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PubMed2006

Dietary and other lifestyle correlates of serum folate concentrations in a healthy adult population in Crete, Greece: a cross-sectional study.

BACKGROUND: Folate has emerged as a key nutrient for optimising health. Impaired folate status has been identified as a risk factor for cardiovascular disease, various types of cancers, and neurocognitive disorders. The study aimed at examining the distribution and determinants of serum folate concentrations in a healthy adult population in Crete, Greece. METHODS: A cross-sectional sample of 486 healthy adults (250 men, 236 women) aged 39 +/- 14 years, personnel of the Medical School and the University Hospital of Crete in Greece, was examined. Serum folate and vitamin B12 concentrations were measured by microbiological assay, and total homocysteine was determined fluorometrically and by high-pressure liquid chromatography. Lifestyle questionnaires were completed, and nutrient intakes and food consumption were assessed by 24-h dietary recalls. Multivariate analyses were performed using SPSS v10.1. RESULTS: The geometric mean (95% confidence interval) concentrations of serum folate were 15.6 micromol/l (14.6-16.8) in men and 19.2 micromol/l (17.9-20.7) in women (p < 0.001). Inadequate folate levels (<or=7 nmol/l) were present in 6.8% of men and 2.1% of women (p < 0.001). Approximately 76% of men and 87% of women did not meet the reference dietary intake for folate (400 microg/day). Serum folate was inversely related to total homocysteine levels (p < 0.001). Increased tobacco and coffee consumption were associated with lower folate concentrations (p < 0.05 for both) but these associations disappeared after controlling for nutrient intakes. In multivariate analysis, intakes of MUFA, fibre, calcium, magnesium, folate, and vitamins A, E, C, B1, and B6 were positively associated with serum folate. Consumption of potatoes, legumes, fruits, and vegetables were favourably related to the serum folate status. CONCLUSION: Serum folate concentrations were associated with various demographic, lifestyle and dietary factors in healthy Cretan adults. Large-scale epidemiological studies should be conducted within the general Greek adult population to assess the prevalence of impaired folate status and further examine associations with dietary patterns and chronic disease risk. Considering the importance of folate in health maintenance, it is important to increase the public's awareness of modifiable lifestyle patterns and diet and tobacco use in particular, which may be associated with improved folate status.

Adult↗
PubMed2005

Tribromomethane exposure and dietary folate deficiency in the formation of aberrant crypt foci in the colons of F344/N rats.

Folate and folic acid are forms of the B vitamin that are involved in the synthesis, repair, and functioning of DNA and are required for the production and maintenance of cells. Low levels of folate have been associated with several forms of cancer, including colon cancer. Aberrant crypt foci (ACF), identified as putative precursor lesions in the development of colon cancer, have been induced by the drinking water disinfection by-product, tribromomethane (TBM). To investigate whether ACF induced by TBM could be promoted by a diet devoid of dietary folate, male F344/N rats were exposed to 500 mg/l of TBM in drinking water and fed either a normal or no folate diet (NFD) for 26 weeks. At the conclusion of the study, colons were excised and examined for ACF. Rats exposed to TBM and fed a NFD, evident by significantly reduced serum folate concentrations and elevated serum homocysteine levels, had significant increases of ACF when compared to rats exposed to TBM and fed a normal diet. This study highlights the important role that diet, especially folate intake, represents in protecting the colon against TBM-induced ACF.

Animals↗
PubMed2002

Hyperhomocysteinemia in children on renal replacement therapy.

Hyperhomocysteinemia is an independent risk factor for the development of atherosclerosis in adult patients on dialysis or after kidney transplantation. There are few data on homocysteine (Hcy) concentrations in children under these circumstances. The aim of our study was to evaluate plasma Hcy levels and their determining factors in children on renal replacement therapy. In 29 children and adolescents on chronic dialysis therapy and in 34 children after renal transplantation (Tx) fasting total plasma Hcy, red blood cell (RBC) folate, and serum vitamin B(12) levels were measured. The plasma Hcy levels were expressed as number of standard deviations (SD) from mean level in age- and gender-matched controls. In dialysis patients the mean plasma Hcy level was elevated (4.4+/-0.8 SDs), without significant difference between patients on hemodialysis or continuous cycling peritoneal dialysis. In the dialysis patients a negative correlation ( r=-0.49) between plasma Hcy levels and RBC folate concentrations was found. Oral folate supplementation was given to 8 of 21 dialysis patients, resulting in high RBC folate levels (>800 micro g/ml) and normalization of the plasma Hcy levels (0.4+/-0.5 SDs). In Tx patients the mean plasma Hcy level was 5.6+/-1.4 SDs. Multivariate regression analysis revealed that the main factor determining Hcy level after kidney Tx was creatinine clearance. Patients with normal kidney function had a mean Hcy concentration of 1.69+/-0.86 compared with 10.0+/-2.2 in children with decreased function. Folate and cyclosporine levels had less significant effects on Hcy concentrations. Seven patients who were evaluated while on dialysis and after a successful kidney Tx demonstrated a significant reduction in Hcy levels. Children and adolescents on dialysis therapy and with impaired renal function after renal Tx have significant hyperhomocysteinemia. Oral folate supplementation normalizes the increased plasma Hcy levels and should be added to the medical treatment of all children with impaired renal function.

