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Folate supplementation reduces serum hsp70 levels in patients with type 2 diabetes.

Type 2 diabetes patients are subject to oxidative stress as a result of hyperglycemia. The aim of this study was to determine whether administration of the antioxidant folic acid, previously shown to reduce homocysteine levels, would reduce circulating levels of Hsp70 while improving the condition of type 2 diabetes patients with microalbuminuria. Plasma homocysteine fell from pretreatment values of 12.9 to 10.3 microM (P < 0.0001). The urine albumin-creatinine ratio fell from 12.4 to 10.4 mg/mM (P = 0.38). Pretreatment Hsp70 levels were higher in patients not taking insulin (5.32 ng/mL) compared with those on insulin (2.44 ng/mL) (P = 0.012). Folic acid supplementation resulted in a significant fall in Hsp70 (5.32 to 2.05 ng/mL) (P = 0.004). There was no change in Hsp70 in those receiving insulin. Folic acid supplementation in non-insulin-treated type 2 diabetes patients, therefore, resulted in a fall in Hsp70, reflecting an improvement in oxidative stress. The data shows that improvement in homocysteine status can lead to a reduction in Hsp70, indicating the possibility of its use as a marker for severity of disease.

Chaperonin 60↗

Folate status and adenomatous colonic polyps. A colonoscopically controlled study.

PURPOSE: The aim of our study was to assess any association of folate with development of colonic adenomas. METHODS: Serum and red blood cell folate levels were measured in 62 colonoscopically and histologically evaluated patients with colon adenomas (Group A) and in 50 selected colonoscopically negative controls (Group B). Patients with colon polyps underwent colonoscopy for alterations of bowel habits or abdominal pain, and detected polyps were found coincidentally. Controls underwent colonoscopy for alterations of bowel habits or abdominal pain. There was no difference in hematocrit between the two groups. RESULTS: The mean serum folate level in patients with colonic adenomas was 4.57 ng/ml +/- 2.8 standard deviations (SD), and the mean red blood cells folate levels were 536 ng/ml +/- 273.3 (SD). In controls the mean folate levels in serum and red blood cells were 5.09 ng/ml +/- 2.7 (SD) and 743.8 ng/ml +/- 297.1 (SD), respectively. The red blood cell folate level of colon adenoma patients was statistically lower than the respective level of controls at a highly significant level (P < 0.01). CONCLUSIONS: We suggest that depressed red blood cell folate levels are associated with development of colonic adenomas.

Adenoma↗

Methylenetetrahydrofolate reductase genotype, vitamin B12, and folate influence plasma homocysteine in hemodialysis patients.

Hyperhomocysteinemia, a well-recognized cardiovascular risk factor, is frequent in hemodialysis (HD) patients. A common polymorphism in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, C-->T substitution at nucleotide 677, is associated with homocysteine (Hcy) level elevation. We examined whether three factors involved in the methionine cycle could influence plasma Hcy concentrations in HD patients: MTHFR polymorphism; vitamin B12, an essential cofactor; and folate, the substrate. In a cross-sectional study, serum vitamin B12, folate, and plasma Hcy were measured and MTHFR genotyping was performed in 534 HD patients. Effects of MTHFR genotypes, vitamin B12, and folate on plasma Hcy levels were examined in 450 HD patients not administered vitamin B12 or folate. To examine the effect of vitamin B12 on plasma Hcy concentrations, we compared plasma Hcy concentrations in HD patients with and without vitamin B12 supplementation. To examine whether functional vitamin B12 deficiency exists even in HD patients with normal vitamin B12 concentrations, 15 HD patients (serum vitamin B12 concentrations, 250 to 2,100 pg/mL) were treated with vitamin B12 (mecobalamin, 1.5 mg/d) for 8 weeks. Serum concentrations of methylmalonic acid (MMA) and vitamin B12 were measured. Hcy levels were higher and folate levels were lower in patients with the TT and CT genotypes compared with patients with the CC genotype. Analysis of covariance to determine independent predictors of high Hcy levels identified low serum vitamin B12 and folate levels and high albumin (Alb) levels in CC-genotype patients, low folate levels and high Alb levels in CT-genotype patients, and low folate levels in TT-genotype patients. Plasma Hcy levels were lower in CC- and CT-genotype patients with vitamin B12 supplementation than in those without supplementation. Vitamin B12 supplementation for 8 weeks significantly reduced MMA concentrations in HD patients with normal serum vitamin B12 concentrations. These results indicate that MTHFR genotype influences the correlation of Hcy level with vitamin B12 and folate levels in HD patients. Functional vitamin B12 deficiency may exist, even in HD patients with normal vitamin B12 concentrations. The efficacy of vitamin B12 and folate supplementation on plasma Hcy levels may depend on MTHFR genotype.

Cross-Sectional Studies↗

Folate and vitamin B12-deficiency anemias in Vietnamese immigrants living in Southern California.

