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PubMed1999

Variability of fasting and post-methionine plasma homocysteine levels in normo- and hyperhomocysteinaemic individuals.

To assess the variability of plasma homocysteine levels, fasting and post-methionine homocysteine levels were measured twice, at baseline and after follow-up of 1-4 months, in 16 individuals with normal and 26 with elevated homocysteine levels after methionine loading. The intra-individual coefficients of variation varied from 15 to 23% for fasting and post-methionine homocysteine levels, whether these levels were within the normal range or not. As a result, test-retest agreement was poor when subjects were dichotomized as having 'normal' or 'abnormal' homocysteine levels (itself a questionable concept). There was a relation between the average post-methionine homocysteine levels (at the first and second measurement) and the difference between both measurements (r = 0.37, P = 0.016). In normohomocysteinaemic individuals, delta (i.e., the difference between baseline and follow-up) fasting homocysteine and delta post-methionine homocysteine were correlated negatively with delta folate serum levels: r = -0.64, P = 0.007 and r = -0.50, P = 0.05, respectively. Individuals homozygous for the 677 C-->T mutation in the 5,10-methylenetetrahydrofolate reductase gene showed a greater variation of fasting homocysteine levels than those homozygous for the wild type (P = 0.017). In summary, we suggest that there is a substantial intra-individual variability in plasma homocysteine levels over time and that this variability is significantly related to the variability in serum folate levels, especially in normohomocysteinaemic individuals.

5,10-Methylenetetrahydrofolate Reductase (FADH2)↗

PubMed1983

Serum and red cell folate and serum vitamin B12 levels in horses.

Vitamin B12 and folate concentrations were determined by radioimmunoassay in groups of horses in Queensland. Highest serum vitamin B12 levels were found in supplemented performance horses. These, together with pastured horses that included pregnant and lactating mares, had significantly greater serum folate activity than permanently stabled animals. The range of red cell folate concentrations was much narrower in horses in training than from any other group. Red cell folate may be a better indicator of a horse's folate status than the serum folate value. Vitamin B12 and folate concentrations were highest in spring and summer. Small intestinal dysfunction in 2 horses was not associated with vitamin B12 or folate malabsorption. Serum folate levels returned to normal 24 h after intramuscular injections of 75 to 150 mg folic acid, whereas serum vitamin B12 values remained elevated for at least one week following injections of 8 to 10 mg to non-supplemented horses. None of the horses in this survey had evidence of vitamin B12 or folate deficiency, or showed significant haematological changes. Nevertheless, permanently stabled horses and some horses in training may require additional folic acid, preferably on a daily basis by the oral route. However, exogenous vitamin B12 administration does not appear to be justified.

Animals↗

PubMed1979

Serum erythrocyte folate levels in thalassaemic patients in Thailand.

The mean serum and adjusted red cell folate levels, as measured by microassay using Lactobacillus casei, respectively were 8.87 +/- SD 3.28 microgram/l and 436 +/- SD 107 microgram/l in 76 normal subjects, 4.22 +/- SD 2.70 microgram/l and 182 +/- SD 114 microgram/l in 55 patients with beta-thalassaemia/Hb E disease and 6.36 +/- SD 2.95 microgram/l and 320 +/- 158 microgram/l in 37 patients with Hb H disease. The mean serum and adjusted red cell folate values of the patients with beta-thalassaemia/Hb E disease and the mean serum folate value of the patients with Hb H disease were significantly lower than those of the normal subjects (P less than 0.001). 33% of the beta-thalassaemia/Hb E patients and 8% of the Hb H patients showed low serum folate levels (less than 3 microgram/l) whereas 84% of the former and 45% of the latter showed low adjusted red cell folate levels (less than 270 microgram/l). The group of beta-thalassaemia/Hb E disease with low serum folate levels had lower mean haemoglobin concentration and lower mean adjusted red cell folate level than the group with normal serum folate levels. Since the Thai diets have high folate content, the observed low serum and erythrocyte folate levels in thalassaemic patients most likely occur from massively increased erythropoiesis. Folate, 5 mg/d, is now routinely prescribed to such patients especially to those with severe anaemia.

