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PubMed1988

Prophylaxis of folate deficiency in acutely ill patients: results of a randomized clinical trial.

A trial was carried out of prophylaxis of folate deficiency in 105 acutely ill patients immediately following admission to an ICU with evaluation of folate status. These patients were fed either orally or by enteral or parenteral nutrition. Three groups were established regardless of the type of nutrition: - Group 1 received 5 mg/day parenteral folinic acid; - Group 2 received 50 mg/week parenteral folinic acid; - Group 3 received no parenteral folinic acid. Before treatment, 19% of the patients presented very low serum folate levels (less than 2.7 ng/ml). Two of them developed acute folate deficiency with severe hematological disturbances quite reversed with folinic acid. Folate levels were inversely correlated with the severity of the clinical status and were lower in septic and feverish patients. The effect of folinic acid administration was assessed after seven days of treatment: daily administration of 5 mg folinic acid appeared to be the best regimen with normalization of serum folate levels in all cases; results appeared to be better than with 50 mg once weekly. Oral and enteral administration of folate supplies considered to be physiological (300 micrograms/day folic acid) did not appear to be sufficient to normalize in all cases blood folate levels in these acutely ill patients.

Acute Disease↗
PubMed1997

Serum levels of folate and cobalamin in women with recurrent spontaneous abortion.

We evaluated the folate and cobalamin status in 29 non-pregnant women with a history of recurrent spontaneous abortion (three or more consecutive) of unknown aetiology in comparison to 29 healthy nulligravidae of similar reproductive age (controls). Serum concentrations of folate and cobalamin showed no significant differences between the two groups. No correlation between age and vitamin concentrations was found. In the study group there was a significant negative correlation of the number of previous abortions and the concentration of serum folate. Patients with at least four previous miscarriages had significantly lower serum values of folic acid than women with three abortions, but not than controls. The underlying cause of this finding remains unclear. In conclusion, the serum concentrations of folic acid and vitamin B12 are not significantly altered in women with unexplained recurrent spontaneous abortions, and an association between a deficiency of these vitamins and an increased risk of pregnancy loss appears to be questionable in the majority of gestations.

Abortion, Habitual↗
PubMed2002

The common mutations C677T and A1298C in the human methylenetetrahydrofolate reductase gene are associated with hyperhomocysteinemia and cardiovascular disease in hemodialysis patients.

BACKGROUND: Plasma total homocysteine (tHcy) level might be an important risk factor for the development of cardiovascular disease (CVD) in dialysis patients. While both renal failure and mutations of the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene may result in hyperhomocysteinemia and CVD, the distinct roles of the thermolabile MTHFR mutation at nucleotide C677T and the more recently described mutation at nucleotide A1298C have not been evaluated concurrently in patients on hemodialysis. METHODS: A cross-sectional study was performed in 120 maintenance HD patients to determine the prevalence of MTHFR C677T and A1298C mutations and their relative association to hyperhomocysteinemia and CVD. RESULTS: Both mutations, the C677T and the A1298C, were highly prevalent in HD patients with allele frequencies of 0.41 and 0.27, respectively. The prevalence of CVD in HD patients was 55% and its significant risk factors included, in descending order, hyperhomocysteinemia, MTHFR C677T mutation, low serum folate levels, diabetes mellitus, hypertension, and double heterozygote state for both MTHFR mutations (677CT/1298AC). MTHFR A1298C mutation alone and gender were not associated with either hyperhomocysteinemia or increased CVD risk, but the HD patients with homozygotes 1298CC and wild alleles 677CC (677CC/1298CC) have significant increase of tHcy (37.7 +/- 12) and high prevalence of CVD. CONCLUSIONS: Hyperhomocysteinemia, serum folate levels and both C677T and A1298C MTHFR mutations are associated with CVD in HD patients.

Adult↗
PubMed1999

Biological variability and reference intervals for total plasma homocysteine.

We determined the intra-individual biological variability of plasma homocysteine in 20 healthy subjects. The intra-individual coefficient of variation was relatively low (8.3%), indicating that a single measurement can be used to characterize the average homocysteine concentration. A population study measuring plasma homocysteine and serum folate levels was conducted on serum samples collected from 1109 randomly selected, fasting adults with a wide age range. We determined age- and gender-specific central 0.95 intervals and found that subjects in the highest quartile of serum folate had significantly lower (P = 0.0001) mean plasma homocysteine concentrations than did those in the lowest quartile of folate values. An 'ideal' homocysteine reference range, based on targeting those subjects who are likely to be folate replete, is preferable to the population-based range using the central 0.95 interval.

