Folate degradation due to ultraviolet radiation: possible implications for human health and nutrition.

Folate is essential for human health in the prevention of megaloblastic anemia and neural tube birth defects and plays important roles in cardiovascular disease and cancer. Therefore, research into environmental factors that may impact folate status, such as solar ultraviolet (UV) radiation, is of great health significance. In vitro studies have shown that UV radiation can degrade folate and folic acid in human blood and this has been confirmed in several human studies. Despite these findings, there is a dearth of epidemiological research into investigating the relationship between folate status and the links to solar UV exposure.

Perinatal folate supply: relevance in health outcome parameters.

The importance of physiological supply of folate is well recognized in human health; the crucial roles of folate in one-carbon metabolism for physiological DNA synthesis and cell division, as well as in the conversion of homocysteine (Hcy) to methionine, and subsequently, to S-adenosylmethionine, have been convincingly demonstrated. Improved folate status may reduce the risk of macrocytic anaemia, cardiovascular diseases, neuropsychiatric disorders and adverse pregnancy outcomes. Inadequate folate status results in a decrease in the methylation cycle and in increased blood levels of the neurotoxic Hcy. The aim of this review is to provide insight into the influence of folate status on pregnancy health outcomes, and to consider increasing evidence of a link between the extent of genome/epigenome damage and elevated risk for adverse obstetrical endpoints. Pregnant women are at risk for folate insufficiency because of the increased need for folate for rapid fetal growth, placental development and enlargement of the uterus. Inadequate folate status may cause fetal malformations, impaired fetal growth, pre-term delivery and maternal anaemia. Even some diseases of the placenta may arise from folate deficiencies. Fetal growth seems to be vulnerable to maternal folate status during the periconception period, because it has the potential to affect both the closure of the neural tube and several epigenetic mechanisms within the placenta and the fetus. Mainly on the basis of the well recognized link between maternal folate status and fetal neural tube defects, women are advised to receive folic acid supplement during the periconceptional period. Because an adequate folate supply seems to play an important role in the implantation and development of the placenta and in improving endothelial function, folic acid supplementation in the late first trimester or early second trimester might also be beneficial.

Integrated risk-benefit analyses: method development with folic acid as example.

With the introduction of novel and functional foods, there is increasing need for an integrated quantitative risk-benefit assessment of foods. Consensus about a quantitative risk-benefit assessment mirroring the risk assessment approach has been reached during a recent EFSA workshop. In line, we propose a risk-benefit model that consists of: (1) hazard and benefit identification, (2) hazard and benefit characterization through dose-response functions, (3) exposure assessment, and (4) risk-benefit integration. The DALY, which combines morbidity and mortality serves as common health measure. The overall health impact of bread fortified with folic acid in the Netherlands has been simulated. The case study showed how the risk-benefit approach may assist a policy maker in decisions on food fortification programs. It illustrates general problems regarding the data demands, the assumptions and uncertainties. A simple sensitivity analysis showed which assumptions were most crucial. Modest fortification (140 microg/100 g bread) seems reasonable to improve public health but the results hinge on the assumptions one makes for the association between colorectal cancer and high folate intake. A precautious policymaker may very well decide against folic acid fortification. The often debated increase in masked vitamin B(12)-deficiency appears negligible compared to the health gain resulting from prevented neural tube defects.

[Management, prevention and control of megaloblastic anemia, secondary to folic acid deficiency]. / Manejo, prevención y control de la anemia megaloblástica secundaria a déficit de ácido fólico.

Folic acid deficiency is the second most common cause of anemia in our environment, after anemia secondary to iron deficiency. Folates are essential components of human and animal diet. Folic acid is mainly in poliglutamate form, and it is hydrolyzed in the proximal jejunum. It is important to identify adequately the exact vitamin deficiency that causes megaloblastic anemia, because vitamin B12 administration in folate deficiency may correct partially megaloblastic alterations, but administration of folic acid in cobalamin deficient patients improves haematological parameters but deteriorates the neurological syndrome. Main causes of anemia secondary to folate deficiency are inadequate dietetic administration, increased requirements, impaired absorption and pharmacologic interactions. Folates are altered by light, high temperature and by water affinity, which facilitates its elimination by washing or cooking.

Manejo, prevención y control de la anemia megaloblástica secundaria a déficit de ácido fólico / Management, prevention and control of megaloblastic anemia, secondary to folic acid deficiency

La deficiencia de ácido fólico es la causa más frecuente de anemia en nuestro medio, después del síndrome anémico de origen ferropénico. Los folatos son componentes esenciales de la dieta humana y animal. En los alimentos el ácido fólico se encuentran principalmente en forma de poliglutamatos, formas que luego son hidrolizadas en el intestino delgado a nivel de yeyuno proximal. Es importante definir con exactitud el defecto vitamínico causante de la anemia megaloblástica, puesto que, la administración de vitamina B12 a pacientes con deficiencia de folatos puede corregir parcialmente las alteraciones megaloblásticas, sin embargo, la administración de ácido fólico a pacientes con deficiencia de cobalamina induce mejoría hematológica, pero empeora el cuadro neurológico. Las principales causas de anemia por deficiencia de folatos son un aporte dietético insuficiente, un aumento de los requerimientos, defectos de su absorción o interacción con fármacos. Los folatos, pueden verse perjudicados por la sensibilidad a la luz y a las altas temperaturas así como por su alta afinidad por el agua, lo que facilita su eliminación por lavado o cocción (AU)

