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A prophylactic trial of iron and folic acid supplements in pregnant Burmese women.

Hemoglobin (Hb) concentration, serum iron level, iron binding capacity and blood folate (Lactobacillus casei) activity were determined in 310 unselected pregnant Burmese women. Hb concentration was less than 11 g/dl in 72% of the women; the serum iron level was less than 50 mug/dl in 33%; serum folate activity was less than 3ng/ml in 13%; and red cell folate activity was less than 100 ng/ml in 17% of the women. Ninety-six of the women in our study were randomly divided into four groups, treated from the 22nd to the 25th week of pregnancy until full term with either ferrous sulfate containing 60 mg elemental iron twice daily, 5 mg folic acid twice daily, a combination of both, or a placebo only. At full term, Hb concentration fell in the groups given placebo or folic acid. On the other hand, in the groups given iron alone or iron plus folic acid there was an increase in Hb of 0.4 and 0.7 g/dl, respectively (intergroup difference not statistically significant). Serum iron and blood folate levels fell in the groups not receiving the appropriate hematinic. In spite of deficient serum and red cell folate levels in 30 and 40%, respectively, of the group on iron alone, the mean Hb concentration increased at full term and none of the women had a Hb concentration lower than 10 g/dl. Blood folate levels were lower in the iron-supplemented group than in the placebo group, indicating that iron deficiency does not aggravate the folate nutritional status.

Adolescent↗

Effect of vitamin B12, folate, and dietary supplements on breast carcinoma chemotherapy--induced mucositis and neutropenia.

BACKGROUND: Although patients with malignant disease frequently use dietary supplements, the effects of these agents with regard to chemotherapy are unclear. Therefore, the authors investigated the influence of vitamin B12, folate, and nutritional supplements on chemotherapy-induced toxicity. METHODS: Women with breast carcinoma were asked to complete a questionnaire that recorded their use of dietary supplements. Blood samples were obtained for the assessment of serum vitamin B12 and folate levels before and after the first cycle of chemotherapy and for weekly complete blood counts. Toxicity was evaluated by measuring absolute neutrophil counts and the frequency and severity of oral mucositis. RESULTS: Of the 49 women who submitted questionnaires, 35 (71%) took a combined total of 165 supplements. Compared with patients in a previous study (performed in 1990), patients in the current study had dramatically increased serum folate levels. Initial neutrophil count, but not type of chemotherapy, patient age, or serum vitamin B12 level, was predictive of nadir absolute neutropenia and the decrease from initial neutrophil count to nadir (Nfall). After adjusting for initial neutrophil count, Nfall was found to be lower for women who were taking supplements compared with women who were not taking supplements (P = 0.01) and for women who were taking multivitamins (P = 0.01) or vitamin E (P = 0.03). Women with serum folic acid levels < 20 ng/mL had a smaller decrease in neutrophil count after chemotherapy than did women with higher folate levels (P = 0.04). No significant association between oral mucositis and initial neutrophil count, nadir neutrophil count, Nfall, age, vitamin B12 level, or folate level was found. CONCLUSIONS: The decrease in neutrophil count caused by chemotherapy was ameliorated by dietary supplementation with a multivitamin or vitamin E. In contrast, high serum folate levels were associated with the exacerbation of this decrease in neutrophil count.

Adult↗

Omeprazole therapy causes malabsorption of cyanocobalamin (vitamin B12)

OBJECTIVE: To evaluate protein-bound cyanocobalamin (vitamin B12) absorption before and after omeprazole (Prilosec) therapy in healthy male volunteers. DESIGN: Clinical trial in which each volunteer served as his own control. SETTING: Outpatient department of a university medical center. PARTICIPANTS: Ten healthy, male volunteers 22 to 50 years old. INTERVENTION: Each participant had a modified Schilling test (protein-bound cyanocobalamin) and a gastric analysis, as well as measurements of serum vitamin B12, gastrin, and folate levels. Five patients were then randomly assigned to take either 20 mg or 40 mg of omeprazole daily. After 2 weeks of omeprazole therapy, these tests were repeated. MEASUREMENTS: The modified Schilling test, gastric analysis, serum gastrin level, folate level, and cyanocobalamin level. RESULTS: At the end of the 2-week treatment period, cyanocobalamin absorption decreased from 3.2% to 0.9% (P = 0.031) in participants receiving 20 mg of omeprazole daily. In patients taking 40 mg of omeprazole daily, cyanocobalamin absorption decreased from 3.4% to 0.4% (P < 0.05). CONCLUSIONS: Omeprazole therapy acutely decreased cyanocobalamin absorption in a dose-dependent manner.