Adolescent↗

PubMed2004

Serum levels of folate, vitamin B12 and homocysteine in complete hydatidiform mole.

OBJECTIVE: To investigate the association, if any, between serum concentrations of folate, vitamin B12 and homocysteine in complete hydatiform mole (CHM). STUDY DESIGN: Blood samples were taken from 37 women with CHM and 52 healthy controls in the first trimester of pregnancy. Serum was analyzed for folate, vitamin B12 and homocysteine using electrochemiluminescence and chemiluminescence assay. RESULTS: In patients with CHM, significantly higher mean levels of serum vitamin B12 were encountered (247.21 versus 180.32 pg/mL, P=.012). Significantly lower mean levels of serum folate were found in patients with CHM as compared with controls (7.91 versus 10.72 ng/mL, P=.008). Homocysteine levels tended to be higher in patients with CHM, but the difference was not statistically significant (10.58 versus 8.79 nmol/mL, P=.104). CONCLUSION: This is the first report to suggest an association between folate, vitamin B12 and CHM. Folate may play a protective role in preventing CHM.

Adult↗

PubMed1976

Folic acid binding protein and folate balance in uremia.

To determine the incidence and importance of folate deficiency in uremia, we studied 41 patients who had chronic uremia but who were not receiving hemodialysis. Serum folate level was assayed by microbiological, whole serum radioassay, and heat-extracted radioassay techniques. Mean serum folate level, as determined with the Lactobacillus casei method, was 6.9 ng/ml (normal, more than 3.0 ng/ml). The mean heat-extracted radioassay serum folate level was 6.6 ng/ml. Only 10% of our patients had subnormal serum folate values, as determined with these techniques. No cases of megaloblastic anemia were discovered, and the hematologic profiles correlated with L casei and heat-extracted radioassay serum folate values. The mean serum folic acid binding protein (FABP) level was significantly greater for the uremic patients than for control patients (26% vs 9.9%, respectively; P = .0005). Our results show that elevated levels of serum FABP spuriously depress the serum folate level, as determined with the whole serum radioassay technique, but apparently do not retard delivery of folate to the tissue in vivo.

Creatinine↗

PubMed1999

Folate levels in psychiatric outpatients.

This study examines folate in psychiatric outpatients. Fifty-three outpatients with schizophrenia and 24 outpatients with depressive disorder assessed with the Schedules for Clinical Assessment in Neuropsychiatry interview are included. Patients with schizophrenia had lower serum folate levels than age- and sex-matched controls, while red cell folate levels did not differ. Serum folate levels showed a negative correlation with the Clinical Global Impression, disorganized dimension, and total Positive and Negative Syndrome Scale score. Patients with depressive disorder had lower serum folate levels than healthy controls, but showed no differences in red cell folate levels. Only two patients with schizophrenia had red cell folate levels below the normal range.

Adult↗

PubMed1990

Vitamin B12 and folate levels in long-term vegans.

Serum vitamin B12, serum folate and red blood cell (RBC) folate levels were examined among 36 strict vegans of 5-35 years' duration. Vitamin B12 levels among the vegans were generally lower than in a control population. Most of the vegans had vitamin B12 values less than 200 pg/ml. RBC folate levels were normal but serum folate levels among the vegans were higher than among the controls. None of the vegans had any hematologic evidence of vitamin B12 deficiency, however four of them had neurologic complaints. Long-standing vegans should be monitored for vitamin B12 levels.

Adolescent↗

PubMed2003

Meta-analysis of plasma homocysteine, serum folate, serum vitamin B(12), and thermolabile MTHFR genotype as risk factors for retinal vascular occlusive disease.

