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PubMed2002

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↗
PubMed2001

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↗
PubMed2000

Low serum folate concentrations are associated with an excess incidence of acute coronary events: the Kuopio Ischaemic Heart Disease Risk Factor Study.

OBJECTIVE: To test the hypothesis that low serum folate concentrations are associated with an increased risk of acute coronary events in men free of prior coronary heart disease. SETTING: Research Institute of Public Health, University of Kuopio, Kuopio, Finland. DESIGN: Prospective study in a cohort of 734 men aged 46-64 y examined in 1991-1993 as part of the Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD) and followed for 5 y and 3 months. INTERVENTION: Acute coronary events during the follow-up period were obtained by national hospital discharge registry. Baseline serum folate concentrations were measured by radioimmunoassay. RESULTS: During the follow-up, six (2.5%) men with higher serum folate concentrations (highest third>11.3 nmol/1) and 28 (5.7%) men with lower serum folate (two lowest thirds) developed an acute coronary event (P=0.008). In a Cox model adjusting for age, examination years, and plasma lycopene concentration, in men with higher serum folate concentrations the relative risk for an acute coronary event was 0.31 (95% CI 0.11-0.90, P=0.031) when compared with men with lower serum folates. CONCLUSION: This prospective cohort study in middle-aged men from eastern Finland indicates that moderate-to-high levels of serum folate are associated with a greatly reduced incidence of acute coronary events.

Adult↗
PubMed2005

Elevated levels of plasma homocysteine in postmenopausal women in Burkina Faso.

BACKGROUND: Low levels of plasma homocysteine have been found in children and adult populations living in Burkina Faso in association with a low prevalence of coronary heart disease. METHODS: Based on this finding, the levels of plasma homocysteine and other thiols (cysteine, cysteinylglycine, glutathione) in postmenopausal women living in Burkina Faso were evaluated with the aim of investigating whether age and life conditions influence plasma homocysteine and other thiol levels. RESULTS: It was found that in older postmenopausal women the mean level of homocysteine was higher (16.4+/-6.6 micromol/L) than in fertile women (6.8+/-1.2 micromol/L) and that this increase was correlated with cysteine levels (166.6+/-44.6 micromol/L). While the glutathione level in postmenopausal women was lower (3.6+/-2.3 micromol/L) compared with fertile women (7.0+/-1.7 micromol/L), cysteinylglycine levels were within the normal range (29.9+/-9.3 micromol/L). No correlation was found between homocysteine levels and serum folate, vitamin B(12), vitamin B(6), cystatin C and serum creatinine levels. The older the women were, the higher were their plasma homocysteine levels: levels up to 20.2+/-9.1 micromol/L were found in those >70 years old. CONCLUSIONS: The elevated levels of homocysteine in the postmenopausal women of Burkina Faso must be viewed as a characteristic of older age and its metabolic consequences.

Adult↗
PubMed1979

Nutritional anemia: its understanding and control with special reference to the work of the World Health Organization.

Since 1949, the World Health Organization, recognizing the public health importance of nutritional anemia, has sponsored efforts directed towards its understanding and control. During this period, often as a result of the work of the Organization, advances have been made in many areas. Basic understanding of iron, folate and vitamin B12 nutrition, and the various factors which may influence the availability and requirements of these factors, has greatly increased. Surveys in a number of countries have highlighted the widespread prevalence of nutritional anemia, particularly in developing countries. The major factor responsible is a deficiency of iron, whith folate deficiency also playing a role in some population groups, especially in preganant women. There is increasing evidence that anemia adversely affects the health of individuals and may have profound socioeconomic consequences. Control of nutritional anemia is possible by providing the deficient nutrient(s) either as therapeutic supplements or by fortification of commonly used foodstuffs. Some control programs are reviewed and suggestions for further action outlined. The Organization still has an important role to play in this field, encouraging the development of control programs and providing advice and technical assistance ot member countries.

Adolescent↗
PubMed1975

Folic acid deficiency in sickle cell anaemia.

Megaloblastic anaemia responding to folic acid has been reported in a number fo patients with sickle cell anaemia. The incidence of reduced serum and erythrocyte folate levels in such patients remains unclear, however. Serum and erythrocyte folate contents were measured microbiologically in patients with sickle cell anaemia as well as in two control groups with sickle cell trait or normal haemoglobin pattern. Low serum and erythrocyte folate values were significantly more common in 61 sickle-cell patients than in each of the two socio-economically-matched control groups including 61 subjects with Hb AS and 69 blacks with Hb AA. There was no correlation between serum folate and haematocrit or reticulocyte count. The erythrocyte folate, measured before and after removal of reticulocytes, remains a reliable indicator of deficiency of folic acid in sickle-cell patients despite variable degrees of reticulocytes. Folate therapy resulted in higher haematocrits in three of four sickle-cell patients with low serum and low erythrocyte folate values, but in only one of 12 patients with low serum folate and normal erythrocyte folate. These findings are consistent with other observations that folate requirement may be increased in chronic haemolytic disorders and suggest that erythrocyte folate values should be obtained in sickle-cell patients suspected of having folate deficiency.