Adult↗

Causes of anemia in renal transplant recipients.

Iron-deficiency anemia is one of the major problems encountered in renal transplant recipients. The aim of this retrospective study was to reevaluate the causes of anemia among 100 anemic kidney recipients. Patients with serum creatinine levels greater than 2 mg/dL were excluded from the study. Female patients were considered to be anemic if the hemoglobin was <12 g/dL for males, <13 g/dL. Complete blood count, serum creatinine, serum iron, iron-binding capacity, ferritin, transferrin saturation, erythrocyte folate, and serum vitamin B(12) levels were measured in all patients. Mean hemoglobin value was 10.2 +/- 1.4 g/dL for female and 9.9 +/- 1.3 for male patients, mean corpuscular volume (MCV) 91.3 +/- 4.9 fL. We observed normocytic anemia in 60, macrocytic anemia in 30, and microcytic anemia in 10 patients. A low level of serum folate was observed in 9 (15%) and of vitamin B(12) in 5 (8.8%) of 60 patients with normocytic anemia. Folate deficiency was found in 18 (60%) and vitamin B(12) deficiency in 12 (40%) of 30 patients with macrocytic anemia. All patients with microcytic anemia had iron deficiency. Splenomegaly was seen significantly more often in patients with macrocytic than normocytic anemia (P =.008). Folate and vitamin B(12) deficiency were the major causes of nutritional anemia; oral or parenteral supplementation with these vitamins is likely to cure the anemia in the majority of cases.

Adult↗

Serum folate and vitamin B12 levels in children from Mozambique.

In order to investigate the behaviour of biochemical parameters in children from Mozambique, we have determined the serum levels of folic acid and vitamin B12, two well known markers of nutritional anemia. We have correlated their values with other blood parameters and have evidenced potential interesting relationship between folate content and platelets count.

Adolescent↗

Red blood cell uptake of supplemental folate in patients on anticonvulsant drug therapy.

A group of epileptics (n = 18) and a control group (n = 10) of subjects aged 21-42 y were given 1-mg supplements of folate daily for 1 mo. Anticonvulsant therapy involved phenytoin alone or in combination with phenobarbital. Serum and red blood cell (RBC) folate levels were determined on days 1, 14, and 28. Mean serum and RBC folate levels were greater (p less than 0.05) for the control subjects compared with the epileptic subjects throughout the study. The percent increase in either serum or RBC folate was not different (p greater than 0.05) between the groups. The percent increase in serum folate when expressed as a percent of RBC folate was greater (p less than 0.05) for those epileptics who initially had deficient blood folate levels (serum folate less than 7 nmol/L; RBC folate less than 317 nmol/L) than those who did not. Deficient epileptics may have had an impaired RBC incorporation of circulating (serum) folate compared with nondeficient epileptics.

Adult↗

Folate deficiency in chronic inflammatory bowel diseases.

In a consecutive study of 216 outpatients with chronic inflammatory bowel diseases (CIBD) low serum and erythrocyte folate levels were found in 59% and 26%, respectively. In patients with low folate levels in both serum and erythrocytes, megaloblastic changes in the bone marrow ere found in 67% (29 out of 44). Their folate intakes were borderline. Absorption studies with tritiated folate showed low absorption values on repeated examinations in 23% of the patients with low folate values (9 out of 40), with no relationship to the intake of salazosulphapyridine. In patients with low folate values the reticulocyte count was elevated (related to the dose of salazosulphapyridine), and the 51Cr erythrocyte survival was decreased. It is suggested that folate deficiency in CIBD is of multiple origin: inadequate diet, malabsorption, and chronic drug-induced low-grade haemolysis. The clinical consequence of the findings remains to be evaluated.

Bone Marrow↗

Factors influencing phenytoin-induced gingival enlargement.