PURPOSE: To assess the role of plasma total homocysteine (tHcy) levels, serum folate and vitamin B(12)levels, and homozygosity for the thermolabile methylenetetrahydrofolate reductase genotype (TT) as risk factors for retinal vascular occlusive disease. DESIGN: Meta-analysis of literature. METHODS: A MEDLINE search was performed to identify all published case-control studies of plasma tHcy levels, serum folate and vitamin B(12) levels, and TT genotype in persons with retinal vascular occlusive disease. Main outcome measures included calculation of plasma tHcy, serum folate, and serum vitamin B(12) standard differences and odds ratios (OR) of TT genotype between cases and controls. RESULTS: In total, 614 patients with all types of retinal vein occlusion had higher plasma tHcy levels than 762 control subjects (standard difference, 0.867; 95% confidence interval [CI] = 0.735, 0.999; P <.001). Plasma tHcy levels were also higher in 154 patients with retinal artery occlusion compared with 358 control subjects (standard difference 1.174; 95% CI = 0.947, 1.402; P <.001). Serum folates, but not vitamin B(12) levels, were lower in 287 patients with retinal vascular occlusion than in the same number of control subjects (standard difference, 0.508; 95% CI = 0.340, 0.675; P <.001; and -0.060; 95% CI = -0.024, 0.104; P =.474, respectively). Similar proportions of 690 patients with retinal vein occlusion and 2754 control subjects demonstrated the TT genotype (OR = 1.332; 95% CI = 0.995, 1.783; P =.054) as did 152 patients with retinal artery occlusions and 435 control subjects (OR = 1.716; 95% CI = 0.977, 3.014; P =.060). CONCLUSIONS: Retinal vascular occlusion is associated with elevated plasma tHcy levels and low serum folate levels, but not serum vitamin B(12) levels and TT genotype. Until a prospective multicenter trial is undertaken, plasma tHcy levels and serum folate levels should be determined in patients with retinal vascular occlusions, and dietary supplementation with low doses of folate and vitamin B(12) should be considered for affected persons.

Folic Acid↗

PubMed1975

Trypanosoma rhodesiense: folate levels in sera and tissues of normal and folic acid-deficient rats.

An experimental model composed of the folic acid deficient Sprague-Dawley rat and Trypanosoma rhodesiense was used to study folate levels in sera and tissues. Serum folate levels in well fed rats inoculated on day 21 averaged 21 plus or minus ng/ml; well fed normal rats averaged 18 plus or minus 4 ng/ml. In rats given the pair-fed control diet, serum folate levels averaged 17.2 plus or minus 4 ng/ml for trypanosome-free animals and 20.2 plus or minus 3 ng/ml for infected ones. In rats given the folic acid-deficient diet, serum folate levels averaged 8.6 plus or minus 2 ng/ml for noninfected control animals and 9.3 plus or minus 2 ng/ml for trypanosome-infected ones. Regardless of diet, the infected animals inoculated on day 56 had higher serum folate levels over the controls on the last day of observation (day 5 of infection). Livers from rats fed complete and pair-fed diets and inoculated on day 21 showed no significant differences in folate content when compared to control animals. However, livers of rats on a deficient diet showed significantly more folate when compared with uninfected controls, reaching a maximum of 362% of day 25. Liver folate levels of rats (regardless of the dietary regimen) inoculated on day 56 showed significantly higher values than the controls on day 60. Irrespective of the time of inoculation or diet, brain and spinal cord of T. rhodesiense-infected rats had significantly higher folate values than their controls on day 5 of infection. The folate level of the brain and spinal cord, at this time, ranged up to 58 and 107% respectively.

Animals↗

PubMed1994

Effect of folate metabolism on the psychopathology of adults with mental retardation and epilepsy.

Different aspects of psychopathology and folate metabolism were studied in a group of 150 adults from hospitals and the community who had mental retardation and epilepsy and compared with an individually matched control group of 150 adults with mental retardation but no epilepsy. Only 4.45% of those receiving anticonvulsant medication had a serum folate level below the normal laboratory reference range. Anticonvulsants other than sodium valproate tended to lower serum folate level. Results showed an inverse relation between the serum anticonvulsant levels and serum folate level. When the serum folate level of the adults with epilepsy who had either severe behavior problems and/or psychiatric illness and/or personality disorder was compared with the adults with epilepsy who did not have these disorders, no major significant intergroup difference emerged in serum folate level.

Activities of Daily Living↗

PubMed2001

Folic acid-responsive neurological diseases in Japan.