Adult↗
PubMed2006

Effects of dietary calcium intervention on adolescent mothers and newborns: A randomized controlled trial.

OBJECTIVE: To evaluate the effects of dietary calcium (Ca) intervention on adolescent pregnant mothers and their newborns. METHODS: Seventy-two pregnant adolescent mothers were randomized into one of 3 groups: control, orange juice fortified with calcium, and dairy. The orange juice and dairy groups were required to take more than 1,200 mg Ca. Calcium tablets were added for those not able to meet required Ca. Maternal and infant weight, length, and blood pressure (BP) were recorded. Maternal dietary records were evaluated. Mother's blood was drawn for serum Ca, phosphate (P), magnesium (Mg), and vitamin 25-hydroxyvitamin D (D). Cord blood was collected for serum Ca and D. Newborn total body Ca was determined. RESULTS: All mothers were similar in weight, height, and BP. Mothers in the orange juice plus calcium and dairy groups had higher intakes of Ca (1,472 mg and 1,771 mg) than controls (862 mg). One half of the mothers in the orange juice plus calcium group required Ca tablets. Mothers in the dairy group had higher intakes of P, D, and Mg, higher serum folate and D, and higher cord D levels. Mothers in the orange juice plus calcium group had higher serum P but lower serum folate and D. Infants (3,517+/-273 g) in the dairy group were heavier than infants in the control (3,277+/-177 g) and orange juice plus calcium (3,292+/-165 g) groups. Infants in the dairy group had higher total body calcium than control infants. CONCLUSION: Calcium diet supplemented with dairy products during adolescent pregnancy resulted in higher maternal vitamin D and folate serum levels and higher newborn weight and bone mineralization compared with controls.

Adolescent↗
PubMed2002

Endothelial function in healthy younger and older hyperhomocysteinemic subjects.

OBJECTIVES: To compare endothelium-dependent vasomotor response in healthy younger and older subjects without classic cardiovascular risk factors, with high and normal fasting homocysteine (tHcy) levels. DESIGN: We compared endothelium-dependent vasodilatation, using ultrasound, in healthy younger (aged 18-40) and older (> or =70) people with normal (<13 micromol/L) and high (>15 micromol/L) tHcy levels. Exclusion criteria were smoking, personal history of cardiovascular disease, hypertension, chronic diseases, vitamin intake, obesity, abnormal serum lipids levels, and creatinine higher than 130 micromol/L. SETTING: Research laboratory. MEASUREMENTS: In addition to tHcy levels, serum folate and vitamin B12 levels were measured. RESULTS: We studied 17 younger and 12 older hyperhomocysteinemic subjects and respective aged-matched normohocysteinemic subjects. Endothelium-dependent vasodilatation was lower in the hyperhomocysteinemic older people (P <.01) than in all younger subjects and in normohomocysteinemic older people. Serum vitamin B12 levels were higher in younger and older normal controls. Folic acid levels were higher in younger controls and in both older groups. CONCLUSIONS: This study shows an effect of high circulating tHcy on vascular reactivity in older people. Because serum levels of tHcy are associated with nutritional status of vitamin B12 and folic acid, prospective studies are necessary to demonstrate the effects of a long-term nutritional supplementation with vitamins on vascular function and global cardiovascular risk.

Adolescent↗
PubMed2000

Effects of supplementation with folic acid and antioxidant vitamins on homocysteine levels and LDL oxidation in coronary patients.

Hyperhomocysteinemia is an important cardiovascular risk factor. Serum homocysteine levels are specially dependent on folate nutritional status. In addition, the oxidative modification of low-density lipoproteins (LDLs) in the endothelial microenvironment is a damaging factor that can be modified with fat-soluble antioxidant vitamins. The present study was done to assess the effect of a supplementation of folic acid and antioxidant vitamins on homocysteine levels and in vitro LDL oxidation in patients with coronary artery disease. Twenty-three patients with angiographically proven coronary artery disease were given supplements for 15 d consisting of one capsule twice a day of a multivitamin preparation containing 0.65 mg folic acid, 150 mg alpha-tocopherol, 150 mg ascorbic acid, 12.5 mg beta-carotene, and 0.4 microgram vitamin B12. Serum lipids, vitamin and homocysteine levels, and in vitro LDL oxidation were measured before and after the supplementation period. During the supplementation period, serum folate levels increased from 5.0 +/- 1.5 to 10.8 +/- 3.8 ng/mL (P < 0.001), vitamin B12 increased from 317.4 +/- 130.4 to 334.5 +/- 123.8 pg/mL (P < 0.05), and alpha-tocopherol increased from 8.2 +/- 5.1 to 13.7 +/- 7.9 mg/L (P < 0.001). Serum homocysteine levels decreased from 8.7 +/- 4.3 to 6.3 +/- 2.2 mumol/L (P < 0.001). In vitro LDL oxidation decreased from 2.6 +/- 1.1 to 1.6 +/- 1.1 nmol malondialdehyde/mg protein (P < 0.001). In comparing patients with healthy controls, basal levels of folate were lower in the patients, whereas vitamin B12, alpha-tocopherol, and homocysteine levels were similar. No changes in serum lipid levels or body weight were observed. In conclusion, a short-term supplementation with folic acid and antioxidant vitamins can reduce serum homocysteine levels and in vitro LDL oxidation in patients with coronary artery disease.

