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Serum vitamin B12, folate, and iron levels in recurrent aphthous ulceration.

Hematologic deficiencies have previously been described in some cases of recurrent aphthous ulceration (RAU). Ninety patients with RAU and twenty-three healthy control subjects were evaluated by complete blood count, serum iron, and total iron-binding capacity, serum vitamin B12, and serum or red blood cell folate. Only three of ninety RAU patients proved to have abnormalities. There were no statistically significant differences between the patient and control populations, and no one in either group had abnormal serum vitamin B12 or serum or RBC folate assays. None of the patients or controls gave a history or symptoms suggestive of iron-deficiency or megaloblastic anemia, and all were without gastrointestinal complaints. These results suggest that hematologic tests other than a complete blood count are not routinely indicated for patients with RAU.

Adolescent↗

Association between serum homocysteine, vitamin B12, folate and Thai coronary artery disease patients.

BACKGROUND: Homocysteine is an intermediate compound formed during metabolism of methionine. The plasma level of homocysteine is dependent on the genetically regulated level of essential enzymes and the intake of folic acid, vitamin B6 (pyridoxine), and vitamin B12 (cobalamine). Elevated serum homocysteine levels are a known risk factor for coronary artery disease (CAD). To establish the magnitude of the CAD that is associated with an increased serum homocysteine level, we compared CAD patients with normal healthy Thai controls. METHOD: In a cross-sectional study design we investigated the association between serum homocysteine, vitamin B12 and folate levels and the coronary heart disease in 178 CAD patients and 178 normal healthy controls by age and sex matching. These comprised 266 men and 90 women, mean age 58 +/- 10 years for normal controls and 60 +/- 10 years for CAD patients. Serum homocysteine, vitamin B12 and folate were measured by ELISA method and electrochemiluminescense method respectively. RESULTS: Paired t-test analysis showed that serum homocysteine concentrations were significantly higher in CAD patients (23.83 +/- 11.29 mumol/L) than in control subjects (19.69 +/- 8.51 mumol/L; p < 0.001). Homocysteine levels were also higher in males than in females. These findings were similar in healthy controls (male: 20.37 +/- 8.5 mumol/L, female: 17.77 +/- 8.2 mumol/L, p < 0.05) and in CAD patients (male: 24.91 +/- 11.8 mumol/L, female: 20.73 +/- 8.9 mumol/L, p < 0.05). Homocysteine above 17 mumol/L occurred more common in CAD patients than in control groups (OR = 1.65, 95% CI = 1.09-2.52, p = 0.0249). Low levels of vitamin B12 and folate did not reaching statistical significance when comparing controls and CAD patients. CONCLUSIONS: Serum homocysteine concentrations were significantly higher in CAD patients than in controls. Serum vitamin B12 and serum folate levels were not statistically significantly different between CAD patients and control groups. The data also demonstrated that the serum homocysteine level is almost always higher in men than in women as previously reported. Although serum vitamin B12 and serum folate levels were not below the upper limit of normal, vitamin B12 and folic acid treatment may reduce serum homocysteine concentrations in CAD patients. We hope that the reversible risk factors will be concern to clinicians for the reduction in the risk of myocardial infarction.

Aged↗

The effect of diphenylhydantoin (phenytoin) on the sequential stages of intestinal folate absorption.

The drug diphenylhydantoin (phenytoin) (DPH) is thought to interfere with the bioavailability of dietary folate through an effect on intestinal folate deconjugation and/or monoglutamate folate transport. In order to determine whether DPH inhibition occurs in the sequential steps of folate deconjugation, uptake, or reduction-methylation, the effect of the drug on the intestinal absorption of hexaglutamate folate (PteGlu6), pteroylmonoglutamate folate (PGA), and N-5-methyltetrahydrofolate (CH3FH4) was studied. Folate absorption was directly quantified by the method of triple lumen tube perfusion in 12 subjects serving as their own controls. All 12 received PGA mixed with and without DPH (20 micrograms/ml), while 6 of the 12 subjects received hexaglutamate and 6 received reduced methylated folate with and without added DPH. With this model DPH was shown not to impair significantly folate absorption by any action upon the process of folate deconjugation, absorption, or reduction-methylation. The previously reported association between DPH intake and reduced levels of serum folate remains unexplained by these studies.

