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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↗

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↗

[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↗

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↗

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↗

Variation in plasma folate levels among groups of healthy persons.

Levels of plasma folate, erythrocyte folate and serum vitamin B12 were measured in 106 essentially healthy persons grouped both as to race and economic--educational status. Whereas the mean values of the three assays did not differ significantly among groups, values of plasma folate below the usual limits of normal were more prevalent in the migrant worker and urban clinic groups. Persons with low plasma folate levels did not have symptomatic deficiency as evaluated by hematocrit, peripheral blood smears and erythrocyte folate levels. The interpretation of the plasma folate requires reference values from a healthy population selected to be comparable to the study group. The diagnosis of deficiency, or at least the degree of deficiency, requires clinical and laboratory evaluations beyond the plasma folate.

Adult↗

Rescue of hypercholesterolemia-related impairment of angiogenesis by oral folate supplementation.

OBJECTIVES: We examined whether oral folate supplementation would rescue a hypercholesterolemia (HC)-related impairment of ischemia-induced angiogenesis. BACKGROUND: Folate protects against endothelial dysfunction, but the effect of folate supplementation on angiogenesis is little known. METHODS: Sprague-Dawley rats were divided into four groups. Control rats were fed a normal diet (n = 18); HC rats (n = 18) were fed 2% cholesterol diet; and HC + folate (HC+F) rats were fed an HC diet with oral folate (0.003% in water). The left femoral artery and vein were surgically excised, and angiogenesis in the ischemic limb was evaluated. We also examined the effects of Nomega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthase, on angiogenesis in the HC+F state. RESULTS: Laser Doppler blood flow (LDBF) analysis showed lower ischemic/normal LDBF ratio in the HC group than in the control group. Angiographic and histologic analyses on day 14 revealed a smaller angiographic score (p < 0.001) and capillary density (p < 0.001) in the HC group than in controls, which were associated with reduced tissue NOx and cyclic guanosine monophosphate (cGMP) levels. The LDBF ratio, angiographic score, and capillary density were significantly restored in the HC+F group (p < 0.01 vs. HC), which were associated with increased serum folate and tissue NOx and cGMP levels. Finally, L-NAME treatment abolished the beneficial action of folate on angiogenesis in the HC state. CONCLUSIONS: Ischemia-induced angiogenesis was inhibited by HC, which was rescued by oral folate supplementation, at least in part, via an NO-dependent manner.

Administration, Oral↗

Vitamin B12 and folic acid deficiency in chronic pancreatitis: a relevant disorder?

Vitamin B12 malabsorption was reported earlier to occur in patients with exocrine pancreatic insufficiency, and pancreatic extracts were shown to improve the absorption of vitamin B12. We investigated serum levels of vitamin B12 and serum folate in patients with chronic pancreatitis and different degrees of pancreatic insufficiency. 137 patients (84 males, 53 females, age 34-72 years) with chronic pancreatitis (C.P.) were included in the study. 123 of 137 (89.8%) patients had a pathologic pancreatic function test result, classified into mild (n = 24), moderate (n = 61) or severe (n = 38) insufficiency. The normal range of serum vitamin B12 and folic acid was established in 58 healthy controls and was found to be 190-1020 pg/ml for serum vitamin B12 and 2.4-16.1 ng/ml for folic acid. 7 patients (5.7%) with C.P. had vitamin B12 serum levels below 190 pg/ml; 4 of these had severe and 3 had mild or moderate exocrine pancreatic insufficiency. However there was no overall correlation between the degree of pancreatic insufficiency and vitamin B12 values. Serum levels of Vitamin B12 were 512 +/- 48 pg/ml in mild, 493 +/- 52 pg/ml in moderate and 428 +/- 45 pg/ml in severe exocrine insufficiency. Serum folic acid below 2.4 ng/ml were present in 5 patients (3.6%). Folic acid serum levels were 8.34 +/- 0.76 ng/ml in mild, 6.34 +/- 0.52 ng/ml in moderate and 7.45 +/- 0.53 ng/ml in severe exocrine insufficiency. We conclude that vitamin B12 deficiency is a rare finding in chronic pancreatitis and does not strictly depend on the degree of exocrine pancreatic insufficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Association of hyperhomocysteinemia with plasma sulfate and urine sulfate excretion in patients with progressive renal disease.