Folic acid (folate) levels were measured in the serum of patients with various neurological diseases in Japan. Thirty-six patients showed decreased serum folate levels among 343 consecutive neurological patients (10.5%). Folate administration (15 mg/d) to folate-deficient patients improved neurological symptoms in 24 of 36 cases (67%). Serum folate levels were significantly lower in female than in male folate-deficient patients. Folate-deficient patients showed predominantly axonal neuropathy, which responded to folate supplementation more markedly. Male patients more frequently exhibited neuropathy, especially demyelinating and motor-dominant neuropathy, than females. Anemia was correlated with male sex and low serum folate levels. Male patients were more responsive than females to folate treatment. More male patients had taken excess alcohol or received gastrectomies than females. Neurological symptoms were more frequently improved by folate supplementation in patients with neuropathy than exclusive encephalopathy. Serum folate levels were lower in patients with encephalopathy, especially those with dementia, while folate therapy was more effective in neurological patients without dementia. Dysgeusia and anemia improved in all patients after folate administration. Neurological patients with malabsorption or treated with continuous drip infusion were resistant to folate therapy. Since folate-responsive neuroencepahlopathies are not rare among patients with neurological diseases in Japan, the serum folate level would serve as a valuable indicator for folate supplement therapy.

Anemia↗

PubMed1985

Serum vitamin B12 levels in parturients, in the intervillous space of the placenta and in full-term newborns and their interrelationships with folate levels.

Serum vitamin B12 levels were determined in a group of 51 parturients as well as in their babies and placentas. The results obtained showed that newborns had 2.3 times higher vitamin B12 levels than their mothers and that the concentrations of this vitamin in the intervillous space of the placenta was 1.3- and 3.2-fold those encountered in the blood of newborns and mothers, respectively. These findings indicate that vitamin B12 accumulation by the placenta may represent an important factor in providing sufficient amount of this essential nutrient to the fetus. The relationship between folate and vitamin B12 concentration in the maternal, fetal and placental sera was also investigated. The highly significant correlation coefficient encountered and significantly higher serum folate concentrations in the group of parturients who received vitamin B12 supplementation during pregnancy indicate a close metabolic interrelationship between vitamin B12 and folate.

Female↗

PubMed1999

Determinants of fasting and post-methionine homocysteine levels in families predisposed to hyperhomocysteinemia and premature vascular disease.

Elevated plasma total homocysteine (tHcy) levels, either measured in the fasting state or after oral methionine loading, are associated with an increased risk of atherothrombotic disease. Fasting and post-methionine hyperhomocysteinemia (HHC) overlap to a limited extent; both can occur as familial traits. We investigated determinants of fasting, postmethionine and delta (ie, post-methionine minus fasting levels) tHcy levels in 510 subjects of 192 HHC-prone families including 161 patients with clinical vascular disease and 349 without vascular disease. We focused on tHcy levels in relation to levels of vitamin B12, B6 and folate and the methylenetetrahydrofolate reductase (MTHFR) C677T mutation. Multivariate linear analyses adjusted for the presence of vascular disease showed that fasting tHcy was significantly related to folate and vitamin B12, and the presence of the MTHFR TT genotype and the T allele, and to age, smoking habits, and serum levels of creatinine. Both post-methionine and delta tHcy levels were related to serum folate levels, and the presence of the MTHFR TT genotype and the T allele, and to postmenopausal status, and body mass index. An interaction was found between MTHFR TT genotype and serum folate levels for both fasting and post-methionine tHcy, ie, for a given decrease in serum folate, homocysteine levels increased more in subjects with the TT genotype than in those with the CC genotype. Fasting, post-methionine and delta tHcy were higher in patients with vascular disease than in their healthy siblings, but these levels were less dependent on serum folate levels (P<0.05), whereas the effect of MTHFR genotype was stronger (P=0.01). This study found evidence that post-methionine and delta tHcy levels are not only influenced by factors affecting homocysteine transsulfuration but also by factors that affect remethylation. The explained variances of fasting, post-methionine and delta tHcy were 49%, 62%, and 78%, respectively. We also found evidence, in patients with premature vascular disease but not in their healthy siblings, for a factor that increases tHcy levels but weakens the normal inverse relation between folate and tHcy and amplifies the effect of the MTHFR genotype.

