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PubMed1983

Demographic analysis of serum folate and folate-binding capacity in hospitalized patients.

Serum folate levels and unsaturated folate-binding capacity (UFBC) in a mixed population of outpatients and inpatients were analyzed with respect to race, sex, and age. The results supported the relatively high prevalence of subnormal serum folates in patient populations, did not find lower serum folates in the elderly, and revealed significantly higher UFBC in Negro patients, in male patients, and in patients older than 50 years.

Adult↗

PubMed2001

Homocysteine, its metabolites, and B-group vitamins in renal transplant patients.

BACKGROUND: Increased plasma total homocysteine (tHcy) levels are an independent risk factor for cardiovascular morbidity in patients with normal and impaired renal function, including stable renal transplant recipients (RTRs). Plasma concentrations of the metabolites of Hcy, such as cystathionine (Cys), methylmalonic acid (MMA), 2-methylcitric acid (MC), and its diastereomers MCI and MCII have been reported in only a few articles. We therefore looked for the serum concentration of these metabolites and their relationship to renal function, cardiovascular diseases, the immunosuppressive treatment, and serum concentrations of cobalamin and folate. METHODS: Fifty RTRs (mean age 50.4 +/- 11.8 years, 35.9 +/- 44.4 months after kidney transplantation) and 35 controls (NP; mean age 43.5 +/- 14.4 years) were studied. Total Hcy and its metabolites were measured by gas chromatography-mass spectrometry (GC-MS). RESULTS: Total Hcy, MMA, Cys, and MC were elevated twofold to sixfold as compared with NP, with a significant interrelationship between these compounds. With the exception of Cys, they were significantly correlated with serum creatinine. Serum folate levels were inversely correlated with tHcy, Cys and cobalamin with MMA and the ratio of MCI/MCII. There was no correlation between tHcy concentration and its metabolites with immunosuppressive treatment (CsA vs. FK506), clinical history, or current findings of cardiovascular complications and blood pressure profile. CONCLUSION: Prospective studies are needed to find out whether the lowering or normalization of serum concentrations of tHcy and its metabolites due to treatment with B vitamins should be achieved to reduce the cardiovascular risk and improve the long-term outcome of allografts and of patients.

Adult↗

PubMed1992

Effects of folate and zinc supplementation on patients undergoing chronic hemodialysis.

Twelve men and nine women undergoing chronic hemodialysis were studied to evaluate folate intake and status in relation to use of folate supplements. Because of possible folate-zinc interactions, zinc status was also evaluated. The patients were classified into four groups based on daily supplementation: no folate or zinc, 22.5 mg zinc, 5 mg folate, and 5 mg folate and 22.5 mg zinc. A food frequency questionnaire was developed to estimate average daily intakes of folate and zinc. Patients' mean dietary folate intake was 30% or more above the Recommended Dietary Allowance (RDA), whereas their mean dietary zinc intake was close to the RDA. No significant differences in dietary folate or zinc intakes existed among groups. Red blood cell (RBC) folate levels of folate-supplemented patients were approximately 10 times higher than those of patients who did not receive folate and who had normal RBC folate levels. Serum zinc levels in all four groups of patients were close to the lower limit of the normal range and were unaffected by supplementation; however, hair zinc levels of six zinc-supplemented patients were significantly higher than those of healthy unsupplemented control patients. Generalization of this study's findings are limited by its descriptive nature; nevertheless, for these patients and presumably for similar patients who also have adequate dietary folate intakes, high-dose folate supplementation does not appear to be necessary to maintain normal folate status. No evidence of a folate-zinc interaction was obtained; however, serum zinc may not be a valid index of zinc status in these patients.

Adult↗

PubMed1998

Absorption of dietary and supplemental folate in women with prior pregnancies with neural tube defects and controls.

