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PubMed1996

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↗
PubMed2005

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↗
PubMed2005

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↗
PubMed1983

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↗
PubMed1980

[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↗
PubMed1992

Maternal vitamin levels during pregnancies producing infants with neural tube defects.

Women at very high risk for having a child with a neural tube defect (NTD) because they had previously delivered affected children significantly reduced their recurrence rate by taking folate supplements before conception. To clarify how these results might apply to a lower-risk general obstetric population, we measured folate, vitamin B12, and retinol levels in maternal serum drawn early in 89 pregnancies resulting in NTD offspring and 178 control pregnancies identified from the Finnish Registry of Congenital Malformations. In 86.5% of the subjects, specimens were collected within 8 weeks after neural tube closure. In the NTD case mothers the mean (+/- SD) levels were not significantly lower than in control mothers: folate, 4.13 +/- 2.36 versus 4.28 +/- 2.52 ng/ml; vitamin B12, 482.8 +/- 161.1 versus 520.3 +/- 191.9 pg/ml; and retinol, 51.2 +/- 17.0 versus 50.5 +/- 16.9 micrograms/dl. After adjustment for age of the specimen, gestational age at which the specimen was drawn, maternal age, and maternal employment status, the odds ratios for being a case mother were 1.00 (95% confidence interval (CI) 0.91 to 1.10) for folate, 1.05 (95% CI 0.92 to 1.19) for vitamin B12, and 0.99 (95% CI 0.88 to 1.10) for retinol. Excluding NTD cases with known or suspected causes unrelated to vitamins, restricting the analyses to interviewed subjects, and excluding subjects whose specimens were collected after 15 gestational weeks confirmed that NTD case and control vitamin levels did not differ significantly. This population-based investigation in a low rate area demonstrated no relationship between maternal serum folate, vitamin B12, or retinol levels during pregnancy and the risk of NTDs.

Adult↗
PubMed1983

Iron supplements versus placebo during pregnancy: its effects on iron and folate status on mothers and newborns.

Iron and folate status of 203 pregnant women have been evaluated at 6 months gestation and on the same women and their newborn infants at delivery. The women who had, at 6 months gestation, a Hb level below 11 g/dl were systematically given iron supplements. Iron or placebo were randomly allocated to the other women. At 6 months of pregnancy, one quarter of the women had a Hb level under 11 g/dl but one third had a serum ferritin level below 12 micrograms/l and more than half had low levels of serum and red cell folate. Iron supplements induced an increase both in Hb levels and in serum ferritin values; however, no significant differences were observed in serum ferritin of the newborn infants, whether their mothers had received iron supplements or not. These results have led us to reconsider the value of ferritin levels at birth as an index of iron stores in the infant. Iron supplements had no effect on the folate status in mothers or infants or on the frequency of obstetrical complications. A significant relationship was found between maternal folate levels and length of gestation. Folate supplementation may reduce the incidence of premature delivery.

Adolescent↗
PubMed2004

Effects of the interaction between the C677T 5,10-methylenetetrahydrofolate reductase polymorphism and serum B vitamins on homocysteine levels in pregnant women.

OBJECTIVE: The purpose of this study was to investigate the effect of the interaction between the C677T mutation in the 5,10-methylenetetrahydrofolate reductase (MTHFR) genotypes and serum levels of B vitamins on serum homocysteine levels in pregnant women. DESIGN: A cross-sectional study. SETTING: Ewha Womans University Hospital, Seoul, Korea. SUBJECTS: A total of 177 normal pregnant women, 24.6+/-1.1 weeks of gestation, in a 6-month period during 2001-2002. INTERVENTIONS: Serum vitamin B2, vitamin B6, and homocysteine analyses were conducted using high-performance liquid chromatography methods. Serum folate and vitamin B12 concentrations were determined using a radioimmunoassay kit. MTHFR gene mutation was investigated by the polymerase chain reaction of a genomic DNA fragment. RESULTS: Serum homocysteine was higher in women with the T/T genotype than those with the C/T or C/C genotype of the MTHFR gene (P<0.05). Serum homocysteine was negatively correlated with serum folate in all MTHFR genotypes (P<0.001), and the correlation between the two serum levels was the strongest in the T/T genotype. Serum homocysteine was higher in the subjects with the T/T MTHFR genotype only when the serum folate was below the median level. Explanatory power of B vitamin status as predictors of serum homocysteine levels was more pronounced in the T/T genotypes (68.5%) compared with the C/T (37.9%) or C/C genotypes (20.6%). CONCLUSIONS: Serum homocysteine levels in pregnant women varied significantly with MTHFR genotype and the serum B vitamin status. Higher serum folate, vitamin B2, and vitamin B12 concentrations may lessen the MTHFR genotypic effect on serum homocysteine levels.

Adult↗
PubMed2000

Plasma total homocysteine levels during short-term iatrogenic hypothyroidism.