Adolescent↗
PubMed2004

Folate and homocysteine levels in pregnancy.

This study aims to determine serum folate and plasma homocysteine levels in healthy pregnant women following a live birth and compare them with healthy non-pregnant women. Fifty healthy gravid multiparous women are included in the study and 25 normal non-pregnant female subjects act as controls (group I). The pregnant women are divided into two groups according to interpregnancy interval: group II (six months or less); group III (18-24 months). Venous blood samples are analysed for red blood cell folate and homocysteine, vitamin B12, serum folate and albumin, and serum aminotransferases (ALT and AST). There was a significant decrease in red cell folate and serum folate in group II compared to the control group (P<0.001). Serum vitamin B12 showed no significant difference. Plasma homocysteine and serum albumin showed significant decreases in both groups II and III compared to the control group. (P<0.001) There was significant positive correlation between homocysteine and serum albumin in the three studied groups. (r=0.42, P<0.001; r=0.45, P<0.001; r=0.51, P<0.001, respectively). There was significant negative correlation between red cell folate and homocysteine in the three studied groups. (r=-0.48, P<0.001; r=-0.53, P<0.001; r=-0.49, P<0.001, respectively). Two cases in group II showed signs of intrauterine growth retardation. The results suggest that pregnant females with short interpregnancy intervals are more likely to develop folate deficiency. Educational strategies are required to increase folate awareness among women to promote the benefits of folic acid supplementation. Mandatory folate fortification of foods should be defined and monitored.

Adult↗
PubMed2001

Folate supplementation in peritoneal dialysis patients with normal erythrocyte folate: effect on plasma homocysteine.

The possible role of folate supplementation in reducing hyperhomocysteinemia in dialysis patients has been reported in several recent papers. However, scant data are available for peritoneal dialysis patients; besides, none of these studies investigated either the role of intraerythrocyte folate concentration or the presence of side effects caused by folate administration. Sixty-six peritoneal dialysis patients with hyperhomocysteinemia (>15 micromol/l) and normal folate status (as assessed by erythrocyte folate level >600 nmol/l) were randomly allocated to receive either oral folate (5 mg/day) or no vitamin supplementation. After 2 months of therapy, patients were requested to answer a questionnaire investigating the occurrence of symptoms possibly related to folate supplementation. Twenty-nine treated patients and 30 untreated controls completed the study. In the treated patients, serum and erythrocyte folate increased significantly (p < 0.0001) (respectively from 10.6 +/- 4.9 to 237 +/- 231 nmol/l and from 1,201 +/- 297 to 2,881 +/- 294 nmol/l) to levels at the uppermost limit of detection by laboratory methods. Serum vitamin B(12) levels did not change. Plasma homocysteine levels decreased from 54 +/- 32 to 23 +/- 14 micromol/l after folate supplementation and remained unchanged in the control group. After 4 months of folate therapy, homocysteine concentration was within the normal range in 5 patients (17%) and below 30 micromol/l in the other 21 (72%). Folate therapy resulted in a decrease in homocysteine of more than 50% in 45% of the patients and decrease of more than 20% in a further 38%. No significant symptoms were reported. Thus, serum and erythrocyte folate increase confirms that normal folate levels are inadequate in dialysis patients, even if serum and erythrocyte levels before folate supplementation cannot predict the effect on homocysteine plasma levels.

Anorexia↗
PubMed1983

[Inherited transcobalamin-II-deficiency: clinical, genetic studies and diagnosis using cultured fibroblasts].

A boy born healthy, developed gastrointestinal symptoms (diarrhea, vomiting, ulcerative stomatitis) and megaloblastic anaemia with thrombocytopenia and neutropenia at the age of five weeks. Serum levels of folate and cobalamin were normal, but there was cobalamin-mal absorption. In his serum apo-TC2 was not detectable and immunoreactive total TC2 was very low (10% of normal values). Cultured skin fibroblasts failed to secrete functioning TC2. Pharmacological amounts of parenteral Cyanocobalamin, administered regularly, led to hematological remission and normal development. Interruption of therapy was followed by relapse within a few weeks. A coexisting hypogammaglobulinemia did not respond to cobalamin therapy at the selected dose level. A family investigation of serum TC2 concentrations and the genetic TC2 variants in 7 persons of three generations yielded evidence of autosomal-recessive inheritance of a silent TC2 allele (TC2 QLFL SEA-like). Three persons with heterozygous deficiency were asymptomatic.

Cells, Cultured↗
PubMed1989

[Folate and vitamin B12 deficiency. Characterization of parameters for early diagnosis].