BACKGROUND: The Public Health Service of the United States recommends that all women capable of childbearing consume .4 mg (400 microg) folic acid per day to decrease the risk of having a pregnancy affected by a neural tube defect such as spina bifida or anencephaly. Three strategies are available to women to achieve this goal: use of dietary supplements; use of fortified foods; and/or increased intake of naturally occurring folate from foods. Identification of the most effective vehicle for delivery of folate to all women is critical in order to prevent these devastating congenital defects. OBJECTIVE: To investigate the difference in response to an oral load of folate both from naturally occurring food sources and synthetic supplements among women with prior pregnancies affected by neural tube defects and controls. METHODS: We compared the absorption of test doses of 400 microg pteroylglutamic acid (unconjugated or synthetic folic acid found in supplements) and 400 microg pteroylpolyglutamic acid (conjugated or food folate) in 10 women with a history of neural tube defect affected pregnancies and eight controls with normal birth outcomes. The folate test dose was given as either 32 fluid ounces of orange juice or a folic acid single supplement pill. All participants received each test dose at separate clinic visits. The response to each test dose was measured by constructing an area under the curve (AUC) from the serum folate levels at 1, 2 and 3 hours post dose and applying a t-test to compare within and between cases and controls. We also compared red cell folate, vitamin B12, zinc and homocysteine between cases and controls. RESULTS: Within group comparisons showed that the area under the curve was significantly greater for the pteroylglutamic acid dose compared to the pteroylpolyglutamic acid dose for both cases and controls (p=0.02 and p=0.03, respectively). In a between group comparison, control women had a greater serum folate response to both forms of the vitamin compared to the case women, but the difference reached statistical significance only for the pteroylglutamic acid dose (p=0.02). Other measured nutrients differed between cases and controls, but did not reach statistical significance. CONCLUSION: We conclude that for all women synthetic folic acid as supplements or fortified foods may be the best way to increase acute folate levels in the blood, and thus delivery to the developing embryo. Further, since case women had a diminished response to both forms of the vitamin, and some case women had almost no response, we speculate that women with prior affected pregnancies may need a larger dose of folate to elicit a plasma response equivalent to the general population.

Absorption↗

PubMedDate not supplied

Vitamin B12 and its relationship to age of onset of multiple sclerosis.

Attention has been focused recently on the association between vitamin B12 metabolism and the pathogenesis of multiple sclerosis (MS). Several recent reports have documented vitamin B12 deficiency in patients with MS. The etiology of this deficiency in MS is unknown. The majority of these patients do not have pernicious anemia and serum levels of the vitamin are unrelated to the course or chronicity of the disease. Moreover, vitamin B12 does not reverse the associated macrocytic anemia nor are the neurological deficits of MS improved following supplementation with vitamin B12. It has been suggested that vitamin B12 deficiency may render the patient more vulnerable to the putative viral and/or immunologic mechanisms widely suspected in MS. In the present communication, we report that serum vitamin B12 levels in MS patients are related to the age of onset of the disease. Specifically, we found in 45 MS patients that vitamin B12 levels were significantly lower in those who experienced the onset of first neurological symptoms prior to age 18 years (N = 10) compared to patients in whom the disease first manifested after age 18 (N = 35). In contrast, serum folate levels were unrelated to age of onset of the disease. As vitamin B12 levels were statistically unrelated to chronicity of illness, these findings suggest a specific association between the timing of onset of first neurological symptoms of MS and vitamin B12 metabolism. In addition, since vitamin B12 is required for the formation of myelin and for immune mechanisms, we propose that its deficiency in MS is of critical pathogenetic significance.

Adolescent↗

PubMed2006

A report of two families with sarcosinaemia in Hong Kong and revisiting the pathogenetic potential of hypersarcosinaemia.

INTRODUCTION: Sarcosinaemia is a rare metabolic disorder which has not been reported in Asia. CLINICAL PICTURE: The urine samples of 2 patients were screened as a routine metabolic screening offered for patients with mental retardation in our hospital. We used gas chromatography-mass spectrometry (GC-MS) which is capable of detecting abnormal pattern in amino acids and organic acids. Plasma sarcosine level was further quantified by GC-MS. The same methods were used in the investigations of asymptomatic family members. Urine examination by GC-MS revealed excessive amount of sarcosine in urine (normally undetectable) and their plasma sarcosine levels were raised. The 2 differential diagnoses of presence of sarcosine in urine--glutaric aciduria type II and folate deficiency--were ruled out by the absence of abnormal organic acids in the initial urine screen and by normal serum folate level respectively. Screening of the 2 families identified excessive sarcosine in urine in 2 siblings, one from each family. However, these 2 siblings of indexed patients thus identified have no neurological or developmental problem. CONCLUSION: Our finding was consistent with the notion that sarcosinaemia is a benign condition picked up coincidentally during screening for mental retardation.

