RBC Folate Concentrations Research Articles

Folate Status of Elderly Women following Moderate Folate Depletion Responds Only to a Higher Folate Intake

Dietary Reference Intakes (DRI) for folate for elderly women have been based primarily on data extrapolated from studies in younger women. This study was conducted to provide the first age-specific data in elderly women (60-85 y) from a controlled metabolic study on which to base folate intake recommendations. Subjects (n = 33) consumed a moderately folate-deplete (118 microg/d) diet for 7 wk, followed by repletion diets providing either 200 or 415 microg folate/d as diet plus folic acid (FA) or a combination of FA and orange juice (OJ) for 7 wk (n = 30). Comparisons among and within groups were made for serum folate (SF), RBC folate and plasma total homocysteine (tHcy) concentrations. SF concentrations decreased significantly (P < 0.001) during depletion (65 +/- 15%). Postrepletion, the adjusted SF concentration for subjects consuming 415 microg folate/d was significantly greater (P = 0.003) than for subjects consuming 200 microg folate/d. RBC folate concentrations decreased (P < 0.001) during depletion (21 +/- 10%) and further (P < 0.001) during repletion (5 +/- 14%). During depletion, plasma tHcy concentrations increased significantly (P < 0.001) and an inverse relationship between SF and plasma tHcy concentrations was observed in 94% of subjects (P < 0.001). Reversal of this inverse relationship was significant only for subjects consuming 415 microg folate/d (P < 0.001). Postrepletion, subjects consuming 200 microg folate/d had a significantly higher (P = 0.009) adjusted plasma tHcy concentration than subjects consuming 415 microg folate/d. These data in elderly women indicate that 415 microg/d folate, provided as a combination of diet, FA and OJ, or diet and FA, normalizes folate status more effectively than does 200 microg/d, thus providing age-specific data for future folate intake recommendations.

Folate Status of Childbearing Aged Women Among Multivitamin Supplement Users and Non-users in the U.S.: NHANES III

Inadequate folate status has been implicated as a risk factor for neural tube defect and cardiovascular disease via hyperhomocysteinemia. Childbearing aged women (15–39 y, n=3,211) in NHANES III who had complete records of 24 h dietary recall, serum and RBC folate were studied. Multivitamin use was self-reported by 26%, 59% and 54% of non-pregnant (n=2,878), pregnant (n=261) and lactating women (n=72), respectively; and by 40%, 26%, 23%, and 25% of White (n=938), Black (n=l,106), Mexican-American (n=1,035) and Other (n=132) subgroups, respectively. Daily folate intake of non-pregnant (221±174 μg/day, mean±S.D.; 178 μg/day, median) was lower than those of pregnant and lactating women (283±212, and 285±191 μg/day, respectively, p<0.01; 219 and 266 μg/day, medians, respectively) among the vitamin non-users as well as among vitamin users. Daily folate intake from food sources of Black (195±154 μg/day, mean±S.D.) was lower than those of White, Mexican and other groups (p<0.01; 218±166, 260±199, 239±179 μg/day, respectively) in both vitamin non-users and users. Folate intake from food sources alone was higher among vitamin users (p<0.05), regardless of ethnicity or pregnant status. Serum and RBC folate concentration was lower in non-pregnant women (4.4±2.5 ng/mL, 142±60 ng/mL, respectively) than in pregnant and lactating women (5.5±2.8, 4.5±2.5; 169±75, 188±76 ng/mL, respectively, p<0.01), in Black (4.2±2.25 ng/mL, 121.9±505 ng/mL, respectively) than in other ethnic subgroups (p<0.01) in both vitamin user and non-user groups (p<0.01). More than 50% of all women had daily folate intake lower than the recommended. Black women were at the highest risk for inadequate folate intake from food sources. Individuals with higher folate intake from food sources took multivitamins more frequently than others

Enzymatic deconjugation of erythrocyte polyglutamyl folates during preparation for folate assay: investigation with reversed-phase liquid chromatography