Adolescent↗
PubMed2003

Homocysteine, methylenetetrahydrofolate reductase C677T polymorphism and the B-vitamins: a facet of nature-nurture interplay.

BACKGROUND: Methylenetetrahydrofolate reductase 677 (MTHFR 677) polymorphism may provoke hyperhomocysteinemia when folate status is low. The influence of MTHFR 677 mutation on homocysteine (HCY) levels in relation to vitamin B12 and folate status was investigated in the current study. SUBJECTS AND METHODS: 113 vegetarians, 123 omnivorous Germans, and 117 omnivorous Syrians were recruited. MTHFR 677 genotype, HCY, methylmalonic acid (MMA), total serum vitamin B12, serum folate, and vitamin B6 were determined using conventional methods. RESULTS: Omnivorous Germans displayed the lowest HCY levels compared with vegetarians and Syrians (median 8.0, 10.4, and 11.3 micromol/l, respectively). The highest serum folate and the highest MMA levels were found in vegetarians (median folate = 30.0; MMA = 355 nmol/l). Among vegetarians and Syrians, TT subjects had higher HCY levels than other genotypes which were, however, no longer significant in the highest folate tertiles. When the data were pooled, the odds ratio (OR, 95% CI) for HCY > 12 micromol/l was 3.81 (1.55-9.34) in TT compared with CC subjects. The OR increased to 28.85 (4.63-179.62) in TT subjects who had folate in the lowest tertile, and to 21.84 (4.81-99.1) in TT subjects who had MMA in the highest MMA tertile. CONCLUSION: MTHFR 677 TT individuals are more liable to hyperhomocysteinemia under vitamin B12 deficiency than the other two genotypes. In such a case, relative folate shortage may progressively increase HCY levels. TT individuals may have increased folate and vitamin B12 requirements compared to the other CC and CT genotypes.

Adolescent↗
PubMed1985

Malaria chemoprophylaxis with chloroquine in young Nigerian children. IV. Its effect on haematological measurements.

Haematological measurements were made in 198 Nigerian children aged three months to two years who received weekly malaria chemoprophylaxis with chloroquine from shortly after birth until the age of one or two years and in 185 age-matched control children. Children protected against malaria had a higher mean haemoglobin level and a higher packed cell volume than control children, and they showed fewer abnormalities of their red cells. Total and differential white blood cell counts, mean plasma folate and mean serum ferritin concentrations were similar in both groups of children. However, the geometric mean red cell folate level of children exposed to malaria was significantly higher than the mean level of control children; and it may be that malaria raises the red cell folate through intracellular synthesis by malaria parasites. Children with malaria parasitaemia had a significantly lower haemoglobin and packed cell volume and a significantly higher geometric mean red cell folate and ferritin level than children without parasitaemia. Serum ferritin is probably an unreliable index of iron status in children with malaria.

Child, Preschool↗
PubMed2006

Hematologic status in patients with recurrent aphthous stomatitis in Jordan.