BACKGROUND: Although the occurrence of iron deficiency anemia and hemoglobinopathies in Vietnamese immigrants has been reported, folate and vitamin B12 deficiencies have not. Proper diagnosis and effective treatment is necessary to achieve a complete correction of anemia. METHODS: We retrospectively analyzed the records of Vietnamese immigrants seen in our medical clinic from 1991 to 1993. Fifty-nine anemic patients (48 females and 11 males) had low levels of red blood cell (RBC) folate and/or serum vitamin B12. RESULTS: The patients' mean age was 37.7+/-17 years. Mean hemoglobin and hematocrit values were 11.4+/-0.7 g/dL and 34.4%+/-2.2%, respectively. Mean corpuscular volume (MCV) was normal in 40 patients (68%) (mean, 89.1+/-5 fL) and low in 19 patients (32%) (mean, 69.7+/-6 fL). Forty-four patients had low RBC folate levels (mean, 157.7+/-41.7 ng/mL). Twenty patients had low serum vitamin B12 levels (mean, 165.6+/-47 pg/mL). Fourteen patients had ferritin levels of <20%. CONCLUSIONS: Concomitant folate, vitamin B12, and iron deficiencies or hemoglobinopathies might have been responsible for either normal or low MCV in some of our anemic patients. In this ethnic group, RBC folate and serum vitamin B12 levels should be determined in all anemic patients.

Adolescent↗

The administration of folic acid to institutionalized epileptic adults with phenytoin-induced gingival hyperplasia. A double-blind, randomized, placebo-controlled, parallel study.

Twenty severely retarded institutionalized epileptic adults with phenytoin-induced gingival hyperplasia were divided into two groups and received a daily 3 mg capsule of either folic acid or lactose for 16 weeks in a randomized, double-blind, parallel study. Serum folate and phenytoin levels were recorded at baseline and on completion of the study. Twelve areas of the gingiva on each patient were graded at 4-week intervals for 16 weeks with respect to the three indexes: hyperplasia, gingival health, and plaque index. There were no significant differences between treatment groups for any of the three indexes over time. The poststudy serum folate levels were three times baseline levels for the active drug group (p less than 0.001) but unchanged in the placebo group. Phenytoin blood levels that began within the therapeutic window (10 to 20 micrograms/ml) tended to remain within the therapeutic window for both groups, with no reported seizure activity. A single daily oral 3 mg capsule of folic acid did not show efficacy as the sole therapeutic agent in the reduction of phenytoin-induced gingival hyperplasia.

Adult↗

[Critical analysis of 1000 systematic assays of serum levels of vitamin B12 and folates].

Between January 15 and April 30, 1988, one thousand assays of serum vitamin B12 and folates were performed, and the reasons why they were requested as well as their clinical usefulness are discussed. In 50 cases these assays were requested for a suspected myeloproliferative syndrome; in some of the patients with polycythaemia vera an excess of B12 was observed without hyperleukocytosis, an argument for keeping the B12 assay as an element of initial evaluation. In numerous cases the assays were performed for aetiological evaluation of a macrocytosis of suspected alcoholic origin in most patients; more than 50 per cent of the patient had folate deficiency and only a few had low B12 values. Folate levels were frequently low and B12 levels generally normal in patients with gastrointestinal disease, but many of them had been supplemented with folate and/or B12 prior to the assay. More than 20 per cent of the 1,000 assays were performed in patients aged 80 years or more, and more than 50 per cent of them had a low folate level; this has no consequences for individual subjects, but it may be of epidemiological or sociological interest. It must be mentioned that too many blood samples (more than 40 per cent) were sent to the laboratory without adequate information and after supplementation in 20 per cent of the cases. Very few patients with very low B12 levels were subjected to Schilling's test, so that the clinical usefulness of this assay, as currently utilized, is questionable in a large number of cases.

Adolescent↗

Effect of long-term gastric acid suppressive therapy on serum vitamin B12 levels in patients with Zollinger-Ellison syndrome.

BACKGROUND AND AIMS: Long-term treatment with H(+)-K(+)-adenotriphosphatase (ATPase) inhibitors, such as omeprazole or lansoprazole, for severe gastroesophageal reflux disease is now widely used. Whether such treatment will result in vitamin B12 deficiency is controversial. We studied whether long-term treatment with omeprazole alters serum vitamin B12 levels in patients with Zollinger-Ellison syndrome. METHODS: In 131 consecutive patients treated with either omeprazole (n = 111) or histamine H2-receptor antagonists (n = 20), serum vitamin B12 and folate levels and complete blood counts were determined after acid secretion had been controlled for at least 6 months. These studies were repeated yearly. Serum vitamin B12 and folate levels were correlated with the type of antisecretory drug and the extent of inhibition of acid secretion. RESULTS: The mean duration of omeprazole treatment was 4.5 years, and for H2-receptor antagonists 10 years. Vitamin B12 levels, but not serum folate levels or any hematological parameter, were significantly (P = 0.03) lower in patients treated with omeprazole, especially those with omeprazole-induced sustained hyposecretion (P = 0.0014) or complete achlorhydria (P < 0.0001). In 68 patients with two determinations at least 5 years apart, vitamin B12 levels decreased significantly (30%; P = 0.001) only in patients rendered achlorhydric. The duration of omeprazole treatment was inversely correlated with vitamin B12 levels (P = 0.013), but not folate levels. Eight patients (6%) developed subnormal B12 levels during follow-up. CONCLUSIONS: Long-term omeprazole treatment leads to significant decreases in serum vitamin B12 but not folate levels. These results suggest patients with Zollinger-Ellison syndrome treated with H(+)-K(+)-ATPase inhibitors should have serum vitamin B12 levels monitored. Furthermore, these results raise the possibility that other patients treated chronically with H(+)-K(+)-ATPase inhibitors may develop B12 deficiency.