Erythrocyte (RBC) folates occur mainly as 5-methyltetrahydrofolate polyglutamates. Determination of RBC folate concentration requires an initial deconjugation of these polyglutamates. In this study, existing HPLC methods were adapted to investigate the rate and extent of this deconjugation process. The action of endogenous plasma pteroyl-polyglutamate hydrolase activity was strongly affected by the conditions of sample preparation, with pH of the incubation mixture more critical to effective deconjugation than incubation time. Dilution of whole blood with 10 g/L ascorbic acid yielded fast hydrolysis of long-chain polyglutamates, and total conversion to 5-methyltetrahydrofolate monoglutamate occurred after 90 min of incubation at 37 degrees C. In contrast, dilution of whole blood with 10 g/L sodium ascorbate, with up to 90 min of incubation at 37 degrees C, yielded a mixture of polyglutamates of 5-methyltetrahydrofolate (glun = 1-8). As documented by direct HPLC analysis and in concurrent assays with Lactobacillus casei, acidification provided by ascorbic acid can have dramatic effects on the measurement of RBC folates.

Hematologic abnormalities in children with down syndrome

We compared the hematologic parameters of 18 otherwise healthy children with Down syndrome (DS) in the age range of 2-6 years to those of 18 healthy non-DS controls matched for age and gender. The children with DS had MCVs and hematocrits increased significantly compared to controls and decreased WBCs compared to controls; 66% of the children with DS compared to 11% of non-DS controls had MCVs greater than the 97th percentile for age (P < 0.0001); the mean MCVs were 86.9 and 80.6, respectively. Although hematocrits were within normal limits for age for all DS and non-DS subjects, the DS patients had significantly higher hematocrits (39.1% vs. 36.9%, P < 0.014). We also found that 33% of the children had WBCs < 5% for age compared to 6% of controls. To determine whether folate deficiency contributed to these observations, we measured serum and RBC folate concentrations: these were not significantly different between the 2 groups. We conclude that macrocytosis and leukopenia are common in children with DS.

An assessment of serum and red blood cell folate concentrations in patients with epilepsy on lamotrigine therapy

Lamotrigine (LTG) is a new antiepileptic drug which is effective in refractory epilepsy and which has been shown to have weak antifolate properties in vitro. The effect of LTG on serum folate and red cell folate (RBC) concentrations was assessed in a series of 14 patients on short-term LTG treatment during a placebo-controlled double-blind study. A further 14 patients who had been treated with LTG for up to 5 years were also assessed. In the short-term double-blind study the baseline mean serum folate concentration was 2.7 ng/ ml and mean RBC folate concentration was 295 ng/ml. After 12 weeks of LTG therapy mean concentrations were 3.3 ng/ml and 339 ng/ ml respectively and corresponding levels after 12 weeks of placebo were 2.4 ng/ml and 288 ng/ml. Patients on chronic LTG therapy showed no significant difference in RBC folate concentrations compared to those prior to LTG therapy (346 compared to 407 ng/ml). Other biochemical and haematological parameters were unaltered by LTG therapy. Thus, neither short-term nor chronic LTG therapy appears to be associated with significant changes in serum or RBC folate concentrations.

RBC and Serum Folate Concentrations in Neuroleptic-treated and Neuroleptic-free Schizophrenic Patients

RBC and serum folate were determined in 20 schizophrenic patients not taking neuroleptic drugs, 63 treated with neuroleptic drugs, and 41 healthy control subjects. the results showed significantly lower concentrations of folate in both RBC and serum in patients who were being treated with neuroleptics compared with those not being treated. Although not significant, lower levels of folate were found in patients who were on more than one drug than in those given a single medication. Moreover, patients who were ‘actively ill’ had lower levels of RBC and serum folate compared to those who were ‘fairly well‘. This was true for both neuroleptic-treated as well as untreated patients. in the neuroleptic-treated group, patients who were ill for 2 years and more had significantly lower concentrations of both RBC and serum folate than more recently ill patients. Although not significant a slow decline in RBC and serum folate was seen with the increasing chronicity of illness in the neuroleptic-free group. Even with ...

