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Effects of Altered Maternal Folic Acid, Vitamin B12 and Docosahexaenoic Acid on Placental Global DNA Methylation Patterns in Wistar Rats  [PDF]
Asmita Kulkarni,Kamini Dangat,Anvita Kale,Pratiksha Sable,Preeti Chavan-Gautam,Sadhana Joshi
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0017706
Abstract: Potential adverse effects of excess maternal folic acid supplementation on a vegetarian population deficient in vitamin B12 are poorly understood. We have previously shown in a rat model that maternal folic acid supplementation at marginal protein levels reduces brain omega-3 fatty acid levels in the adult offspring. We have also reported that reduced docosahexaenoic acid (DHA) levels may result in diversion of methyl groups towards DNA in the one carbon metabolic pathway ultimately resulting in DNA methylation. This study was designed to examine the effect of normal and excess folic acid in the absence and presence of vitamin B12 deficiency on global methylation patterns in the placenta. Further, the effect of maternal omega 3 fatty acid supplementation on the above vitamin B12 deficient diets was also examined. Our results suggest maternal folic acid supplementation in the absence of vitamin B12 lowers plasma and placental DHA levels (p<0.05) and reduces global DNA methylation levels (p<0.05). When this group was supplemented with omega 3 fatty acids there was an increase in placental DHA levels and subsequently DNA methylation levels revert back to the levels of the control group. Our results suggest for the first time that DHA plays an important role in one carbon metabolism thereby influencing global DNA methylation in the placenta.
Addition of Multimodal Therapy to Standard Management of Steady State Sickle Cell Disease  [PDF]
Iheanyi Okpala,Osita Ezenwosu,Anthony Ikefuna,Augustine Duru,Barth Chukwu,Anazoeze Madu,Theresa Nwagha,Sunday Ocheni,Obike Ibegbulam,Ifeoma Emodi,Uche Anike,Charles Nonyelu,Chukwudi Anigbo,Kingsley Agu,Ifeoma Ajuba,Awele Chukwura,Ogechukwu Ugwu,Uche Ololo
ISRN Hematology , 2013, DOI: 10.1155/2013/236374
Abstract: Most people on folic acid to boost erythropoiesis and prophylactic antimicrobials, the standard management of steady state sickle cell disease (SCD), have unacceptable numbers of crises. The objective of this study was to evaluate the effects of adding multimodal therapy with potassium thiocyanate and omega-3 fatty acids to the standard management of steady state SCD. Pre- and post-treatment numbers of crises and other disease indices were compared in 16 HbSS individuals on folic acid and paludrine after 12 months of adding eicosapentaenoic acid 15?mg/kg/day, docosahexaenoic acid 10?mg/kg/day, and potassium thiocyanate 1-2?mL/day, each milliliter of which contained 250?mg of thiocyanate and 100 micrograms of iodine to prevent hypothyroidism: a possible side-effect due to competitive inhibition of the transport of iodide into the thyroid gland by thiocyanate. Median number of crises reduced from 3/yr to 1/yr ( ). There was no evidence of impaired thyroid function. Plasma level of tri-iodothyronine improved ( ). Steady state full blood count and bilirubin level did not change significantly. The findings suggest that addition of potassium thiocyanate and eicosapentaenoic and docosahexaenoic acids to standard management of steady state SCD reduces the number of crises. This observation needs to be evaluated in larger studies. 1. Introduction The inherited blood condition sickle cell disease (SCD) affects 20–25 million people worldwide and constitutes a major health problem on a global scale. This multiorgan disease is characterised by crescent-shaped (sickle) red blood cells, premature destruction of erythrocytes (haemolysis) resulting in anaemia, susceptibility to infections, and recurrent obstruction of blood vessels which causes tissue ischaemia or infarction—the pathological process underlying the episodes of generalised (ischaemic) pain called vasoocclusive crisis. The period of relative good health between crises is referred to as “steady state.” Sickle cell disease in steady state is currently managed with folic acid to boost production of red blood cells, antimicrobial drugs to prevent infections, and, in severely affected individuals who constitute less than 5% of all patients, either haemopoietic stem cell transplantation or the cytotoxic drug hydroxycarbamide (hydroxyurea) which increases the proportion of foetal haemoglobin inside erythrocytes and so inhibits sickling. The majority of people with SCD who are neither on hydroxyurea nor have had haemopoietic stem cell transplant (over 95%) still have considerable numbers of crises despite taking
The importance of folic acid in woman and child health  [cached]
Nurten BUDAK
Erciyes Medical Journal , 2002,
Abstract: Research indicates that neural tube defects – common birth defects - are related to folic acid deficiency and it is accepted that inadequate folic acid intake of the fetus during embryogenesis is the most important cause. A daily intake of 400 mcg of folic acid by women may prevent the disease. In this article, relationship between folic acid and neural tube defects was summarized and three main approaches for the prevention of folic acid deficiency in women at childbearing age are discussed. These are supplementation and fortification of diet with folic acid in order to increase folic acid intake. Most appropriate approaches to overcome this problem in our country, Turkey, are also discussed.
