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PubMed2001

Effects of growth hormone (GH) administration on homocyst(e)ine levels in men with GH deficiency: a randomized controlled trial.

GH deficiency is associated with increased cardiovascular mortality and early manifestations of atherosclerosis. Elevated serum homocyst(e)ine levels have been found to be associated with increased cardiovascular risk. The effect of GH replacement on homocyst(e)ine has not been investigated to date. We evaluated the effect of GH replacement on fasting homocyst(e)inemia in a group of men with adult-onset GH deficiency in a randomized, single blind, placebo-controlled trial. Forty men with adult-onset GH deficiency were randomized to GH or placebo for 18 months, with dose adjustments made according to serum insulin-like growth factor I (IGF-I) levels. Fasting serum homocyst(e)ine, folate, vitamin B12, and total T(3) levels were determined at baseline and 6 and 18 months. Anthropometry, IGF-I levels, insulin, and glucose were measured at 1, 3, 6, 12, and 18 months. Nutritional assessment, body composition, total T(4), thyroid hormone binding index, and free T(4) index were assessed every 6 months. Homocyst(e)ine decreased in the GH-treated group compared with that in the placebo group (net difference, -1.2 +/- 0.6 micromol/L; confidence interval, -2.4, -0.02 micromol/L; P = 0.047). Homocyst(e)ine at baseline was negatively correlated with plasma levels of folate (r = -0.41; P = 0.0087). Total T(3) increased in the GH-treated group vs. that in the placebo group (net difference, 0.17 +/- 0.046 ng/dL; confidence interval, 0.071, 0.26 nmol/L; P = 0.0012). Folate and vitamin B12 levels did not significantly change between groups. Changes in homocyst(e)ine were negatively correlated with changes in IGF-I. For each 1 nmol/L increase in IGF-I, homocyst(e)ine decreased by 0.04 +/- 0.02 micromol/L (P = 0.029). In contrast, changes in homocyst(e)ine did not correlate with changes in folate, vitamin B12, total T(3), C-reactive protein, interleukin-6, or insulin levels. This study shows that GH replacement decreases fasting homocyst(e)ine levels compared with placebo. This may be one of the mechanisms involved in the putative modulation of atherosclerosis and cardiovascular risk by GH replacement.

Adult↗
PubMed1988

Increased plasma levels of peptide YY in coeliac disease.

Peptide YY (PYY) is exclusively localized in endocrine cells in the gut, and these cells are most numerous in the distal small intestine, colon, and rectum. We have earlier shown that PYY coexists with enteroglucagon in the gut endocrine cells. High basal and postprandial plasma enteroglucagon concentrations have earlier been found in patients with untreated coeliac disease. PYY circulates in human plasma and is detectable in most healthy adults. We have therefore studied the basal PYY levels in patients with coeliac disease. Marked elevated basal plasma PYY levels were found in patients with coeliac disease compared with an age- and sex-matched control group. The PYY levels were inversely correlated to the concentration of folate acid in serum. The PYY levels were studied in four patients with newly diagnosed disease and had normalized within 8 months on a gluten-free diet.

Adolescent↗
PubMed2001

Folate, homocysteine and methionine loading in patients on carbamazepine.

OBJECTIVES: Some antiepileptic drugs (AEDs) are associated with low levels of serum (S-FA) and erythrocyte folate (E-FA) and high levels of plasma total homocysteine (p-tHcy). We have explored the concentrations of S-FA, E-FA and p-tHcy in patients on carbamazepine (CBZ). The methionine loading test was applied for better assessment of mildly impaired homocysteine metabolism. MATERIAL AND METHODS: The study comprised 42 adult patients on CBZ and 42 matched healthy controls. Blood samples were drawn prior to and 6 h post methionine loading (6 h-PML) (0.1 g/kg body weight). RESULTS: The patients on CBZ had significantly lower concentrations of fasting S-FA and E-FA than the controls (P=0.0004, P=0.003, respectively). Fasting and 6 h-PML p-tHcy concentrations were significantly higher in the patients than in the controls (P=0.03 and P=0.0001, respectively). The methionine loading test identified additional patients with hyperhomocysteinemia undetected by fasting p-tHcy. CONCLUSION: CBZ therapy may be associated with low folate and high p-tHcy levels.