BACKGROUND: Plasma total homocysteine (tHcy) level is increased in patients with renal disease, parallel to serum creatinine concentration. In renal failure, the final product of sulfated amino acid metabolism, sulfate, also accumulates as renal function declines. We hypothesized that the elevation in sulfate level could cause hyperhomocysteinemia and tested the relation between tHcy level and both urinary excretion and plasma levels of sulfate. METHODS: Forty patients with renal disease were divided into three groups: patients without renal failure (nRF; creatinine clearance [CCr] > or = 80 mL/min/1.73 m2 [> or =1.33 mL/s/1.73 m2]), patients with mild renal failure (mRF; 80 > CCr > or = 25 mL/min/1.73 m2 [1.33 > CCr >/ or 0.42 mL/s/1.73 m2]), and patients with severe renal failure (sRF; CCr < 25 mL/min/1.73 m2 [<0.42 mL/s/1.73 m2]). Daily urinary excretion and plasma levels of tHcy, total cysteine (tCys), and sulfate were measured. A healthy control (HC) group also was tested. Serum methionine, taurine, vitamin B12, and folate levels also were determined in patients with renal disease. RESULTS: Plasma tHcy and sulfate concentrations in the groups with mRF and sRF were greater than in the HC group. Plasma tCys concentrations in the mRF and sRF groups were greater than in the nRF group. Daily urinary Hcy and Cys excretion did not differ among the four groups. Daily urine sulfate and urea nitrogen excretion in the sRF group were significantly less than in the HC and nRF groups. Multiple regression analyses showed that plasma creatinine (beta = 0.40) and sulfate (beta = 0.43) levels were independently associated with plasma Hcy level; among urine parameters, only daily urine sulfate excretion (beta = -0.52) was independently associated with plasma Hcy level. CONCLUSION: The elevated plasma sulfate level, in accordance with renal function, is associated with plasma tHcy level. Decreased sulfate excretion, which might parallel the intake of sulfated amino acid or protein, may increase tHcy levels.

Analysis of Variance↗

Use of atypical antipsychotics during pregnancy and the risk of neural tube defects in infants.

OBJECTIVE: Folate deficiency in early pregnancy and maternal adiposity, independent of folate intake, lead to a greater risk of neural tube defects in infants. Atypical antipsychotics cause various degrees of weight gain. The authors assessed folate status and obesity among patients with schizophrenia receiving atypical antipsychotics. METHOD: A sample of 70 inpatients and outpatients (21 of them women) who were taking antipsychotics was randomly selected. Body weight, body mass index, daily folate intake, and folate serum concentrations were determined. RESULTS: The majority of the patients were overweight. Only eight of 37 patients had folate intake above 400 microg/day, the level shown to be protective against neural tube defects. Mean serum folate was significantly lower than in a general hospital group of 810 patients. CONCLUSIONS: Women with schizophrenia who take atypical antipsychotics have a higher risk of neural tube defects in their infants because of the associated low intake of folate and obesity.

Adult↗

Hyperhomocysteinemia in relation to plasma free amino acids, biomarkers of inflammation and mortality in patients with chronic kidney disease starting dialysis therapy.

BACKGROUND: Plasma levels of total homocysteine (tHcy) and free amino acids (AAs) are influenced by nutritional status in patients with chronic kidney disease (CKD), whereas the role of chronic inflammation is not clear. METHODS: In a cross-sectional analysis, fasting levels of plasma tHcy, total cysteine (tCys), AA, serum albumin (Alb), and several inflammation markers, including C-reactive protein (CRP), were analyzed in a cohort of 250 patients with CKD starting renal replacement therapy. Patients were followed up during a 4-year period to assess overall mortality in relation to basal tHcy level. RESULTS: Ninety-three patients (37%) with signs of inflammation (CRP > or = 1 mg/dL) had significantly lower levels of tHcy, tCys, and serum Alb than 157 noninflamed patients. tHcy and tCys levels correlated positively with serum Alb levels and negatively with CRP levels (rho = -0.24; P < 0.0001; rho = -0.15; P < 0.05, respectively) and other inflammation markers. tHcy and tCys correlated significantly with levels of several AAs. The presence of both inflammation and malnutrition was associated with lower tHcy levels than when malnutrition was present without inflammation. Multivariate analysis showed that serum Alb, CRP, plasma folate, and vitamin B12 levels were independently associated with tHcy levels after adjustment for other variables. tHcy, but not tCys, level was significantly greater in survivors than nonsurvivors, and Kaplan-Meier analysis showed that greater tHcy level was associated with better survival. CONCLUSION: Plasma tHcy and tCys levels are interrelated to plasma AA levels and were lower in patients with inflammation. Thus, inflammation may contribute to the reverse association between tHcy level and mortality in patients with CKD starting renal replacement therapy.