Adult↗

Unsuspected hyperhomocysteinemia in chronically anticoagulated patients.

Hyperhomocysteinemia is a risk factor for arterial and venous thrombosis. The aim of this study was to evaluate plasmatic homocysteine levels in patients under chronic anticoagulant treatment with dietary restriction of green vegetables. This kind of food is a very important source not only of vitamin K but also of folates, which are involved in Hcy metabolism. It is known that the lower the folate levels, the higher the Hcy concentration, so we suspected that these patients could show hyperhomocysteinemia. A group of patients receiving oral anticoagulant treatment and a restricted diet (Group I, n = 20) was compared with a group of untreated subjects of a similar age that were not on a restricted diet (Group II, n = 35). Group I showed significantly higher levels of plasmatic Hcy and significantly lower levels of serum folate than Group II. Therefore, a diet restricted in vitamin K applied to oral anticoagulated patients could induce an unwanted increase of homocysteine levels.

Aged↗

Plasma homocysteine is not a major risk factor for vascular disease in growth hormone deficient adults.

OBJECTIVE: Several cardiovascular risk factors have been investigated in patients with adult growth hormone deficiency (GHD) to explain the observed increase in vascular mortality. Plasma homocysteine concentration has been identified recently as an independent risk factor for atherosclerosis. We wished to determine whether plasma homocysteine contributes to cardiovascular risk in adult GHD. METHOD: Plasma homocysteine was measured by fluorescence polarization immunoassay in 45 GH-deficient adults on stable conventional hormone replacement (25M, 20F), age range 23-76 years, and compared with 55 matched controls (30M, 25F), age range 21-77 years. All subjects were free from clinical hypertension, diabetes, ischaemic heart disease and peripheral vascular disease. Blood pressure, body mass index and waist hip ratio were recorded. Serum creatinine and fasting lipids were measured. Serum vitamin B12 and folate levels, important cofactors in the homocysteine metabolic pathways, were also measured. RESULTS: Homocysteine levels were not different in patients and controls (9.75 [7.8-11.6] micromol/l vs. 9.65 [8.3-11.5] micromol/l, respectively, P = 0.88). Serum vitamin B12 was also not different (320.5 [262.0-427.5] pmol/l vs. 313.5 [277.0-460.5] pmol/l, respectively, P = 0.77). Serum folate levels were significantly lower in the patient group (7.05 [5.12-8.27] ng/ml vs. 7.80 [6.52-10.60] ng/ml, respectively, P = 0.03). When separated by gender, in males folate was not significantly different between patients and controls 7.05 [5.17-9.19] vs. 7.65 [6.15-10.22], P = 0.264, whereas in females, folate was significantly lower in patients at 7.05 [4.57-7.75] compared to controls at 8.4 [6.60-12.20], P = 0.01. CONCLUSION: Plasma homocysteine levels are not significantly elevated in GH-deficient adults and are unlikely to be a major risk factor for vascular disease in these individuals.

Adult↗

[Megaloblastic changes in cervical epithelium associated with oral contraceptives and changes after treatment with folic acid].

OBJECTIVE: To study the influence of oral contraceptives on cervical epithelium, serum and red blood cell folate levels of users and to observe the changes after treatment with folic acid. METHODS: Morphology of cervical epithelium, serum folate and red blood cell folate levels were studied in 101 women who had used oral contraceptives for over 6 months and 33 intrauterine devices users served as controls, 29 women using oral contraceptives with cervical megaloblastic changes were treated with folic acid (5mg daily) for 3-4 weeks and followed up for observation on morphological changes of cervical epithelium. RESULTS: The mean nuclear diameter of cervical epithelial cells was larger in the oral contraceptive group than that in the control group (P < 0.001). Megaloblastic changes in cervical epithelium occurred in 29 women in the oral contraceptive group (28.7%). There was significant difference in the occurrence of cervical megaloblastic changes between the two groups (P < 0.01). The level of red blood cell folate was lower in the oral contraceptive group than that in the control group (P < 0.05). There was no difference in serum folate, hemoglobin and neutrophil nuclear index between the two groups (P > 0.05). The mean nuclear diameter of cervical epithelial cells decreased significantly (P < 0.001) and multinuclear and vacuolar changes disappeared after folic acid therapy in 26 women with megaloblastic changes. CONCLUSIONS: Oral contraceptives reduced folate storage in the body and resulted in megaloblastic changes in cervical epithelium. This condition was improved with folic acid therapy.