Adult↗

PubMed1989

Repletion of folate-depleted rats with an amino acid-based diet supplemented with folic acid.

Folate depletion and repletion protocols are not well standardized. Weanling rats were moderately depleted of folate in 28 d with a folate-free purified diet based on 17% amino acids as the nitrogen source. They were then folate repleted for 23 d with the amino acid diet supplemented with either 125, 250, 500, 1000 or 2000 micrograms folic acid/kg. Hematology, growth and tissue folate levels were measured in subsets of the rats when they were 24 (baseline), 52 (depleted) and 75 d old (repleted). The same measurements were made in control rats that had been fed 2 mg folic acid/kg of the amino acid diet for the same period of time. Our findings show that with repletion, growth of previously depleted rats is in direct proportion with the level of supplementation up to 1000 micrograms folic acid/kg diet. Serum folate levels of repleted rats also increased in proportion to supplementation between 500 to 2000 micrograms/kg diet, and liver folate levels increased proportionally with the level of supplement within the range of 125 to 2000 micrograms/kg diet. The 2000 micrograms/kg supplement was sufficient to restore liver folate levels equivalent to that of controls, but body weight and serum folate levels failed to catch up with that of controls in the 23-d repletion period. There was a nonlinear relationship between serum and liver folate levels: serum folate remained constant at about 6 micrograms/l as liver folate increased to about 7 micrograms/g, then serum folate diverged by increasing to 120 micrograms/l with only minor increases in liver folate.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗

PubMed1975

Clinical and laboratory observations on serum folate-binding protein.

We studied the effect of serum folate-binding protein (FBP) on folate radioassays and the relationship of the serum level of unsaturated FBP to the serum folate level in various clinical states. Our modification of a heat-extracted radioassay was compared to a whole serum radioassay. Our results confirmed the existence of elevated serum levels of unsaturated FBP in some normal subjects, in some women taking oral contraceptives, and in most patients with uremia. Elevated levels of unsaturated FBP will produce falsely low results in folate radioassay unless the FBP has been destroyed by heat, as was done in the modified radioassay here presented. In normal and uremic subjects, serum folate and unsaturated FBP levels tended to correlate, whereas in patients taking large doses of folic acid the level of unsaturated FBP fell as the level of serum folate rose.

Administration, Oral↗

PubMed1995

Folic acid improves phenytoin pharmacokinetics.

Phenytoin (PHT) therapy to control seizures decreases serum folate levels in half of epileptic patients, thus increasing the risk of folate depletion. Supplementation with folic acid prevents deficiency but also changes PHT pharmacokinetics. Kinetic monitoring of PHT when folic acid is provided as a supplement has not been reported in women of child-bearing age. This study of six fertile women examined the interdependence of PHT and folic acid in a randomized crossover study of two treatments: treatment 1 consisted of 300 mg sodium PHT per day and treatment 2 consisted of 300 mg sodium PHT plus 1 mg folic acid per day. Dietary folic acid intake was calculated daily. During treatment 1, serum folate level decreased 38.0 +/- 18.6% (mean +/- standard deviation) and serum PHT concentration was in the low therapeutic range (43.92 +/- 14.52 mumol/L). During treatment 2, serum folate level increased 26.0 +/- 33.4%, and serum PHT level (39.04 +/- 14.16 mumol/L) was similar to that in treatment 1. Only one subject attained PHT steady state during treatment 1, but four subjects achieved steady state during treatment 2. Dietary folate intakes during treatments 1 and 2 were not significantly different. This study suggests an interdependence between PHT and folic acid and supports the observation that fertile women treated with PHT require folic acid supplementation to maintain a normal serum folate level.

Adult↗

PubMed1979

Serum vitamin B 12 and folic acid levels in patients with fasciolopsiasis.

