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PubMed1971

Folate metabolism in epileptic and psychiatric patients.

Serum and red cell folate levels and serum vitamin B(12) levels have been estimated in 33 normal controls; 34 epileptic outpatients, 19 of whom also suffered from psychiatric illness; 33 epileptic inpatients with psychiatric illness; and 30 non-epileptic inpatients with psychiatric illness. Significant lowering of serum folate and red cell folate levels was observed in epileptic patients with psychiatric illness, and a less significant fall in red cell folate levels was found in non-epileptic psychiatric patients. Serum folate levels less than 2·5 ng/ml. were found in two controls, seven outpatient epileptics, 29 inpatients, and 10 non-epileptic patients. Red cell folate levels less than 100 ng/ml. were found in two controls, nine outpatient epileptics, 23 inpatient epileptics, and seven non-epileptic patients. A significant correlation was found between serum and red cell folate values in control, epileptic, and non-epileptic patients. In the epileptic patients there was a significant association between low serum and red cell folate levels and the presence of psychiatric illness. The origin and possible significance of these findings are discussed.

Adult↗

PubMed1984

[Functional, morphological and biochemical study of the jejunal mucosa in cryptogenetic colitis].

The function of the jejunum has been assessed in patients with ulcerative colitis (n = 23) and Crohn's disease of the colon (n = 20) by measurement of serum folate levels, oral folic acid and D-xylose absorption. Forty-six normal subjects served as controls. The mean serum folate level was 4.5 +/- 2.0 ng/ml in patients with the disease and 7.8 +/- 1.7 ng/ml in controls (p less than 0.001) and was similarly decreased in both ulcerative colitis and Crohn's disease patients. It was lower in patients under sulphasalazine therapy (n = 15) than in those untreated: 3.5 +/- 1.5 vs. 4.8 +/- 2.1 ng/ml (p less than 0.05). Serum folate correlated with disease activity in the latter only. The peak serum folate obtained during the oral absorption test was decreased in patients: 38.9 +/- 12.9 vs. 60.8 +/- 19.3 ng/ml in controls (p less than 0.001); this decrease was similar in ulcerative colitis and Crohn's disease, in treated and untreated patients and was independent of disease activity. Basal serum folate did not correlate with peak serum folate in any patient group. D-xylose absorption was normal in every case. Jejunal biopsies were performed in 23 patients, 13 of whom had folic acid malabsorption (13 with ulcerative colitis, 10 with Crohn's disease of the colon). The crypt height/villus height ratio was abnormal (greater than 0.6) in only 2 patients and borderline in 9 others. The fragility of enterocyte brush-borders and lysosomes, as assessed by biochemical methods, was normal in all cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Colitis, Ulcerative↗

PubMed1975

Serum folate and vitamin B12 levels in hypothyroid and hyperthyroid patients.

We measured the levels of serum folate and vitamin B12 in newly discovered hypothyroid (n =56) and hyperthyroid (n =47) patients and in age- and sex-matched control subjects (n =103). Except for one patient with latent pernicious anemia, serum folate and vitamin B12 levels did not differ greatly in our patients and in our control subjects. Another patient was receiving monthly injections of cyanocobalamin for previously diagnosed pernicious anemia. We conclude that abnormalities of thyroid function per se did not alter serum folate or vitamin B12 levels in our patients.

Adult↗

PubMed2004

Effectiveness of a free folic acid supplement program in family planning clinics.

BACKGROUND: Adequate periconceptional folic acid consumption lowers the risk for neural tube defects. We report the results of an evaluation of a folic acid intervention in Georgia family planning clinics that provided free folic acid supplements or fortified breakfast cereal. METHODS: Six family planning clinics participated in the evaluation. Three clinics provided folic acid pills and educational materials to clients, two provided super-fortified cereal and educational materials, and one clinic provided educational materials only. Participants between the ages of 18 and 45 who visited the clinics in 2000 completed a brief survey and provided a blood sample. Of the 1093 women who participated, we evaluated the 165 women who had returned to the clinic at least once during the study period. We compared participants' survey and serum folate data from their first and subsequent visits. RESULTS: Participation in the intervention was associated with increased knowledge about folic acid, (odds ratio, 1.94; 95% confidence interval, 1.37-2.76), but was not directly associated with increased self-reported folic acid consumption or increased serum folate levels. Reported use of folic acid supplements or cereal within two days of a visit was associated with higher serum folate levels. Knowledge about folic acid was one of the best predictors of self-reported folic acid consumption. CONCLUSIONS: Participation in the intervention increased clients' knowledge about folic acid but did not directly increase reported folic acid consumption. Because knowledge predicted folic acid consumption, the intervention may be indirectly associated with increased consumption of folic acid.

