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Correlations between cognitive, behavioural and psychological findings and levels of vitamin B12 and folate in patients with dementia.

BACKGROUND: Associations between low levels of folate and vitamin B12 and cognitive impairment in patients with dementia have been reported. Some studies revealed correlations between low levels of vitamin B12 and behavioural and psychological signs and symptoms of dementia (BPSD) in Alzheimer's disease (AD) patients. Given the lack of studies in frontotemporal dementia (FTD) and on folate and given the methodological shortcomings of former publications, we set up a prospective study. METHODS: At inclusion, AD (n=152) and FTD (n=28) patients underwent a neuropsychological examination. Behaviour was assessed using a battery of behavioural assessment scales. Determination of serum vitamin B12 and red cell folate levels were performed within a time frame of two weeks of inclusion. RESULTS: In both patient groups, significantly negative correlations between levels of serum vitamin B12 and red cell folate and the degree of cognitive deterioration were found. No correlations with BPSD were found in the AD patient group. In FTD patients, levels of vitamin B12 were negatively correlated with both hallucinations (p=0.022) and diurnal rhythm disturbances (p=0.036). CONCLUSIONS: The observed negative correlations between levels of vitamin B12 and folate and cognitive impairment in both AD and FTD patients, raise the possibility of a non-specific etiological role. Although levels of vitamin B12 and folate did not correlate with BPSD in AD patients, negative correlations between serum vitamin B12 levels and BPSD in FTD patients were revealed. Decreased serum vitamin B12 levels may predispose FTD patients to develop hallucinations and diurnal rhythm disturbances.

Adult↗

The C677T thermolabile variant of methylene tetrahydrofolate reductase on homocysteine, folate and vitamin B12 in a hemodialysis center.

Homocysteine is a risk factor for cardiovascular disease. Mutations in a key enzyme in homocysteine metabolism, methylenetetrahydrofolate reductase, may contribute to hyperhomocysteinemia and alter folate and cobalamin levels. After starting hemodialysis, 10 mg oral folate daily and 500 micrograms intravenous methylcobalamin once weekly were prescribed to 27 hemodialysis patients (time on hemodialysis > or = 12 months) and two groups were defined: Group A normal; Group B heterozygous. Initial, third and twelfth month measurements of homocysteine, serum folate and vitamin B12 levels were collected and analyzed. Heterozygous state of methylenetetrahydrofolate reductase prevalence was 48% and homozygozity 4%. Hyperhomocysteinemia was present in both groups. Cobalamin final levels were significantly lower in Group B compared to Group A. Homocysteine, serum folate and cobalamin levels at third and twelfth month were significantly different from baseline levels but non-different between them in both groups. In Group B, vitamin B12 at third month was significantly higher than initial, but final measurements were not different from baseline determinations. In conclusion, the heterozygous prevalence of the enzyme in hemodialysis patients is similar to that reported in the general population; hyperhomocysteinemia is frequent in hemodialysis patients and final levels in heterozygous patients are significantly higher than in normal patients. Cobalamin levels are lower in the heterozygous group. After one year of treatment, homocysteine tends to increase, suggesting a secondary resistance phenomenon to vitamin supplementation in heterozygous patients.

Adult↗

Does the mean corpuscular volume help physicians evaluate hospitalized patients with anemia?

The authors analyzed the value of using mean corpuscular volume (MCV) as a guide for selecting tests for further evaluation of anemia in hospitalized patients. Of the 2,082 patients with anemia admitted to the medical service of a teaching hospital over one year, 655 (31%) had further diagnostic tests to evaluate the cause of the anemia. Within this group of 655 patients, 399 (61%) had normal MCVs. Over half the patients with abnormal serum vitamin B12, folate, or ferritin levels, or with low serum iron (Fe) levels with elevated total iron-binding capacity (TIBC), did not have the MCVs expected according to the classification of anemia proposed by Wintrobe. Furthermore, 5% of patients with evidence of iron deficiency had high MCVs, and about 12% of patients with decreased vitamin B12 levels had low MCVs. The MCV was quite specific in identifying patients who had low ferritin levels: specificity was 83%; however, sensitivity was only 48%. The MCV was also specific (88%) for identifying patients who had low Fe with elevated TIBC; however, sensitivity was only 43%. The MCV was poor in identifying patients with abnormalities of serum vitamin B12 and folate levels. In this study the MCV did not provide sufficient diagnostic accuracy to be a useful criterion for the selection of more definitive tests in the evaluation of anemia in hospitalized patients.

