Folate and Vitamin B12 Function

The history of folic acid.

Vitamin B₁₂Deficiency and Depression in the Elderly

After completing this article, readers should be able to:Birth defects are the leading cause of infant mortality and a major contributor to heightened morbidity in the United states. The basic definition of a birth defect is a structural abnormality present at birth. Infant mortality attributable to birth defects has not declined as rapidly as overall infant mortality; from 1968 to 1995, the proportion of infant mortality due to birth defects increased from 14.5% to 22.2%. It has been estimated that approximately 20% to 25% of all birth defects are due to gene mutations, 5% to 10% to chromosomal abnormalities, and another 5% to 10% to exposure to a known teratogenic agent (such as prescription drugs, chemicals, or radiation)or a maternal factor. Together, these percentages account for only 30% to 40% of birth defects, leaving the etiology of more than 50%unexplained. It has been speculated that environmental factors account for no more than 10% of all congenital anomalies. Genetic factors are responsible for 30% of pediatric hospital admissions.Birth defects rank somewhere between second and fifth among causes of death in children younger than 1 year of age; 3% to 4% of infants in their first year of life are diagnosed as having major birth defects. Of the 120,000 to 150,000 infants born with serious birth defects each year, approximately 6,000 die during their first 28 days of life and another 2,000 die before reaching their first birthdays.In an aggregate analysis of the expense of illness in the United States, congenital abnormalities as a group was estimated to cost$6.3 billion in 1980 or 1.4% of the total cost of illness. This estimate did not include nonmedical direct costs, such as special education and developmental services. Although recent advances in medical technology have increased the chances of survival for children who have birth defects and disabilities, the quality of life for most of these children remains compromised. The economic cost of medical conditions such as birth defects often is discussed without a full understanding of how these conditions affect the lives of infants and families.Because estimates of the cost per new case of birth defects represent the savings from preventing a case,an incidence-based approach enables assessment of the value of prevention strategies. This type of approach was used to estimate the cost of illness for some of the major, most clinically important structural birth defects in the United States. This report used data from a California birth defect monitoring program (adjusted to provide national estimates) and national data to estimate the costs of major structural birth defects occurring in the United States during 1992 (Table 1). The birth defects were selected based on their clinical significance and broad representation of the organ systemThese findings are subject to at least four limitations. First,California data used to estimate incidence rates and treatment costs may not be representative of the United States;total costs per case may vary from state to state. Second, the contribution of time and effort by family members to the provision of care were not estimated and may be substantial for some cases. Third, the psychological costs of these types of illness, which may exceed traditional human capital costs, were not included. For these and other reasons, the use of the human capital approach underestimates what the public is willing to pay to prevent these conditions. Finally, excess medical and educational costs probably were underestimated for some conditions because they could not be ascertained completely. If all of the approximately 120,000 to 150,000 infants born each year in the United States who have serious birth defects had been included in this analysis, the economic costs would have been higher.NTDs are among the most serious and common birth defects to cause infant mortality, morbidity, and disability in the United States. Each year, approximately 4,000 births that involve NTDs as well as other defects result in miscarriage or stillbirth. There are several forms of NTDs, and they vary widely in severity. The birth prevalence of these conditions has declined substantially over the past 60 years due to better medical care. NTDs are reported in 3.6 to 4.6/10,000 live births in the United States. These rates underestimate true incidence,however, because affected pregnancies may be spontaneously or electively aborted and because not all cases are detected and reported at birth. Population-based active surveillance programs that include prenatal diagnosis have reported NTD rates of 7.2 to 15.6/10,000 liveborn and stillborn infants. Women in the United States who have had a pregnancy resulting in an infant or fetus who has an NTD have a 2% to 3% risk for having another pregnancy resulting in a similarly affected infant or fetus.Spina bifida is an inclusive name for various conditions characterized by incomplete fusion of the vertebral arches with a protruding sac that contains meninges, spinal cord, or nerve roots that cause permanent damage to the spinal cord and spinal nerves. It is a complicated and common birth defect that can affect pregnancy without warning. Results of prenatal examinations suggest that affected fetuses exhibit leg movement until the third trimester but become paralyzed later in pregnancy, several months after the initial spinal cord defect occurs. The Centers for Disease Control and Prevention (CDC) estimates that 300,000 to 400,000 infants are born each year with spina bifida worldwide. In the United States,approximately 2,500 infants are born annually with spina bifida and anencephaly, and an estimated 1,500 fetuses affected by these birth defects are aborted.Based on 1992 cohort data, the estimated lifetime cost of spinal bifida is $294,000 per case. Spina bifida can range from mild (spina bifida occulta) to severe(myelomeningocele). Depending on the pattern and level of spinal cord involvement, the resultant deficit can include a lifelong handicap due to