Adolescent↗

PubMed1975

Oral contraceptives, serum folate, and hematologic status.

Previous reports have suggested deleterious effects on folate balance in users of contraceptives. A study of folate in 526 women attending a family-planning clinic demonstrated, both with the Lactobacillus casei assay and with a new radioassay, that the mean serum folate level for women taking oral contraceptives was not significantly lower than that for women in a control group. There was no correlation between serum folate level and length of time oral contraceptives were taken. Also, there was no macrocytosis or hypersegmentation of polymorphonuclear leukocytes and no case of macrocytic anemia in the 280 users of oral contraceptive agents. Probably, oral contraceptive agents do not cause folate deficiency anemia in otherwise normal subjects.

Analysis of Variance↗

PubMed1991

Transcobalamin II deficiency: case report and review of the literature.

A male Caucasian infant presented at 6 weeks of age with failure to thrive, diarrhoea, macrocytic anaemia, and decreased IgG. He had normal serum B12 and folate levels. Serum cobalamin binding capacity showed no detectable transcobalamin II. Both parents showed levels consistent with a heterozygous state. The literature is extensively reviewed, and the importance of early diagnosis to prevent neurological dysfunction is stressed.

Failure to Thrive↗

PubMed1978

Folate-induced remission in aplastic anemia with familial defect of cellular folate uptake.

Severe aplastic anemia developed in a young man with an extensive family history of leukemia, pancytopenia, and neutropenia. Megaloblastic changes became evident, and treatment with high doses of folic acid resulted in striking clinical improvement. However, red-cell folate levels remained persistently low despite high serum folate levels. A defect in cellular folate uptake was suspected, and, indeed, uptake of 5-14CH3-H4-folate by stimulated lymphocytes and by bone-marrow cells from the patient was significantly reduced (P less than 0.05 as compared to normal cells. Further characterization of folate metabolism showed that intestinal absorption of the vitamin, membrane transport of 5-14CH3-H4-folate by mature red cells, folate utilization in the conversion of deoxyuridylate to thymidylate and polyglutamate formation were all normal. At least five other family members manifest decreased uptake of 5-14CH3-H4-folate by stimulated lymphocytes. These studies suggest that a genetically induced abnormality of folate uptake contributed to this patient's severe, but reversible, aplasia.

Adult↗

PubMed1989

[Megaloblastic anemia associated with diffuse intestinal Crohn's disease].

A 40-year-old man who was resected ascending colon and terminal ileum (10 cm) in Aug. 1978, with the diagnosis of Crohn's disease, was admitted to our hospital with general fatigue, paresthesia and tremor in May. 1984. A peripheral blood examination on admission revealed Hb 10.1 g/dl, RBC 234 X 10(4)/mm3, MCV 131.4 fl, MCH 43.2 pg. A bone marrow specimen showed marked erythroid hyperplasia (W/E 1.44) with megaloblastic change. While serum folate level was normal, serum vitamin B12 value was low and Schilling test showed vitamin B12 malabsorption. Roentgenologic and endoscopic examinations revealed diffuse cobblestone appearances in small intestine (from anastomosis part to duodenal bulb). These examinations suggested vitamin B12 malabsorption with diffuse Crohn's disease caused megaloblastic anemia. The patient had been treated with vitamin B12 1,000 micrograms/day injection and, in Sep. 1984, he recovered from megaloblastic anemia (Hb 13.4 g/dl, RBC 440 X 10(4)/mm3, MCV 90.7 fl, MCH 30.4 pg).

Adult↗

PubMed1983

Folate deficiency in operated terminal ileitis (Crohn's disease).