Aged↗

[Evaluation of the polymorphisms in methylenetetrahydrofolate reductase gene and the levels of folate and B12 in HIV-infected patients under antiretroviral therapy].

In this study we sought to investigate the B12 and folate levels regarding the influence of methylenetetrahydrofolate reductase genotypes, immunological profile and antiretroviral therapy in the Brazilian HIV-infected population. The study group comprised 89 HIV-infected individuals and 29 blood donors. There was a decrease in the B12 levels in the HIV-infected group with higher TCD4+ lymphocyte counts. No differences in the genotype distribution for methylenetetrahydrofolate reductase polymorphisms between the HIV-infected individuals and the controls were found. HIV-infected individuals carrying the C677C genotype presented lower B12 levels (313.91 +/- 154.05) than those with the same genotype in the control group (408.27 +/- 207.69). Also, the antiretroviral therapy was not a source of variation of the folate and B12 serum levels. Further studies are needed to reanalyze the prevalence of low levels of folate and B12 and hyperhomocysteinemia among HIV-infected patients with regard to the use of HAART and the increased life expectancy of such patients.

Adult↗

Elevated plasma homocysteine concentrations six months after gastroplasty in morbidly obese subjects.

OBJECTIVE: To investigate whether the increased homocysteine levels occur in the first 6 months postoperatively, when nutritional intake is the most inadequate and weight reduction is the most drastic. PATIENTS AND METHODS: Fasting glucose, insulin, lipoprotein, homocysteine, folic acid and vitamin B12 levels and oral glucose, tolerance test (OGTT) were determined in 12 morbidly obese subjects (3 men and 9 women with a mean age of 31+/-3 years, mean+/-SEM) before, 6 and 12 months after banded gastroplasty. RESULTS: Gastroplasty resulted in significant weight loss, from 120+/-6 to 92+/-6 and 88+/-7 kgs, 6 and 12 months postoperatively (all p<0.001). Fasting plasma insulin and triglyceride concentrations, the ratio of total cholesterol to HDL cholesterol, glucose and insulin responses to OGTT, and the degree of insulin resistance as expressed by the Homeostasis model index decreased significantly (p<0.05-0.001) following gastroplasty. Fasting plasma homocysteine concentrations increased from 10.2+/-0.8 to 12.1+/-0.6 at 6 months (p=0.036) and 12.0+/-1.2 micromol/l at 12 months (p=0.040), respectively. Pooled plasma homocysteine levels were negatively correlated with serum folate concentrations (r=-0.42, p=0.013). However, serum folate and vitamin B12 levels did not change after gastroplasty, nor did the relation between the loss of body weight and increase in homocysteine levels. CONCLUSION: We observed that elevated circulating homocysteine levels occurred as early as 6 months after gastroplasty despite improvement in carbohydrate and lipoprotein metabolism in morbidly obese Chinese subjects.

Adult↗

Multifactorial megaloblastic anaemia.

Ninety-five patients who had megaloblastic anaemia, and who lived in a subtropical climate, were studied to elucidate the importance of puerperium, malabsorption, gastric dystrophy, diet and infection in the aetiology of the disease. All 5 factors were found to be common, and to occur in a variety of combinations, producing a wide spectrum of illness variously resembling nutritional megaloblastic anaemia, sprue, pernicious anaemia and many stages in between. It is concluded that megaloblastic anaemia in this population is a multifactorial disease, and a tentative scheme, relating the aetiological factors, is drawn up. Neither serum vitamin B(12) levels, nor folate estimation in serum or red cells emerged as very reliable guides to the underlying biochemical deficiency.

Adolescent↗

[Folic acid deficiency in patients hospitalized with depression? A pilot study of clinical relevance].

Seventy-seven depressive inpatients were studied in a pilot study to determine their serum and red cell folate levels at admission. Only one depressive inpatient with a low serum folate value had a history of an illness-related lack of nutrition prior to admission, and the low value was only on day 1 of the study. Our results demonstrate that folate acid deficiency is not as common in depressive inpatients as reported, especially in British studies for two reasons: different eating habits and a methodological problem.

Adult↗

Folate assays: serum or red cell?