AIM: To ascertain the prevalence and severity of phenytoin-induced gingival enlargement (PIGE) as well as the relationship between PIGE and risk factors. METHOD: An outpatient population of patients on phenytoin treatment and attending the epilepsy clinic at Prince Mshiyeni Memorial Hospital (PMMH) in Durban, South Africa, was requested to participate. A structured questionnaire was used to collect data on patients' demographics, social habits (e.g., drinking and smoking), dental and oral hygiene practices and medication history. Gingival enlargement, dental plaque and gingival bleeding was also measured to assess gingival health. Venous blood was collected for serum folate and phenytoin serum levels measurements. A regression analyses was then undertaken to ascertain the association between PIGE and the risk factors. Factors tested for correlation were serum phenytoin and folate levels, age, bacterial plaque, gingival inflammation, toothbrushing, smoking and alcohol consumption. The association between PIGE and the risk factors was assessed either individually, i.e., as a single entity or in combination--multifactorially. RESULTS: Of the 134 patients studied, 62% had PIGE scores > or = 1, while 8% had a PIGE score of zero. With the exception of plaque, which showed a moderate association with PIGE (r=0.4), no other factor on its own was statistically significantly related to PIGE. In the multiple linear regression analysis, factors which on their own did not have a strong influence became more important. Bacterial plaque (p=0.0001), younger age (p=0.01) and higher free serum phenytoin levels (p= 0.03), were associated with PIGE. Although known to be associated with periodontal diseases, smoking and alcohol, (p=0.03 and p=0.04 respectively), appeared to give some protection against PIGE. CONCLUSION: Risk factors associated with PIGE may have a synergistic effect. Bacterial plaque, however, appears the most important determinant of PIGE severity. This latter finding emphasises the importance of instituting a preventive plaque-control programme, particularly in young patients on phenytoin therapy.

Adolescent↗

Megaloblastic anaemia in vegetarian Asians.

Of 27 Asians with a megaloblastic bone marrow, 22 (81%) had nutritional deficiency of vitamin B12 (NMA), while five (19%) had true pernicious anaemia (PA). All the patients were Hindu vegetarians except for a single Muslim who had PA. Dietary intakes of calories, protein, iron, vitamin B12 and folate were below the recommended level in both groups. The PA group had lower levels of serum B12 and higher levels of serum folate than the NMA group. Despite low levels of red cell folate (RCF) in the NMA patients, the abnormality in deoxyuridine (dU) suppression was always corrected by vitamin B12. The dU suppressed value showed a significant inverse relationship to the RCF level. Nutritional deficiency of vitamin B12 is the most common cause of megaloblastic anaemia in Hindu vegetarians but the incidence of true PA is higher than previously thought and may approximate to that of the white population.

Adolescent↗

Observations on the determination of serum and red-cell folate levels by a radiometric assay method.

Our experience with the Bio-Rad "Quanta-Count" folate radioassay kit has revealed very good in-run precision and good day-to-day reproducibility in the assay of both serum and red-cell folate levels. Ascorbic acid is not required as folate preservative if blood samples are frozen within hours after collection. For the determination of red-cell folates, our data clearly show the need for maintenance of a certain level (6-8 gm%) of protein in the assay system. Protein (albumin or folate-free human serum) must be added to the red-cell lysate to compensate for the serum loss resulting from the high dilution factor necessary. In the absence of this added protein, red-cell values are markedly lower. A good correlation exists between red-cell folate values obtained from the assay of washed red cells and from the assay of whole blood with corrections for serum folate levels.

Ascorbic Acid↗

Serum folate and folic acid binding proteins in iron deficiency anaemia.

Serum and red cell folate and folic acid binding protein (FABP) concentrations were determined on 20 iron deficiency anaemic children of both sexes aged 6--12 years. All cases had haemoglobin level less than 12 gm% or haematocrit less than 36% with low serum iron and elevated unsaturated iron binding capacity. Serum folate levels in the anaemic group was not significantly different from that of normal subjects while red cell folate level was significantly lower in the anaemic group. However, all cases had red cell folate levels higher than 100 ng/ml. There was a direct relationship between the haemoglobin concentration and serum folate level. Serum FABP level in the anaemic group was found to be significantly higher than that of normal subjects and showed no correlation with haemoglobin, haematocrit, serum or red cell folate levels. The significance of elevated serum FABP was discussed.

Anemia, Hypochromic↗

Serum folate and chronic disease risk: findings from a cohort of United States adults.