In a series of 39 subjects previous results for serum folate levels were confirmed while intraglobular folate did not differ from those in a control group. To verify the hypothesis that SASP administration could be responsible for serum folate deficiency three different sub-groups were considered. 11 patients had never taken SASP (sub-group I), 16 patients had taken SASP in the past but the treatment had been withheld at least 2 months before (sub-group II), 12 patients were still taking the drug at the time of the study (sub-group III). Differences in serum folate levels between each one of the three sub-groups and the control group were significant. The same was not true for the differences between each one of the three sub-groups and the other. These findings seem to confirm that SASP treatment is not the major cause of serum folate deficiency, but a multifactorial pathogenesis might account for it.

Adolescent↗

PubMed2004

Body mass index and serum folate in childbearing age women.

BACKGROUND: Higher pre-pregnancy body mass index (BMI) is associated with increased risk of neural tube defects (NTDs) and possibly other negative birth outcomes in the offspring. The mechanism for this association remains unknown. Lower maternal folate level has been implicated in the etiology of NTDs in general. The association of BMI with folate level, however, has not been investigated. METHODS: The present study examines the association of BMI with folate level in childbearing age women before and after the 1998 U.S. folate fortification program of cereal products, using data from two cross-sectional surveys of the U.S. population, the third wave of the National Health and Nutrition Examination Survey (NHANES III; 1988-1994) and the more recent wave of this survey (NHANES 1999-2000). RESULTS: After controlling for intake of folate in food and nutritional supplements, increased BMI in childbearing age women was associated with a lower serum folate level in both surveys (p < 0.001). Using data from NHANES 1999-2000, it was estimated that women in the 30.0 + kg/m2 BMI category would need to take an additional 350 microg/day of folate to achieve the same serum folate level as women in the < 20.0 kg/m2 category. CONCLUSION: Lower folate level may be one mechanism linking higher maternal BMI and increased risk of NTDs in the offspring. If corroborated in future studies, findings from this study suggest a need for a higher dose of folate supplement in heavier childbearing age women.

Adolescent↗

PubMed1977

Neutrophilic hypersegmentation as an indicator of incipient folic acid deficiency.

The authors have identified a group of subjects with neutrophilic hypersegmentation who are normal or near-normal with respect to other hematologic indices (hemoglobin, mean corpuscular volume). In a high proportion of these subjects, serum folate levels are abnormally low. In this group and a non-hypersegmented-neutrophil control group there was a significant negative correlation between average numbers of neutrophilic lobes and serum folate levels. In the subjects with hypersegmented neutrophils the predominant alteration is a shift from three-lobed to five-lobed neutrophils. It is believed that neutrophilic hypersegmentation can be a valuable adjunct in documenting and/or uncovering incipient folate deficiency.

Erythrocytes↗

PubMed1983

Oxygenation alters red cell folate levels.

Folate activity is consistently higher in deoxygenated than oxygenated human blood as measured by both radioassay and Lactobacillus casei growth. Red cell, but not serum, folate levels are rapidly mutable: when fully oxygenated, the mean red cell folate level of 15 samples was 489 ng/ml; after deoxygenation the mean rose to 553 ng/ml; following re-oxygenation the mean returned to 488 ng/ml. Transport of folate across the red cell membrane apparently does not contribute to these changes in folate levels, since agents known to inhibit permeation (N-ethyl-maleimide, p-chlormercuriphenyl sulfonic acid and ethacrynic acid) do not affect the rise with deoxygenation. Moreover, new synthesis of folate compounds seems unlikely, since the changes are observed in energy-depleted cells. Instead, direct binding of folate to haemoglobin is suggested by experiments in which the rise with deoxygenation was not seen in red cells exposed to carbon monoxide or treated with cyanate. Similar changes also occur in vivo: canine red cell, but not serum folate levels are significantly higher (P less than 0.05) in samples collected from five different veins compared with blood from the paired artery (carotid-jugular, renal, mesenteric, splenic, femoral) of four animals. Thus red cell folate levels are predictably influenced by the levels of oxygenation of the erythrocyte both in vitro and in vivo, possibly by reversibly binding to haemoglobin.

Animals↗

PubMedDate not supplied

Antiepileptic therapy, folate deficiency, and psychiatric morbidity: a general practice survey.