infectious complications, motor and sensory paraplegia, bladder and bowel incontinence, Arnold-Chiari malformations, and hydrocephalous.Unlike spina bifada, in which 80%to 90% of infants survive into adulthood, anencephaly is a lethal malformation characterized by the absence of the cranial vault and the cerebral hemisphere that usually results in stillbirth or death within hours or days. Fifty percent of anencephalic fetuses are aborted spontaneously, but if pregnancy goes to term, the infants quickly succumb,showing only slow, stereotyped movements and frequent decerebrate posturing. The incidence of anencephaly is 1/1,000 live births and is responsible for about 50% of all NTDs.Encephalocele is a rare congenital defect of the skull that results in herniation of meninges and brain tissue. It is seen most commonly in the occipital region, where it may be associated with other anomalies,such as brainstem and skull base deformities and hydrocephalous. The incidence of occipital encephalocele is 1/10,000 live births. Most encephaloceles are detected in children shortly after birth, and the outcome relates to the position of the defect and to the associated anomalies. The primitive nervous system begins as a flat neural plate 2 weeks after conception, which becomes indented by a longitudinal groove at 20 days,with neural folds on the flanks. These folds begin to fuse in the midline, forming a cylinder in the middle of the plate. In a zipper fashion, this dorsal closure is promulgated rostally and caudally, resulting in a tubular structure with an open anterior and posterior aperture. At 26 days, the anterior aperture closes,followed at 29 days by the posterior aperture. Factors necessary for formation of the neural tube are intrinsic in the neural ectoderm and adjacent mesoderm. A teratologic insult in embryogenesis timed to interfere with the closure of the anterior aperture will result in anencephalus. Failure of the posterior aperture to close results in an exposed spinal cord, which is recognized later as spina bifida. In broad terms, NTDs result from incomplete neurulation and refer to a wide spectrum of congenital malformations in which separations of the midline vertebral and cranial elements are the common feature,but they usually are taken to mean anencephalus, spina bifida, and encephalocele.Despite considerable progress having been made in understanding NTDs, they remain the most common serious birth defect, and the etiology of most cases still is unknown. It is accepted that there is a genetic-environmental interaction in the causation of NTDs. Genetic and epidemiologic studies have suggested high-risk groups: those who have a past history of NTDs; a maternal age of less than 20 or more than 35 years; parity (primipara and grand multipara); and low socioeconomic status with gross nutritional deficiency and inadequate antenatal care.Several clinical and epidemiologic studies have reported various teratogens that produce NTDs in offspring, including radiation;maternal hyperthermia such as prolonged high fever; exposure to heat and hot-tub use; hypo- and hypervitaminosis A; maternal viral infections such as rubella, toxoplasma, and cytomegalovirus; and drugs such as aminopterin, pyrimethamine,trimethoprim, triamterane,sulfasalazine, methotrexate, anticonvulsants(eg, valproic acid and carbamazepine),aliphatic nitrites, phenothiazines, cyclophosphamide,and cyanide. Teratogens cause NTDs by acting as folic acid antagonists or by being associated with inadequate folic acid availability to the embryo.A number of environmental agents also have been hypothesized as etiologic, particularly dietary agents such as soft water, blighted potatoes, nitrite-cured corn beef,canned peas treated with magnesium salts, effluent from factories, and zinc deficiency. However, none of these factors has been proved scientifically to be linked with NTDs.Certain occupations such as male painters, female agricultural workers, and male welders have been associated with an increased risk of NTDs in offspring. Also, several studies suggested that compared with women of normal weight,women who are extremely obese before pregnancy have a significantly increased risk of having an infant who has NTDs and several other malformations, such as central nervous system, great vessel, ventral wall, or other intestinal defects.Mildly elevated maternal plasma homocysteine (Hcy) levels recently have been observed in some pregnancies that resulted in NTDs and other birth defects. In the past 2 decades, research has shown mild hyperhomocysteinemia to be linked to an increased risk of premature atherosclerosis, pregnancies complicated by NTDs, early pregnancy loss, and venous thrombosis. Plasma Hcy is governed by both genetic and nutritional factors. A lack of B vitamins (folic acid), mutation of the 5,10-methylenetetrahydrofolate reductase genes, or a combination of the two can explain elevated Hcy levels in blood plasma. Genetic mutations were found on the first chromosome (677 C T and 1298 A–C) and can explain up to 50% of the protective effect of folic acid against NTDs. A personal or family history of a pregnancy affected by an NTD is associated with an increased risk of having an affected pregnancy, as is maternal type 1 diabetes, but about 90% to 95% of cases occur in the absence of any positive history. Infants of women who have type 1 diabetes have a 1% to 2% risk of NTDs. NTDs are seen more frequently in certain racial/ethnic groups, particularly Hispanics and Caucasians of European extraction,and are less common among Ashkenazi Jews, most Asians, and African-Americans. NTDs also appear to occur more frequently in association with fetal alcohol syndrome. Folic acid supplementation is not known to prevent NTDs or other teratogenic effects of alcohol on the embryo and fetuses of alcoholic women. The primary goal for such women is to avoid excessive alcohol ingestion during pregnancy. Women who have a folic acid deficiency because of intestinal disorders (such as celiac disease,small intestine malabsorption, or intestinal bypass) and those who have epilepsy and are using certain anticonvulsants may be at