Amino Acid Metabolism, Inborn Errors↗

PubMed1991

Effect of residual splenic function and folate levels on the frequency of micronucleated red blood cells in splenectomized humans.

Frequencies of micronucleated erythrocytes in the peripheral blood of splenectomized individuals can be used as an index of genetic damage to erythrocyte precursor cells in the bone marrow. This is in contrast to non-splenectomized humans, whose micronucleated erythrocytes are removed by the spleen. Many subjects whose spleen has been removed surgically have residual spleen tissue and consequent residual spleen function (RSF), which can be measured by the percentage of 'pitted' peripheral red blood cells. In this study evidence of RSF was associated with decreased frequencies of micronucleated erythrocytes. Analysis of data limited to subjects with minimal spleen function suggested an inverse association between the incidence of micronucleated erythrocytes and serum folate levels that was not apparent in the absence of stringent control for RSF.

Chromosome Aberrations↗

PubMed2000

Folate supplementation in pregnancy.

BACKGROUND: Folate depletion may result in anaemia during pregnancy. OBJECTIVES: The objective of this review was to assess the effects of folate supplementation in pregnancy on haematological and biochemical parameters and measures of pregnancy outcome. This review did not address the role of periconceptual folate supplementation to diminish the risk of fetal malformation. SEARCH STRATEGY: A comprehensive electronic search included that of the Cochrane Pregnancy and Childbirth Group trials register. SELECTION CRITERIA: Acceptably controlled trials of folate supplementation compared with placebo or no treatment to pregnant women with normal haemoglobin levels. DATA COLLECTION AND ANALYSIS: Trial quality was assessed. Study authors were contacted for additional information when necessary. MAIN RESULTS: Twenty-one studies were included. The trials varied in quality. Compared to placebo or no supplementation, folate supplementation was associated with increased or maintained serum folate levels (odds ratio 0.18, 95% confidence interval 0.13 to 0.24) and red cell folate levels (odds ratio 0.18, 95% confidence interval 0.09 to 0.38). Folate supplementation was associated with a reduction in the proportion of women with low haemoglobin level in late pregnancy (odds ratio 0.61, 95% confidence interval 0.52 to 0.71) and megaloblastic erythropoiesis (odds ratio 0.65, 95% confidence interval 0.45 to 0.95). Apart from a possible reduction in the incidence of low birthweight, folate supplementation appears to have no measurable effect on any other substantive measures of pregnancy outcome. REVIEWER'S CONCLUSIONS: Folate supplementation during pregnancy appears to improve haemoglobin levels and folate status. There is not enough evidence to evaluate whether folate supplementation has any effect, beneficial or harmful, on clinical outcomes for mother and baby.

Anemia↗

PubMed1983

Comparison of haematological indices between women of four ethnic groups and the effect of oral contraceptives.

Six-hundred-and-eighty-two women volunteers from four ethnic groups--Black, Indian, Oriental and White took part in a study to assess differences in haematological indices between the groups. This study was part of a broad investigation into the metabolic effects of oral contraceptives. The effect of the oral contraceptive (OC) on haematological indices was analysed but not found to be significant. The haemoglobin concentrations were lower than normal laboratory reference values for White subjects in 12.5% of Indian, 16.5% of Black and 4.3% of Oriental control groups respectively. All the White control group were within the normal range. These findings were considered in relation to age, weight, pregnancies, smoking, alcohol consumption, nutritional status, and disorders of haemoglobin synthesis. A deficient iron intake accounted for the high incidence of low haemoglobin in the Indian group in whom low transferrin saturation and serum ferritin were observed. With the possible exception of inherited disorders of haemoglobin synthesis, none of the factors we considered could account for the low haemoglobins found in the Black group. Separate reference values for haematological indices in different ethnic populations are considered.

Adolescent↗

PubMedDate not supplied

[Reversible dementias and treatable dementias].