Tests for folate and vitamin B12 deficiency are frequently requested by clinicians in many different specialties. An audit of folate assay methodology was undertaken to establish the number of tests and types of assay performed in different centres, and to analyse the indications for these investigations, with a view to advising on the most appropriate assay for use in the laboratory. A questionnaire was sent to 30 centres, 24 (80%) of which participated in the audit. The types of folate assay performed, number of requests, reference range and method of analysis differed between centres. The major specialty users of the service were general practitioners, general physicians and geriatricians. A detailed analysis of 1,259 consecutive requests for folate assays from a single representative laboratory showed a significant correlation between serum and red cell folate levels (r = 0.49, p < 0.001). However, in patients with low serum folate, there was no correlation with red cell folate in the absence of macrocytosis. The major indication for folate analysis was for haematological abnormalities but 36% of cases were for nonspecific indications. A haematologist with an interest in folate metabolism was invited to moderate the results at an audit meeting of haematologists. The consensus was that the most appropriate screening test for folate deficiency is the serum assay, which can be combined easily with vitamin B12 assay.

Anemia, Macrocytic↗

Nutritional status of vitamin A, E, C, B1, B2, B6, nicotinic acid, B12, folate, and beta-carotene in young women.

To investigate the vitamin status of young Japanese women, dietary intakes of vitamin A, E, C, B1, B2, B6, B12, niacin, folate, and beta-carotene were assessed by a 3-d weighed food record in 150 female students aged 21-22. Whole blood levels of vitamin B1, B2, and nicotinic acid, and serum levels of retinol, alpha-tocopherol, vitamin B6, and beta-carotene were determined by HPLC. Vitamin B12 and folate in serum were measured by chemiluminescence immunoassay, and serum vitamin C was done by dinitrophenylhydrazine method. When the 6th revision RDAs for the Japanese (physical activity level 1) were applied, 46.7% of the females showed sufficient intake for vitamin A, 28.7% for E, 80.7%, for B1, 92.7% for B2, 54.7% for B6, 99.3% for niacin, 76.0% for B12, 34.0% for folate, and 54.0% for C. Fifty-nine percent of total vitamin A (microgRE) intakes were derived from beta-carotene. The mean+/- SD of energy intakes was low, 1.572+/-315 kcal. Significant correlations among intakes of energy and all these vitamins were found. Serum folate and ascorbic acid levels in the females with corresponding vitamin intakes above the RDA were significantly higher than in those with intakes below the RDA. There were significant correlations between blood vitamin levels and vitamin intakes in vitamin B12 (r=0.185), folate (r=0.255), vitamin C (r=0.272), and beta-carotene (r=0.319). Mean blood levels of folate, ascorbic acid, vitamin B2, B12, and beta-carotene were higher in the highest quartile of intake than in the lowest. The 95% confidence intervals of blood vitamin levels obtained from the females with sufficient vitamin intakes were nearly equal to those obtained from all subjects. Only a few females (0.7-4.7%) had their blood vitamin levels below the lower limits. Serum alpha-tocopherol levels were significantly correlated with serum levels of retinol, beta-carotene, and vitamin C. This data suggested that young women should increase suitable dietary food intakes in order to maintain good status of vitamin. Moreover, sufficient amount of physical activity would be expected for prevention of excessive energy intake.

Adult↗

Studies on the effect of folic acid supplement on folate and vitamin B12 status in children.

The effect of folic acid supplement (15 mg folic acid per day) for 5 weeks was studied on a group of 5 children aged 8-12 years who were admitted to hospital. The result was compared to a control group of 5 children who were given a placebo. After supplementation, both serum and red cell folate levels in the experimental group significantly increased, i.e., 15 fold (82.0 ng/ml) and 4 fold (880 ng/ml), respectively. Serum UFBP decreased considerably while TFBP showed no significant alteration which resulted in the elevation of the % saturation to its maximum value. These findings indicated that the supplementary folic acid not only increased both serum and red cell folate levels and saturated nearly all serum UFBP but also elevated the % saturation markedly. There were no definite changes of serum vitamin B12, UBBC, TBBC and TC levels of the experimental group from those of the control group. There were slightly but not significantly increased blood haemoglobin and haematocrit levels in both groups of children. This indicated that folic acid supplement had no definite effect on vitamin B12 and haematological findings in this study.

Carrier Proteins↗

Reversible optic neuropathy associated with low-dose methotrexate therapy.

A 66-year-old woman had progressive bilateral optic neuropathy with dense central scotomas and dyschromatopsia. She had been taking oral methotrexate 2.5 mg three times per week for rheumatoid arthritis for the previous 10 months (total intake 322.5 mg) without folic acid supplementation. She had never smoked or abused alcohol and her diet was healthy. Serum folate was reduced at 1.6 ng/mL (normal >4 ng/mL) and vitamin B12 levels were normal. After stopping methotrexate and after administration of oral folic acid, she experienced complete recovery of vision. Serum folate levels returned to normal during folic acid treatment but decreased to below normal once folic treatment was stopped. The persistently low folate level remains unexplained and may reflect a genetic defect in folate metabolism. Methotrexate can cause toxic side effects resulting from folate inhibition but has not been shown definitively to cause a reversible optic neuropathy associated with low serum folate.