The primary prevention of birth defects: Multivitamins or folic acid?  [cached]
Czeizel Andrew E.
International Journal of Medical Sciences , 2004,
Abstract: Periconceptional use of folic acid alone or in multivitamin supplements is effective for the primary prevention of neural-tube defects. The Hungarian randomized and two-cohort controlled trials showed that periconceptional multivitamin supplementation can reduce the occurrence of some other structural birth defects, i.e. congenital abnormalities. These findings were supported by many, but not all observational studies. Recently there have been two main debated questions. The first one is whether the use of folic acid alone or folic acid-containing multivitamins is better. The second one is connected with the dilemma of whether high dose of folic acid (e.g. 5 mg) might be better than a daily multivitamin with 0.4 – 0.8 mg of folic acid. Comparison of the pooled data of two Hungarian trials using a multivitamin containing 0.8 mg folic acid and the data of the Hungarian Case-Control Surveillance of Congenital Abnormalities using high dose of folic acid seemed to be appropriate to answer these questions. Multivitamins containing 0.4 – 0.8 mg of folic acid were more effective for the reduction of neural-tube defects than high dose of folic acid. Both multivitamins and folic acid can prevent some part of congenital cardiovascular malformations. Only multivitamins were able to reduce the prevalence at birth of obstructive defects of urinary tract, limb deficiencies and congenital pyloric stenosis. However, folic acid was effective in preventing some part of rectal/anal stenosis/atresia, and high dose of folic acid had effect in preventing some orofacial clefts. The findings are consistent that periconceptional multivitamin and folic acid supplementation reduce the overall occurrence of congenital abnormalities in addition to the demonstrated effect on neural-tube defects.
Pre-natal effects of ethanol and folic acid supplements on the mineralisation of bones in Wistar rat
SS Adebisi
Annals of African Medicine , 2003,
Abstract: Background: Alcohol consumption has long been implicated as capable of inducing folic acid deficiency, in particular at pregnancy; thus inflicting severe skeletal dysgenesis on the conceptuses particularly the mineralisation of the bones. Methods: In the present study, 120 adult female Wistar rats were grouped into three: A, B and C. Group A received 0.79g/kg of 30% ethanol from day 1 to day 10 of gestation, group rats received same dosage of ethanol plus 0.14g/kg folic acid supplements for the same period, and group C served as the control. Bone calcium and phosphorus contents were assessed daily from day 12 to 21 in the conceptuses of the three groups; and also the detailed sequence of calcification in the foetal bones were simultaneously monitored with alizarin red S stains. Results: Low mineral levels and a lag or delay in calcification of about 2 days were recorded in the ethanol rats compare with the folate supplement group; with respect to the control, reparative or ‘catch-up' growth was displayed in the ethanol plus folate treated rats. Conclusion: These observations attest to the toxic consequences of gestational ingestion of ethanol on bone, and the possible alleviating effects of folic acid supplementation.
Folic Acid Consumption in Fars Province, Southern Iran  [cached]
MR Kadivar,F Moradi,SJ Massumi,R Shenavar
Journal of Research in Health Sciences , 2011,
Abstract: Background: Spina bifida and anencephaly are among serious and fatal anomalies in infants that may lead to a 50-70% of reduction in incidence when folic acid is consumed before conception. Methods: In a cross sectional study, 2997 pregnant women were evaluated to determine the level of their knowledge and practice about using folic acid in Fars Province, southern Iran. Results: Eighty percent of pregnant women were familiar with the name of folic acid, 44.7% had the knowledge of its importance during pregnancy, 31.2% and 8% had the knowledge about its effect in reduction of fatal and neurotic anomalies in fetuses, respectively. 86.6% consumed folic acid and 11% used it before awareness of their pregnancy. Conclusion: Regarding the importance of the starting time of folic acid consumption in prevention of neural tube defects, the women should be trained in relation to starting of its consumption before conception.