Antioxidants↗
PubMed1977

Acute and chronic effects of ethanol on fluid transport in the human small intestine.

The effect of acute and chronic administration of ethanol on jejunal and ileal water and electrolyte transport was studied in healthy volunteers by the triple lumen intestinal perfusion technique. The acute perfusion of a glucose-free electrolyte solution containing 2 to 10 g per 100 ml of ethanol in the jejunum or ileum did not cause any significant alterations of sodium or water transport. In contrast, the administration of a folate-deficient diet and ethanol for 2 weeks produced a marked reduction in sodium and water absorption or a small net secretion (control, mean +/-SE: H2O = 0.91 +/- 0.06 ml per min, Na = 130 +/- 8 micronEq per min per 30 cm of intestine versus H2O = -0.13 +/- 0.14 ml per min, Na = -20 +/- 29 micronEq per min per 30 cm, P less than 0.001). These changes were not accompanied by a reduction in serum folate levels. The administration of ethanol with a folate-supplemented diet also produced significant but less pronounced changes in sodium and water transport control: H2O = 1.33 +/- 0.2 ml per min, Na = 185 +/- 34 micronEq per min per 30 cm of intestine versus H2O = 0.48 +/- 0.17 ml per min, Na =65 +/- 16 micronEq per min per 30 cm of intestine, P less than 0.05). From this study it appears that the diarrhea seen in chronic alcoholics can be explained in part by the effect of ethanol on intestinal sodium transport, without any accompanying changes in serum folate levels.

Adult↗
PubMed1998

Oral contraceptives did not affect biochemical folate indexes and homocysteine concentrations in adolescent females.

OBJECTIVE: The study was designed to determine the impact of currently available oral contraceptive agents (OCAs), smoking, and alcohol on biochemical indexes of folate and vitamin B-12 in adolescent females. DESIGN: Subjects completed a 3-day weighed food record along with a detailed lifestyle questionnaire that included questions on OCA, cigarette, and alcohol use. After subjects had fasted overnight, blood samples were collected and analyzed for levels of serum and red blood cell (RBC) folate and serum B-12 and homocysteine. SUBJECTS/SETTINGS: Two hundred twenty-nine adolescent females (aged 14 to 20 years) were recruited from southern Ontario, Canada, by advertisements in newspapers, high schools, universities, shopping malls, adolescent drop-in centers, and community groups. STATISTICAL ANALYSES PERFORMED: Multiple regression models were used to determine the effect of lifestyle factors and covariates (e.g., dietary folate intake, supplemental folate intake, and age) on biochemical indexes. RESULTS: OCA use, alcohol use, and smoking were not significantly associated with lower serum or RBC folate levels, after controlling for folate intake. Serum homocysteine levels were not associated with smoking or OCA use; however, we estimated a 13% higher concentration among alcohol users than nonusers. Smoking and alcohol use were not associated with serum B-12 levels, but OCA use was associated with an estimated 33% lower serum B-12 level than nonuse. APPLICATIONS: Our findings provide no evidence to suggest that currently available OCAs have a negative impact on the folate status of adolescent females; thus, dietary advice designed to specifically encourage an increase in folate intake among adolescents who use OCAs is not supported. In contrast, serum B-12 levels were lower among OCA users than nonusers, which suggests that an interaction between OCA and some vitamins may persist. The suboptimal biochemical folate indexes of smokers may have more to do with the dietary quality of smokers than previously appreciated. Thus, efforts to improve dietary folate intakes of adolescents who smoke may be an important strategy for improving the folate status of young women.

Adolescent↗
PubMed1992

A practical approach to the differential diagnosis and evaluation of the adult patient with macrocytic anemia.