Hematologic values and plasma and tissue folate concentrations in dogs given phenytoin on a long-term basis

SUMMARY During earlier investigations of the hepatic effects in dogs of long-term administration of phenytoin alone or in combination with primidone, erythrocytic macrocytosis, neutropenia, neutrophilic hypersegmentation, and thrombocytopenia were observed. Such abnormalities were observed most often in dogs given phenytoin and resembled those known to be attributable to folate deficiency in human beings with epilepsy treated with phenytoin. To pursue the theory that these hematologic aberrations were caused by drug-induced folate deficiency, 12 dogs were given a diet specifically formulated to contain a minimally adequate concentration of folate. After 2 weeks, phenytoin was administered daily (400 mg, po, q 8 h) to 8 of the 12 dogs for 54 weeks. A cbc, bone marrow aspiration biopsy, and measurement of plasma and rbc folate concentrations were done every 3 weeks. Bone marrow aspirates were examined by transmission electron microscopy after 24 and 36 weeks, and at the end of the treatment period. Hepatic folate concentration was also determined in all dogs before and after treatment. Excretion of formiminoglutamic acid, as a marker of folate deficiency, was measured in all dogs at the end of the study. All dogs remained healthy throughout the treatment phase. Consistent abnormalities were not observed in the blood or bone marrow of treated dogs. Plasma and RBC folate concentrations decreased in control and treated dogs as a result of dietary restriction (P &lt; 0.02), and remained stable until the end of the study. The rbc folate content decreased further in treated dogs (P &lt; 0.02), although the hepatic folate content was similar in control and treated dogs. Treated dogs did not excrete formiminoglutamic acid more rapidly than did control dogs. Gross necropsy or histologic abnormalities were not identified in control or treated dogs. We concluded that long-term administration of phenytoin was not associated with clinical, hematologic, or biochemical evidence of folate deficiency in dogs.

Haematological studies on pre-menopausal Indian and Caucasian vegetarians compared with Caucasian omnivores

Full blood counts, serum ferritin, vitamin B12 and folate, erythrocyte folate concentrations and nutrient intakes were estimated in twenty-three Indian vegetarian, twenty-two Caucasian omnivores and eighteen Caucasian vegetarian women aged 25-40 years. Energy and copper intakes were lower in the Indian women than in the Caucasians. Intakes of dietary fibre, vitamin C and folate were greater and the proportion of energy derived from fat was lower in the vegetarians than in the omnivores. Vitamin B12 and protein intakes were lower in both vegetarian groups than in the omnivores. Fe intake was similar in all the groups but haem Fe provided one-quarter of the Fe intake of the omnivores. Haemoglobin concentrations were generally inside the normal range in all groups, but were lower in the Indians as were mean corpuscular volume (MCV) and mean corpuscular haemoglobin (MCH). Higher MCV, MCH and lower erythrocyte (RBC) counts were observed in Caucasian vegetarians compared with the Caucasian omnivores. In both groups of vegetarians, concentrations of serum vitamin B12 and ferritin were markedly lower than in the omnivores. RBC folate concentrations were lower in the Indians than in either of the Caucasian groups when subjects taking supplements were excluded. It is concluded that vegetarians need to ensure they have adequate intakes of Fe and vitamin B12.