Hypothyroidism is associated with increased cardiovascular morbidity, which cannot be fully explained by the atherogenic lipid profile observed in these patients. We have previously found elevated levels of the cardiovascular risk factor, plasma total homocysteine (tHcy), in hypothyroidism. We conducted a longitudinal study on 17 patients who had undergone total thyroidectomy for thyroid cancer. During 6 weeks of discontinued T4 substitution before radioscintigraphy (phase I), they attained a hypothyroid state, which was reversed by resupplementation (phase II). Plasma tHcy, serum creatinine, serum and red blood cell folate, serum cobalamin, and serum cholesterol were determined at 2-week intervals throughout phases I and II. There was a progressive and parallel increase in tHcy (mean, 27%), serum creatinine (37%), and serum cholesterol (100%) during phase I, and these values returned to the original level within 4-6 weeks after reinitiating T4 therapy. Serum and red blood cell folate levels showed only minor, but statistically significant, changes. In a bivariate model, serum creatinine and serum cholesterol were strongly associated with the changes observed in tHcy during short term hypothyroidism. In conclusion, we found a transient increase in both plasma tHcy and serum cholesterol during short term iatrogenic hypothyroidism, and the tHcy response is probably mainly explained by concurrent changes in renal function. The increase in both plasma tHcy and serum cholesterol may confer increased cardiovascular risk in hypothyroid patients.

Adult↗
PubMed1997

Is metabolic evidence for vitamin B-12 and folate deficiency more frequent in elderly patients with Alzheimer's disease?

BACKGROUND: It is still unclear whether there is an association between Alzheimer's disease and vitamin B-12 or folate deficiency. This study was designed to investigate whether patients with Alzheimer's disease are particularly prone to metabolically significant cobalamin or folate deficiency as compared to nondemented hospitalized controls and healthy elderly controls living at home. METHODS: Evaluation for the diagnosis of Alzheimer's disease, routine laboratory tests, serum folate and vitamin B-12, serum methylmalonic acid (MMA), total homocysteine (tHcy), and radiological tests was performed in 52 patients with Alzheimer's disease (AD), 50 nondemented hospitalized controls, and 49 healthy elderly subjects living at home. RESULTS: Serum vitamin B-12 and folate levels are comparable between patients with AD, hospitalized control patients, and subjects living at home. Patients with AD have the highest serum MMA and tHcy levels. The MMA levels of patients with AD and hospitalized controls are not different, but the mean tHcy level is significantly higher in patients with AD as compared to nondemented patients or subjects living at home. CONCLUSION: The interpretation of the vitamin B-12 and folate status in patients with AD depends largely on the methodology (i.e., serum vitamin vs metabolite levels) and the selection of the control group. Although patients with AD have the highest tHcy and MMA levels, metabolically significant vitamin B-12 and folate deficiency is also a substantial problem in nondemented elderly patients.

Aged↗
PubMed2006

Reference range of total serum homocysteine level and dietary indexes in healthy Greek schoolchildren aged 6-15 years.

Elevated total serum homocysteine (tHcy) may be a possible risk factor for CVD. A 5 micromol/l increase in tHcy is associated with an approximately 70 % increase in relative risk of CVD in adults. Data for children and adolescents are, however, limited. The purpose of the present study was to provide a reference range for tHcy and investigate any relationship between tHcy and nutritional indexes in a Greek paediatric population. tHcy, folate, vitamin B12 levels and dietary indexes were measured in 520 healthy schoolchildren (274 boys, 246 girls) aged 6-15 years. As in adults, the tHcy distribution skewed to the right, with a geometric mean for both genders of 7.4 (range 3.4-29 micromol/l). Concentrations were lower in young children and increased with age. No statistically significant difference in tHcy level was observed between gender. The 95th percentiles for the three age groups were as follows: 6-9 years, 9.98 micromol/l; 10-12 years, 10.62 micromol/l; 13-15 years, 14.4 micromol/l. Using Pearson's coefficient analysis, tHcy level was correlated with age, serum folate, BMI and systolic blood pressure. Dietary analysis showed that folate, vitamin B12 and fibre intake were inversely related with tHcy; conversely, sugar and fat were positively associated with tHcy. However, in multiple linear regression analysis, only age (odds ratio 0.246, P < 0.05) and folate (odds ratio -0.346, P < 0.05) were significantly and independently associated with tHcy. This study provides age-specific reference data regarding tHcy concentration in a Greek paediatric population. tHcy levels increased as a function of age. Serum folate levels were significantly and independently associated with tHcy levels.

Adolescent↗
PubMed1982

Cerebrospinal fluid and blood thiamine concentrations in phenytoin-treated epileptics.