Amino Acids↗

Functionality of endogenous folates from rye and orange juice using human in vivo model.

BACKGROUND: Cereals contribute about a quarter of the daily folate intake from a typical diet in several European countries. However, studies on bioavailability of endogenous folates, in particular of cereal sources, are scarce. AIM OF THE STUDY: We aimed to study how well natural folates from rye (different rye breads and muesli made of malted rye) and orange juice function in improving folate status of human volunteers compared to a diet containing folic acid fortified wheat bread. METHODS: Healthy human volunteers aged 20-66 y took part in a four-week intervention trial in which bread, breakfast cereal and juice were provided. The study had a parallel design with two groups, 1) rye and orange juice group (33 volunteers) and 2) fortified wheat bread and apple juice group (31 volunteers). The test foods provided on average 184 microg and 188 microg folate per day in rye and wheat groups, respectively. Test foods were consumed as part of the subjects' normal diet. RESULTS: In both groups statistically significant increases in serum and red cell folates were observed after the intervention period. The serum folate increased 26 % and 31 %, and red cell folate levels increased 17 % and 15 % in rye and orange juice and wheat and apple juice groups, respectively. The effects did not differ between the rye and wheat groups. Increases in serum and red cell folate were more profound among subjects with low starting folate levels. Decrease in the plasma homocysteine concentrations was observed only in the highest tertile of both groups but not in the group means. CONCLUSIONS: Endogenous folates incorporated into a healthy diet, even in moderate amounts, is an efficient way to improve folate status among healthy adults. Folates from different rye products and orange juice showed good bioavailability that was similar to folic acid from fortified white bread.

Adult↗

A common polymorphism in methionine synthase reductase increases risk of premature coronary artery disease.

BACKGROUND: Methionine synthase reductase (MTRR) catalyzes the regeneration of methylcobalamin, a cofactor of methionine synthase, an enzyme essential for maintaining adequate intracellular pools of methionine and tetrahydrofolate, as well as for maintaining homocysteine concentrations at nontoxic levels. We recently identified a common A-->G polymorphism at position 66 of the cDNA sequence of MTRR; this variant was associated with a greater than normal risk for spina bifida in the presence of low levels of cobalamin. OBJECTIVE: To investigate whether the polymorphism was associated with alterations in levels of homocysteine, folate, and vitamin B12, and with risk of developing premature coronary artery disease (CAD), in a population of individuals presenting for cardiac catheterization procedures. METHODS: We screened 180 individuals aged < 58 years with angiographically documented coronary-artery occlusions or occlusion-free major arteries for the presence of the 66A-->G MTRR polymorphism using a polymerase-chain-reaction-based assay. RESULTS: We identified a trend in risk of premature CAD across the genotype groups (P = 0.03) with a sex-adjusted relative risk of premature CAD equal to 1.49 (95% confidence interval 1.10-2.03) for the GG versus AA genotype groups. There was no difference in fasting levels of plasma total homocysteine, serum folate, and vitamin B12 among the three MTRR genotypes. CONCLUSIONS: Our findings suggest that the GG genotype of MTRR is a significant risk factor for the development of premature CAD, by a mechanism independent of the detrimental vascular effects of hyperhomocysteinemia. This association needs to be confirmed in other studies.

Age Factors↗

Homocysteine blood level in long-term care residents with oropharyngeal dysphagia: comparison of hand-oral and tube-enteral-fed patients.

