean levels of serum folates were decreased, although still within the normal range. It is worth underlining that to evaluate vitamin B12 it is necessary to measure analogous inefficient components from a metabolic point of view and the assessment of serum folates is not important as an index of normal erythropoietic activity. To overcome this limitation, we assayed intraerythrocytic folates which are vitamin-B12-dependent and these too proved to be within the normal range. Leucocyte hypersegmentation was also excluded by evaluating the mean of PMN lobes. A clearly normal RDW was also observed in macrocytic anemia in hepatopathic patients and this may represent a further difference from hepatocytic macrocytosis.
Erythrocytes↗
Serum folic level in abortion.
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Abortion, Incomplete↗
COMT genotype, micronutrients in the folate metabolic pathway and breast cancer risk.
Catechol-O-methyltransferase (COMT) catalyzes the O-methylation of catechol estrogens (CEs), using S-adenosylmethionine (SAM) as a methyl donor. Several studies have indicated that the val108met COMT polymorphism, which results in a 3-4-fold decrease in activity, is associated with increased breast cancer risk. Folate, whose intake levels have also been associated with breast cancer risk, and other micronutrients in the folate metabolic pathway influence levels of SAM and S-adenosylhomocysteine (SAH), a COMT inhibitor generated by the demethylation of SAM. Because these micronutrients have been shown to alter SAM and SAH levels, we hypothesized that they could also affect COMT-catalyzed CE methylation. Although measurements of SAM and SAH were not initially collected, a secondary analysis of data from two nested case-control studies was performed to examine whether serum levels of folate, vitamin B12 (B12), pyridoxal 5'-phosphate (PLP), cysteine and homocysteine, in conjunction with COMT genotype, were associated with breast cancer risk. COMT(HH) (high activity COMT homozygote) breast cancer cases had statistically significantly lower levels of homocysteine (P = 0.05) and cysteine (P = 0.04) and higher levels of PLP (P = 0.02) than COMT(HH) controls. In contrast, COMT(LL) (low activity COMT homozygote) cases had higher levels of homocysteine than COMT(LL) controls (P = 0.05). No associations were seen between B12, COMT genotype, and breast cancer risk. An increasing number of COMT(L) alleles was significantly associated with increased breast cancer risk in women with below median levels of folate (P(trend) = 0.05) or above median levels of homocysteine (P(trend) = 0.02). These findings are consistent with a role for certain folate pathway micronutrients in mediating the association between COMT genotype and breast cancer risk.
Breast Neoplasms↗
Homocysteine, malondialdehyde and endothelial markers in dialysis patients during low-dose folinic acid therapy.
OBJECTIVES: Haemodialysis patients have elevated levels of the atherogenic amino acid homocysteine. We wanted to assess the effects of small doses of intravenous folinic acid (the active form of folic acid) on some biochemical risk factors of cardiovascular disease. DESIGN: Longitudinal and open intervention study. SETTING: Two dialysis units in the County of Rogaland. SUBJECTS: All patients on maintenance haemodialysis were invited, and 32 of 35 patients gave their informed consent. INTERVENTIONS: After each dialysis session, the patients were given 1.0 mg of folinic acid intravenously thrice a week for a period of 3 months. Prior to and during the study, all patients were on maintenance supplementation with small doses of vitamins B1, B2, B3, B5, B6 and B12. MAIN OUTCOME MEASURES: Changes in the levels of (i) plasma total homocysteine (p-tHcy) and folate, (ii) circulating endothelium related proteins--markers of endothelial activation and (iii) serum malondialdehyde (S-MDA)--a marker of oxidative stress and lipid peroxidation. RESULTS: The p-tHcy levels were reduced by 37% (P < 0.0001), whilst the serum and erythrocyte folate levels increased by 95 and 104%, respectively (P < 0.0001 for both). The circulating levels of endothelium related cellular adhesion molecules and haemostatic factors remained high and unchanged, except the thrombomodulin (TM) levels increased (P = 0.0004). The high levels of S-MDA were reduced by 26% (P = 0.003). CONCLUSIONS: Low doses of folinic acid given intravenously to dialysis patients reduced their levels of p-tHcy and S-MDA and thus improved their cardiovascular risk profile. The concurrent increment in TM levels was unexpected and of unknown clinical significance.
Creatinine↗
Assessment of three levels of folic acid on serum folate and plasma homocysteine: a randomised placebo-controlled double-blind dietary intervention trial.