Adult↗

Homocysteinemia in rats induced by folic acid deficiency.

The effect of folate deficiency on homocysteine metabolism was examined in rats given a folate-deficient diet. Total homocysteine was determined in serum stored at -22 degrees C for 3 wk. All animals in the control group had more than 20 ng.ml-1 of serum folate and more than 1000 pg.ml-1 of serum cyanocobalamin throughout the experimental period. In contrast, serum folate in animals given the folate-deficient diet decreased to less than 3 ng.ml-1 after 4 wk and to less than 2 ng.ml-1 (a subnormal level) after 10 wk of the experiment while serum cyanocobalamin remained at more than 1000 pg.ml-1 throughout the experiment. In the control group, mean serum total homocysteine +/- SD was 4.04 +/- 1.07 nmol.ml-1 during the 20 wk of experiment. At the 10th wk before serum folate reached subnormal levels, the animals given the folate-deficient diet had a mean serum total homocysteine of 7.67 +/- 1.53 nmol.ml-1, demonstrating a significant increase (P less than 0.001). No further significant increase of mean serum total homocysteine concentrations was observed after serum folate became subnormal. This study demonstrated for the first time that a selective deficiency of folic acid caused a 2-4 fold increase in serum total homocysteine when serum folate was at low normal and at subnormal levels in rats.

Animals↗

Folate and cancer prevention: a new medical application of folate beyond hyperhomocysteinemia and neural tube defects.

Folate is an important cofactor in the transfer of one-carbon moieties and plays a key role in DNA synthesis, repair, and methylation. The role of folate has greatly evolved from the prevention of macrocytic anemia to the prevention of cardiovascular disease and neural tube defects. More recently, epidemiologic, animal, and clinical evidence suggests that folate may also play a role in cancer prevention. Two recently published large, prospective epidemiologic studies suggest that maintaining adequate levels of serum folate or moderately increasing folate intakes from dietary sources and vitamin supplements can significantly reduce the risk of pancreatic and breast cancer, respectively. This protective effect of folate appears to be operative in subjects at risk for developing these cancers, namely, male smokers for pancreatic cancer and women regularly consuming a moderate amount of alcohol for breast cancer. Because the expanding role of folate nutrition in cancer prevention has major public health implications, research is required to clearly elucidate the effect of folate on carcinogenesis.

Adolescent↗

Methylenetetrahydrofolate reductase deficiency in four siblings: a clinical, biochemical, and molecular study of the family.

A diagnosis of methylenetetrahydrofolate reductase (MTHFR) deficiency was made in four sibs at different ages. The first three, including a pair of twins, had retarded psychomotor development, poor social contact, and seizures. Biologically, hyperhomocysteinemia and hypomethioninemia were found associated with low folate levels in serum and red cells, especially undetectable methyltetrahydrofolate in red cells. In the fourth child, prenatal diagnosis was not conclusive because of moderate decrease of enzymatic activity in chorionic villi and trophoblast. The girl was also affected, as shown by hyperhomocysteinemia and low folate levels found several days after birth. A 677C-->T (Ala-->Val) mutation was found in a homozygous state in the four children and in the father. Additionally, a second homozygous mutation, 1081C-->T, changing an arginine to cysteine also was identified in all of the children, whereas the distantly consanguineous parents were heterozygous. This amino acid substitution affecting an arginine residue in a sequence located at the end of catalytic domain seems critical for the function of the enzyme. The difficulty of prenatal diagnosis is discussed given the variability found in enzymatic activity and in the clinical phenotypes.

Adolescent↗

Determinants of the blood lead level of US women of reproductive age.