Aged↗

Occult cobalamin and folate deficiency in Indians.

BACKGROUND: Our aim was to assess cobalamin and folate levels in normal Indian subjects before undertaking a prospective study of megaloblastic anaemia. METHODS: We took samples from 25 men and 25 women to establish the normal range. The exclusion criteria for subjects were age below 18 years and above 65 years, haemoglobin < 12 g/dl, and those who were pregnant, lactating or on any medication including vitamin supplements. A complete blood count and blood film examination for hypersegmented neutrophils were done. Serum cobalamin and folate assays were performed by a competitive immunoassay. The reference range supplied with the kits for serum cobalamin was 100-700 pg/ml and for serum folate it was 3-22 ng/ml. RESULTS: Since many 'normal' subjects in the sample showed values below the normal reference range, the numbers sampled were increased to 46 men and 50 women. Of all the subjects tested, 46.9% had subnormal values of one of the two vitamins. The normal ranges for serum cobalamin established in this study were--men 100-388 pg/ml and women 105.3-434 pg/ml. Of the 46 men tested, 17 (36.9%) had low cobalamin levels and of the 50 women tested, 23 (46%) had low cobalamin levels. Levels < 50 pg/ml were seen in 46.9% of these subjects. The normal ranges for serum folate in the study were--men 3.1 to > 22 ng/ml, women 3-12.26 ng/ml. In the study group, 8 men (17.3%) and 6 women (12%) had folate deficiency. Eight subjects (17%) had combined deficiency of the two vitamins. The mean corpuscular volume was not informative and was elevated in only 1 subject. Hypersegmentation of neutrophils was present in 75% of deficient subjects. CONCLUSION: We established normal levels for serum cobalamin and folate in our study group. Of the subjects studied, 46.9% had subnormal levels of serum cobalamin or serum folate, cobalamin deficiency being five times more common than folate. Hypersegmentation of neutrophils was a better indicator of occult megaloblastosis than the mean corpuscular volume.

Adolescent↗

Changes in serum levels of cobalamin and cobalamin analogues in folate deficiency.

The recent introduction of radioassays for 'true' cobalamin, as opposed to cobalamin and its analogues, has resulted in significantly lower levels of cobalamin being found in patients with folate deficiency. In study of 81 patients, cobalamin analogue levels were found to increase and cobalamin to decrease as red cell folates decreased. Cobalamin absorption studies in 15 patients with low cobalamin and folate levels were found to be normal in 10 patients, all of whom demonstrated high levels of analogues relative to true cobalamin. We have found that the mean serum cobalamin increased from 210 ng/l (range 100-380) to 309 (150-470) and analogues fell from 226 ng/l (150-280) to 127 (65-190) in folate deficient patients when treated with folic acid. It appears that cobalamin analogue concentrations are increased in folate deficiency, and that in these patients treatment with folic acid alone may correct both the low cobalamin and the high analogue levels.

Folic Acid↗

Cigarette smoking, serum lipids, folate, and vitamin B12 in lung cancer.

The purpose of our study was to evaluate the effects of cigarette smoking and serum lipids, folate, and vitamin B12 on the development of lung cancer in the Turkish population. The study group consisted of patients with histologically proven lung cancer and the control group comprised healthy smokers being followed in our smoking cessation outpatient department. Smoking history was obtained from all subjects and serum total cholesterol, HDL cholesterol, triglycerides, vitamin B12, and folate levels were measured. Pack/years of cigarettes smoked were significantly higher in the subjects with lung cancer than in the control group (p < 0.01). Serum total cholesterol, HDL cholesterol, triglyceride, serum folate, and vitamin B12 levels were within normal limits in both groups (p < 0.05), but serum vitamin B12 levels were statistically significantly higher (p < 0.01) in the cancer group than in the controls. In our study, we did not observe low levels of serum cholesterol, vitamin B12, or folate in the lung cancer patients.

Adolescent↗

Effect of folate and mecobalamin on hip fractures in patients with stroke: a randomized controlled trial.