Folic acid deficiency is the second most common cause of anemia in our environment, after anemia secondary to iron deficiency. Folates are essential components of human and animal diet. Folic acid is mainly in poliglutamate form, and it is hydrolyzed in the proximal jejunum. It is important to identify adequately the exact vitamin deficiency that causes megaloblastic anemia, because vitamin B12 administration in folate deficiency may correct partially megaloblasticalterations, but administration of folic acid in cobalamin deficient patients improves haematological parameters but deteriorates the neurological syndrome. Main causes of anemia secondary to folate deficiency are inadequate dietetic administration, increased requirements, impaired absorption and pharmacologic interactions. Folates are altered by light, high temperature and by water affinity, which facilitates its elimination by washing or cooking (AU)

Manejo, prevención y control de la anemia perniciosa / Management, prevention and control of pernicious anemia

La anemia perniciosa es la causa más frecuente de anemia megaloblástica en nuestro medio y es consecuencia de una deficiencia de vitamina B12 debido a su vez a la disminución o ausencia de factor intrínseco (FI) por atrofia de la mucosa gástrica o por destrucción autoinmune de las células parietales productoras de éste. Ante la existencia de una atrofia gástrica intensa, se origina un descenso en la producción de ácido y FI y una posterior alteración en la absorción de vitamina B12. En un 50% de los casos se asocia a anticuerpos anti FI, cuya presencia en otras enfermedades auto-inmunes es excepcional. En pacientes con anemia perniciosa la determinación de anticuerpos anti FI tiene una alta especificidad (95%), sin embargo, la determinación de anticuerpos anticélulas parietales cuentan con una especificidad baja. El tratamiento de elección es la administración de B12 intramuscularmente. La pauta consiste en administrar 1 mg. de Vitamina B12 diariamente durante una semana, posteriormente semanal durante un mes y después cada 2-3 meses de por vida (AU)

Pernicious anemia is the most frequent cause of megaloblastic anemia in our area, and it is the result of a vitamin B12 deficiency due, itself, to the de-crease or absence of intrinsic factor (IF) because of gastric mucosa atrophy or autoimmune destruction of IF-producing parietal cells. With the existence of a severe gastric atrophy, there is a decrease in acid and IF production and a further change in vitamin B12 absorption. Fifty percent of the cases are associated to anti-IF antibodies, which presence in other autoimmune diseases is exceptional. In patients with pernicious anemia, measurement of anti-IF antibodies has high specificity (95%); however, measurement of anti-parietal cells antibodies has low specificity. The first-choice treatment is adminis-tration of vitamin B12 intramuscularly. The regimen is the administration of 1 mg of vitamin B12 daily for one week, weekly thereafter for one month and, then, every 2-3 months for life (AU)

High prevalence of folic acid and vitamin B12 deficiencies in infants, children, adolescents and pregnant women in Venezuela.

BACKGROUND: There is increased worldwide concern about the consequences of folic acid and vitamin B12 deficiencies on health, which include megaloblastic anemia, neural tube defects and cardiovascular disease. OBJECTIVE: This study intended to determine the prevalence of folic acid and vitamin B12 deficiencies in vulnerable groups in labor and poor socioeconomic strata of the Venezuelan population. METHODS: A total of 5658 serum samples were processed to determine folic acid and vitamin B12 concentrations. The study involved three surveys performed during 2001-2002 and included infants, children, adolescents and pregnant women from labor and poor socioeconomic strata of the population. The method used was a radio immunoassay designed for the simultaneous measurement of serum folic acid and vitamin B12. RESULTS: The prevalence of folic acid deficiency was higher than 30% for all groups studied, reaching 81.79% in adolescents. Vitamin B12 deficiency was 11.4% in samples collected nationwide, but there was also a similar prevalence of high serum levels. The prevalence of folic acid and vitamin B12 deficiencies in pregnant women reached 36.32 and 61.34%, respectively. CONCLUSION: This work shows that there is a high prevalence of folic acid deficiency, especially in women of reproductive age, pregnant adolescents and in the whole population studied in Vargas state. This situation requires immediate intervention as supplementation or food fortification programs.