greater risk for having offspring who have NTDs. Infants of women treated with valproic acid and carbamazepine during pregnancy have an estimated 1% to 2% and 1% risk for spina bifida in offspring,respectively. It seems prudent to determine whether women who have epilepsy and are planning a pregnancy have a folic acid deficiency. It is not known, however, whether folic acid supplementation would decrease the risk of NTDs in the offspring of these women.Thirty years ago, it was suggested that maternal intake of certain vitamins during pregnancy affected the incidence of serious fetal malformations. Subsequent research has revealed that folate (folic acid), a B vitamin, plays a crucial role in the development of the central nervous system during the early weeks of gestation, which generally is before pregnancy is confirmed. In a significant number of embryos, an inadequate supply of folate at this time leads to failure of the primitive neural tube to close and differentiate normally, resulting in NTDs. Numerous studies have confirmed the importance of an adequate intake of folate during the weeks just before and after conception. Randomized placebo-controlled trials and nonrandomized controlled trials in pregnant women who had a prior pregnancy affected by an NTD have demonstrated that folic acid supplements substantially reduce the risk of recurrent NTDs.It has been suspected that diet has a role in the causation of NTDs. The possibility that folic acid might be involved was raised in 1964 by Hibbard. In 1980 and 1981, the results of two other interventional studies were published in which vitamin supplementation was instituted around the time of conception among women who already had had a child who had an NTD. In the first study, which was not randomized,participating women were given a mixture of eight vitamins that included folic acid (0.36 mg/d), with women who already were pregnant or who had declined to take part in the study serving as controls. The risk of recurrence in the supplemented group was about one-seventh that of the group who received no supplements. The second study was a small randomized trial of folic acid supplementation alone (4 mg/d). It yielded inconclusive results when analyzed according to randomly allocated treatment group (so avoiding bias), but when analyzed after transferring to the control group those women in the folic acid group who did not take their capsules (ie, ignoring the randomization and so introducing the possibility of bias), the supplemented women had a significantly lower risk.To avoid bias, an international multicenter, double-blind,randomized British Medical Research Council (MRC) prevention trial was initiated in July 1983. Conducted at 33 centers (17 in the United Kingdom and 16 in six other countries), it was designed to determine whether supplementation with 4 mg folic acid(one of the vitamins in the B group)or a mixture of seven other vitamins(A, D, B1, B2, B6, C, and nicotinamide) around the time of conception could prevent NTDs. A total of 1,817 women who had previous pregnancies affected by an NTD that was not associated with the autosomal recessive disorder were eligible for the study if they were planning another pregnancy and were not already taking vitamin supplements. Women who had epilepsy were excluded in case the folic acid supplementation adversely affected their treatment. The effect of both forms of supplementation was investigated by use of a factorial study design.The women were allocated randomly to one of four groups—folic acid, other vitamins, both, or neither. The four groups were similar with respect to age and the occurrence of previous pregnancies. Women were asked to take a single capsule each day from the date of randomization until 12 weeks of pregnancy (estimated from the first day of the last menstrual period). Of 1,817 women, 1,195 had a completed pregnancy in which the fetus or infant was known to have or not have an NTD. A total of 27 infants had known NTDs, with 6 in the folic acid groups and 21 in the two other groups. Sequential analysis showed a 72% protective effect(relative risk, 0.28; 95% confidence interval [CI], 0.12 to 0.71). The other vitamins showed no significant protective effect (relative risk, 0.80;95% CI, 0.32 to 1.72). There was no demonstrable harm from the folic acid supplementation, although the ability of the study to detect rare or slight adverse effects was limited. The study result is unlikely to be due to chance, and the randomized double-blind design excluded bias as an explanation. The results also demonstrate that folic acid, rather than any other vitamins, is responsible for the preventive effect.Another significant study was a randomized, double-blind, controlled trial from Hungary that enrolled 4,753 women planning pregnancy. Results documented that the first occurrences of NTDs could be prevented significantly by administering periconceptional multivitamin supplements daily that included 0.8 mg of folic acid. This study was extended to examine the effect of supplementation on other congenital abnormalities. Periconceptional administration of multivitamin supplements reduced NTDs by 50% and the incidence of other major genetic congenital abnormalities, such as cardiovascular anomalies, defects of the urinary tract, congenital hypertrophic pyloric stenosis, and congenital limb defects.Six observational studies of dietary folate or the use of folic acid and other vitamin supplements and NTDs and one nonrandomized folic acid supplementation study have been published. All but one showed an association, but all may have suffered from selection bias, and none could identify folic acid specifically as the responsible vitamin.Results of the British MRC randomized, controlled trial proved that folic acid can prevent spina bifida and anencephaly and provided critical scientific data on which to base public health policy for preventing these birth defects. Within weeks of publication of this study, the CDC developed and issued guidelines for women who had had a pregnancy affected by spina bifida or anencephaly. In September 1992, the United States Public Health