OBJECTIVE: To determine the prevalence of hematinic deficiencies in patients with recurrent aphthous stomatitis. METHODS: The study took place in the Oral Medicine Clinic of the Jordan University Hospital in Amman, Jordan, between January 1993 and December 2000. We studied the hemoglobin, serum ferritin, vitamin B12 and folate levels in 143 patients with recurrent aphthous stomatitis. We compared the results with a control group of 143 age- and gender-matched patients with a range of other oral diseases. RESULTS: In recurrent aphthous stomatitis patients, 14% were anemic and 37.8% showed hematinic deficiencies; 16.8% showed low serum ferritin; 26.6% showed low serum vitamin B12 and 4.9% showed low serum folate. In the control group, 10.5% were anemic and 18.2% showed hematinic deficiencies; 9.8% showed low serum ferritin; 12.6% showed low serum vitamin B12 and none showed serum folate deficiency. CONCLUSION: Patients with recurrent aphthous stomatitis have more hematinic deficiencies, particularly vitamin B12 deficiency, compared with controls. Correction of these hematinic deficiencies could help in the management of the disease.

Adolescent↗
PubMed2002

Effect of folic acid and vitamin C supplementation on folate status and homocysteine level: a randomised controlled trial in Italian smoker-blood donors.

BACKGROUND: This trial sought to examine the effects of high dosage of folic acid and vitamin C supplementation on red blood cell folate (RCF), serum folate (SF) and homocysteine (Hcy) levels in subjects who smoke more than 15 cigarettes per day. METHODS: A prospective study of 100 Italian repeat blood donors was undertaken to measure RCF, SF and Hcy levels before and after 45 days of vitamin supplementation. All subjects were randomised into four groups: [A] folic acid (FA) 5 mg/day, [B] vitamin C 500 mg/day, [C] FA 5 mg/day plus vitamin C 500 mg/day [D] no supplementation. RESULTS: Before supplementation the median RCF, SF and Hcy levels were similar in the four groups; 32 (40%) subjects had an RCF level below 340 nmol/l, 15 (18.8%) had an SF level below 6.8 nmol/l and 21 (26.3%) had an Hcy level above 16 micromol/l. After 45 days the median RCF and SF levels were significantly (P<0.01) increased in all supplemented subjects. The median Hcy level was significantly (P=0.008) reduced in subjects supplemented with FA and significantly (P=0.01) increased in those supplemented with vitamin C alone. CONCLUSION: The supplementation with 5 FA mg/day is able to increase significantly both RCF and SF levels and reduce Hcy level in Italian smoker-blood donors.

Adult↗
PubMed2001

Antiepileptic drugs as independent predictors of plasma total homocysteine levels.

Low folate levels have consistently been reported in patients with epilepsy on phenytoin (PHT), phenobarbital (PB) and primidone (PRD), while data on valproate (VPA) are conflicting. Furthermore, antiepileptic drugs (AEDs) may be associated with high levels of plasma total homocysteine (p-tHcy). Therefore, we have investigated the levels of p-tHcy, serum folate (S-FA) and erythrocyte folate (E-FA) in patients on PHT, PB and PRD (Group 1, n=21) and VPA (Group 2, n=24). Both groups had their own matched controls. Blood samples were drawn fasting and 6 h post methionine loading (6 h-PML). The Group 1 patients had fasting and 6 h-PML p-tHcy levels significantly higher than their controls (P=0.05 and <0.0001, respectively), and patients without dietary multivitamin supplementation (n=14), had lower fasting S-FA and E-FA levels than their controls (P=0.02 and 0.0003, respectively). The Group 2 patients had fasting and 6 h-PML levels of p-tHcy, S-FA and E-FA not different from their controls. In a multiple stepwise regression model comprising all subjects (n=90), the AEDs of Group 1 and the S-FA levels were independent predictors of p-tHcy levels. Thus, PHT, PB and PRD are associated with high p-tHcy and low folate levels, whereas VPA does not influence S-FA, E-FA and p-tHcy levels in adult patients.

Adult↗
PubMed1986

Methotrexate metabolism analysis in blood and liver of rheumatoid arthritis patients. Association with hepatic folate deficiency and formation of polyglutamates.

Serum and red blood cell methotrexate (MTX) levels, as well as hepatic levels of MTX and folate, were analyzed in 24 patients who had received long-term oral MTX weekly for the treatment of rheumatoid arthritis. The serum MTX level peaked rapidly and was insignificant after 24 hours. The red blood cell MTX level was not related to the interval from the last MTX dose. In hepatic tissue obtained by liver biopsy, MTX was found in a predominantly polyglutamated form with depleted hepatic folate stores when compared with baseline specimens. A brief period of therapy with oral folinic acid repleted hepatic folate. It is possible that MTX hepatotoxicity is related to reduced hepatic folate levels and formation of MTX polyglutamates.

Arthritis, Rheumatoid↗
PubMed1987

Dietary folate and biogenic amines in the CNS.