OBJECTIVES: Blood lead concentration of an infant is largely affected by maternal blood lead recycling. This study aimed to identify sociodemographic, lifestyle, and nutritional determinants for blood lead levels (BLLs) of women of reproductive age in the United States. METHODS: Subjects (n = 4,394) were women (20-49 years old) included in the most recent complete National Health and Nutritional Survey (NHANES III). Certain sociodemographic, lifestyle and nutritional determinants for BLL were identified. RESULTS: The BLL of reproductive age women was 1.78 microg/dL geometric mean, The BLL was inversely associated with poverty income ratio and education level, hematocrit, intake of thiamine, and serum levels of folate, and positively associated with ethnicity (Black, Hispanic), living in urban areas or the Northeast region, age, alcohol consumption, cigarette smoking, serum protoporphyrin, and intake of pyridoxine, iron, and folate. Subjects in the lowest decile for serum ascorbic acid had significantly higher BLLs than those in the 2nd through 8th deciles. CONCLUSION: Infants born to women who smoke, drink and maintain poor nutritional status for selected nutrients are at a greater risk of lead toxicity than those born to other women. Nutritional manipulation of thiamine, ascorbic acid and folate may impact BLL in women.

Adult↗

Is there any relationship between lipids and vitamin B levels in persons with elevated risk of atherosclerosis?

BACKGROUND: There is increasing evidence that plasma homocysteine level is an independent risk factor for atherosclerosis. Low levels of serum folates, cobalamin and pyridoxine are associated with increased risk of cardiovascular disease. Most dietary products contain cholesterol as well as methionine, so hyperlipidemia could be associated with a higher level of homocysteine and inversely with lower levels of B vitamins. The aim of this study was to investigate the differences in levels of lipids and vitamins affecting homocysteine metabolism in different groups of patients. MATERIAL/METHODS: We examined 38 healthy persons, 55 patients hospitalised for cardiac surgery, and 62 patients without clinical evidence of atherosclerosis but with one of the atherosclerosis risk factors (hypercholesterolemia, NIDDM or chronic renal insufficiency). The levels of total cholesterol, triglycerides, vitamin B12, folic acid and vitamin B6 index in serum were determined using routine laboratory methods. RESULTS: We found no association between lipids and B vitamins in any examined group. There were significant differences between concentrations of analysed parameters in all groups of patients as compared to controls. CONCLUSIONS: The lack of correlation between the levels of lipid parameters and B vitamins in serum indicates that these may be independent, additional risk factors for atherosclerosis. Higher vitamin B6 deficiency in dialysis patients is probably caused by low intake combined with the increased requirements of uremic patients. Permanent monitoring of B vitamins in serum is necessary in patients with elevated risk of atherosclerosis, as well as long-term education, careful diet planning and supplementation.

Adult↗

Effect of folic acid supplement on birth weights of infants.

Earlier observations from this Institute have indicated that the infants born to mothers receiving folic acid supplements in addition to iron during pregnancy were heavier than those born to mothers receiving iron alone. Since birth weights are influenced by maternal factors like height and parity, a trial was carried on in matched controls with iron and iron and folic acid during the last 12 to 16 weeks of pregnancy. Simultaneously, placental function was also assessed. The effect of the folic acid supplements was more marked on first born children. Incidence of small-for-dates births was half in the iron and folate-supplemented group as compared with the iron-supplemented group. The heights of mothers did not make any difference on the effect of folate supplement. The improvement in the birth weights seem to have been brought about by increase in placental size, cell number, and protein content in the folate supplement group. In view of multivariant deficiency and practical problems in implementing food supplement programs to expectant mothers, supplements of folate and iron to expectant mothers in large scale may bring about an improvement in the incidence of pregnancy anemia and also reduce the infant morbidity and mortality rate due to the high incidence of low-birth weight babies.

Birth Weight↗

Low dose colestipol in adolescents with familial hypercholesterolaemia.