INTRODUCTION: When studying patients with dementia the search of reversible or treatable entities has a primordial role. Many patients do not recover the previous cognitive level; however, that does not signify that the disease is not treatable with partial recovery or prevention of secondary progression. DEVELOPMENT: The prevalence of reversible dementias is around 15% in most series. Rutine studies include complete blood cell count, erythrocyte sedimentation rate, electrolytes and chemistry panel, liver function tests, vitamin B12 and folate serum levels, urianalysis and syphilis serology. Special tests such as thyroid function tests, protein electrophoresis, human immunodeficiency virus serology, heavy metals serum levels, electrocardiography, cerebrospinal fluid analysis, and chest roentnography should be performed according to the patient clinical profile. Neuroimaging should be done in all cases. Non-contrasted computed tomography must be performed first. Magnetic resonance imaging is most useful for searching for more subtle structure abnormalities. Electroencephalogram, positron emission tomography and single photon emission computed tomography are not recommended as routine studies. Brain biopsy is indicated in few cases. CONCLUSION: Most common causes of reversible and treatable dementias include: medications, obstructive hydrocephalus, infectious, vascular, immunological, psychiatric, toxic and metabolic disorders, among others.

Dementia↗

PubMed1981

[Folate determination in serum for clinical use (author's transl)].

Folate deficiency may be diagnosed in man by measuring serum folate activity using either a microbiological procedure with L. casei or a radioassay. The microbiological procedure tends to be time consuming and tedious, as compared with the radioassay; nevertheless it allows the accurate determination of each folate derivative that is normally present in serum. The comparison of serum folate levels obtained by the two methods shows an adequate correlation. However, it results from individual samples show that the values obtained by the radioassay are lower than the microbiological ones by 10-30%. The lower results in the radioisotope test may be caused by the presence of high levels of unsaturated endogenous protein binders in serum and/or by the difference in affinity of lactoglobulin - the binding protein used in the test - for folic acid (standard) and 5-methyl FH4 or 10-formil FH4 (serum).

Biological Assay↗

PubMed2003

Predictors of vitamin B12 deficiency: age and Helicobacter pylori load of antral mucosa.

BACKGROUND/AIMS: The aim of this study was to assess the frequency of vitamin B12 deficiency in patients with non atrophic gastric mucosa and any relationship between the presence of vitamin B12 deficiency and demographic, hematologic, and histopathologic parameters. METHODS: Three hundred and ten patients with no gastric mucosal atrophy on histologic evaluation were included in the study. Chronic inflammation, neutrophil activity and H. pylori load were scored using the Sydney classification system. Variables that might influence or predict the presence of vitamin B12 deficiency (age, gender, hemoglobin, mean corpuscular volume, serum folate level, scores of histologic parameters) were evaluated by univariate/multivariate analysis. RESULTS: The percentages of patients with vitamin B12 concentrations of < 250 pg/mL, < 200 pg/mL, and =100 pg/mL were 67.4%, 46.8% and 6.5% respectively. Patient age and all three histologic were inversely related to vitamin B12 deficiency (p<0.05). By multivariate analysis, factors independently associated with serum vitamin B12 deficiency were age and antral H. pylori load (p<0.05). CONCLUSIONS: The higher frequency of vitamin B12 deficiency in this study compared with a western study may be a reflection of the effect of H. pylori infection on serum vitamin B12 level. In addition, age was shown to be an independent risk factor for vitamin B12 deficiency irrespective of gastric atrophy. It is already known that the presence of H. pylori on gastric mucosa influence serum vitamin B12 levels. Hematologic parameters are not useful in predicting the deficiency of this vitamin.

Adult↗

PubMed2005

Biochemical indicators of nutritional status and dietary intake in Costa Rican Cabécar Indian adolescents.