BACKGROUND: Levels of homocysteine, methylmalonic acid, and relevant vitamins were measured and evaluated in patients with oral dysphagia (OD) receiving long-term care (LTC). METHODS: Group A was composed of 26 orally fed patients, and group B was composed of 25 patients who were fed by nasogastric tube. All patients were hospitalized in the LTC departments of the Geriatric Medical Center, Shmuel Harofe. General and nutritional status were assessed, and levels of vitamins including B12, folate, and B6 were measured along with serum homocysteine and urine methylmalonic acid levels. RESULTS: Homocysteine levels were significantly higher in the orally fed patients (p < .001); 92% had higher-than-normal homocysteine levels. The levels of vitamins B12, folate, and B6 were significantly lower in the orally fed patients (p < .001), although in most patients levels were in the normal range. Notably, the levels of homocysteine were significantly correlated with the levels of all vitamins but not with the albumin or hemoglobin values. Levels of methylmalonic acid were also higher in the orally fed patients, but the difference was not statistically significant, and there was no correlation between vitamin level and methylmalonic acid level. CONCLUSIONS: Orally fed patients with OD have substantially higher homocysteine levels and appreciably lower levels of the relevant vitamins than patients with OD who receive tube feeding. Therefore, homocysteine measurement may be the preferred indicator of vitamin intake in orally fed patients with OD.

Aged↗

Methylmalonic acid in amniotic fluid and maternal urine as a marker for neural tube defects.

To evaluate the implication of methymalonic acid (MMA) in the early diagnosis of neural tube defects (NTD), a quantitative assay for MMA was established by using gas chromatography-mass spectrometry with stable isotope of MMA as an internal standard. Amniotic fluid and maternal urine MMA concentration, maternal serum folate, red blood cell folate and vitamin B12 levels were measured in the middle term of NTD-affected and normal pregnancies. Amniotic fluid and maternal urine MMA concentrations in the middle term of NTD affected pregnancies (1.4 +/- 0.9 micromol/L, and 22.1 +/- 12.6 nmol/micromol creatinine) were significantly higher than that of normal pregnancies (1.0 +/- 0. 4 micromol/L, and 2.5 +/- 1.1 nmol/micromol creatinine). There was no significant difference between normal and NTD pregnancies for serum folate, red blood cell folate and vitamin B12 levels. The results suggested that MMAs in amniotic fluid and maternal urine are sensitive markers for early diagnosis of NTD. Vitamin B12 is an active cofactor involved in the remethylation of homocycteine and its deficiency is an independent risk factor for NTD. MMA is a specific and sensitive marker for intracellular vitamin B12 deficiency. This study suggests that it is necessary to monitor the vitamin B12 deficiency and advocates vitamin B12 supplementation with folate prevention program.

Adult↗

Platelet MAO-B activity and vitamin B12 in old age dementias.

Platelet MAO-B activity, serum vitamin B12 levels, and plasma folate were measured in patients suffering from presenile (AD) and senile (SDAT) dementia of Alzheimer-type, and vascular dementia (VD). MAO-B was higher in the SDAT group than in AD and controls. An inverse relationship between MAO-B activity and vit. B12 levels was documented in the whole group and in each category studied; furthermore, MAO-B was positively related to age. All the patients were then divided into two groups, according to vit. B12 levels (Group I: less than 200 pg/mL; Group II: greater than or equal to 200 pg/mL); Group I showed a significantly higher MAO-B activity with respect to Group II. The results indicate the existence of a negative association between platelet MAO-B activity and serum levels of vitamin B12 and confirm the existence of biological differences between presenile and senile dementia of Alzheimer type.

Aged↗

Relationships of vitamin B1, B12, folate and the cognitive ability of the Thai rural elderly.

The comparisons of the levels of vitamin B1, B12 and folate between the elderly with good and poor cognitive ability are the goals of this study. 203 subjects enrolled in 3 geriatric centers of Ratchaburi province and nearby were recruited. All the subjects were tested with structured Thai Mini Mental State Examination (TMSE) questionnaire by trained examiners. With the cut off point of 23 out of 30 in TMSE, 31 per cent were designated as poor cognitive group. Radiodilution assay was used to determine the level of serum B12 and red cell folate while the TPP effect was processed by spectrophotometry. The prevalence of vitamin B1, B12 and folate deficiency were 30.2 per cent, 3.8 per cent and 8.2 per cent consecutively. None of the studied vitamin levels was shown to be significantly different between the poor and good cognitive group suggesting no proved indication to the use of vitamin B1, B12 and folate in the healthy elderly with poor cognitive function.

Aged↗

[Effects of blood transfusion on the serum assays of iron, the total binding capacity of transferrin, vitamin B12 and folates].

To evaluate the influence of blood transfusion on the serum levels of different nutrients, the levels of total iron binding capacity, ferritin, cobalamin and folate were determined before and 24 hours after 2 or 3 packed red cell transfusions, by forty patients with anemia of various causes. No significant change was found in these levels before and after blood transfusion, except for iron and folate.

Adult↗