Abnormal biogenic amine biosynthesis has been observed in humans and animals with endogenous and exogenous disturbances in folate metabolism. In an attempt to study this interaction biochemically, rats were depleted or repleted with folate for 10 weeks. Folate levels in depleted animals in serum and CSF correlated with stores in liver and brain, respectively. In depleted or repleted animals, there was no significant effect on biogenic amine metabolism in the CNS, as determined by quantitation of biogenic amines in brain and their respective metabolites in brain and CSF. These results are contrary to studies by other investigators. We suspect, however, that specific genetic defects in folate metabolism do result in impaired biogenic amine metabolism and probably at the level of disturbed biopterin cofactor functions.

Animals↗
PubMed1986

Haematological laboratory findings in the elderly: influence of age and sex.

The effects of age and sex on haematological laboratory parameters were studied in connection with a population study in people over the age of 65 years (n = 347). Serum vitamin B12 was the only parameter which decreased significantly with advancing age. Blood leucocyte count, haemoglobin concentration, haematocrit, erythrocyte count, mean erythrocyte volume, mean erythrocyte haemoglobin and serum ferritin values were significantly higher in males than in females. Serum iron, serum transferrin, and plasma and erythrocyte folate levels did not differ between males and females. Thirteen subjects were anaemic and three of them had iron deficiency anaemia. Five subjects had iron deficiency based on serum iron and transferrin but no anaemia. Serum ferritin measurement did not reveal any further subjects with iron deficiency. No case of folate deficiency anaemia was revealed. Although many of the participants were on medication, most of them were living at home and taking care of themselves and represent relatively fit elderly people. Therefore we suggest that these laboratory data can also serve as reference values for the elderly people.

Aged↗
PubMed2003

Association between hyperhomocysteinemia and primary pulmonary hypertension.

STUDY OBJECTIVE: This case-control study was conducted to test the hypothesis that fasting homocysteine levels are higher in PPH patients than in healthy controls. DESIGN: Levels of plasma total homocysteine, serum folate, vitamin B-12, and serum creatinine in 18 consecutive patients with PPH were compared with data from 36 age- and sex-matched controls. RESULTS: Eight of the 18 patients (44.4%) and three of the 36 controls (8.3%) had elevated plasma total homocysteine (tHcy) levels (> or = 15 mol/l, odds ratio 8.8; 95% CI: 2.0-39.6; P = 0.005). There was an inverse correlation between tHcy levels and creatinine clearance in patients with PPH (P = 0.036). CONCLUSION: PPH patients are significantly more likely to have hyperhomocysteinemia, and higher mean plasma total homocysteine levels than in controls. Plasma total homocysteine may be an important factor in the pathogenesis of PPH.

Adolescent↗
PubMed1983

Ascorbic acid, vitamin A, folic acid, and amino acids in blood of patients with hemophilia.

Blood levels of ascorbic acid, vitamin A, folic acid, and amino acids were studied in patients at the South Texas Comprehensive Hemophilia Center, San Antonio, TX. The mean plasma ascorbic acid level in hemophiliacs was significantly lower than controls (p less than 0.0001). This was observed despite a dietary ascorbic acid intake in excess of 66% of the Recommended Dietary Allowances (RDA). However, those subjects receiving specific factor replacement therapy at home and consuming at least 66% RDA of ascorbic acid maintained a mean plasma ascorbic acid level not significantly less than controls. Hemophilic subjects not on home therapy, on the other hand, had a mean plasma ascorbic acid level significantly below that of controls while receiving optimal dietary ascorbic acid. With prompt adequate medical care of bleeding episodes and with optimal nutrition, the demand for ascorbic acid needed for tissue repair in hemophilic patients may be lessened. Hemophiliacs had mean serum vitamin A, mean serum folate, and mean red cell folate levels that were not significantly different from controls. Significantly higher mean plasma arginine and lower, but not significantly lower, mean plasma ornithine levels were found in hemophilic subjects, suggesting altered arginase activity.

Adolescent↗
PubMed2006

Hyperhomocysteinemia and low B vitamin levels are independently associated with venous thromboembolism: results from the EDITH study: a hospital-based case-control study.