Service(USPHS) issued the recommendation that all women of child-bearing age who are capable of becoming pregnant should be offered treatment with 0.4 mg of folic acid daily to reduce their risk of having an NTD-affected pregnancy. For women who already have had an NTD-affected pregnancy, the USPHS also administration of of folic acid day 1 to months prior to the conception and the first months of during the past years it that who not take folic acid supplements are at increased risk for folate which has been to cause spina bifida and anencephaly and has been associated with an increased risk for cardiovascular The that of folic acid during the periconceptional can reduce the number of NTDs has been for several data are from randomized control nonrandomized interventional and observational studies (Table Research on adverse effects from folic acid supplementation is limited. that folic acid supplements in daily of 1 to mg can the of vitamin diagnosis and treatment and leading to permanent is to interventional studies and case in also has been reported in some folic acid of less than 1 but the is not particularly at lower this has been as one to avoid supplementation or with folic acid. However, it also has been that it is to and the deficiency diagnosis at the risk of an NTD. of folate and levels and high Hcy levels with NTDs, that a for these defects may be an abnormality in a and If these results are supplementation with both folic acid and may be to prevent NTDs. This could reduce the for adverse effects of folate supplementation in in of the trials of pregnant women reported serious adverse effects associated with folic acid In the infants born to women who received a with folic acid did not in mortality, and and total serious or disorders at to 21 of age from those born to women only The of and was significantly increased among those received but more affected infants in the supplemented group also had a family history of these This also may be a effect due to the number of A group of children born to women who had taken daily mg of folic acid to prevent NTD revealed no adverse effects on developmental status at age to years compared with the There were significant in but whether this was attributable to folic acid or to other causes to having had a affected is of the randomized and nonrandomized controlled trials showed that among women at high risk of having a child who had an who received 4 of folic acid had approximately cases of NTD-affected offspring than those who received no supplements. interventional and studies also this the of this is 30% of NTDs appear to folic acid with the a of The administration of to the can such defects, but this not occur in The by which this is is to be by the of the acid in the which a folate did not reduce NTDs, but The has been to determine the agents that prevent NTDs in Prevention has been found with acid, C, vitamin C, and vitamin prevention was seen with folic acid, acid, vitamin B6, vitamin or of of folic acid still is being suggested that there may be a rather than a deficiency have found that the Hcy level is significantly for of infants who have NTDs during pregnancy than for vitamin controls. is a and a defect in it would to increased levels of an abnormality in Hcy particularly an abnormality of by folic acid is is in to produce basic and for of which may be the responsible for incidence of NTDs is the the of and of maternal and The two are as and should not be as part of the of women at risk of NTDs. is used both as a and as a after positive results on All cases of anencephaly and approximately of cases of spinal bifida could be by of and in the rates of NTDs in the United States before the availability of prenatal the of a substantial environmental in the etiology of these defects data that folic acid can to NTDs when at of 4 to women who already have had an NTD-affected pregnancy. Results of the British MRC study suggest that the of other vitamins to the folic acid no in of NTDs. on the findings from several folic acid supplementation at a of 4 1 to months prior to conception and the first trimester is for women planning pregnancy who have had a pregnancy affected by an results of controlled trials that folic acid supplementation will not prevent all NTDs. The protective effect demonstrated in studies of folic by the of NTD from none to it is to estimate that administration of folic acid supplementation to all women capable of pregnancy would reduce the incidence of NTDs in the United use of periconceptional folic acid supplements not for the of such is to be reduced if there is a lower risk of The possibility of the number of cases of NTDs in the United States by with the of of folic acid per day an important in public should be made to that all women capable of becoming pregnant 0.4 mg of folic acid daily to this of this recommendation a because 50% of the pregnancies in the United States are it is if not to a daily intake of 0.4 mg of folate diet the protective of vitamin supplementation, women begin to take supplements before conception a less if pregnancy of is a health that can intake of folic acid during the critical of In the USPHS that folic acid of and corn would become as of is to the daily intake of folic acid among women of age by about would prevent about spina bifida and anencephaly birth defects each year and as as premature each year from most commonly risk of is the of that often is associated with vitamin might the diagnosis and treatment of this the for should be of this possibility and that vitamin although occurring most commonly in the can occur at any Also, care should be taken to total folate to less than 1 the of a intake of folate in the periconceptional may be by women who could become pregnant to a diet with a daily vitamin with folic or these should be to other health and the public about the value of folic acid supplementation in preventing NTDs. surveillance programs should the prevalence of NTDs in fetuses and and clinical research into the by which folic acid NTDs should be In more clinical trials are to determine the of folic acid in preventing the occurrence and recurrence of NTDs.