Thiamine and folate levels in blood and cerebrospinal fluid (CSF) were determined by microbiological assays in 23 control subjects and 11 phenytoin-treated epileptics. There was no significant difference between the two groups for serum and CSF folate levels. There was, however, a statistically significant difference between the groups for both whole blood thiamine and CSF thiamine levels. Epileptic patients being treated with phenytoin had lower values than control subjects.

Epilepsy↗
PubMed2002

Optimal use of markers for cobalamin and folate status in a psychogeriatric population.

BACKGROUND: Cobalamin/folate deficiency is common in elderly subjects and may lead to psychiatric symptoms, but even more often it increases the severity of other organic and non-organic mental diseases. It is therefore of importance to evaluate the optimal use of different markers of cobalamin/folate status in a psychogeriatric population. METHODS: We measured serum cobalamin, blood folate, plasma homocysteine (tHcy) and serum methylmalonic acid (MMA) in 475 well-defined psychogeriatric patients. RESULTS: The findings in the present study showed that many (41%) of the patients with normal levels of serum MMA (< 0.41 micromol/l) had pathological values of at least one of the other markers for cobalamin/folate status, whereas only 17% of patients with normal plasma tHcy (< 19.9 micromol/l) had pathological levels of other markers. If patients with decreased levels of serum cobalamin and/or blood folate were also excluded from these patients, only nine patients with slightly elevated levels of serum MMA remained. In the present study different upper reference limits were also tested for both serum MMA and plasma tHcy. However, the use of these limits did not cause any diagnostic improvement in the evaluation of cobalamin-folate status. Plasma tHcy was increased in almost all diagnosis groups of the psychogeriatric patients, whereas serum MMA was increased in only some groups. The distribution of the two common polymorphisms of the methylenetetrahydrofolate reductase gene (C677T and A1298C) was similar in patients with elevated and normal plasma tHcy. CONCLUSIONS: The findings in the present study suggest the use of plasma tHcy, serum cobalamin and blood folate to evaluate cobalamin-folate status in psychogeriatric patients and to omit the use of serum MMA.

Aged↗
PubMed1979

[Folate- and iron-deficiency in pregnancy (author's transl)].

In an open study the influence of a pure iron-therapy (Aktiferrin) and a combined iron-folic-therapy (Aktiferrin F) on the blood and the folate levels in the serum of 60 anaemic pregnant women was compared. The prophylactic administration and the therapy of iron and folate acid in pregnancy is demanded because of the results of this examination.

Anemia, Hypochromic↗
PubMed2004

Association between serum homocysteine, folate and B12 concentration with coronary artery disease in Thai patients.

BACKGROUND: Hyperhomocysteinemia, associated with low folate and low B12 levels, is known to be an independent risk factor for atherosclerosis. Only a few available data has been demonstrated in Thai patients. OBJECTIVE: To evaluate serum fasting homocysteine, folate and B12 levels whether to see they are associated with coronary artery disease (CAD). METHOD AND RESULT: Three hundred and one consecutive suspected CAD patients who underwent coronary angiography at the Police General Hospital were studied. The mean age of the patients, 195 males and 106 females, was 63.0 +/- 10.0 year (range 39-85). A total of 218 patients were angiographically demonstrated as having CAD. The mean serum homocysteine level of CAD patients had a non significant higher level than those of 83 non CAD patients: 11.4 +/- 6.2 vs 10.2 +/- 4.2 umol/L, p = 0.06. Means of folate and B12 level in the CAD patients and non CAD patients were 6.6 +/- 4.6 vs 7.0 +/- 4.3 nmol/L, p = 0.49 and 650.9 +/- 415.4 vs 613.3 +/- 443.2 pmol/L, p = 0.56 respectively. No significant correlations were found between homocysteine with folate and B12 levels. Logistic regression analysis showed a significant association between homocysteine and CAD with OR = 1.08 (95%CI, 1.01-1.16), p = 0.03 after being adjusted for age, sex, DM, HT history of hyperlipidemia, smoking, BMI, folate and B12 levels. No significant association between homocysteine level with the number of coronary vessel stenosis, age, BMI, DM, HT smoking and history of hyperlipidemia was observed in the present study. CONCLUSION: Hyperhomocyteinemia, but not folate and B12 levels, may be an independent risk factor for coronary artery disease in Thai patients.

Coronary Disease↗
PubMed2001

The effect of vitamin B6 and folate supplements on plasma homocysteine and serum lipids levels in patients on regular hemodialysis.