The effects of orange flavoured colestipol granules, 10 g/day, in 37 boys and 29 girls aged 10-16 years with familial hypercholesterolaemia were examined first in an eight week double blind, placebo controlled protocol, then in open treatment for 44-52 weeks. All patients were on a low fat diet. Low density lipoprotein cholesterol levels were reduced by 19.5% by colestipol v 1.0% by placebo. Levels of serum folate, vitamin E, and carotenoids were reduced in the colestipol group, but not the vitamin E/cholesterol and carotenoid/cholesterol ratios or serum concentrations of vitamins A and D. After one year of colestipol, two thirds of the participants remained in the study, of whom half took > or = 80% of the prescribed dose. Those who took > or = 80% of the dose had a greater decrease in serum 25-hydroxyvitamin D levels than those who took < 80%. No adverse effects on weight gain or linear growth velocity were observed. Although low dose colestipol effectively reduces low density lipoprotein cholesterol levels, only a minority of adolescents adhered to the new formulation for one year. Folate and possibly vitamin D supplementation is recommended.

Adolescent↗

[Treatment of post-transplant erythrocytosis: comparison of lisinopril and theophylline].

OBJECTIVE: The proposal of this study is to compare the efficacy of lisinopril and theophylline, alone or in association, on erythrocytosis in renal-transplanted patients. DESIGN: Prospectic, case-control study. PATIENTS/ENVIRONMENT: 15 inpatients meeting 3 main criteria: 1) ACE therapy for past erythrocytosis, 2) actual erythrocytosis, 3) symptomatic increase of haematocrit (Hct). INTERVENTION: The treatment has been divided into 3 consecutive phases of 30 days each: 1) lisinopril (5 mg/die), 2) theophylline (4 mg/kg/die), 3) association of 2 drugs. MEASUREMENTS: The evaluations were scheduled at the beginning and every month and consisted of renal function control, haemochromocytometric exam, serum level of folates, B12 vitamin and erythropoietin (EPO), iron level, cyclosporinemia, as well as clinic control and adverse events detection. RESULTS: A significative decrease of Hct values and a decrease of serum erythropoietin values was observed in patients treated with lisinopril. Patients treated with theophylline showed a significant reduction of Hct values causing a reduction of erythropoietin serum level in 8/13 patients. Lisinopril and theophylline administered in combination presented a significant decrease of Hct values, while EPO values diminished compared to basal values. CONCLUSIONS: These data showed that lisinopril is a valid therapy for the treatment of posttransplanted patients affected by erythrocytosis and, moreover, has the benefit of antihypertensive action. Theophylline remains an alternative therapy when ACEi are contraindicated. The combination of the 2 drugs doesn't produce additional benefits.

Cardiotonic Agents↗

Psychomotor retardation, spastic paraplegia, cerebellar ataxia and dyskinesia associated with low 5-methyltetrahydrofolate in cerebrospinal fluid: a novel neurometabolic condition responding to folinic acid substitution.

INTRODUCTION: Normal brain development and function depend on the active transport of folates across the blood-brain barrier. The folate receptor-1 (FR 1) protein is localized at the basolateral surface of the choroid plexus, which is characterized by a high binding affinity for circulating 5-methyltetrahydrofolate (5-MTHF). PATIENTS AND METHODS: We report on the clinical and metabolic findings among five children with normal neurodevelopmental progress during the first four to six months followed by the acquisition of a neurological condition which includes marked irritability, decelerating head growth, psychomotor retardation, cerebellar ataxia, dyskinesias (choreoathetosis, ballism), pyramidal signs in the lower limbs and occasional seizures. After the age of six years the two oldest patients also manifested a central visual disorder. Known disorders have been ruled out by extensive investigations. Cerebrospinal fluid (CSF) analysis included determination of biogenic monoamines, pterins and 5-MTHF. RESULTS: Despite normal folate levels in serum and red blood cells with normal homocysteine, analysis of CSF revealed a decline towards very low values for 5-methyltetrahydrofolate (5-MTHF), which suggested disturbed transport of folates across the blood-brain barrier. Genetic analysis of the FR 1 gene revealed normal coding sequences. Oral treatment with doses of the stable compound folinic acid (0.5-1 mg/kg/day Leucovorin(R)) resulted in clinical amelioration and normalization of 5-MTHF values in CSF. CONCLUSION: Our findings identified a new condition manifesting after the age of 6 months which was accompanied by low 5-MTHF in cerebrospinal fluid and responded to oral supplements with folinic acid. However, the cause of disturbed folate transfer across the blood-brain barrier remains unknown.