The effect of anticonvulsant drugs on folate metabolism and mental symptoms has been investigated extensively in hospital-based studies, but never before in the community or general practice setting. Blood count, serum vitamin B12, red blood cell (RBC), and serum folate were measured in a sample of 82 adult epileptic patients drawn from 5 group practices (14 general practitioners) in southeast London. All patients were receiving antiepileptic medication at the time of examination and were interviewed with a standardized measure of psychopathology. Serum folate values below the lower limit of the normal range (3-15 micrograms/L) were obtained in 9 (10.9%) subjects, and in 50 (60.9%) patients, serum folate concentrations were less than the mean (6.02 micrograms/L) for the whole sample. Macrocytosis was detected in 20 (24.3%) patients. RBC and serum folate levels were significantly correlated with one another, but not with vitamin B12 concentrations. Levels of RBC and serum folate were significantly lower in patients on polytherapy (n = 40) than in those on monotherapy (n = 42); the folate concentrations were also significantly lower in the group with psychiatric morbidity. The association between folate deficiency and affective morbidity was demonstrated for depression but not for anxiety. There was no relationship between serum vitamin B12 and psychiatric disturbance. These findings are discussed in the light of relevant literature regarding the mechanism of action of anticonvulsant drugs in folate depletion and the neuropsychiatric sequelae.

Adolescent↗

PubMed1985

Cerebrospinal fluid folate and cobalamin levels in febrile convulsion.

Folate and cobalamin parameters were studied in the serum and cerebrospinal fluid of 40 febrile paediatric patients. Eighteen of these children were in a state of febrile convulsion while the remaining 22 were non-convulsing. The serum folate concentration of all the patients was higher than that of the control group but the highest value was found in the convulsing children. There was no significant difference in the CSF folate levels between the two groups of patients. The serum cobalamin levels of the patients were significantly lower than those of the control children and the lowest mean was observed in the convulsing state. On the other hand, there was no difference in the CSF cobalamin between the convulsing and non-convulsing children. These results confirm that there is an effective blood-brain barrier system for folate even when serum folate levels are higher than normal. There is also a definite decrease in serum cobalamin during pyrexia but this decrease is more apparent in the convulsing state. The role of cobalamin metabolism in convulsion is not clear.

Blood-Brain Barrier↗

PubMed2006

Serum homocysteine concentration as a marker of nutritional status of healthy subjects in Crete, Greece.

BACKGROUND: Dietary habits are an important determinant of serum homocysteine (tHcy), which may be a marker rather than a cause of progression of the atherosclerotic process. The aim of the present study was to evaluate the nutritional status, and to determine the serum tHcy concentrations in healthy subjects who live in rural areas of Crete, and who theoretically follow a contemporary Mediterranean-style diet. METHODS: Serum tHcy, folate, vitamin B(12), creatinine, glucose, and the lipid profile, were measured in 203 (141 men and 62 women) healthy subjects, aged 33-78 years. The major risk factors for cardiovascular disease such as age, gender, cigarette smoking, obesity were recorded and dietary data were assessed using a 3-day weighed food intake record. RESULTS: Our population had high serum tHcy, low serum folate concentrations and lower than the traditional Cretan dietary folate intake [median (range): 12.0 (3.6-44.7) micromol L(-1), 7.9 (1.9-15.5) ng mL(-1) and 241 (68-1106) microg, respectively]. Dietary intake of fibre, omega-3, and mono- or/ polyunsaturated fatty acids was also low. An inverse relation was observed between serum tHcy concentrations and serum folate (r = -0.28; P < 0.01) and vitamin B(12) levels (r = -0.33; P < 0.001). CONCLUSIONS: Nowadays, the Cretan diet has changed towards a more westernized eating pattern. Given the analytic difficulties in determining the amount of folate in food and the inverse correlation between serum tHcy and folate levels, serum tHcy concentrations may be a useful marker for nutritional status, especially folate deficiency, in healthy subjects.

Adult↗

PubMed1998

A controlled study of folate levels in Chinese inpatients with major depression in Hong Kong.