High frequencies of vitamin B12 and folic acid deficiencies and hyperhomocysteinemia in Taiwanese male patients with oral submucous fibrosis

Vitamin B12 deficiency in infancy may cause failure to thrive, severe neurological disorders and megaloblastic pancytopenia. It is well known that infants born with deficient vitamin B12 storage have increased the risk of vitamin B12 deficiency. Vitamin B12 deficiency is more prevalent in infancy in Sanliurfa province (at the southeast region of Turkey). The aim of this study was to determine the frequencies of vitamin B12, folic acid and iron deficiencies in pregnants and their babies at birth and to what extend the mothers' deficiency becomes effective on babies' deficiencies. The study groups were constituted by 180 pregnant women and their single and term babies. Venous blood samples of pregnants were obtained 1-3 h before delivery and babies' cord bloods were collected at birth. Vitamin B12 and folic acid levels were measured with electro chemiluminiscence method; serum iron and iron binding capacities were measured by colorimetric method and complete blood counts were performed by automatic blood counter. Mean vitamin B12 levels in maternal and cord blood serum were 130 +/- 61.7 pg/ml and 207 +/- 141 pg/ml; mean folic acid levels were 8.91 +/- 6.46 ng/ml and 17.8 +/- 11.8 ng/ml; mean serum iron levels were 56.9 +/- 37.5 microg/dl and 147 +/- 43.2 microg/dl; and mean transferrin saturations were 11.8 +/- 8% and 65.6 +/- 24%, respectively. There were vitamin B12 deficiency (<160 pg/ml) in 72% of the mothers and 41% of the babies, and severe deficiency (<120 pg/ml) in 48% of the mothers and 23% of the babies. Folic acid deficiency was found in 12% of the mothers, but was not found in the babies. There were iron deficiency in 62% of the mothers and 1% of the babies. There were statistically significant correlation between maternal and cord blood serum vitamin B12 levels (r = 0.395, P < 0.001) and folic acid levels (r = 0.227, P = 0.017), while there were no correlation between maternal and cord blood iron levels and transferrin saturations. The study results showed that vitamin B12 deficiency is prevalent in pregnants in this region and that 41% of infants have born with deficient vitamin B12 storages. Therefore, prophylactic use of vitamin B12 by pregnant women in Sanliurfa and other poor communities could have considerable benefits to prevent vitamin B12 deficiency and its complications in infants.