OBJECTIVE: To determine the minimum effective dose of folic acid required to appreciably increase serum folate and to produce a significant reduction in plasma total homocysteine (tHcy). DESIGN: Double-blind, randomised placebo-controlled intervention trial. SETTING: Community-based project in a New Zealand city. SUBJECTS: Seventy free living men and women with tHcy> or =10 micromol/l. Mean age (range) was 58 (29-90) y. INTERVENTIONS: Daily consumption over 4 weeks of 20 g breakfast cereal either unfortified (placebo) or fortified with 100, 200 or 300 microg folic acid. Dietary intake was determined by weighed diet records and consumption of commercially fortified products was avoided. MAIN OUTCOME MEASURES: Plasma tHcy and serum folate concentrations. RESULTS: Average serum folate concentrations (95% CI) increased significantly in the treatment groups relative to the control group by 28(9-51)%, 60(37-87)% and 79(51-114)% for supplementation with 100, 200 and 300 microg folic acid, respectively. A reduction in tHcy was observed, being 16(8-22)%, 12(4-18)% and 17(9-24)% in the three treatment groups, respectively. CONCLUSIONS: A regular intake of as little as 100 microg folic acid per day was sufficient to lower tHcy in persons at the upper end of the normal range for tHcy. Low-level fortification may also be appropriate for lowering the risk of neural tube defects given that, when aggregated from all sources, the total intake of folic acid may be sufficiently high to adequately improve the folate status of young women.
Adult↗
A phase II study of fixed-dose capecitabine and assessment of predictors of toxicity in patients with advanced/metastatic colorectal cancer.
The purpose of this study was to evaluate the safety and activity of fixed-dose capecitabine in patients with advanced colorectal cancer and to correlate pretreatment plasma concentrations of homocysteine and serum and red cell folate with toxicity. Patients received capecitabine 2000 mg (4 x 500 mg tablets) twice daily on days 1-14 every 3 weeks. They were reviewed weekly during the first cycle and then three weekly for safety assessment. Eligibility criteria were advanced/metastatic colorectal cancer, < or = 2 prior chemotherapy regimens, ECOG performance status 0-2 and life expectancy >12 weeks. A total of 60 patients were enrolled and 55 were evaluable for efficacy. The median age was 72 years and 63% of patients had a performance status of 1 or 2. Confirmed tumour responses were reported in 15 patients (28%; 95% confidence interval (CI), 15.7-40.3%). The median time to disease progression was 4.9 months and median overall survival was 11.2 months. The median ratio of fixed dose to body surface area (BSA)-calculated dose was 88% (range 65-108%). Significant myelosuppression was not observed. Grade 2/3 treatment-related adverse events were diarrhoea (34%), fatigue (27%), stomatitis (15%) and hand-foot syndrome (22%). Dose reduction due to adverse events was required in 16 patients (29%) and multiple reductions in five patients (9%). There was no grade 3/4 haematological toxicity, any grade 4 adverse events or treatment-related deaths. Patients with higher pretreatment levels of serum folate experienced significantly greater toxicity (P = 0.02, CI: 1.0-1.2) during cycle 1 and over the entire treatment period (P = 0.04, CI: 1.0-1.3). Pretreatment homocysteine concentrations did not predict for toxicity. In conclusion, fixed-dose capecitabine appears to have similar efficacy and safety compared to the currently recommended dose schedule based on body surface area and simplifies drug administration. A high pretreatment folate may be predictive of increased toxicity from capecitabine.
Administration, Oral↗
[Do oral contraceptives affect the folic acid level in blood?].
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Adult↗
Maternal serum folacin levels during and after normal pregnancy.
Maternal serum folacin levels decrease during pregnancy. This decrease could not be explained by hemodilution. Postpartum levels did not increase significantly compared to values measured at partum. In a healthy Dutch pregnant population receiving no vitamin supplementation the folacin status is at risk and after pregnancy it takes considerable time to refill folacin stores.
Adult↗
Estrogen stimulation of conjugase activity in the uterus of ovariectomized rats.
Recent observations have indicated that uterine folic acid conjugase (pterolypolyglutamyl hydrolase) undergoes rhythmic variation during the reproductive cycle of the rat. In the present study conjugase activity and ratios of "total" folate to "free" folate were determined in uterine homogenates of ovariectomized rats, with ane without estrogen stimulation. An increase in conjugase levels and a relative increase in the "free" folate component occurred in castrated animals 12 to 18 hours following injection of 10 mug of estradiol-17beta.
Animals↗