The purpose of this study was to determine the blood levels of selected nutritional status indicators and the dietary intake of Costa Rican Cabécar Indians aged 10 to 16 years. The results showed that 65% of the adolescents had an adequate body mass index (BMI) for their age, and 32% had a BMI < 5th percentile. Likewise, the study revealed a high prevalence of anemia (57%), deficient serum folate levels (54%), deficient vitamin B12 levels (31%), and subclinical vitamin A deficiency (10%). Additionally, the youngsters had elevated prevalences of high triglyceride levels (77%), borderline high-density lipoprotein (HDL) cholesterol levels (46%), homocysteine levels > 10 micromol/L (29%), and homozygous mutation of methylenetetrahydrofolate reductase (MTHFR) (49%). The diet was poor, being high in saturated fat and low in polyunsaturated fat, fiber, and several micronutrients. The dietary intakes of more than 55% of the adolescents did not meet 50% of the estimated average requirements (EAR) for zinc, vitamin A, vitamin C, vitamin B12, vitamin B2, and folate. Furthermore, a high prevalence of parasitosis was found (68%). Our results show an adolescent Cabécar population with a mosaic of nutritional deficiencies and cardiovascular risk factors.

Adolescent↗

PubMed1998

Human parvovirus B19 capsid antigen in granulocytes in parvovirus-B19-induced pancytopenia after bone marrow transplantation.

A patient with refractory anemia with an excess of blasts in transformation developed pancytopenia and a concurrent interstitial pneumonia 110 days after allogeneic bone marrow transplantation. Bone marrow examination showed 0.4% giant proerythroblasts and 86.2% granulocytes, some of them large with a bizarre configuration and the others of normal size. Serum folate level was found low, 0.6 ng/ml. Immunocytochemistry with a B19-specific monoclonal antibody MAB8292 revealed B19 capsid antigen only in erythroblasts and large, bizarre granulocytes, but not in granulocytes of normal size. In situ hybridization of bone marrow cells using digoxigenin-labeled DNA probes detecting parvovirus B19 also demonstrated positive signals in 8.5% of marrow cells. Parvovirus B19 DNA was isolated from the serum and the bronchoalveolar lavage fluid of this patient by the polymerase chain reaction. These findings suggest that neutropenia may be caused by an involvement with parvovirus B19 though a deficiency of folic acid may have in part contributed to the genesis of neutropenia in the patient. The relevance of parvovirus B19 to the interstitial pneumonia remains unclear.

Adult↗

PubMed1976

Folic acid absorption in regional enteritis.

The authors have investigated intestinal absorption of folic acid by jejunal perfusion with a triple lumen tube in five subjects with regional enteritis. The subjects' intestinal disabilities ranged from terminal ileitis to short bowel syndrome. Two had steatorrhea and two had low serum folate levels. Absorption of pteroylglutamic acid was normal in all five. This suggests that folic acid deficiency, common in this disorder, is largely caused by malnutrition, not malabsorption.

Adult↗

PubMed1999

Folic acid improves arterial endothelial function in adults with hyperhomocystinemia.

OBJECTIVES: To evaluate whether oral folic acid supplementation might improve endothelial function in the arteries of asymptomatic adults with hyperhomocystinemia. BACKGROUND: Hyperhomocystinemia is an independent risk factor for endothelial dysfunction and occlusive vascular disease. Folic acid supplementation can lower homocystine levels in subjects with hyperhomocystinemia; however, the effect of this on arterial physiology is not known. METHODS: Adults subjects were recruited from a community-based atherosclerosis study on healthy volunteers aged 40 to 70 years who had no history of hypertension, diabetes mellitus, hyperlipidemia, ischemic heart disease or family history of premature atherosclerosis (n = 89). Seventeen subjects (aged 54 +/- 10 years, 15 male) with fasting total homocystine levels above 75th percentile (mean, 9.8 +/- 2.8 micromol/liter) consented to participate in a double-blind, randomized, placebo-controlled and crossover trial; each subject received oral folic acid (10 mg/day) and placebo for 8 weeks, each separated by a washout period of four weeks. Flow-mediated endothelium-dependent dilation (percent increase in diameter) of the brachial artery was assessed by high resolution ultrasound, before and after folic acid or placebo supplementation. RESULTS: Compared with placebo, folic acid supplementation resulted in higher serum folate levels (66.2 +/- 7.0 vs. 29.7 +/- 14.8 nmol/liter; p < 0.001), lower total plasma homocystine levels (8.1 +/- 3.1 vs. 9.5 +/- 2.5 micromol/liter, p = 0.03) and significant improvement in endothelium-dependent dilation (8.2 +/- 1.6% vs. 6 +/- 1.3%, p < 0.001). Endothelium-independent responses to nitroglycerin were unchanged. No adverse events were observed. CONCLUSION: Folic acid supplementation improves arterial endothelial function in adults with relative hyperhomocystinemia, with potentially beneficial effects on the atherosclerotic process.