Background: Vitamin B12 deficiency in pregnant women is an important health issue which not only affects mothers but also their infants. The aim of this study is to reveal the frequency of vitamin B12 and folic acid deficiency in pregnant women and their newborn babies, to evaluate the relationship between maternal and neonatal vitamin B12 and folic acid levels, and to determine the risk factors for vitamin B12 deficiency. Materials and Methods: This prospective study included 600 pregnant women (gestational age: 38-42 weeks) who presented to obstetrics departments in Şanlıurfa Province and their newborn infants without perinatal complication (birth weight≥2500 g). The lower limit for vitamin B12 was defined as 200 pg/mL. Data regarding age, number of child, medication, comorbid disease or being vegetarian or not were recorded in all mothers. Results: Vitamin B12 deficiency was found in 73.8% of the included pregnant women, and folic acid deficiency was found in 10.3%. Again, 70.5% of newborn babies were found to have vitamin B12 deficiency and 3.7% to have folic acid deficiency. It was concluded that vitamin B12 levels in newborn babies were related to maternal levels. Conclusions: As a result, it has been shown that a significant portion of newborns in Turkey have vitamin B12 deficiency. Vitamin B12 levels were quite low in mothers who gave birth recently. The deficiency of vitamin B12, which plays a major role in brain development upon intrauterine period, is a preventable cause of neurological deficit. Thus, it is highly important to screen and treat vitamin B12 deficiency before onset of clinical symptoms. We believe that our study is beneficial in this regard.

Vitamin B₁₂ Deficiency Masquerading as Clozapine-Resistant Psychotic Symptoms in Schizophrenia

Background and Aim: DNA synthesis, which is required for cell division and proliferation, is provided by transformation of homocysteine to methionine. Vitamin B12 is the cofactor of methionine synthesis that plays a role in this reaction. vitamin B12 deficiency causes the accumulation of homocysteine. Hyperhomocysteinemia has been associated with arteriosclerosis and cerebral embolism. Proton pump inhibitors are widely used drugs that inhibit H+/K+-ATPase, which is found in parietal cells. Because HCl is required for separation of vitamin B12 from food, the ingestion of proton pump inhibitors can cause vitamin B12 deficiency, which can lead to hyperhomocysteinemia. In our study, we investigated the effect of the use of proton pump inhibitors on vitamin B12 and serum homocysteine levels. Material and Methods: In this study, 44 patients who had been using proton pump inhibitorsfor at least 3 months because of various indications and 38 patients (control group) who had never used proton pump inhibitors who admitted to our outpatient clinic between March and July 2009 were included. The ages of the patients and the control group, serum levels of homocysteine, vitamin B12 and folic acid, mean corpuscular volume (MCV) values, and duration of proton pump inhibitors use were recorded. In addition, among the patients on proton pump inhibitors, the fasting serum levels of homocysteine, vitamin B12 and folic acid and MCV values were compared between patients using proton pump inhibitors for less than 2 years or more than 2 years. Results: The average duration of proton pump inhibitors use was 19.5 months in the patient group. There was no significant difference between patients and controls in mean age (in patient group: 39±14, in control group: 41±5; p=0.7) and gender (patient group: 19 men, 25 women, control group: 13 men, 25 women; p=0.4). No significant difference was detected between patient and control groups when comparing in terms of homocysteine (patients: 9.98±4.79, controls: 9.40±0.527; p=0.5), VB12 (patients: 328±305, controls: 264±105; p=0.2), folic acid (patients: 9.20±3.20, controls: 8.91±2.94; p=0.7), and MCV (patients: 83±11, controls: 86±8; p=0.1). There were no differences between homocysteine, vitamin B12, folic acid and MCV levels when the patients were compared among themselves regarding the use of proton pump inhibitorsfor more or less than 2 years. Conclusion: According to our study, long-term use of proton pump inhibitors showed no significant effect on the levels of vitamin B12 and consequently on the level of homocysteine. For this reason, we can say that these patients do not have greater cardiovascular risks caused by hyperhomocysteinemia with respect to the general population.