Adolescent↗
PubMed1988

Elevation of total homocysteine in the serum of patients with cobalamin or folate deficiency detected by capillary gas chromatography-mass spectrometry.

To determine if levels of serum total homocysteine are elevated in patients with either cobalamin or folate deficiency, we utilized a new capillary gas chromatographic-mass spectrometric technique to measure total homocysteine in the serum of 78 patients with clinically confirmed cobalamin deficiency and 19 patients with clinically confirmed folate deficiency. Values ranged from 11 to 476 mumol/liter in the cobalamin-deficient patients and 77 of the 78 patients had values above the normal range of 7-22 mumol/liter as determined for 50 normal blood donors. In the cobalamin-deficient patients, serum total homocysteine was positively correlated with serum folate, mean corpuscular volume, serum lactate dehydrogenase, serum methylmalonic acid, and the degree of neurologic involvement, and inversely correlated with platelets and hematocrit. In the folate-deficient patients, values for serum total homocysteine ranged from 17 to 185 mumol/liter and 18 of the 19 patients had values above the normal range. Some patients with pernicious anemia who were intermittently treated with cyanocobalamin were found to have elevated serum levels of total homocysteine while they were free of hematologic and neurologic abnormalities. The measurement of serum total homocysteine will help define the incidence of cobalamin deficiency and folate deficiency in various patient populations.

Adult↗
PubMed1995

[Serum folic acid and vitamin B12 in depressed inpatients. A study of serum folic acid with radioimmunoassay in 121 depressed inpatients].

According to the newer literature on folate deficiencies in depressive patients serum folate and vitamin B12 levels were studied (RIA) in 121 consecutively admitted depressive inpatients (47 male, 74 female depressives; age 17-86 years, mean age 48 years, diagnostic by ICD-9 300.4, 296.1) during the first (1-3) days of admission (normal volumes folate 3-17 ng/ml, vitamin B12 200-900 pg/ml). Only in two patients serum folate below 3 ng/ml were found, low vitamin B12 levels (below 200 pg/ml) showed 14 patients. This result is in contrast to other authors who found folate deficiencies in 10-50% of psychiatric patients.

Adolescent↗
PubMed2000

Folate and vitamin B12 status of adolescent girls in northern Nigeria.

The diets of populations in many developing countries are low in folate and vitamin B12 and a deficiency of either of these vitamins results in increased risk for cardiovascular disease and neural tube defects. The rates of neural tube defects in Nigeria are among the highest reported worldwide. Since many girls marry at an early age in northern Nigeria, we therefore determined the folate and vitamin B12 status of adolescent girls between 12 and 16 years of age in Maiduguri, Nigeria. The mean serum folate concentration for subjects was 15.3 +/- 5.2 nmol/L. Whereas only four subjects (2.4%) had serum folate concentrations lower than 6.8 nmol/L, a level indicative of negative folate balance, 9% of the subjects had serum vitamin B12 concentrations at or below 134 pmol/L, the lower limit of the reference range for their age group. Serum homocysteine was measured in 56 of the 162 subjects and the mean level was 15.9 +/- 5.0 mumol/L. The majority of subjects had serum homocysteine concentrations above the upper limit of the reference range for their age group. We conclude that the adolescent girls we studied were at greater risk for vitamin B12 deficiency than folate deficiency. This conclusion is consistent with the fact that their diet included few foods that contained vitamin B12.

Adolescent↗
PubMed1995

Biochemical indices of vitamin B12 nutrition in pregnant patients with subnormal serum vitamin B12 levels.