Administration, Oral↗

PubMed2003

Anemia at the end of life: prevalence, significance, and causes in patients receiving palliative care.

While data exist on the prevalence and causes of anemia in defined groups of the elderly, information on palliative care patients is limited. Compared to actively treated oncology patients, for whom anemia treatment has demonstrated improved quality of life and symptom alleviation, studies of treatment outcomes in palliative care patients are limited. Knowledge of the extent and causes of anemia in palliative care patients is needed, as correction of anemia in these patients could potentially improve their physical, emotional, and cognitive functioning. In the present study, clinical data and blood test results of 105 patients meeting specific eligibility criteria were examined to estimate the prevalence of anemia and investigate its causes. Ninety-five (90.5%) patients had advanced cancer. Based on World Health Organization criteria, anemia was found in 77% of men (Hb <130 g/l) and 68.2% of women (Hb <120 g/l). The diagnosis was anemia of chronic disease in 76.7% of women and 46.8% of men. Patients with prostate cancer had a significantly lower mean Hb level (P=0.007) and more evidence of bone metastases (P=0.0007) than those with other cancers. Neutrophil hypersegmentation, suggesting occult folate deficiency, was present in 28.6% of patients, being more common in those with major weight loss (58.3%) than those with moderate (37%) or mild/no weight loss (26%) (P=0.019). The findings suggest that anemia is highly prevalent in the palliative care setting. Although anemia of chronic disease is most common, occult folate deficiency may be more prevalent than previously suspected. The findings suggest that a low serum folate level is an insensitive marker of occult folate deficiency. A randomized controlled trial of folic acid treatment is proposed.

Adult↗

PubMed2003

10-propargyl-10-deazaaminopterin: an antifolate with activity in patients with previously treated non-small cell lung cancer.

PURPOSE: 10-propargyl-10-deazaaminopterin (PDX) has superior antitumor efficacy in mouse xenograft models, likely attributable to increased uptake by the RFC-1 folate transporter and greater intracellular polyglutamylation. In a previous Phase I trial, stomatitis was the dose-limiting (and only clinically significant) toxicity of PDX. The recommended Phase II dose was 150 mg/m(2) i.v. every 2 weeks. Responses observed in patients with non-small cell lung cancer (NSCLC) in the Phase I trial prompted this Phase II trial. EXPERIMENTAL DESIGN: Patients had stage IIIB or IV NSCLC and either no previous chemotherapy or progression after initial response or stable disease to one previous chemotherapy regimen. Initially, PDX was administered at a dose of 150 mg/m(2) every 2 weeks. However, to decrease the frequency of stomatitis, the last 10 patients were treated at a dose of 135 mg/m(2). We planned to correlate PDX effects with folate and homocysteine levels and the expression of genes associated with folate transport and polyglutamylation. RESULTS: Thirty-nine patients were enrolled, 38 of whom were evaluable for response. Four patients had confirmed, major objective responses (10% based on intent to treat, 95% confidence interval 3-25) lasting 4, 9, 12, and 15 months. Twelve patients (31%) had stable disease. The median survival was 13.5 months. The predicted 1- and 2-year survival rates were 56 and 36%, respectively. Two patients (5%) suffered grade 4 stomatitis, and 6 (15%) had grade 3. No clinically significant myelosuppression occurred. No correlation between homocysteine or serum folate levels and severity of stomatitis was observed. Area under the curve (calculated using a limited sampling model) correlated with mucositis grade. A trend was noted between folate transporter expression and treatment effect. CONCLUSIONS: The broad applicability of this new antifolate with limited toxicity and proven efficacy in NSCLC encourage further development of this compound. Several trials are now underway combining PDX with other chemotherapeutic agents and testing its efficacy in other cancers.

Adult↗