True vitamin B12/folate deficiency is more common than is currently appreciated; it appears in many guises and the classic hematological features of megaloblastic anaemia are often absent. The single most reliable predictor of megaloblastic anaemia is serum vitamin B12/folate concentration, but this determination in a screening program for all patients is difficult in terms of laboratory overload and cost. Early recognition of nutritional anaemias is, however, mandatory and we undertook this study to explore the possibility of identifying, on a demographic basis or because of routine laboratory results, a group of subjects at risk for vitamin B12/folate deficiency. Results obtained in simultaneous radioassay of serum B12 and folate levels and erythrocyte folate concentration in 1.200 hospitalized patients are presented. Coexisting iron deficiency was excluded by ferritin assay. We found no significant difference between males and females and no correlation between serum folate and B12 concentrations and aging. Low serum folic and cobalamin levels were found in 53% of patients with macrocytosis and elevated MCH, even in the absence of anaemia. These observations suggest that increased MCV and MCH may be present before a related anaemia and that serum folate and cobalamin levels must be monitored early in these patients to prevent a deficiency.

Age Factors↗
PubMed2000

Iron and folate supplementation in pregnancy.

BACKGROUND: Anaemia in pregnancy is a major health problem in many developing countries where nutritional deficiency, malaria and other parasitic infections contribute to increased maternal and perinatal mortality and morbidity. OBJECTIVES: The objective of this review was to assess the effects of routine iron and folate supplementation on haematological and biochemical parameters and on pregnancy outcome. SEARCH STRATEGY: The Cochrane Pregnancy and Childbirth Group trials register was searched. Study authors were also contacted. SELECTION CRITERIA: Acceptably controlled trials of routine iron and folate supplementation for pregnant women. DATA COLLECTION AND ANALYSIS: Eligibility and trial quality were assessed by one reviewer. Study authors were contacted for additional information. MAIN RESULTS: Eight trials involving 5449 women were included. Routine supplementation with iron or folate raised or maintained the serum iron and ferritin levels and serum and red cell folate levels. Supplementation resulted in a substantial reduction of women with a haemoglobin level below 10 or 10.5 grams in late pregnancy. Routine supplementation with iron and folate had no detectable effect on any substantive measures of either maternal or fetal outcome. REVIEWER'S CONCLUSIONS: Routine supplementation with iron and folate appears to prevent low haemoglobin at delivery. There is very little information on other outcomes for either mother or baby. There are few data derived from communities where iron and folate deficiency is common and anaemia is a serious health problem.

Anemia↗
PubMed2000

Blood homocysteine and vitamin B levels are not associated with cognitive skills in healthy normally ageing subjects.

Increased plasma total homocysteine (tHcy) levels are a known risk factor for vascular disease and have been reported in association with cognitive impairment of old age. Alternatively, however, increased tHcy levels may simply be an indicator of B vitamin deficiency. We evaluated the relationship between plasma tHcy levels, serum vitamin B12 and folate levels, and the scores at a battery of neuropsychological tests in 54 healthy cognitively normal subjects aged 65 years and over. Hyperhomocysteinemia prevalence (plasma tHcy>15 micromol/L) was about 24%. In univariate analysis, vitamin B12 levels were associated with both verbal memory and visuo-spatial skills, whereas no association was found between psychometric test scores and folate levels or tHcy levels. However, none of the univariate associations of neuropsychological test scores and serum B12 vitamin levels was confirmed when adjusting for age, education and other confounding variables. In conclusion, although a relationship between homocysteine, B vitamins and poor cognitive skills in the elderly is plausible, this study does not suggests that such relationship is biologically important.

Aged↗
PubMed1977

Anemia in the elderly patients with special reference to folic acid status.

To investigate the role of folic acid deficiency in the pathogenesis of anemia in the elderly, hematological examinationa and assays of serum iron, vitamin B12 and folate were carried out on the 86 elderly patients admitted to a home for the aged. Means of red blood cell counts, hemoglobin levels and hematocrit were 385.3 x 10(4)/mm3, 12g/dl and 36%, respectively. These levels were lower than any other report in Japan. Anemia was detected in 23 out of 86 patients. Judging from mean corposcular volume and mean corposcular hemoglobin, most of them were normocytic and normochromic. Although low serum levels of iron and folate were rather frequently observed, the results on hematological examinations suggest that deficiency of these factors alone is not the cause of the anemia in the elderly patients. Rapid clearance of 5-methyl-tetrahydrofolic acid and increased excretion of formiminoglutamic acid after histidine loading were revealed in some of those who had subnormal serum folate levels. Therefore, supplementation of folic acid is recommended to those who had poor dietary intake.

Aged↗
PubMed1997

Nutrition and depression: the role of folate.

A relationship between folate and neuropsychiatric disorders has been inferred from clinical observation and from the enhanced understanding of the role of folate in critical brain metabolic pathways. Depressive symptoms are the most common neuropsychiatric manifestation of folate deficiency. Conversely, borderline low or deficient serum or red blood cell folate levels have been detected in 15-38% of adults diagnosed with depressive disorders. Recently, low folate levels have been linked to poorer antidepressant response to selective serotonin reuptake inhibitors. Factors contributing to low serum folate levels among depressed patients as well as the circumstances under which folate and its derivatives may have a role in antidepressant pharmacotherapy must be further clarified.

Adult↗
PubMed1982

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

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

Adolescent↗
PubMed2000

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

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

Aged↗
PubMed1983

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

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

Adult↗