To determine the significance of the commonly observed fall in serum vitamin B12 levels during pregnancy, serum levels of the B12 metabolites methylmalonic acid (MMA) and homocysteine (Hcy) were measured in a group of 50 pregnant patients with subnormal serum B12 (range 45-199 pg/ml) and the results compared with those of 25 pregnant controls (serum B12(208-580) pg/ml). Mean values for serum MMA and total Hcy in the subnormal B12 group were 445.4 nmol/L and 7.03 mumol/L, respectively, which were not significantly different from the mean MMA of 440.5 nmol/L and Hcy of 6.88 nmol/L in the controls. For the total group of patients, neither serum MMA nor serum Hcy levels correlated with serum B12. One-third of pregnant patients showed elevated serum MMA values, independent of B12 status. Significant elevation of serum Hcy was detected in only two patients, both with subnormal serum B12 and hematological evidence of B12 deficiency. We conclude that the usual fall in serum B12 concentration in pregnancy does not reflect B12 deficiency at the biochemical level. In establishing true B12 deficiency in pregnancy, the serum Hcy level (in the absence of folate deficiency) but not serum MMA, is of value.

Female↗
PubMed1984

Folic acid and reproductive performances of sows.

Two-hundred nine sows were used in a 2 X 2 split-plot unbalanced design to measure the effect of folic acid against control, and flushing against a normal level of feeding, between weaning and mating on the following variables: serum folates at weaning and at 60 d of gestation, blood hemoglobin (Hb) and hematocrit (Ht) after 15 wk of gestation and reproductive performance at farrowing. Folic acid was administered im according to a schedule that maintained serum folates at approximately the same level between weaning and 60 d of gestation. The treatments had no effect on Hb or Ht after 15 wk of gestation. Average live litter size was 12.0 piglets/litter for sows receiving the folic acid and flushing treatments as compared with 10.5 for sows without any treatment; the main effect of folic acid was significant (P less than or equal to .04). Intralitter variation in birth weight and total litter weight tended to be increased by folic acid administration. Results showed that the administration of folic acid during gestation could appreciably improve the reproductive performance of sows.

Animals↗
PubMedDate not supplied

Analysis of folate and vitamin B12 in beta thalassemia minor.

To evaluate whether anemia of heterozygote beta thalassemic subjects depends on folate or vitamin B12 deficiency, the serum values of these two vitamins were assessed in 176 adult subjects: 81 healthy heterozygote beta thalassemic subjects, 76 healthy normal controls and 15 subjects with microcytic iron deficient anaemia and no thalassemic trait. Mean serum folate and vitamin B12 levels in heterozygote beta thalassemic subjects were not statistically different when compared to control groups. No statistically significant correlation was found between mean serum levels of the two vitamins and hematocrit in beta thalassemic carriers and in normal subjects.

Aged↗
PubMed2000

Effects of dietary folate on intestinal tumorigenesis in the apcMin mouse.

Dietary folate appears to be inversely related to colorectal cancer risk. This study investigated the effects of dietary intervention with folate or the development of intestinal polyps in Min (Apc +/-) mice. Weanling Mil mice were fed diets containing 0, 2 (basal requirement), 8, or 20 mg folate/kg diet. At 3 and 6 months of dietary intervention, 50% of the mice from each group were sacrificed, and the small intestine and colon were analyzed for polyps and aberrant crypt foci (ACF). Serum folate concentrations accurately reflected dietary folate levels (P < 0.001). At 3 months no significant difference in the average number of total small intestinal polyps was observed among the four groups. However, increasing dietary folate levels significantly reduced the number of ileal, but not duodenal or jejunal, polyps in a dose-dependent manner (P-trend = 0.001); folate supplementation at 20 mg/kg diet was associated with a 68-78% reduction in the number of ileal polyps compared with the other three diets (P < 0.007). The number of ileal polyps was inversely correlated with serum folate concentrations (P = 0.03). At 3 months, increasing dietary folate levels significantly decreased the number of colonic ACF in a dose-dependent manner (P = 0.05); the control and two folate supplemented diets significantly reduced the number of colonic ACF by 75 100% compared with the folate-deficient diet (P < 0.04). The number of colonic ACF was inversely correlated with serum folate concentration (P = 0.05). No significant difference in the number of colonic adenoma was observed among the four groups at 3 months. At 6 months, no significant differences in the average number of total small intestinal, duodenal, and jejunal polyps, colonic adenomas, and colonic ACF wer observed among the four groups. However, the folate-deficient diet had 62-76% lower number of ileal polyps compared with the control and two folate-supplemented diets (P < 0.003). Serum folate concentrations, but not dietary folate levels, were directly correlated with the number of ilea polyps (P = 0.006). These data suggest that dietary folate supplementation suppresses the development of ileal polyps and colonic ACF in this model However, at later time points, folate supplementation appears to have an opposite effect on ileal polyps. These data generally support the role of folate in intestinal tumorigenesis suggested in epidemiological studies and chemical carcinogen animal models. Notwithstanding the limitations associated with this model, these data suggest that the optimal timing and dose of folate intervention need to be determined for safe and effective folate chemoprevention.