Context:This study summarizes the prevalence of vitamin B12 and folic acid deficiency in the population coming to tertiary care center in Western Maharashtra along with the main presenting symptom routinely misinterpreted in daily practice.Aims and Objectives:1. To study the prevalence of vitamin B12 and folic acid deficiency in the population of western Maharashtra. 2. To correlate the symptoms with serum vitamin B12 and folic acid levels.Materials and Methods:The present study is a cross-sectional observation study carried out on patients from western Maharashtra seeking medical attention on outpatient and inpatient basis in the medicine department of a teaching institute in Karad. One-hundred patients were selected on basis of below mentioned symptoms viz. tingling and numbness in extremities, dizziness, unsteady gait, early tiredness, forgetfulness, proximal weakness, distal weakness, chronic headache, less interest in work, chronic loose stools, strict vegetarians, alcoholics, intake of medications like anti-tubercular treatment, surgery involving terminal ileum. Serum vitamin B12 and folic acid levels of these patients were observed. Deficiency of vitamin B12 and folic acid was studied in 4 groups: (a) Absolute vitamin B12 deficiency; (b) Absolute folic acid deficiency; (c) Borderline vitamin B12 deficiency; (d) Combined vitamin B12 and folic acid deficiency.Results:Of the 100 cases, 33% patients were vegetarian. Folic acid deficiency formed the major chunk of deficiency group. Six percent patients had neuropsychiatric manifestations. Depressive illness in 1% patients, dementia in 0% patients, forgetfulness in 1% patients, mania/hallucination in 0% patients each, and chronic headache in 1% patients. Neuropathy in form of loss of reflexes, decreased touch sensation was present in 9% patients. Posterior column involvement viz. Loss of joint position, vibration, positive Romberg's sign were present in 34% patients of vitamin B12 and folic acid deficiency.Conclusion:In a small study, it was found that megaloblastic anemia may have symptoms and signs referable to several systems including hematology, dermatology, gastrointestinal, neurology, and neuropsychiatry.

The effects of dietary vitamin B12 and methionine deficiency, and the in vitro addition of methionine, homocysteine, or folic acid on the methylation of dUMP to dTMP were studied in rat bone marrow culture. Vitamin B12 or methionine deficiency had no effect on the methylation reaction or on bone marrow folate levels although the vitamin B12 content in bone marrow was reduced in vitamin B12 deficiency. In vitro addition of vitamin B12 or folic acid also had no effect on the methylation of dUMP. In vitro addition of methionine reduced the methylation of dUMP and increased the proportion of 5-methyltetrahydrofolate at the expense of other folate coenzymes. The reason for this 'anti-folate' effect of methionine, which is the opposite to that found in liver, was not clear. The presence of 5,10-methylenetetrahydrofolate reductase and 5-methyltetrahydrofolate-homocysteine methyltransferase were confirmed in rat bone marrow and they were inhibited by S-adenosylmethionine and methionine, respectively, in a similar fashion to that found with the liver enzymes. Homocysteine had no effect on the proportions of the various folate coenzymes in bone marrow but did inhibit the incorporation of deoxyuridine and deoxythymidine into DNA. It appeared that homocysteine exerted at a non-folate dependent step beyond the formation of dTMP.

Aim:The most important function of vitamin B12 is to accomplish DNA synthesis, which isnecessary for cell division and proliferation. Deficiency of vitamin B12 causesmegaloblastic anemia, retardation of growth, and delay in neuromotor maturation.Newborns whose mothers have vitamin B12 deficiency are born with low vitamin B12storages, and are at risk in terms of vitamin B12 deficiency symptoms during infancy.The aim of our study was to investigate the frequency of anemia and deficiency ofvitamin B12, folic acid, and iron in pregnant women living in our region, in theirnewborn babies, and during the infancy period of these babies. Another aim of our studywas to investigate the correlation between the levels of these vitamins in newborns andin their mothers.Material and Methods:In our study, 250 pregnant women at 38–42 gestational weeks, who were admittedfor delivery to Gynecology and Obstetrics Clinic and their babies with a birth weightover 2500 g were included in the study.Results:We determined that 24.8% of the pregnant women had anemia, 28% had lowferritin levels, 90.4% had vitamin B 12 deficiency, and 22.4% had folicacid deficiency. Some 3.2% of the newborns had anemia, 2.8% had lowferritin levels, and 72.4% had vitamin B12 deficiency. Among the infants whopresented for a follow-up visit at 6 months of age, 22.3% had anemia,14.9% had low ferritin levels, 40.4% had vitamin B12 deficiency, and1.06% had folic acid deficiency. In addition, we found that the levels of vitaminB12 and folic acid in newborns were related to the levels of vitamin B12 and folic acidin their mothers.Conclusion:Development of low vitamin B12 stores in newborns and the development of vitamin B12deficiency during infancy, which may result in irreversible complications includingneurologic complications, can be prevented by preventing vitamin B12 deficiency duringpregnancy.