BACKGROUND: Hyperhomocysteinemia is an independent risk factor for cardiovascular events. The aim of this study was to show the results of the reduction of homocysteine in end stage renal failure patients on hemodialysis, as it is known, have higher levels of homocysteine than other groups of subjects. METHODS: Plasma homocysteine concentration was determined before and after the administration of vitamin B6 and folic acid in 12 patients (males: 6) on regular dialysis therapy. Mean monthly fasting serum concentrations of total cholesterol (TCHOL), HDL-chol, LDL-chol and triglycerides (TRG) were determined for a period 68 months (12-120 months) before and 26 months after the administration of vitamin B6 and folic acid. RESULTS: Mean serum concentrations for folic acid and vitamin B12 before and after the administration were: folic acid: 5.03 +/- 4.9 and 18.0 +/- 19.2 ng/mL, (p < 0.0001) and B12: 456 +/- 257 and 514.38 +/- 307 pg/mL respectively). Plasma homocysteine was reduced significantly after the administration of above drugs (from 47 +/- 14 to 29 +/- 9 micromol/mL, p < 0.001). This reduction of homocysteine resulted in a modification of the patients' lipidemic profile: Serum LDL-chol was decreased significantly (119 +/- 38 mg/dL to 110 +/- 35 mg/dL, p<0.005). TCHOL and TRG were also decreased but not significantly (190 +/- 45 mg/dL to 187 +/- 43 mg/dL and 116 +/- 63 mg/dL to 108 +/- 47 mg/dL respectively)). Serum concentrations HDL-chol were increased significantly (from 42 +/- 10 mg/dL to 47 +/- 10 mg/dL, p < 0.001). The atherogenic index for cholesterol, LDL/HDL, was 1.6 times lower after the drugs receiving (before: LDL/HDL = 3.1 and after: LDL/HDL = 2.5, p < 0.001). CONCLUSIONS: These results indicate that the folate and vitamin B6 supplementation resulted in reduction of homocysteine levels and improvement of lipidemic profile in regular dialysis patients.

Adult↗
PubMed2004

Plasma homocysteine after insulin infusion in type II diabetic patients with and without methionine intolerance.

BACKGROUND: A high prevalence of hyperhomocysteinemia has been reported in type II diabetic patients with documented vascular disease; hence the hypothesis that hyperhomocysteinemia may contribute to overall mortality in diabetic patients. The link between insulin and homocysteine metabolism has not been completely clarified yet; in particular, only few data are available on the effects of insulin in vivo on homocysteine metabolism in the presence of abnormalities of sulphur amino acid metabolism (methionine intolerance). MATERIALS AND METHODS: To establish whether methionine intolerance and which of its determinants could influence total plasma homocysteine in response to insulin infusion in vivo in type II diabetic patients, we submitted 18 patients (Group A) with normal and 18 patients with abnormal (hyperhomocysteinemia) (Group B) response to oral methionine load to a glucose/clamp study. At time 0, and 30, 60 and 120 minutes after hyperinsulinemia, homocysteine and methionine plasma levels were assessed. In order to evaluate the cause of methionine intolerance, all patients were assayed for fasting homocysteine-cysteine ratio (as a marker of suspected heterozygosis for cystathionine-beta-synthase deficit), MTHFR C (677)T status and homocysteine-related vitamin status (serum vitamin B (6) [PLP], vitamin B (12) and folate). RESULTS: After hyperinsulinemia, plasma methionine was reduced (by about - 30 % at 120 minutes vs. basal values) within both groups, whereas tHcy tend to decrease in group A following insulin administration (up to - 6.6 +/- 3.6 % vs. basal values at 120 minutes) with a significantly higher variability, while in patients with "methionine intolerance" (group B) tHcy tended to increase (up to + 29.05 +/- 8.3 % vs. basal values at 120 min from the clamp). Serum folic acid (7.45 +/- 2.8 vs. 4.82 +/- 2.5 nmol/L, p < 0.05), Vit. B (12) (348 +/- 78 vs. 242 +/- 65 pmol/L, p < 0.05) and PLP (84.1 +/- 23.6 vs. 50.6 +/- 32.4 nmol/L; p < 0.01) were significantly higher in group A than in group B; PLP levels significantly correlated with homocysteine after 4 h methionine load (n = 36; r = - 0.327, p < 0.05); group A showed also a significantly lower prevalence of suspected heterozygosis for cystathionine-beta-synthase deficit (1/18 [11.1 %] vs. 5/18 [33.3 %], p < 0.05) and MTHFR T allele presence (4/18 [22.2 %] vs. 11/18 [61.1 %], p < 0.01). A stepwise regression analysis with tHcy plasma level variations (event A = reduction; event B = increase) as the dependent variable showed that low serum folate and PLP levels and presence of MTHFR T allele were the variables associated with insulin-induced tHcy increase. CONCLUSIONS: Methionine intolerance may influence the effect of insulin administration on plasma homocysteine in patients affected by type 2 diabetes. To prevent a possible acute (and repeated) hyperhomocysteinemia due to insulin administration in cases of methionine intolerance, it may be useful to assess the presence of methionine intolerance (tHcy after oral methionine loading) and Hcy-related vitamin status in all patients due to be subjected to insulin therapy.

Blood Glucose↗