Adenoma↗
PubMed2005

Analysis of 5-methyltetrahydrofolate in serum of healthy children.

5-Methyltetrahydrofolate (5MTHF) is the active one-carbon donor and the principal circulating form of plasma folates. It is involved in a number of metabolic and neurodevelopmental processes and analysis of cerebrospinal fluid (CSF) 5MTHF is of great importance in the diagnosis of cerebral folate deficiency (CFD). Serum 5MTHF levels and the 5MTHF serum/CSF ratio may be important additional parameters for the understanding of CFD. We developed a HPLC method for the measurement of 5MTHF in serum and established reference values for the pediatric population. Serum samples from 64 healthy children were extracted with Sep-Pak C18 cartridges and 5MTHF was separated by RP-HPLC and quantified by electrochemical detection. 5MTHF was separated from other folates and detected after 8.7 min with linearity of up to 1600 nmol/L. The detection limit was 4.5 nmol/L and recovery during solid-phase extraction for low and high concentrations of 5MTHF was 66 and 62%, respectively. Within-run imprecision (13.5%) was slightly higher than run-to-run imprecision (8.5%). 5MTHF levels in healthy children were found to be age-dependent, decreasing from 158.0 nmol/L in newborns to 60.1 nmol/L in children older than 16 years. The method we describe is sensitive, selective, and reliable for the analysis of 5MTHF from 400 microL of serum.

Adolescent↗
PubMed1975

Folate and monoamine metabolism in epilepsy.

In 27 drug-treated epileptics there was a significant fall in serum, red cell and CSF folate levels compared with 15 untreated epileptics and 22 neurological controls. The 3 folate parameters were positively correlated with each other and negatively correlated with serum phenobarbitone, diphenylhydantoin and primidone. There was also a significant elevation of CSF 5-hydroxyindoleacetic acid (5HIAA) in the drug-treated epileptics; but this was not seen until "therapeutic" serum levels of phenobarbitone and diphenylhydantoin had been achieved and was most marked in clinically intoxicated patients. Similar trends were observed in CSF homovanillic acid (HVA). CSF 5HIAA and HVA were positively correlated with each other, especially in the drug-treated patients, in whom both amine metabolites were also negatively correlated with CSF folate. A possible relationship between folate and monoamine metabolism is discussed with particular reference to the antiepileptic and toxic effects of phenobarbitone, diphenylhydantoin and primidone.

Adolescent↗
PubMed2000

Common C677T polymorphism in the methylenetetrahydrofolate reductase gene increases the risk for deep vein thrombosis in patients with predisposition of thrombophilia.