Serum vitamin B12, serum and red cell folate concentrations and vitamin B12 absorption were studied in 100 patients with fasciolopsiasis. A mean value of serum vitamin B12 level in the patient group was found to be significantly lower than that of normal subjects and 14% of these patients had serum vitamin B12 level less than 100 pg/ml. Serum UBBC and TBBC levels in the patients were significantly higher than those of the normal subjects. Serum TCI and TCIII increased significantly while TCII decreased. Vitamin B12 absorption was found to be impaired in 3 of 9 patients studied. There was no relationship seen between serum vitamin B12 level and vitamin B12 absorption. The mean values of serum folate and red cell folate levels in the patient group were significantly lower than those of normal subjects. Fifteen of 100 patients (15%) had serum folate level less than 3 ng/ml, while all of them had red cell folate higher than 100 ng/ml. Serum folic acid binding protein levels (FABP) in these patients, were not significantly different from those of normal subjects.

Child↗

PubMed1966

Method of assay of red cell folate activity and the value of the assay as a test for folate deficiency.

A simplified microbiological assay for determining the folate content of red cells is described. As in previously reported methods Lactobacillus casei is used as test organism but two modifications are introduced. First, haemolysis is carried out in water containing 1 g.% of ascorbic acid; secondly, haemolysates are not incubated before the assay. Using this assay, recovery of pteroylglutamic acid added in two different concentrations to five different whole blood samples was 97.0 +/- 1.9 S.E. % and 106.1 +/- 4.7 S.E. % respectively. The coefficient of variation of the assay was between 11.2 and 15.0%. Haemolysates were best stored deep frozen, showing no significant loss of L. casei activity for three to five months at -20 degrees C. On the other hand, non-haemolysed blood samples were best stored at 4 degrees C. when there was no loss of activity for seven to 10 days. Experiments confirmed that plasma is necessary for the maximum release of red cell L. casei activity, and showed that only small amounts of plasma are necessary; folate- and B(12)-deficient plasma released slightly lower L. casei activities from red cells than did normal plasma. The red cell folate levels of 40 healthy normal subjects ranged from 160 to 640 mmug. per ml. of packed red cells. One hundred and twenty patients with subnormal serum folate levels due to idiopathic steatorrhoea, nutritional folate deficiency and Crohn's disease, partial gastrectomy, myelosclerosis, and polycythaemia vera were studied. Red cell folate levels were subnormal (range from 7 to 143 mmug. per ml.) in 40 patients with megaloblastic anaemia, the lowest levels occurring in the most anaemic patients. Subnormal red cell folate levels also occurred in 23 (29%) of the 80 non-anaemic patients. There was a good correlation between red cell folate level and severity of folate deficiency assessed by polymorph nuclear lobe counts, and, in the non-anaemic patients bone marrow morphology. It is concluded that, in the absence of B(12) deficiency, the red cell folate level is a precise guide to the severity of folate deficiency. Patients with serum folate levels less than 3.0 mmug. per ml. almost always had megaloblastic anaemia or obvious morphological changes of folate deficiency. In patients with borderline serum folate levels (3.0-5.9 mmug. per ml.) haematological changes varied widely. The degree of change correlated with the red cell folate level in these patients. The formiminoglutamic acid (Figlu) test was positive (range 20-660 mg. excreted in eight hours) in all 30 patients with megaloblastic anaemia due to folate deficiency tested and also in 17 (31%) of 54 non-anaemic patients who were folate deficient. The amount of Figlu excreted paralleled the red cell folate level in both the anaemic and non-anaemic, folate-deficient patients tested. Figlu excretion, like the red cell folate level, appeared to be a satisfactory index of tissue folate stores. In 46 patients with pernicious anaemia, the red cell folate levels ranged from 26 to 396 mmug. per ml., 29 (63%) of them having subnormal levels. The ratio of mean red cell to mean serum folate level, 13.0:1, was lower than that of normal subjects. As in folate deficiency the patients with the lowest haemoglobin concentrations had the lowest red cell folate levels. Figlu was positively excreted in 10 (59%) of 17 patients with pernicious anaemia tested, being particularly increased in those with low red cell folate levels. Reticulocytes of patients with pernicious anaemia on treatment and with haemolytic anaemia were shown to have higher folate levels than their corresponding mature cells. It is concluded that reticulocytes in general have relatively high folate levels.

Anemia, Macrocytic↗