BACKGROUND: Moderate hyperhomocysteinemia and B vitamins deficiency are thought to be risk factors for venous thromboembolism (VTE). The causality and independence of those associations are still questioned. METHODS: We measured fasting serum total homocysteine, folates, and vitamin B12 levels as well as 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T genotypes in 467 patients hospitalized with a first well-documented deep vein thrombosis and/or pulmonary embolism not related to a major acquired risk factor and 467 controls matched for gender and age. RESULTS: Mild hyperhomocysteinemia, low serum folates, and vitamin B12 were associated with VTE independently of each other. In multivariate analysis, odds ratios (OR) (95% CI) for VTE associated with mild hyperhomocysteinemia (>15 micromol L(-1)), low serum folates (< or = 4.9 nmol L(-1)), and vitamin B12 (< or = 253 pmol L(-1)) were 1.48 (1.05-2.08), 3.14 (1.35-7.32) and 1.42 (1.03-1.98), respectively. An MTHFRC677T genotype was not significantly associated with VTE; OR (95% CI): 1.13 (0.70-1.81) CONCLUSIONS: The current data provides further knowledge in the complex relationship between hyperhomocysteinemia, low vitamin levels, and VTE.

Adolescent↗
PubMed2002

[Methylenetetrahydrofolate reductase gene polymorphism and plasma homocysteine levels in hemodialysing patients].

OBJECTIVE: To study the influence of mutation of 677 C to T in the methylenetetrahydrofolate reductase (MTHFR) gene on the plasma total homocysteine (tHcy) levels in hemodialysis patients. METHODS: The study population included 40 healthy subjects and 53 patients with end-stage renal disease (ESRD) undergoing hemodialysis. C 677 T transition in the MTHFR gene was detected by Hinf 1 restriction enzyme analysis. Plasma tHcy concentrations were determined by HPLC with fluorescent detection. Serum folate and vitamin B(12) levels were measured with chemiluminescent immunoassay. RESULTS: The allelic frequency of the 677 C to T transition in the MTHFR gene in hemodialysis patients was 52.8% versus 53.8% in healthy controls. The mean tHcy level was significantly higher in hemodialysis patients than that in control subjects (38.68 micro mol/L versus 15.47 micro mol/L, P < 0.01). The folate and vitamin B(12) concentrations were higher in patients than those in controls. There was a significant influence of the +/+ genotype, folate and vitamin B(12) status on plasma tHcy level. CONCLUSION: It is demonstrated that the extent of hyperhomocysteinemia in hemodialysis patients is not only the result of impaired metabolism and elimination of Hcy in uremia, but is also genetically determined by the MTHFR genotype. Folate and vitamin B(12) status also influences the homocysteine concentration of hemodialysis patients.

Adult↗
PubMed1997

Reduced red-cell folate in mania.

Forty-five hospitalised patients with DSM-III-R diagnosis of mania, were found to have a mean red-cell folate level of 193 nmol/l, as compared to 896 nmol/l in the control group (P < 0.00001). Assessment of serum folate in both groups showed no significant differences in the levels. Furthermore the manic patients and the controls were matched by the socio-economic status. This indicated that the reduced red-cell folate in mania is associated with the illness and not due to reduced absorption or dietary deficiency of folate. Considering previous studies that showed reduced red-cell folate in depression, our findings suggest that reduced red-cell folate occurred in both phases of bipolar disorders.

Adult↗
PubMed1976

Serum "uracil+uridine" levels in pernicious anaemia.

The serum "uracil+uridine" level, expressed as uracil, has been measured in 21 cases of vitamin B12 deficiency, in which the serum folate was normal, and compared with the level in 97 normal subjects. The level in the vitamin B12 deficient group (11.9 mumol/1). was significantly lower than in the controls (15.7 mumol/1., P less than 0.005). Nine of the former were complicated by stystemic illness but the clinical and haematological features in the remaining 12 were consistent with the diagnosis of pernicious anaemia in relapse. The serum uracil level in this group was even lower (10.21 mumol/1., P less than 0.01). This finding is unexpected in view of the generally accepted indirect role of vitamine B12 in the methylation of deoxyuridine monophosphate to deoxythymidine monophosphate. Reasons are given for not accepting these results as reflecting the main biochemical lesion in vitamin B12 deficiency. Although they do not give direct support to an impairment in the methylation of deoxyuridine monophosphate, they do not exclude it as they test only one possible metabolic pathway and moreover they could represent the result of more than one action of vitamin B12 on uracil metabolism. They do show, however, that some aspect of uracil metabolism other than methylation is affected in vitamin B12 deficiency in man.

Anemia, Pernicious↗