Estimates of Total Dietary Folic Acid Intake in the Australian Population Following Mandatory Folic Acid Fortification of Bread  [PDF]
Jacinta Dugbaza,Judy Cunningham
Journal of Nutrition and Metabolism , 2012, DOI: 10.1155/2012/492353
Abstract: Mandatory folic acid fortification of wheat flour for making bread was implemented in Australia in September 2009, to improve the dietary folate status of women of child-bearing age, and help reduce the incidence of neural tube defects in the population. This paper presents estimates of folic acid intake in the target population and other subgroups of the Australian population following implementation of the mandatory folic acid fortification standard. In June/July 2010 one hundred samples from seven bread categories were purchased from around the country and individually analysed for the amount of folic acid they contained. A modification to the triple enzyme microbiological method was used to measure folic acid in the individual bread samples. The folic acid analytical values together with national food consumption data were used to generate estimates of the population’s folic acid intake from fortified foods. Food Standards Australia New Zealand’s (FSANZ) custom-built dietary modelling program (DIAMOND) was used for the estimates. The mean amount of folic acid found in white bread was 200?μg/100?g which demonstrated that folic-acid-fortified wheat flour was used to bake the bread. The intake estimates indicated an increase in mean folic acid intake of 159?μg per day for the target group. Other sub-groups of the population also showed increases in estimated mean daily intake of folic acid. 1. Introduction This paper focuses on estimates of the Australian population's (including women of child bearing age, the target group for folic acid fortification) intake of folic acid from voluntary and mandatory fortified foods, and not their intake of total dietary folate from all foods consumed. Folic acid as used in this paper refers to added folic acid in the fortified foods reported as consumed by the respondents of the two national food consumption datasets used for the dietary modelling. Folic acid is the chemical form of folate normally used by the food industry as a fortificant. FSANZ is able to estimate the target population's intake of folic acid because the Australia New Zealand Food Standards Code (the Code) clearly specifies foods that can be fortified under the voluntary and mandatory fortification permissions. Before implementation of the mandatory folic acid fortification standard, specific foods in the Australian market could be fortified under the voluntary folic acid permission outlined in Standard 1.3.2 of the Code. It was therefore possible to identify these foods that individuals reported as consumed and apply a factor accounting for the
Safety and fortification with folic acid in neonatal period  [cached]
Tatiana ?ikavská,Ingrid Brucknerová
Potravinarstvo : Scientific Journal for Food Industry , 2013, DOI: 10.5219/269
Abstract: Folic acid, the essential vitamin, and its active forms are substantial parts of many biochemical processes in the human body. In the period of rapid growth of organism or in cell growth, body’s demands for folate increase. Its impact in neonatal period varies even in premature newborns. Fortification with folic acid and its substitution in the treatment of anaemia are the important parts in the comprehensive care in premature newborns. To determine optimal dose in this group of patients is difficult. The determination of red blood cell folate concentration levels is the most accurate indicator of long-term folate level status in the body. Unmetabolised folic acid in circulation of newborns could have potentially adverse effects. Toxicity of folic acid is not a concern as folate is water-soluble and easily excreted by kidneys when in excess but on the other side growing organism of preterm newborn and disruption of metabolic balance could be potential risks. doi:10.5219/269
Estimates of Total Dietary Folic Acid Intake in the Australian Population Following Mandatory Folic Acid Fortification of Bread  [PDF]
Jacinta Dugbaza,Judy Cunningham
Journal of Nutrition and Metabolism , 2012, DOI: 10.1155/2012/492353
Abstract: Mandatory folic acid fortification of wheat flour for making bread was implemented in Australia in September 2009, to improve the dietary folate status of women of child-bearing age, and help reduce the incidence of neural tube defects in the population. This paper presents estimates of folic acid intake in the target population and other subgroups of the Australian population following implementation of the mandatory folic acid fortification standard. In June/July 2010 one hundred samples from seven bread categories were purchased from around the country and individually analysed for the amount of folic acid they contained. A modification to the triple enzyme microbiological method was used to measure folic acid in the individual bread samples. The folic acid analytical values together with national food consumption data were used to generate estimates of the population’s folic acid intake from fortified foods. Food Standards Australia New Zealand’s (FSANZ) custom-built dietary modelling program (DIAMOND) was used for the estimates. The mean amount of folic acid found in white bread was 200 μg/100 g which demonstrated that folic-acid-fortified wheat flour was used to bake the bread. The intake estimates indicated an increase in mean folic acid intake of 159 μg per day for the target group. Other sub-groups of the population also showed increases in estimated mean daily intake of folic acid.
Effect of Folic Acid Fortification on the Characteristics of Strawberry Yogurt
C.A. Boeneke,K.J. Aryana
Journal of Food Technology , 2013,
Abstract: Development of dairy products with new flavours and health benefits helps the dairy industry increase sales of products as well as provide consumers with products they enjoy. Folic acid is used in the prevention of neural tube defects, heart defects, facial clefts, urinary tract abnormalities and limb deficiencies. The objective of this study, was to determine the effect of different concentrations and stage of addition of folic acid on the physico-chemical and sensory characteristics of strawberry yogurt over a storage period. Strawberry yogurts were manufactured with 0, 25, 50, 75 and 100% of the RDA of 400 g folic acid per 226 mL cup. Folic acid was added before and after pasteurization of yogurt mix. Moisture, ash, fat and protein concentrations were measured at week 1 only. Folic acid concentration was measured at weeks 1 and 5. Viscosity, pH, TA, syneresis, colour and sensory analysis were measured at weeks 1, 3 and 5. No differences in electrophoretic migration patterns were found over the 5 week storage period. Storage time did not affect product viscosity.
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