BACKGROUND: Previous studies have suggested that folate may provide protection against various chronic conditions. METHODS: We examined the effect of serum folate concentration on mortality and chronic disease incidence in a nationally representative sample of 3059 adults of the National Health and Nutrition Examination Survey Epidemiologic Follow-up Study who were first examined from 1971 through 1975 and who were followed for about 19 years through 1992. Proportional hazards regression was used to estimate hazard ratios for the lowest quintile of serum folate compared with the highest quintile for selected causes of death and disease incidence. RESULTS: The hazards ratio for all-cause mortality was 1.18 (95% CI: 0.91-1.52); for mortality for diseases of the circulatory system, 1.31 (95% CI: 0.82-2.12); and for cancer mortality, 0.99 (95% CI: 0.46-2.11). The hazard ratio for incidence of diseases of the circulatory system was 1.04 (95% CI: 0.86-1.26); and for cancer incidence, 1.00 (95% CI: 0.61-1.66). The hazards ratio for all-cause mortality was 1.26 (95% CI: 1.01-1.57) for participants with a serum folate of <9.3 nmol/l compared with other participants. CONCLUSIONS: Low levels of serum folate may be associated with mortality from all-causes and cardiovascular disease. However, the study lacked power to adequately examine the association between folate and disease-specific endpoints. Additional studies, using serum and other measures of folate nutritional status, are needed to examine the relationship between folate nutrition and other more specifically defined health outcomes.

Adolescent↗

Major malformations in offspring of women with epilepsy.

BACKGROUND: The offspring of women with epilepsy are at an increased risk of major congenital malformations, but the impact of the various contributing factors remains unresolved. METHOD: In 1980 through 1998, the authors prospectively followed up 970 pregnancies in women with epilepsy at a single maternity clinic. Of their 979 offspring, 740 were exposed to maternal antiepileptic drugs (AED) during the first trimester of pregnancy and 239 were not exposed. Maternal AED levels and serum folate concentrations were measured at the end of the first trimester. Logistic regression analysis was applied to identify factors associated with the occurrence of major malformations in the fetuses and newborns. RESULTS: Major malformations were detected in 28 fetuses (3.8%) exposed to maternal AED and in 2 (0.8%) not exposed (p = 0.02). After logistic regression analysis, the occurrence of major malformations was independently associated with use of carbamazepine (adjusted OR 2.5; 95% CI 1.0 to 6.0), use of valproate (4.1; 1.6 to 11), use of oxcarbazepine (10.8; 1.1 to 106), low serum folate concentration (5.8; 1.3 to 27), and low maternal level of education (3.0; 1.3 to 6.8). Major malformations were not associated with seizures during the first trimester (0.6; 0.1 to 2.9). CONCLUSIONS: Major malformations in the offspring of mothers with epilepsy are associated with use of AED during early pregnancy, and also with low serum folate concentrations and a low level of education.

Abnormalities, Drug-Induced↗

Relation of total homocysteine and lipid levels in children to premature cardiovascular death in male relatives.

We assessed the relative importance of lipid, apo B, lipoprotein(a) [Lp(a)], and total homocysteine (tHcy) levels in children in relation to premature cardiovascular disease in family members. Parents of 381 girls and 375 boys age 8-12 y completed family history questionnaires. Nonfasting serum lipid and lipoproteins and plasma tHcy and cysteine levels were measured in the children. Serum folate and vitamin B12 levels were determined in a random subsample of 23% of the children, who participated in a food frequency interview. Children whose parents reported hypercholesterolemia had higher total and non-HDL cholesterol and apo B levels than the rest, but these levels were not associated with cardiovascular disease. tHcy levels were similar in girls and boys. tHcy was higher in children whose father, grandfather, or uncle died at age < or = 55 y of myocardial infarction or sudden cardiac arrest (n = 42) than in control children [5.92 mumol/L (95% confidence interval [CI] of 5.47-6.36) versus 5.25 mumol/L (95% CI, 5.16-5.34)], also after adjustment for socioeconomic group. Intake and serum levels of vitamin B12 and folate were within recommended or reference ranges. In a stepwise multiple regression analysis, serum folate (negative correlation), plasma creatinine, and sugar intake as percent of dietary energy (positive correlations) were significantly associated with tHcy (multiple r = 0.44, adjusted r2 = 18%; 95% CI, 5-30%). Our data show that a modest elevation in tHcy in children was related to premature cardiovascular death in their male relatives and may partly account for the contribution of family history to risk of cardiovascular disease. tHcy may be modifiable through the diet, even in children with apparently adequate vitamin nutriture.

Age of Onset↗

Effect of incremental doses of folate on homocysteine and metabolically related vitamin concentrations in nondiabetic patients on peritoneal dialysis.