Blood-Brain Barrier↗

A critical evaluation of the relationship between serum vitamin B, folate and total homocysteine with cognitive impairment in the elderly.

BACKGROUND: Serum homocysteine increases with age and is also considered a marker for low serum vitamin B(12) and folate. Furthermore, raised serum total homocysteine has been associated with atrophic changes in the brain. An association between serum vitamin B(12)/folate and cognitive impairment would be of considerable public health importance in view of the increasing numbers of elderly people. AIM: To systematically review published studies on the relationship between serum vitamin B(12), folate and total homocysteine and cognitive function in the elderly. DESIGN AND DATA SOURCES: A systematic review was undertaken of published evidence in English, examining the association between low serum vitamin B(12)/folate and raised total homocysteine with cognitive impairment (as indicated by low scores on neuropsychological testing) in subjects aged over 60 years. Sixteen electronic databases and cited articles were searched. Of 383 potential articles, six fulfilled the eligibility criteria: three case control and three cohort studies were identified. 'The Cochrane Non-Randomized Studies Methods Group' guidelines were used for assessment and extraction of data from these studies. RESULTS: All three case control studies found that serum total homocysteine was significantly higher in cases when compared with controls, and there was wide variation for both serum vitamin B(12) and folate in both groups of participants. The relationship of serum folate and vitamin B(12) status with cognitive impairment was heterogeneous and one case control study reported decreasing cognitive scores with increasing serum vitamin B(12). In the cohort studies, although serum total homocysteine could predict the rate of decline in neuropsychological testing, the overall odds ratio/relative risk (RR) of developing cognitive impairment in relation to levels of serum B(12) and serum folate were not significant. Although one study reported a significant RR of developing Alzheimer's disease when both serum folate and B(12) levels were low. One cohort study reported an increased prevalence of Alzheimer's type dementia in subjects who had normal serum vitamin B(12) at baseline. CONCLUSION: Serum total homocysteine is negatively correlated with neuropsychological tests scores. But the evidence does not support a correlation between serum vitamin B(12) or folate and cognitive impairment in people aged over 60 years. Hence, there is little evidence to justify treating cognitive impairment with vitamin B(12) or folate supplementation. This is consistent with the findings from recent systematic reviews of randomized double-blind trials, which have not found any evidence of potential benefit of vitamin supplementation. Further research is required in order to establish whether raised serum total homocysteine is a cause or consequence of disease.

Aged↗

[Homocysteinemia and its relationship with the methylentetrahydrofolate reductase polymorphism in various ethnic groups from western Venezuela].

The prevalence of hyperhomocysteinemia and C677T MTHFR polymorphism was studied in various ethnic groups from Western Venezuela (60 Wayuu Indians, 42 italian immigrants and 77 Venezuelan mestizos) in relation with the prevalence of hyperhomocysteinemia and the C677T MTHFR polymorphism. Homocysteinemia was determined by polarized fluorescence immunoassay in an IMX system, serum folate was measured by radioimmunoanalysis and the MTHFR genotype was determined by PCR and restriction analysis. Hyperhomocysteinemia was defined as a value over 2 SD above the mean value for normal MTHFR (CC677) in each group. The prevalence of MTHFR variants (C677T and 677TT) was elevated in all ethnic groups (78% among the wayuu, 76% among Italians and 63% among mestizos) with a significant association between the concentrations of homocysteine and the levels of serum folate among the wayuu (p < 0.0001) and the mestizos (p < 0.001) only. Hyperhomocysteinemia was associated with MTHFR variants in 23% of the wayuu (OR: 6.17, CI 95: 0.74-51.36), 9.5% of the Italians (OR: 0.93, CI 95: 0.085-10.10) and 20.7 of the Venezuelans mestizos (OR: 5.2, CI 95: 1.08-24.90, p > 0.03). There was no relationship between hyperhomocysteinemia and folate deficiency in any of the groups studied. In conclusion, despite a high prevalence of C677T MTHFR variants in these ethnic groups of western Venezuela, the lack of no evidence of hyperhomocysteinemia combined with folate deficiency may imply that the nutritional status of these groups plays an important role in the control of hyperhomocysteinemia as a risk factor for cardiovascular disease.

Adolescent↗