The most common causes of macrocytic anemias in the adults are (1) alcoholism, (2) liver diseases, (3) hemolysis or bleeding, (4) hypothyroidism, (5) folate or vitamin B12 deficiency, (6) exposure to chemotherapy and other drugs, and (7) myelodysplasia. A carefully obtained history and examination with evaluation of a peripheral blood smear and reticulocyte count should be performed in most patients with macrocytosis. Serum vitamin B12 and folate levels, serum thyroid studies, liver function studies, and bone marrow aspirate and biopsy with cytogenetic analysis are frequently required to confirm a diagnosis suspected on the basis of the initial evaluation.

Anemia, Macrocytic↗
PubMed1969

Prognosis in early adult life of coeliac children treated with a gluten-free diet.

Long-term follow up of 57 young adults with coeliac disease diagnosed in childhood showed that 13 had relapsed clinically and had resumed a gluten-free diet Of the remainder, who were taking a normal diet and were apparently normal, 19 had low serum folate levels and 11 low serum iron levels. Pregnancy was found particularly likely to provoke an overt relapse.Only six patients were found to be stunted in height, while the menarche had occurred within the average range. The study also confirmed the very low present-daymortality rate of coeliac disease in childhood, which at the Hospital for Sick Children in London has been 0.4% between 1951 and 1968. In view of the finding that childhood coeliac disease usually persists, even though not causing symptoms, it is suggested that the use of a gluten-free diet should be lifelong.

Adolescent↗
PubMed1975

Serum pyridoxal, folate, and vitamin B12 levels in institutionalized epileptics.

Serum pyridoxal, folate, and vitamin B12 concentrations were measured in 68 institutionalized patients with severe epilepsy. Twenty-five patients had a reduced level of pyridoxal and thirty-three a reduced level of folate. There was no instance of a low serum vitamin B12 although in three patients the levels were found to be abnormally high. Fifteen patients had both a low serum pyridoxal and a low serum folate but there was no significant correlation. All patients had a normal hemoglobin concentration and a normal mean corpuscular volume. There was no close relationship between reduced serum vitamin levels and single or groups of anticonvulsant agents, although the size of the groups was too small to permit a detailed study.

Adolescent↗
PubMed1988

Do antidepressants cause folic acid depletion? A pilot study.

Chronic administration of tricyclic antidepressants is common; folic acid depletion is a potential consequence adversely affecting the mental state. In a pilot study prior to research in the community, serum and red cell folate and serum vitamin B (12) levels were measured in the following elderly psychiatric inpatients: 14 controls (patients not receiving any drugs with known antifolate activity), 11 receiving tricyclic antidepressants, 13 receiving antipsychotics (phenothiazines) and four receiving an anticonvulsant (carbamazepine). Patients on prolonged treatment with carbamazepine or phenothiazine drugs had lower concentrations of folate in serum and erythrocytes compared with controls; the decrease was statistically significant for the effect of phenothiazines on serum folate levels. Tricyclic antidepressants, which are in widespread use in the community, did not cause folate depletion during the first two years of treatment.

Aged↗
PubMed2006

Are inflammatory factors related to retinal vessel caliber? The Beaver Dam Eye Study.

OBJECTIVE: To examine the relationship of systemic markers of inflammation, endothelial dysfunction, and serum folate level to retinal vessel diameter. METHODS: Cross-sectional analyses were completed for data from a random sample of 396 persons aged 50 to 86 years who underwent a baseline examination from 1988 to 1990. Standardized protocols for blood collection and measurement of markers were used. Diameters of arterioles and venules were measured from digitized photographs. Standard univariate and multivariate analyses were performed. RESULTS: While controlling for age, smoking status, diabetes status, serum high-density lipoprotein cholesterol, and hematocrit, wider retinal venular diameters were associated with higher serum high-sensitivity C-reactive protein, interleukin 6, and amyloid A levels. While controlling for age, systolic and diastolic blood pressure, smoking, serum high-density lipoprotein cholesterol level, and gout, smaller arteriolar diameters were associated with higher serum amyloid A and lower serum albumin and folate levels but not high-sensitivity C-reactive protein or interleukin 6 levels. Levels of serum soluble intercellular adhesion molecule-1 and serum soluble E-selectin, markers of endothelial dysfunction, were not associated with retinal arteriolar or venular diameters. CONCLUSIONS: These data show an association of inflammatory markers with larger retinal venular diameter, suggesting that retinal venular caliber may be a marker of systemic inflammation.

Aged↗
PubMed2005

Prevalence of hyperhomocysteinaemia, activated protein C resistance and prothrombin gene mutation in inflammatory bowel disease.