The alanine/valine (A/V) gene polymorphism of 5, 10-methylenetetrahydrofolate reductase (MTHFR), one of the key enzymes catalyzing remethylation of homocysteine, has been reported and the VV genotype is associated with increased plasma homocysteine levels as a result of the reduced activity and increased thermolability of this enzyme. Although previous studies have suggested that the VV genotype is a risk factor for arterial occlusive disease, whether the VV genotype is a risk factor for venous thrombosis is still controversial. Here we screened 72 Japanese patients with deep venous thrombosis (DVT) and 85 controls for this mutation, and we measured plasma levels of homocysteine to determine whether the thermolabile variant with the VV genotype is a risk factor for DVT in a Japanese population. Of the 72 patients with DVT, 10 (13.9%) were found to be homozygous for the VV genotype, and in 6 (7.0%) of 85, control individuals and the difference was not significant (odds ratio=2.12, 95% CI=0.73-6.16, p=0.19). When we divided the DVT patients into subgroups, with and without predisposition of thrombophilia, including deficiencies of proteins C and S, plasminogen, and lupus anticoagulant, the prevalence of the VV genotype in DVT patients with predisposition was significantly higher than that of the normal controls (odds ratio=5.99, 95% CI=1. 56-22.96, p=0.01). However, the prevalence of the VV genotype in DVT patients without predisposition was not significantly different from that of the normal controls (odds ratio=1.20, 95% CI=0.32-4.47, p=0. 75). The plasma homocysteine levels in patients with DVT (11.6+/-5.2 nmol/ml) was not significantly different from that of the control subjects (11.6+/-3.7 nmol/ml). Individuals with the VV genotype showed higher plasma homocysteine levels (15.4+/-6.9 nmol/ml) than did individuals with the AV genotype (11.2+/-3.7 nmol/ml, p=0.009) or in individuals with the AA genotype (11.1+/-4.2 nmol/ml, p=0.004). Serum folate and vitamin B12 levels were not correlated with the plasma homocysteine levels. In conclusion, even though homozygosity for the VV genotype of the MTHFR gene was associated with higher plasma homocysteine levels, we found no association between plasma levels of homocysteine and DVT or between the genotype of the MTHFR gene and the DVT incidence. However, we found that the VV genotype of the MTHFR gene is a risk factor for DVT only when combined with the predisposition of thrombophilia.

Adult↗
PubMed2003

High vitamin B12 level and good treatment outcome may be associated in major depressive disorder.

BACKGROUND: Despite of an increasing body of research the associations between vitamin B12 and folate levels and the treatment outcome in depressive disorders are still unsolved. We therefore conducted this naturalistic prospective follow-up study. Our aim was to determine whether there were any associations between the vitamin B12 and folate level and the six-month treatment outcome in patients with major depressive disorder. Because vitamin B12 and folate deficiency may result in changes in haematological indices, including mean corpuscular volume, red blood cell count and hematocrit, we also examined whether these indices were associated with the treatment outcome. METHODS: Haematological indices, erythrocyte folate and serum vitamin B12 levels were determined in 115 outpatients with DSM-III-R major depressive disorder at baseline and serum vitamin B12 level again on six-month follow-up. The 17-item Hamilton Depression Rating Scale was also compiled, respectively. In the statistical analysis we used chi-squared test, Pearson's correlation coefficient, the Student's t-test, analysis of variance (ANOVA), and univariate and multivariate linear regression analysis. RESULTS: Higher vitamin B12 levels significantly associated with a better outcome. The association between the folate level and treatment outcome was weak and probably not independent. No relationship was found between haematological indices and the six-month outcome. CONCLUSION: The vitamin B12 level and the probability of recovery from major depression may be positively associated. Nevertheless, further studies are suggested to confirm this finding.

Adult↗
PubMed2004

Plasma trace elements, vitamin B12, folate, and homocysteine levels in cirrhotic patients compared to healthy controls.

Increased serum homocysteine (Hcy) can induce liver diseases and can play a remarkable role in hepatic disorders. The purpose of the present study therefore was to investigate the relationship between serum vitamin B(12), folate, zinc and copper, cysteine, and Hcy level differences between cirrhotic patients and healthy subjects. We studied 32 cirrhotic patients (12 females and 20 males) aged 45 +/- 11 years and 32 control subjects (12 females and 20 males) aged 39 +/- 9 years. There was an inverse correlation between Hcy and vitamin B(12) in controls (r = -0.442, p < 0.011) but not in cirrhotic patients (r = -0.147, not significant). Also, mean plasma folate was decreased in cirrhotic patients compared to controls (p < 0.001). Copper increased whereas zinc decreased significantly in cirrhotic patients. A positive correlation was seen between the Cu/Zn ratio and Cu in controls (r = 0.690, p < 0.01), but the correlation between the Cu/Zn ratio and Cu was not significant in the cirrhotic group. Negative correlations were seen between plasma concentration of zinc and the Cu/Zn ratio in controls and cirrhotic patients (r = -0.618, p < 0.01 and r = -0.670, p < 0.01, respectively). Cirrhotic patients displayed multiple abnormalities, including changes in cysteine metabolism and in zinc and copper levels. Although hyperhomocysteinemia is known as an atherogenic and thrombogenic risk factor for cardiovascular disease, it might also be a risk factor for cirrhotic patients. Plasma Hcy, vitamin B(12), and folic acid measurement may be useful in the evaluation of cirrhotic patients.