CONTEXT: Stroke increases the risk of subsequent hip fracture by 2 to 4 times. Hyperhomocysteinemia is a risk factor for both ischemic stroke and osteoporotic fractures in elderly men and women. Treatment with folate and mecobalamin (vitamin B12) may improve hyperhomocysteinemia. OBJECTIVE: To investigate whether treatment with folate and vitamin B12 reduces the incidence of hip fractures in patients with hemiplegia following stroke. DESIGN, SETTING, AND PATIENTS: A double-blind, randomized controlled study of 628 consecutive patients aged 65 years or older with residual hemiplegia at least 1 year following first ischemic stroke, who were recruited from a single Japanese hospital from April 1, 2000, to May 31, 2001. Patients were assigned to daily oral treatment with 5 mg of folate and 1500 microg of mecobalamin, or double placebo; 559 completed the 2-year follow-up. MAIN OUTCOME MEASURE: Incidence of hip fractures in the 2 patient groups during the 2-year follow-up. RESULTS: At baseline, patients in both groups had high levels of plasma homocysteine and low levels of serum cobalamin and serum folate. After 2 years, plasma homocysteine levels decreased by 38% in the treatment group and increased by 31% in the placebo group (P<.001). The number of hip fractures per 1000 patient-years was 10 and 43 for the treatment and placebo groups, respectively (P<.001). The adjusted relative risk, absolute risk reduction, and the number needed to treat for hip fractures in the treatment vs placebo groups were 0.20 (95% confidence interval [CI], 0.08-0.50), 7.1% (95% CI, 3.6%-10.8%), and 14 (95% CI, 9-28), respectively. No significant adverse effects were reported. CONCLUSION: In this Japanese population with a high baseline fracture risk, combined treatment with folate and vitamin B12 is safe and effective in reducing the risk of a hip fracture in elderly patients following stroke.

Aged↗

Autoantibodies to folate receptors in the cerebral folate deficiency syndrome.

In infantile-onset cerebral folate deficiency, 5-methyltetrahydrofolate (5MTHF) levels in the cerebrospinal fluid are low, but folate levels in the serum and erythrocytes are normal. We examined serum specimens from 28 children with cerebral folate deficiency, 5 of their mothers, 28 age-matched control subjects, and 41 patients with an unrelated neurologic disorder. Serum from 25 of the 28 patients and 0 of 28 control subjects contained high-affinity blocking autoantibodies against membrane-bound folate receptors that are present on the choroid plexus. Oral folinic acid normalized 5MTHF levels in the cerebrospinal fluid and led to clinical improvement. Cerebral folate deficiency is a disorder in which autoantibodies can prevent the transfer of folate from the plasma to the cerebrospinal fluid.

Adolescent↗

Folate status in patients receiving maintenance doses of sulfasalazine.

Hematologic studies, including serum and RBC folate assays, were done on 45 outpatients with chronic colitis who either took sulfasalazine (n = 27) or did not use it (n = 18). Overall, sulfasalazine users and nonusers had similar mean hemoglobin, hematocrit, serum folate, and RBC folate levels. However, within the drug users, RBC folate was inversely correlated with drug dose; serum folate was not. Patients taking 2 g or more of sulfasalazine daily had lower mean RBC folate levels (221.2 +/- 27.3 ng/mL) than patients either taking less (371.7 +/- 35.0 ng/mL) or nonusers (330.3 +/- 30.3 ng/mL). Mean corpuscular volume was also related to drug dose but not to RBC folate. Although maintenance sulfasalazine use rarely causes clinically significant folate deficiency, subclinical tissue depletion occurs as a dose-related effect.

Colitis↗

[Investigation or oral substitution of iron and folic acid (author's transl)].

In a study of apparently healthy volunteers (5 male, 5 female) the bioavailability of iron and folacin was calculated using Tardyferon¿ resp. Tardyferon-Fol¿ as test substances. Blood samples for serum iron and folacin level determinations were obtained before and 1/2, 1, 2, 4, 6 and 8 hours after dosing. Because of the diurnal fluctuation of serum iron and folate levels, baseline levels were obtained at the corresponding 0, 1/2, 1, 2, 4, 6 and 8 hours one week prior to the study. Serum iron and folacin levels above the baseline values and the area under the curve were calculated. The data suggested a good bioavailability of the tested substances. The folacin absorption after a single dose of 0.35 mg produced a maximal serum concentration of mean = 28 ng/ml. Twice the dose resulted in a maximum of serum folacin level of mean = 51 ng/ml. The oral administration of 80 mg Fe2+ resp. 160 mg Fe2+ resulted in a significant increase of the serum iron levels, too.

Administration, Oral↗