Milk folate secretion and folate status of suckling pups during iron deficiency

The present study was designed to determine when in lactation maternal iron deficiency results in a depression of milk folate secretion and the extent to which the quantity of folate delivered to the nursing rat pup is diminished. Dams (n=42) were fed diets containing 2 mg/kg folate and either 8 (Fe-) or 250 (Fe+) mg/kg iron throughout gestation and lactation. On either d 7, 12 or 17, dams were milked and animals were sacrificed. Both free and total milk folate activities increased from d 7 to d 17 among Fe+ animals (p<0.0001). In contrast, total milk folate decreased (52%) among Fe- dams after d 12 of lactation. Total milk folate contents were 29%, 42% (p<0.05), and 81% (p<0.0001) lower in samples from iron-deficient compared to control dams on d 7, 12 and 17, respectively. In addition, iron-deficient dams secreted milk with a substantially reduced percentage of long chain folylpholyglutamates. Iron-deficient pups ingested 40% (p<0.05) and 72% (p<0.0004) less total fotate (pmol/g) on d 12 and 17 of lactation, respectively. Plasma and kidney folate concentrations were significantly reduced in Fe-dams (p<0.001). Plasma folate concentrations (d 17) were significantly lowered but liver and RBC folate concentrations were significantly elevated in Fe- pups. Results show that reduced milk folate secretion is an early manifestation of maternal iron deficiency which worsens as lactation advances and that total folate ingestion by nursing pups is likewise progressively reduced.

Micronutrients status of children with down syndrome: A comparative study of the effect of megadoses of vitamins with minerals or placebo

Fifty children with Down syndrome between the ages of 5 and 16 years were included in an experimental study where half the children received a megavitamin and mineral preparation and the other half received a placebo. The children were in matched pairs for a number of physical and psychosocial variables. The study lasted 8 months and biochemical studies were done at the start of the study and repeated at 4 and 8 months. Blood plasma samples were analyzed for Zn, Cu, folate, vitamin A, carotene, B 6, retinol binding protein, and RBC transketolase and glutathione reductase and serum proteins. Generally, no gross malnutrition was evident as judged by the mean values for most of the baseline laboratory data. No change in mental status was detected between the two groups at the end of the study. The blood values except RBC folate concentrations did not increase significantly on supplementation. There appeared to be an increased prevalence of low plasma zinc levels among the subjects in both the experimental and placebo groups at baseline which seemed to improve regardless of supplementation.

Folate intake and blood concentrations of term infants

Folate nutrition of 67 full-term infants was studied longitudinally from birth to 1 year. Infants were grouped according to type of milk consumed during early infancy: group I (n = 14) received human milk; group II (n = 31), a standard cow-milk infant formula; and group III (n = 22), the same formula with added iron (12.3 mg/L). Solid foods were introduced after 3 months. Folate status, as indicated by serum and red blood cell folate concentrations, and folate intake were measured periodically. Blood folate concentrations of all groups were higher than or similar to adult control values. No differences in indices of folate status were observed between formula-fed groups at any time frame. At 6 weeks and 3 months formula-fed infants had folate intakes and blood concentrations significantly greater than human milk-fed infants. With the introduction of solid foods, decreases in blood folate concentrations paralleled decreases in milk folate intake within each group. Serum folate concentrations correlated with both total folate intake and milk folate intake, whereas RBC folate concentrations correlated with only milk folate intake. The results indicate that milk, regardless of type (human milk, formula, and cow milk), is an important dietary source of folate during the first year of life and that both human milk and proprietary formula feeding during early infancy provide more than sufficient folate to maintain blood folate concentrations well above acceptable limits.

The importance of red cell B12 and folate levels after partial gastrectomy

In 107 partially gastrectomized patients, B1 2 and folate concentrations were measured in serum and red cells. Diminished B12 levels were found much more frequently in red cells than in serum (68 versus 37%). In patients with low serum B12, coexistent iron deficiency was associated with more pronounced depletion of RBC B12, the mean RBC:serum B12 ratio being 0.55 and 1.15 in iron-deficient and normoferremic groups, respectively. Fourteen partially gastrectomized patients had low RBC B12 levels as the sole biochemical criterion of B12 deficiency; five of these patients were anemic, five had macrocytosis, and all 14 had neutrophil hypersegmentation. Abnormally low serum and red cell folate levels were detected in 33 and 17% of the 107 patients, respectively. Iron deficiency was accompanied by increased RBC folate concentrations (mean 467 ng/ml versus 306 ng/ml in the normoferremic group). The results indicate that l) in gastrectomized patients, decreased RBC B12 concentration is the most sensitive index of B12 deficiency; 2) iron deficiency appears to accentuate RBC B12 depletion and to increase red cell folate levels.