Adult↗
PubMed1986

Fundic atrophic gastritis in an elderly population. Effect on hemoglobin and several serum nutritional indicators.

The ratio of pepsinogen I to pepsinogen II in the circulation decreases progressively with increasing severity of atrophic gastritis of the fundic gland mucosa. Fasting blood was obtained from 359 free-living and institutionalized elderly people (age range, 60 to 99 years). A pepsinogen I/pepsinogen II ratio less than 2.9, indicating atrophic gastritis, was found in 113 (31.5%) subjects. The prevalence of atrophic gastritis increased significantly with advancing age (P less than .05). Within the atrophic gastritis group, 84 had a pepsinogen I level greater than or equal to 20 micrograms/L, indicating mild to moderate atrophic gastritis, and 29 had a pepsinogen I level less than 20 micrograms/L, indicating severe atrophic gastritis or gastric atrophy. A significant increase in the prevalences of elevated serum gastrin levels (P less than .005), low serum vitamin B12 levels (P less than .005), circulating intrinsic factor antibody (P less than .005), and anemia (P less than .025) was observed with stepwise increases in severity of atrophic gastritis. Subjects with atrophic gastritis exhibited a lower mean serum vitamin B12 level (P less than .05) and a higher mean folate level (P less than .05), but no difference was detected in mean hemoglobin levels or serum levels of iron, ferritin, retinol or alpha-tocopherol. It is concluded that serum pepsinogen I and pepsinogen II levels can be used to determine the prevalence and severity of atrophic gastritis, that atrophic gastritis is common in an elderly population, and that atrophic gastritis is associated with vitamin B12 deficiency and anemia. Further, higher folate levels in atrophic gastritis may be related to an accumulation of 5-methyl tetrahydrofolate in serum due to vitamin B12 deficiency and/or greater folate synthesis by the intestinal flora resulting from bacterial overgrowth secondary to hypo- or achlorhydria.

Aged↗
PubMed2005

Brain MRI white matter hyperintensities and one-carbon cycle metabolism in non-geriatric outpatients with major depressive disorder (Part II).

The objective of this study was to investigate the relative impact of brain white matter hyperintensities (WMHs), cardiovascular risk factors and elements of the one-carbon cycle metabolism (including serum folate, vitamin B12 and homocysteine levels) on the outcome of antidepressant treatment in non-elderly subjects with major depressive disorder (MDD). Fifty MDD subjects were administered brain magnetic resonance imaging (MRI) scans at 1.5 T to detect T2 WMHs. The severity of brain WMHs was classified with the Fazekas scale (range=0-3). We assessed cardiovascular risk factors in all MDD subjects (age, gender, smoking, diabetes, family history, hypertension, cholesterol). MDD patients also had serum folate, vitamin B12 and homocysteine levels measured. All MDD subjects received treatment with fluoxetine 20 mg/day for 8 weeks. In a logistic regression, the severity of subcortical WMHs and the presence of hypofolatemia were independent predictors of lack of clinical response to antidepressant treatment. Separately, hypofolatemia also predicted lack of remission to antidepressant treatment. These associations were independent of the presence of smoking, diabetes, family history, hypercholesterolemia, hyperhomocysteinemia and low B12 levels. Although preliminary, the results of the present work suggest that subcortical brain WMHs and hypofolatemia may have an independent negative impact on the likelihood of responding to antidepressant treatment in non-geriatric subjects with MDD.

Adolescent↗