Anaemias of oral significance

Anaemia is not a disease in itself. It is a sign of a single or multiple diseases. Anaemia is said to exist when the haemoglobin concentration is below normal for the age and sex of an individual. The synthesis and normal circulatory level of haemoglobin in any given individual depend on factors such as an adequate supply of haemopoietic nutrients, normal functioning of bone marrow, and proper utilization of haemoglobin. Based on these factors anemia can be broadly grouped into three categories: 1. Anaemia due to lack of haemopoietic nutrients (nutritional anemia) 2. Anaemia due to bone marrow dysfunction (aplastic anaemia) 3. Anaemia due to excessive breakdown of red blood cells (haemolytic anaemia) (AU)

Pregnancy- and lactation-related folate deficiency in South Africa--a case for folate food fortification.

OBJECTIVE: Characterisation of patients presenting with megaloblastic anaemia according to clinical, sociological, haematological and aetiological aspects of their disease, and use of these findings to increase awareness among clinicians and to make recommendations regarding changes in national health policy. METHODS: This study included 104 patients presenting with megaloblastic anaemia to a large referral hospital over a 1-year period. Data were collected and analysed in terms of age, gender, parity, gravidity, duration of lactation, socio-economic status, geographical origins, diet, previous haematinic treatment, clinical presentation and haematological measurements. RESULTS: The most common cause of megaloblastic anaemia was pernicious anaemia or probable pernicious anaemia (50%), followed by pregnancy- and lactation-related folate deficiency (32%); of these patients, the majority (28) presented postpartum while lactating; 5 patients were in the immediate puerperal period of 6 weeks, and a further 16 were seen during the first year and 7 during the second year following delivery. Only 4 patients were pregnant, and it is noteworthy that 2 of these were still lactating at 34 weeks' gestation. CONCLUSION: Pregnancy- and lactation-related folate deficiency up to 2 years after delivery remains a common cause of megaloblastic anaemia in South Africa. Certain communities in rural South Africa have recently been shown to have high incidences of both neural tube defects and folate deficiency. The fortification of a staple food (e.g. maize or flour) with folic acid is feasible, inexpensive, safe and likely to be beneficial. This practice should reduce the prevalences of megaloblastic anaemia in fertile women, neural tube defects, other congenital abnormalities, intra-uterine growth retardation, prematurity and possibly cardiovascular disease. There is urgent need for a national policy in this regard.

Megaloblastic anaemia in Zimbabwe. II: Diagnostic significance of red cell indices in.

Studies of red cell indices viz: Rbc count, Hb, Hct ratio, MCV, MCH and MCHC were carried out in normal subjects (n = 62) and in patients with: B12 deficiency (n = 34); folate deficiency (n = 17); and B12 and folate deficiency (n = 18). Although these red cell parameters were diagnostically useful (2P less than 5 x 10(-3)) in distinguishing the patients' groups from the control group; they showed no ability to distinguish the deficient groups from each other. However, their practical and diagnostic significance as screening tests in the local environs is briefly highlighted.

Bone marrow status of anaemic pregnant women on supplemental iron and folic acid in a Nigerian community.

The bone marrow status of 31 consecutive pregnant women who had been on supplemental oral iron and folic acid since early pregnancy at the University of Benin Teaching Hospital was assessed later in pregnancy to test the efficacy of oral iron and folic acid in preventing iron deficiency and/or megaloblastic anaemia in our community. Only those pregnant patients with haemoglobin genotype AA or AS took part in the study. Nobody was excluded except those with CC or SC. 96.77% (30 out of 31 patients) had iron deficiency with no stainable iron in the bone marrow. 35.4% (11 out of 31 patients) had megaloblastic changes in the bone marrow. 32.2% (10 out of 31 patients) had a combined iron deficiency and megaloblastic anaemia while only one out of 31 patients (3.23%) had megaloblastic anaemia without concurrent iron deficiency. 60.4% (20 out of 31 patients) had iron deficiency alone without concomitant megaloblastic changes in marrow. The bone marrow in all the patients were normal in other respects except with regards to iron-deficiency and/or megaloblastic status. The significance of this high incidence of iron-deficiency and/or megaloblastic anaemia in patients already on routine pre-natal drugs is discussed.

Folic acid supplementation in low birth weight infants.

Low birth weight infants (246) entered a trial to folic acid supplementation from 3 weeks to 12 months of age. The folic acid group had significantly higher mean hemoglobin levels at 6 and 9 months of age but the differences were only about 0.5 gm/dl, there was no significant difference in hematocrit, and in both groups of infants the mean hemoglobin levels were higher than those of normal birth weight infants. The differences in hemoglobin, although statistically significant, are of uncertain clinical significance. Median red cell folate levels remained within the normal adult range in both groups of infants. A minority of infants in the untreated group had low red cell folate levels but this was usually temporary, corrected by dietary folate, and not associated with low hemoglobin. Weight gain was not affected by folic acid supplementation. The infants in this trial were fed with a milk preparation containing 3.5 microgram/100 ml of folic acid which is a similar concentration to that of human milk and we recommend that the folate content of milks fed to low birth weight infants should not fall below this level. We do not have sufficient grounds to recommend routine folic acid supplements for all low birth weight infants throughout the first year of life but there is a possibility that their folate intake may sometimes be suboptimal.