BACKGROUND: Although Western and, in particular, British studies have revealed a substantial rate of hypofolatemia in patients with depression, few such studies have been conducted in Asian populations. METHODS: A group of 117 newly admitted inpatients with DSM-III-R major depression and 72 healthy controls underwent blood investigations and psychometric assessments. RESULTS: Patients had a significantly lower mean serum folate level (24.6+/-10.2 vs. 30.3+/-11.4 nmol/l, P < 0.001) but a higher mean erythrocyte folate level (801.8+/-284.6 nmol/l vs. 699.5+/-248.7 nmol/l, P < 0.01) than control subjects. No patient or control subjects had low folate, while only four patients (3.4%) and six control subjects (8.3%) had low erythrocyte folate. Folate levels were not related to patients' age, duration of illness, Hamilton Depression Rating Scale, Beck Depression Inventory and Global Assessment Scale scores, and prior psychotropic drug usage. Both patients and control subjects revealed a high intake of green vegetables. CONCLUSION: Patients' lower serum folate level was likely to be secondary to their depression but, being well in the normal range, should not have aggravated their depressive symptoms. Culturally patterned health beliefs and dietary practices can influence the connection between folate status and depression in different societies. LIMITATIONS: Patients were not drug-free, while the lack of detailed dietary analysis and longitudinal data on folate level and psychiatric outcome tempered the above conclusion. CLINICAL RELEVANCE: Since normofolatemia is normative in Hong Kong, the routine screening of folate levels in Chinese depressive patients is not indicated. However, a double-blind, placebo-controlled trial may be useful for finding out whether Chinese patients will still benefit from folate pharmacotherapy.

Adolescent↗

PubMed2007

Photodegradation of folic acid during extracorporeal photopheresis.

BACKGROUND: Photodegradation of folic acid (FA) by ultraviolet (UV) radiation is a well-documented photochemical reaction, and decreased serum levels of FA have been found in patients receiving photochemotherapy (psoralen plus UVA). During extracorporeal photopheresis (ECP) leucocytes and plasma are subjected to 8-methoxypsoralen (8-MOP) plus UVA. OBJECTIVES: To investigate whether ECP leads to the photodegradation of FA in the extracorporeal system. METHODS: In 30 patients undergoing ECP on two consecutive days the FA levels were measured in the extracorporeal collected plasma prior to and after UVA exposure. Healthy donor plasma was exposed to 8-MOP and increasing doses of UVA in vitro. In five patients serum folate levels were determined before and after ECP. RESULTS: We found a mean reduction of 44% and 46% on the first and second day of treatment, respectively. This effect could be reproduced in vitro: the irradiation of healthy donor plasma with UVA led to a dose-dependent reduction of FA of up to 54.75% at 16 J cm(-2). This was independent of the presence of 8-MOP and the base concentration of 5-methyltetrahydrofolate; minimal changes were observed for vitamin B(12) and homocysteine, not undergoing photodegradation. Serum folate levels did not change significantly before and after ECP. CONCLUSIONS: We conclude that extracorporeal exposure of plasma to UVA during ECP leads to photodegradation of FA. Further investigations are required to determine the biological effects of folate photoproducts and whether clinically relevant loss of FA might be a consequence of ECP.

Case-Control Studies↗

PubMed1977

Dietary folate intake and concentration of folate in serum and erythrocytes in women using oral contraceptives.

Conflicting reports regarding the possible effect of oral contraceptives agents (OCA's) on folate status prompted us to evaluate the relationship between dietary folate intake and the concentration of folate in serum and erythrocytes among users and nonsuers of OCA's during two consecutive menstrual cycles. Twenty-two women (ages 19 to 28) had been on combination type OCA's for 4 months or more and a control group of 18 women (ages 18 to 29) had not used OCA's for at least 6 months prior to this study. The serum folate levels were lower in the OCA users than in the controls and the difference was statistically significant on day 5 of the menstrual cycle (P less t-an 0.05) but not on day 20. However, the differences in the erythrocyte folate levels and dietary folate intakes were not statistically significant between the two groups of subjects. There was a consistently higher degree of correlation between serum folate and folate intake among the control women than among the OCA users. Hematological parameters such as hemoglobin, hematocrit, mean corpuscular volume, mean corpusclar hemoglobin, mean corpuscular hemoglobin concentration and red cell count were similar in the two groups. It is concluded that the use of OCA's produces significantly lower serum folate levels during the first week of the menstrual cycle in spite of adequate folate intake.

Adult↗