The role of folate supplementation in reducing hyperhomocystinemia in patients on dialysis has been reported, but the optimal dose of folate is still unknown. The aim of the present study was to investigate whether greater than 5 mg/day folate supplementation provides any additional effect on plasma homocysteine (HCY) levels. The study was prospective, open, and had no control group. Of the 64 eligible nondiabetic patients on peritoneal dialysis with hyperhomocystinemia (>20 micromol/L), 56 were given oral folate (5 mg/day) for 3 months. When Hcy did not fall below 20 micromol/L, folate doses were increased by 5 mg every 3 months to up to 15 mg/day. With 5 mg/day supplementation, serum folate concentrations increased above the upper confidence limit in 23 patients and erythrocyte folate concentrations in 27 patients. Hcy levels decreased to less than 15 micromol/L in 6 cases and by more than 50% in 12 cases. Nineteen of the remaining patients were given 10 mg/day folate. After increasing the dose, serum and erythrocyte folate levels rose above the upper detection limit. In one patient, plasma Hcy concentrations decreased to less than 15 micromol/L. Ten patients were given 15 mg/day oral folate for an additional 3 months with no effect on homocystinemia. This study confirms that oral folate supplementation may improve hyperhomocystinemia even in patients on dialysis with normal serum or erythrocyte folate concentrations. In fact, serum and erythrocyte levels cannot predict the effect of supplementation on plasma Hcy levels. However, 5 mg/day folate supplementation normalized Hcy in 10% of cases and reduced Hcy levels in another 21%. Increasing the folate dose to greater than 5 mg/day had a minimal (10 mg/day) or no (15 mg/day) additional effect on Hcy concentrations. Despite the minimal effect of increasing folate doses, given the low cost, the absence of side effects, and the high cardiovascular risk for patients on peritoneal dialysis, a careful attempt to increase the dose of oral folate up to 10 mg/day might be suggested.

Administration, Oral↗

Protein, iron, and folate status of patients prior to and following surgery for morbid obesity.

Food intake recall and biochemical and anthropometric measurements were used to determine protein, iron, and folate nutritional status of 12 patients before and four months after gastric bypass surgery. Post-surgery intake of the nutrients was significantly lower than the Recommended Dietary Allowances. Highest levels of serum folate were observed after surgery, while serum iron levels showed no significant changes. Deficit protein intake, very low creatinine-height index, and significant changes in anthropometrics all indicated the loss of body mass. Serum transferrin levels did not differ significantly, suggesting visceral proteins were intact.

Adult↗

Serum folate, vitamin B12, and homocysteine in major depressive disorder, Part 2: predictors of relapse during the continuation phase of pharmacotherapy.

OBJECTIVE: In the present study, we assessed the relationship between serum folate, vitamin B12, and homocysteine levels on the rate of relapse in outpatients with remitted major depressive disorder (MDD) during a 28-week continuation phase of treatment with fluoxetine. METHOD: Seventy-one outpatients (mean +/- SD age = 40.2 +/- 11.1 years; 56.3% women) with MDD (as assessed with the Structured Clinical Interview for DSM-III-R) who had remitted and who were enrolled in the continuation phase of treatment with fluoxetine had serum folate, vitamin B12, and homocysteine measurements completed at baseline (prior to acute-phase treatment). Patients were followed for 28 weeks of continued treatment with fluoxetine 40 mg/day to monitor for depressive relapse. Folate levels were classified as either low (< or = 2.5 ng/mL) or normal. Vitamin B12 levels were classified as either low (< or = 200 pg/mL) or normal. Homocysteine levels were classified as either elevated (> or = 13.2 micromol/L) or normal. With the use of separate logistic regressions, we then assessed the relationship between folate, vitamin B12, and homocysteine level status and relapse. The study was conducted from November 1992 to January 1999. RESULTS: The presence of low serum folate levels (p =.004), but not low B12 (p >.05) or elevated homocysteine levels (p >.05), was associated with relapse during continuation treatment with fluoxetine. The relapse rates for patients with (N = 7) and without (N = 64) low folate levels were 42.9% versus 3.2%, respectively. CONCLUSION: Low serum folate levels were found to place patients with remitted MDD at risk for depressive relapse during the continuation phase of treatment with fluoxetine.

Adult↗

The effects of blood transfusion on serum ferritin, folic acid, and cobalamin levels.

Thirty patients with anemia of various causes received packed red cell transfusions. To evaluate the influence of blood transfusion on the serum levels of different nutrients, serum ferritin, folate, and cobalamin levels were determined before and 2, 2 to 4, 5 to 7, 8 to 10, and 11 to 14 days after blood transfusion. No significant change was found in these levels before or at any time after blood transfusion. Blood transfusion exerted little effect on the serum levels of ferritin, cobalamin, or folate. Moreover, if the blood for testing was drawn 1 to 14 days after transfusion, nearly all cases of nutritional deficiency anemia could have been diagnosed without the influence of blood transfusion.

Adult↗