Aging is associated with increased incidence and prevalence of chronic diseases, and the role of micronutrient deficiencies in the development of diseases is important. Vitamin B12 and folic acid deficiency are often associated with increased homocysteine (Hcy) levels. In our study, we aimed to detect the relationship between Hcy levels by examining vitamin B12 and folate levels in the healthy elderly Turkish population. In our study, the levels of vitamin B12, folate, and Hcy were analyzed and examined in 657 elderly and 642 non-elderly healthy adults admitted to the Internal medicine outpatient clinic. Vitamin B12 &lt;200 pg/mL was considered to be deficient. Folic acid &lt;5 ng/mL was considered a deficiency, and Hcy&gt;15 µmol/L was considered a high concentration. Vitamin B12 levels were detected to be significantly decreased in the elderly group compared to the non-elderly group, while Hcy levels were marked to be increased (p&lt;0.05). Women had lower levels of Hcy and higher levels of vitamin B12 and folate (p&lt;0.05). There was a moderate negative correlation between Hcy and vitamin B12 levels in the elderly group (r=-0.576; p&lt;0.0001), and a moderate negative correlation between Hcy and folate (r=-0.510; p&lt;0.0001). In the elderly group, 21.5% had vitamin B12 deficiency and 21.6% had folate deficiency. An increase in Hcy level was detected in 54.8%. Those with Hcy levels &gt;15 µmol/L had vitamin B12 deficiency in 38.4%, folate deficiency in 36.0%, and both vitamin B12 and folate deficiency in 15.8%. Our results indicate that it is important to measure vitamin B12, folate, and Hcy in the elderly, given the significant growth in the elderly population. We predict that vitamin B12 and folate supplementation, when necessary, may be beneficial in preventing some common diseases in the elderly and increasing the standard of life of the elderly and their relatives.

Food-cobalamin malabsorption in the elderly

Higher frequencies of anemia, vitamin B12 deficiency, and gastric parietal cell antibody positivity in folic acid-deficient Taiwanese male oral submucous fibrosis patients

Objective: Descriptive study on maternal serum vitamin B12 and folic acid in term pregnancy and in umbilical cord blood that was performed in an inner city hospital with a mixed ethnic population in the region of Flanders in Belgium. Materials and Methods: A prospective cohort study that took place from April 1 until May 31, 2011. Plasma folic acid and vitamin B12 were measured in maternal and umbilical cord blood from all term uncomplicated deliveries in a single regional hospital. Data on age, previous obstetric history, ethnicity, nutritional intake, and use of vitamin supplements were registered. Results: Data were collected from 110 patients, mean maternal serum vitamin B12 was 243.9 pmol/l and mean folic acid level was 43.0 nmol/l. Using a cutoff of respectively 150 pmol/l for vitamin B12 and 7.1 nmol/l for folic acid, 13% of the women were classified as vitamin B12-deficient and 23% were deficient for folic acid. Vitamin B12 deficiency was only seen in autochthonous Belgian women. A correlation between the maternal and umbilical cord levels was noted (R = 0.7 for vitamin B12, R = 0.85 for folic acid), but none of the umbilical cord levels demonstrated deficiency. Number of previous pregnancies and intake of supplements had no influence. Conclusion: Pregnant women in Antwerp, Belgium, frequently show vitamin B12 and folic acid deficiency, although a correlation exists with lower umbilical cord levels, the present limited data did not demonstrate any case of deficiency in umbilical cord blood. The frequency is highest in the autochthonous population and is not influenced by intake of vitamin supplements.