Achlorhydria↗

The coelomic cavity: an important site of materno-fetal nutrient exchange in the first trimester of pregnancy.

OBJECTIVE: To measure levels of folate and vitamin B12 in matched samples of amniotic fluid and extra-embryonic coelomic fluid from 9 to 12 weeks' gestation. DESIGN: Prospective observational study. SETTING: Homerton Hospital, London. SUBJECTS: Twenty-two women with ultrasonographically normal pregnancies before surgical termination. METHODS: Transvaginal ultrasound-guided needle aspiration of amniotic fluid and extra-embryonic coelomic fluid was performed. Pure samples of amniotic fluid and extra-embryonic coelomic fluid were obtained from each pregnancy, and folate and vitamin B12 were measured using microbiological assays. RESULTS: Levels of folate and vitamin B12 were higher in extra-embryonic coelomic fluid than in amniotic fluid and maternal serum. Amniotic fluid folate levels were lower than in maternal serum whereas vitamin B12 levels in amniotic fluid were higher than in maternal serum. All differences in concentration were significant (P < 0.0005; paired t-test). Positive correlations were found between the concentrations of folate and vitamin B12 in each fluid. There was a linear correlation between gestational age and amniotic fluid folate levels (r = 0.648; P = 0.001). CONCLUSIONS: High concentrations of folate and vitamin B12 in coelomic fluid suggest that the coelomic cavity plays an important role in the materno-fetal exchange of these nutrients.

Amniotic Fluid↗

The Chilean flour folic acid fortification program reduces serum homocysteine levels and masks vitamin B-12 deficiency in elderly people.

Hyperhomocysteinemia is considered a risk factor for cardiovascular disease and is prevalent in the elderly. Supplementation with folic acid, vitamin B-6 and B-12 lowers homocysteine levels. In January 2000, the Chilean government initiated a flour folic acid fortification program to decrease the occurrence of neural tube defects. The aim of this study was to evaluate the effect of this program on serum homocysteine and folate levels in elderly subjects after 6 mo. A total of 108 elderly people were studied. We measured serum folate, homocysteine and vitamin B-12 levels before the fortification started and 6 mo later. At baseline, folate deficiency (<6.8 nmol/L) was present in 1.8%, vitamin B-12 deficiency (<165 pmol/L) in 27.6% and hyperhomocysteinemia (>14 micromol/L) in 31% of the sample. Six months later, serum folate levels increased from 16.2 +/- 6.2 to 32.7 +/- 7.1 nmol/L (P < 0.001), homocysteine levels decreased from 12.95 +/- 3.7 to 11.43 +/- 3.6 micromol/L (P < 0.001) and vitamin B-12 levels were unchanged. Flour fortification with folic acid had a moderate lowering effect on homocysteine levels. Given that vitamin B-12 deficiency was more common than folate deficiency, it may be more appropriate to add vitamin B-12 to food, at least in foods for this age group.

Aged↗

Restless legs syndrome and sleep disturbance during pregnancy: the role of folate and iron.

Restless legs syndrome (RLS) is a neurosensory disorder that typically begins in the evening and often prevents a person from falling asleep. It has been associated with iron deficiency anemia and dopaminergic pathways and is often treated with iron infusion or dopamine agonists. The purpose of this secondary analysis of longitudinal data collected on women before, during, and after pregnancy is to document the prevalence of RLS during pregnancy, contrast its effect on sleep and mood state, and explore the role of folate and iron in the expression of RLS, specifically during the third trimester when the syndrome is most distressing. The prevalence increased from 0 during preconception to 23% (n = 7) during the third trimester of pregnancy. Only 1 subject continued to experience RLS after delivery. Compared with those without complaints of restless legs, those with restless legs had low serum ferritin at preconception and significantly lower folate levels during preconception and at each trimester. In addition, time to sleep onset was significantly delayed and depressed mood was significantly higher in the RLS group. Rather than indicators of iron deficiency anemia (serum ferritin, serum iron, and hemoglobin) or pernicious anemia (vitamin B(12)), it was reduced serum folate level that was associated with RLS in this sample of pregnant women. Findings indicate a need to reconsider recommendations about the normal ranges of serum ferritin and serum folate levels during pregnancy to minimize the complaints of restless legs and promote more consolidated sleep and better daytime mood state during pregnancy.

Adult↗