BACKGROUND: Thromboembolic disease is a significant cause of morbidity and mortality in patients with inflammatory bowel disease (IBD). A hypercoagulable state exists in IBD that may involve many components of haemostasis and is closely linked to the disease pathogenesis. It has been proposed that microvascular thrombosis and infarction may trigger the underlying inflammatory process. AIM: To determine the prevalence of prothrombotic factors including hyperhomocysteinaemia, activated protein C (APC) resistance and prothrombin gene mutations as well as vitamin levels in the local IBD population. METHOD: A total of 68 patients (37 men and 31 women) attending the IBD clinic were enrolled into the study. Citrated and ethylenediamine tetraacetic acid blood samples were collected from all patients as well as from 30 controls. Homocysteine levels were measured using the IMX immunoassay. APC resistance was measured using an unmodified activated partial thromboplastin time-based clotting assay. Prothrombin mutations were determined using polymerase chain reaction with the HB-gene factor II detection system. RESULTS: Mean homocysteine levels were significantly higher and APC resistance ratios significantly lower in IBD patients compared with controls. No significant difference was detected between patients with ulcerative colitis or Crohn's disease. There was no significant increase in the incidence of prothrombin mutation in IBD patients. IBD patients had lower vitamin B12 and higher serum folate levels than controls. CONCLUSION: High homocysteine and high serum folate may be associated with low vitamin B12 levels in IBD patients. We did not find any association between a low APC ratio and the factor V Leiden mutation or high factor VIII levels. Both hyperhomocysteinaemia and a low APC ratio may contribute to an increased risk of thromboembolic disease in IBD patients.

Activated Protein C Resistance↗
PubMed2005

Genetic, dietary, and other lifestyle determinants of serum homocysteine levels in young adults in Costa Rica.

OBJECTIVE: Elevated serum total homocysteine (tHcy) is considered an independent risk factor for cardiovascular disease. The objective of this study was to develop the first-ever information on the prevalence of hyperhomocysteinemia and its determinants in a population in Costa Rica. METHODS: A cross-sectional study was conducted to determine serum levels of tHcy, vitamin B(12), folate, and creatinine, as well as the presence of the genotype TT for the methylenetetrahydrofolate reductase (MTHFR) enzyme. Additionally, dietary vitamin intakes and other lifestyle risk factors were assessed. A total of 399 Costa Rican adults from the central valley of the country (where the capital city, San José, is located), aged 20 to 40 years, participated in this study in the year 2000. Analyses of variance were performed for continuous variables, and the chi-square test was used for categorical data. Spearman correlation tests were calculated to determine associations between variables. Three linear regression analyses and one binary logistic model were developed in order to determine the predictors for homocysteine levels in the population studied. RESULTS: The overall prevalence of hyperhomocysteinemia (>15 micromol/L) in the population was 6%, 31% of the population were in the range of 10 to 15 micromol/L, 29% had the genotype TT for the enzyme MTHFR, 18% presented a vitamin B(12) deficiency (<165 pmol/L), and none of the persons had low serum folate levels (<7.0 nmol/L). No significant associations were found between tHcy and age, smoking, consuming alcohol, or dietary vitamin intake. CONCLUSIONS: Only serum vitamin B(12) levels and the genotype TT of the enzyme MTHFR were considered significant predictors of high serum tHcy levels in the Costa Rica population studied.

Adult↗
PubMed1993

[Is it necessary to supplement with folic acid patients in chronic dialysis treated with erythropoietin?].

The need for folate supplementation in patients on chronic hemodialysis receiving erythropoietin (EPO) remains to be determined. Thirty five patients on chronic hemodialysis were studied; of these 10 did not receive EPO nor folic acid, 12 received EPO with folic acid supplementation and the rest only EPO. In these groups, after 9 +/- 2.9 months of treatment, serum folate levels were normal, although higher in those patients supplemented with folate. An additional group of 8 patients, previously supplemented with 2 mg/week of folate, was studied during the first 10 weeks of EPO treatment. In these patients a significant decrease in serum folate was observed from the first to the tenth week (from 18 +/- 29 to 7 +/- 4 ng/ml). Red cell folate had an unexplained raise during the first four weeks and went back to near basal levels during the next weeks. As expected serum ferritin levels decreased at the end of the study period, but remained over 100 ng/ml Red blood cell protoporphyrin remained normal. We thus recommend the measurement of serum and red cell folate levels during the first and tenth weeks of the induction phase of EPO treatment. Also, folic acid supplementation in doses of 2 mg/week is recommended to maintain adequate body stores, specially in extremely anorectic hemodialysis patients or those in whom strict diets without fruits are prescribed.

Adult↗